HW path notes Flashcards

Question

ATYPICAL LOBULAR HYPERPLASIA

Answer 1

A premalignant lesion of the breast which falls at the milder end of the spectrum of lobular neoplasia Considered borderline breast disease Pathology: Proliferation of monomorphic cells which are morphologically identical to lobular carcinoma in situ (LCIS) The distinction is that ALH occurs in a non-distended lobule or small lobular duct, whereas LCIS is characterised by distension Treatment is controversial. Some centres surgically excise, others do not. The risk of subsequent breast cancer is 4-6x higher after diagnosis (11x after LCIS)

Answer 2

Represents the next step up from atypical lobular hyperplasia along the malignant spectrum of lobular breast carcinoma Predominately occurs in pre-menopausal women, average age ~45yo. 10-15yrs younger than the mean age when invasive breast carcinoma occurs Pathology; Like most other lobular breast pathology, LCIS originates in the terminal ductal lobular unit Unlike ALH, the malignant cells fill and distend the lobular acini in LCIS Unlike invasive, they leave the basement membrane intact Do not express E-cadherin Usually incidentally identified The exception may be pleomorphic LCIS which is a more aggressive subtype A high risk marker for future development of invasive 15-30% chance of developing an infiltrating ductal or lobular carcinoma in the breast in which LCIS is discovered or in the contralateral breast Usually diagnosed with a core needle biopsy > excisional biopsy should be performed

Answer 3

An uncommon subtype of breast cancer Accounts for ~5% of all breast cancers Tend to occur in younger women, more than other breast cancer types Mean age of presentation varies 46-54yo, but in 10% under 35yo Pathology: - Typically arises from supporting stromal cells of the breast - A well-circumscribed carcinoma composed of poorly differentiated cells with scant stroma and prominent lymphoid infiltration - Large pleomorphic nuclei, prominent nucleoli and high mitotic activity may be seen - The histological appearance can mimic poorly differentiated intraductal carcinoma no - Areas of necrosis may be present - More common in the BRCA 1 gene mutation setting Two types: Typical Atypica Better prognosis than for intraductal carcinoma. 89-95% 5yr survival

Answer 4

Mammography: Typically seen as a circular/oval type mass lesion with ill-defined or circumscribed margins at mammography There can be varying degrees of lobulation Calcification isn't usually a feature Ultrasound: Either homogenously hyperechoic, or hypoechoic with mild heterogeneity Enhanced through transmission may be present The level of hypoechogenicity can sometimes be marked MRI : May show diffuse enhancement post contrast

Answer 5

A form of breast malignancy characterised by infiltration of the nipple epidermis by malignant cells Most cases have an underlying focus or foci of in situ or invasive carcinomas, some are confined to the skin of the nipple-areola without underlying neoplastic foci Can represent 1-5% of breast malignancies The average age at diagnosis is ~6th decade 53-59yo Eczematous appearing changes of the nipple include reddening, scaling, hyperkeratosis and crusting of the nipple surface Can be classified into 4 clinical stages: 0: lesion is confined to the epidermis, without underlying ductal carcinoma in situ of the breast 1: associated with DCIS just beneath the nipple 2: associated with extensive DCIS 3: associated with invasive ductal carcinoma Treatment: traditionally a mastectomy with nodal dissection

Answer 6

In most cases there are malignant ductal cells that extend to the nipple surface through the terminal lactiferous ducts Malignant epithelial cells infiltrate and proliferate in the epidermis, causing an eczema-like rash of the nipple and areolar skin There are several histological variants: Adenocarcinoma-like cell Spindle cell Anaplastic cell Acantholytic cell Pigmented cell

Answer 7

Undetectable in ~50% of cases on mammo Apparent features: Skin thickening, nipple retraction, subareolar or more diffuse malignant microcalcifications, and discrete subareolar masses MRI: Abnormal nipple enhancement and linear clumped enhancement indicative of DCIS in association with Paget disease

Answer 8

Benign excess of male breast tissue, usually reversible Not a risk factor for male breast cancer Greater prevalence in two groups: Adolescent boys 50-60% Older men 70% Symptomatic cases are much lower Pathology: - Enlargement of the male breast due to benign ductal and stromal proliferation - A hallmark is its central symmetrical location under the nipple - Tends to be unilateral and/or asymmetrical - Key is the imbalance between oestrogen action relative to androgen action at the breast tissue level Aetiology: Hormonal Neonate – maternal oestrogen Puberty – high oestradiol levels Elderly – decline in testosterone levels Hypogonadism/androgen deficiency states: - Klinefelter syndrome - Anorchism - Testicular failure e.g. testicular cancer Drugs Systemic disorders - Advanced alcoholic cirrhosis - Chrnic pulmonary disease e.g. emphysema, - TB - Haemodialysis in chronic renal failure - Hyperthyroidism - Malnutrition Tumours – particularly oestrogenic tumours - Adrenal carcinoma - Hepatoma - Lungcancer - Pituitary adenoma - Testicular cancer – including sex-cord stromal, and germ cell tumours Idiopathic

Answer 9

A rare benign inflammatory disease of the breast that can mimic breast cancer Diabetic mastopathy is a closely related entity, sometimes used synonymously May present as a palpable mass, may be painful, and may be bilateral Associated with autoimmune disease e.g. Hashimoto thyroiditis, SLE and sjogrens syndrome Dense fibrous tissue with hard lesions that can be large – up to 6cm.

Answer 10

A benign breast condition that represents calcification of inspissated secretions in or immediately adjacent to ectatic benign ducts Typically seen in non-pregnant and non-lactating females Thought to represent aseptic inflammation with infiltration of plasma cells and lymphocytes in the breast tissue from the extravasation of intraductal sections into periductal connective tissue Imaging: Thick, linear, rod-like or cigar-shaped calcifications Can be up to 10mm long Tend to be bilateral, often symmetrical and orientated to point towards the nipple. Branching may be seen Larger in length and calibre than DCIS, with a smoother outline Benign entitiy. No increased risk of malignancy

Answer 11

Within the breast, a pathological process that occurs when there is saponification of local fat Benign inflammatory process, increasingly more common with the greater use of breast-conserving surgery and mammoplasty procedures Most at risk are middle aged women with pendulous breasts Onset can be delayed 10+ years after surgery

Answer 12

Disruption of fat cells, with the formation of vaculoes containing the remnants of necrotic fat cells The vaculoes are surrounded by lipid-laden macrophages, multinucleated giant cells and acute inflammatory cells Fibrosis develops during the reparative phase, peripherally enclosing an area of necrotic fat and cellular debris Eventually fibrosis may replace the area of degenerative fat with a scar, or loculated and degenerated fat may persist for years within a fibrotic scar Aetiology: Direct trauma Nodular panniculitis Plasma cell mastitis

Answer 13

Variable appearance Initially can be an ill-defined and irregular, spiculated mass-like area Calcification may be present - Usually peripheral with a stippled curvilinear appearance, creating the appearance of lucent 'bubbles' in the breast parenchyma Low density centre Tumour formation is not part of fat necrosis, although it may be clinically palpable With time, becomes more well defined and well-circumscribed, giving rise to an oil cyst - Oil cyst – fine curvilinear calcification of the walls - The centre becomes increasingly homogenous with fat density - Calcifies in 5% Ultrasound: - Acute – increased echogenicity due to oedema of the fatty tissue - Subacute – ill defined complex cystic lesion surrounding oedematous fat - Late – calcified walls, posterior shadowing Aspiration: milky, emulsified fat appearance - Can have fat globules drifting

Answer 14

A rosette-like proliferative breast lesion Not related to surgical scarring An idiopathic process with sclerosing ductal hyperplasia A mimicker of scirrhous breast carcinoma Diagnosis cannot be made on imaging alone Rare in women <40yo and >60yo Clinically – not palpable, no skin thickening or retraction Considered a high risk breast lesion, and histological differentiation is requried Associations 30% of cases, associated with DCIS and tubular carcinoma of the breast - Occurrence is higher when associated atypia on histology Other associations: Atypical ductal hyperplasia Atypical lobular hyperplasia FNA and core biopsies can underestimate the underlying associated malignancy = vacuum assisted biopsy is recommended

Answer 15

Benign hyperplastic proliferative disease of the breast Mechanisms include localised inflammatory reaction and chronic ischaemia with subsequent slow infarction Histopathologically: Hyperplastic tissue cells and a central fibrous core, with a radial extension of tubular structures mimicking infiltrating carcinoma The tubular formation has two rows of cells, epithelial and myoepithelial The malignant potential is 2x greater than in the normal population without radial scar

Answer 16

Spiculated appearance, similar to carcinoma, but the centre tends to be translucent, low-density rather than a mass Breast tissue behind the lesion is usually as dense centrally as peripherally No mass Spicules running from the centre are in general longer and gracile than those of a carcinoma Long, thin with radiating radiolucent linear structures, which against a radiolucent fat background gives a black star appearance Microcalcifications are possible but rare Other features of a carcinoma are rare e.g. skin thickening and retraction No visible scirrhous reaction in the radial scar Ultrasound: - Often ill-defined and disturbs the architecture of surrounding breast parenchyma - Usually round, oval or lobulated - Variable internal echoes can be found

Answer 17

Breast carcinoma limited to the ducts with no extension beyond the basement membrane – so the disease has not infiltrated the parenchyma of the breast and lymphatics, and therefore cannot metastasize Associations: Up to 11% of predetermined ductal carcinoma in situ on imaging may have an invasive component at the time of biopsy 20-25% may have an invasive component following surgical excision Risk factors: Increasing age Family history of breast cancer Nulliparity Age 30+ at the birth of first child Most are asymptomatic

Answer 18

Pathology: Precursor of invasive breast carcinoma Represents a spectrum of disease Ductal carcinoma in situ isn't a single entity, but a spectrum of disease Markers: E-cadherin may help to differentiate from lobular Subtypes: Largely two, based on central necrosis, grade and cell type: - Comedo – large cell: more aggressive form "comedocarcinoma" - Non-comedo – small cell: less aggressive, can be further divided into - Cribiform - Micropapillary - Papillary - Solid

Answer 19

Varied manifestation, with casting-type calcifications being more common 50-75% of cases Other manifestations include a soft tissue opacity either with or without associated calcifications Linear calcs are more likely to be comedo-type, while granular calcs are more often non-comedo Occasionally can present as a simple mass or asymmetry without calcification ~8% Calc underestimates the distribution, since not all the DCIS calcifies US Microlobulated mild hypoechoic mass with ductal extension and normal acousitc transmission MRI Non-mass enhancement, most commonly with a segmental or linear distribution and clumped or heterogenous internal enhancement pattern

Answer 20

A relatively common benign localised proliferative lesion in the breast Mainly seen in young women ~19-23yo, unusual over 30 Present with a firm, well-defined, mobile mass often in the periphery of the breast Usually with no nipple discharge Pathology: - A papillary proliferation of the ductal epithelium which partly fills up smaller ducts and distends them - Well-circumscribed mass containing multiple small cysts (<2cm) within a dense fibrous stroma - Can vary in size 1-8cm US: - Ill defined, inhomogenous hypoechoic mass with multiple small (up to 4mm) predominantely peripheral cysts Mammo: typically negative, occasionally may show pleomorphic or amorphous `microcalcifications, asymmetric density or a prominent intraductal pattern Galactography: multiple irregular filling defects within the breasts Benign, but considered to be a marker for familial breast cancer

Answer 21

A subtype of invasive ductal carcinoma Account for ~1% of breast cancer Peak age at presentation may be comparatively younger than other types of breast cancer Majority are non-palpable and invariably found incidentally at screening rather than manifesting with clinical findings

Answer 22

Pathology: May contain other histologic elements, but an excess of 75% tubular elements is usually required for the diagnosis of tubular carcinoma A distinguishing feature is a single layer of cells lining tubules with loss of lobular architecture and surrounding infiltration The glands in tubular carcinomas lack myoepithelial cells Lesions may be multifocal or multicentric in ~15% Variants : Tubulolobular carcinoma - an invasive lobular carcinoma with features of tubular carcinoma, but behaves as other ILCs with regard to prognosis Associations: Ductal carcinoma in situ (DCIS) - can be an association in more than 50-65% of tubular carcinomas

Answer 23

Typically small (<1cm), spiculated and can occur without calcifications The appearance mimics typical IDC not otherwise specified, manifesting as one or more small spiculated masses The spicules are often longer than the central mass Amorphous microcalcifications may be present in 10-15% US: Also mimic IDC not otherwise specified, manifesting as a hypoechoic solid mass with ill-defined margins and posterior acoustic shadowing The lesions are often rounded, tall as broad Differentials: Radial scar/complex sclerosing lesion The tubular carcinoma is dense centrally, where the radial scar is not

Answer 24

Sclerosing lymphocytic lobulitis

Answer 25

A benign proliferative condition of the terminal duct lobular units characterised by an increased number of acini and their glands Manifests as multiple small, firm, tender nodules, fibrous tissue and variable microcysts within the breast Can be considered a borderline breast disease Clinical presentation: - Recurring pain that tends to be linked to the menstrual cycle - Usually detected during screening, with biopsy confirmation - Can appear as a focal or diffuse lesion - Not palpable in 80% of cases, although in some it may cause skin retraction Not premalignant, but an independent risk factor for the development of subsequent breast cancer 1.5-2x higher risk of developing breast cancer

Answer 26

A type of adenosis in which enlarged acini become slightly distorted by surrounded stromal fibrosis The normal lobular architecture of the breast is maintained but becomes exaggerated and distorted Assoc: Can be seen as a component of other proliferative lesions - Intraductal and/or sclerosing papilloma - Complex sclerosing lesion - Fibroadenoma - Breast cancer, both invasive and in situ

Answer 27

Mammography - has a wide range of mammographic presentations, and can be difficult to distinguish from an infiltrating carcinoma Mass - with irregular to well defined contours Architectural distortion Microcalcifications - Present in 40-55% of cases - May be amorphous, pleomorphic or punctate - More commonly clustered, but may be diffusely scattered

Answer 28

The presence of a benign tumour like breast mass in women with long-standing type 1 or 2 insulin-dependent diabetes mellitus Pathology: - A form of lymphocytic mastitis and stromal fibrosis - There is dense fibrosis and predominantly B-cell lymphocytic infiltrate surrounding the ducts, lobules and vessels - The exact pathogenesis is poorly understood and likely multifactorial US Irregular hypoechoic masses with marked posterior acoustic shadowing

Answer 29

A benign, relatively uncommon form of stromal (mesenchymal) overgrowth within breast tissue that derives from a possible hormonal aetiology Typically affects women of reproductive age, rarely affects males Clinical presentation: the tumoural form of PASH commonly manifests as a single, circumscribed, palpable mass in a premenopausal female Can be large (5-6cm) in diameter Often grow over time and may recur after excisional biopsy in 10% of cases Neither associated with malignancy or considered to be premalignant

Answer 30

Represents a clinicopathologic spectrum ranging from focal, incidental microscopic findings to clinically and mammographically evident breast masses The development is presumed to be related to the interaction of progesterone receptions Lesions can be microscopic or nodular (tumourous) On gross pathology, typically a well-circumscribed, firm, rubbery mass with solid, homogenous, grey-white cut surface Microscopic - characterised by the presence of open slit-like spaces in dense collagenous stroma which is lined by a discontinuous layer of flat, spindle-shaped myofibroblasts with bland nuclei Can also contain complex anastomosing spaces that may be confused with angiosarcoma on histo

Answer 31

Features are not specific enough for a prospective diagnosis Mammography: - A circumscribed or partly circumscribed mass - Often present as an asymmetry/focal asymmetry - Typically lack calcification US - Most often an oval or round circumscribed mass - Often hypoechoic and may be slightly heterogenous - imaging appearance may be similar to that of a fibroadenoma

Answer 32

Tends to occur in older women, where prevalence of as much as 7% is found among women 75+ yo, whereas the prevalence is only 1% in women younger than 35 If palpable, tend to be soft masses Purely mucinous subtype carries a good prognosis compared to other adenocarcinomas 5yr survival 95% stage 2, 75% stage 3 and 35% stage 4 Lower tendency to metastasise

Answer 33

The dominant feature is the presence of mucin within and surrounding cancer cells - The mucin: cell ratio can vary from lesion to lesion A core biopsy specimen usually gives a gelatinous appearance Microscopically, it is formed by large mucin lakes surrounded by mucous-producing cancer cells Histologically divided into: - Hypocellular A - pure mucinous breast cancer - Hypercellular B - variable area of DIC-NOS component - Can be infiltrative and carries a worse prognosis

Answer 34

The majority of well-marginated breast masses are benign, but 10-20% of breast malignancies could be well-circumscribed, such as mucinous but also papillary, medullary, metaplastic carcinomas and a malignant phyllodes tumour The presence of mucin results in a low-density and relatively well-defined lobular mass Sometimes they have partly faded or obscure margins Up to 20% can be occult on mammo Calcifications an be rare in pure mucinous types US - Often display mixed echogenicity with mixed solid and cystic components - Posterior acoustic enhancement is common - At times, the lesion can be isoechoic to breast tissue on US - Mixed cystic and solid components, distal enhancement and microlobulated margins are commonly found - Homogeneity on sonography is associated with the pure type of MCB, where the margins are usually well defined, and the tumour is iso-echogenic relative to the fat surrounding the breast tissue on US MRI One of the few high T2 signal lesions

Answer 35

Exceptionally rare, and only accounts of <0.25% of male malignancies The diagnosis is sometimes delayed The average age is 60-70yo, later than female breast cancer Most commonly men present with a painless subareolar mass Location - Favours the subareolar area or upper outer quadrant - Favours a slightly eccentric location relative to the nipple

Answer 36

Majority are invasive ductal carcinoma (85-90%) or ductal carcinoma in situ Risk factors: Exposure to ionising radiation Cryptorchidism Testicular injury/infectious orchitis Increased levels of oestradiol Klinefelter syndrome Hepatic cirrhosis BRCA2 gene mutation Family history Prostate cancer Chest trauma Imaging: Subareolar mass, often round/oval/lobulated, Calcifications tend to be fewer in number and coarser than in female breast cancer

Answer 37

A rare vascular breast malignancy Tend to occur in younger women, in their 3rd-4th decades Secondary angiosarcoma, related to prior therapy of breast cancer occurs in older women (peak 6th decade) The classical presentation is painless localised blue or purple colour change of the breast skin, with singular or multifocal lesions which may resemble other benign vascular lesions such as angioma or telangiectasis Patients may present with swelling, a sensation of fullness, or rapid breast growth Extremely aggressive with a poor prognosis

Answer 38

Pathology: Primary Secondary - Radiation induced - Lymphoedema-associated cutaneous angiosarcoma Location - Primary: within the breast parenchyma, with secondary involvement of the skin - Secondary: mainly involves the skin, with or without involvement of the underlying breast parenchyma Associations: - Prior radiation induced breast angiosarcoma tends to occur after a significant latent period post-radiation ~5yrs - Stewart-Treves syndrome Imaging Can be occult MRI

Answer 39

Involvement of the breast with lymphoma, may be primary or secondary Both primary and secondary are rare Secondary is the most common type Typically 60-70yo Presents as a palpable mass or diffuse thickening of the breast Axillary lymph nodes are enlarged in a substantial minority

Answer 40

Primary - Typically a B-cell type non-Hodgkin lymphoma, usually diffuse large B cell lymphoma It must: - Disease should be in the breast or in close proximity to breast tissue - No previous history of extramammary lymphoma - No evidence of widespread disease, except ipsilateral axillary LN may be involved Secondary - More frequently NHL than HL

Answer 41

Papillary carcinoma of the breast is a rare ductal breast malignancy Typically present in postmenopausal patients, 63-67yo May manifest clinically as a palpable mass or nipple discharge Approximately 50% arise in the retro-areolar/subareolar region of the breast Better prognosis than commoner types of malignancy Imaging - The most common mammographic pattern is a round, oval or lobulated mass - The margins are usually circumscribed, but may be obscured or indistinct - Accompanying microcalcifications or a dilated ductal pattern may be present US - Hypoechoic and solid mass, often with posterior acoustic enhancement - Complex cystic and solid masses may be evident - Relatively vascular, often colour flow components Galactography - may be helpful for patients with nipple discharge May demonstrate ductal obstruction, filling defects or focal/diffuse ductal wall irregularity MRI Usually round or oval mass with well-defined margins

Answer 42

May be solitary or multiple Several subtypes: - Papillary ductal carcinoma in situ - features of intraductal carcinoma - Intracystic papillary carcinoma - if a cystic component is present - Solid papillary carcinoma - if no cystic component is detected Typically well-circumscribed, often contain haemorrhagic and cystic areas Characterised by a frond-like growth pattern on a fibrovascular core lacking a myoepithelial layer Four potential cellular patterns: - Cribriform - Compact columnar epithelial - Stratified spindle cell - Transitional form - similar to urothelial tumours

Answer 43

The most common mass within the milk ducts of the breast Benign, but may contain atypia or carcinoma Epidemiology: Exclusively women Classically 40-50yo Often asymptomatic or with nipple discharge Discharge is more common in central vs peripheral papillomas Bloody discharge may have a higher association with atypical or malignant lesions

Answer 44

Proliferative tumours originating from the walls of the milk ducts, typically growing within the ducts and tending to cause local ductal obstruction Composed of monotonous epithelial/myoepithelial cells encompassing a papillary fibrovascular core Characteristically grow to form smooth well-circumscribed nodules Typically small <10mm Most commonly ~3.5cm from the nipple, but can be anywhere from anterior to posterior depth The central question is whether there is any evidence of cellular atypia - Any > surgical excision Can occur adjacent to other significant lesions e.g. atypical ductal hyperplasia or DCIS May be solitary or multiple Multiple = more than 5, papillomatosis Increased malignancy Subtypes Sclerosing papilloma of the breast Location: Central - within a major subareolar duct, often solitary Peripheral - with the terminal duct lobular unit, may be multiple

Answer 45

Mammogram Frequently normal Solitary or multiple dilated ducts, and a circumscribed benign-appearing mass, or a cluster of calcifications Galactography Filling defects, may outline the number, location, extent and distance from the nipple US A well defined solid nodule or intraductal mass which may either fill a duct or be partially outlined by fluid - either within a duct or by forming a cyst Colour doppler will demonstrate a vascular stalk MRI T2 bright Round ~75%, irregular ~25% Spiculated margin suggests malignancy 90% are solid

Answer 46

Caused by a mutation to either BRCA1 or BRCA2 genes These are tumour suppressor genes that encode proteins involved in DNA repair - Located on chromosome 17 and 13 respectively The risk of specific cancer types varies depending on the mutation BRCA1 Breast cancer Male breast cancer Ovarian Prostate Pancreatic Colorectal - 5x increase if <50yo Primary fallopian tube cancer BRCA2 Breast cancer Male breast cancer Ovarian cancer Prostate cancer Pancreatic cancer Colorectal cancer

Answer 47

A rare fibroepithelial tumour of the breast, which has some resemblance to a fibroadenoma Typically a large, fast growing mass that forms from the periductal stroma of the breast Predominantly a tumour of adults women, age 40-60yo - About 15yrs older than the typical age of a patient with a fibroadenom A locally invasive tumour . Treatment is usually with surgical excision Imaging Can be quite large at presentation Typically a non-specific large rounded oval or lobulated, generally well circumscribed Calcification may be seen in a very small proportion US - Non-specific - Inhomogenous solid appearing mass - Contain single or multiple, round or cleft-like cystic spaces and demonstrate posterior acoustic enhancement which is strongly suggestive of a phyllodes - Vascularisation is usually present in the solid component Indistinguishable from fibroadenomas on mammo and US

Answer 48

Leaf-like pattern of growth May be benign, borderline or malignant depending on the histologic features including stromal cellularity, infiltration at the tumour edge and mitotic activity Can resemble a giant fibroadenoma with both epithelial and stromal components

Answer 49

A relatively uncommon but aggressive form of invasive breast carcinoma with a characteristic clinical presentation and unique radiographic appearances. Inflammatory carcinomas account for 1-4% of all breast cancers, typically occurring in women between the 4th to 5th decades. Mimics mastitis: enlarged breast, indurated, erythematous, warm and may be tender and painful The skin is thickened and oedematous, classically with a "peau d’orange" appearance. Systemic symptoms of infection are absent While any subtype of primary breast carcinoma may be present, invasive ductal carcinoma tends to be the most prevalent histological type. Dermal lymphatic invasion is pathognomonic of inflammatory breast cancer, but doesn't necessarily need to be demonstrated to make the diagnosis The presence of tumorous cells in dilated lymphatics may be present in ~80% of cases Inflammatory breast cancer is a T4 tumour according to the standard TNM staging classification of breast cancer. If no results with biopsy, a skin biopsy may be indicated Tends to metastasise early Chemotherapy before surgery or radiation therapy is the current standard treatment

Answer 50

Mammographic findings include tumour mass and malignant microcalcifications. More specifically, inflammatory changes such as extensive skin and trabecular thickening/coarsening, and/or diffusely increased breast density are important clues that should lead the radiologist to suggest the diagnosis. US Hypoechoic shadowing mass which can be obscured on mammo by diffusely increased breast density Skin thickening, pectoral muscle invasion and axillary involvement ddx - Infective mastitis: painful breast with prominent erythematous changes and fevers - Locally advanced invasive breast carcinoma - Lymphomatous involvement of the breast - Other causes of breast oedema - Venous or lymphatic obstruction

Answer 51

"idiopathic medial aortopathy" or "pulseless disease" A granulomatous large vessel vasculitis that predominantly affects the aorta and its major branches May also affect the pulmonary arteries Strong female predominant 9:1 and tends to affect the younger patient Typical onset 15-30yo

Answer 52

Segmental and patchy granulomatous inflammation of the aorta which results in stenosis, thrombosis and aneurysm formation Half present with an initial systemic illness, the other 50% with late-phase complications Two phases of the disease: Pre-pulseless phase – characterised by non-specific symptoms Pulseless phase – presents with limb ischaemia or renovascular hypertension Chronically, there is inflammatory and obliterative changes in the aorta and its branches Cardiac complications can occur in up to 60% of cases Pulmonary artery involvement can occur in some situations

Answer 53

Type 1 – solely the aortic arch branches Type 2 A – ascending portion and/or at the aortic arch +/- branches of the aortic arch B – descending thoracic aorta +/- ascending or aortic arch + branches Type 3 – thoracic and abdominal aorta distal to the arch and its major branches Type 4 – sole involvement of the abdominal aorta and/or renal arteries Type 5 – generalised involvement of all aortic segments

Answer 54

A systemic inflammatory necrotising vasculitis that involves the small to medium-sized arteries More common in males, typically presents ~5th- 7th decade Associations: Hepatitis B and C Presents with systemic or focal symptoms Renal arteries are the most commonly involved, with pulmonary circulation typically spared Renal 80-90% - prominent site and major cause of death Cardiac ~70% GIT 50-70% Hepatic 50-60%

Answer 55

Transmural and necrotising inflammation of medium-sized arteries – mostly involving part of the circumference which causes weakening of the wall leading to microaneurysm formation and subsequent focal rupture Predilection for branch points Fibrinoid necrosis of vessels promotes thrombosis of vessels followed by infarction of the tissue supplied Fibrous thickening and mononuclear infiltration occur at a later stage Different stages of inflammation can occur in the same vessel at different points. PANCA – may correlate with disease activity

Answer 56

A common granulomatous vasculitis, affecting medium to large-sized arteries. Also known as temporal arteritis due to its propensity to involve the extracranial ECA branches –esp superficial temporal artery The most common primary systemic vasculitis, typically in older individuals >50, with a peak ~70-80 Female predilection Associations: polymyalgia rheumatica – seen in ~50% Markers: Serum erythrocyte sedimentation rate – markedly raised Serum C-reactive protein (CRP) - often markedly raised Complications: Thoracic aortic aneurysm – commonly ascending aorta Aortic dissection – more commonly the ascending aorta Vision loss Location: Any medium – large sized vessel, affecting the aorta ~20% of cases and its major branches, particularly the extracranial branches of the carotid artery Treatment: corticosteroid therapy and aspirin Differentials: Takayasu arteritis – young patients, and more proximal vessels Atherosclerotic disease

Answer 57

Similar to others Granulomatous inflammation of arteries with infiltration predominantly by histiocytes, lymphocytes and multinucleated giant cells Characteristic multinucleated giant cells are only found in ~50% of cases Areas of normal superficial temporal artery interspersed within inflamed sections – skip lesions in 8-28% 4 main histological patterns: Adventitial pattern – inflammatory cells restricted to the adventitia Adventitial invasive pattern – local invasion of the media with preservation of the intima Concentric bilayer pattern – inflammatory infiltration of adventitia and intima with preservation of the media Panarteritic pattern – inflammatory infiltrates in the three arterial layers

Answer 58

A heterogenous group of vascular lesions is characterised by an idiopathic, non-inflammatory, non-atherosclerotic angiopathy of small and medium-sized arteries Prevalence is unknown, typically young women 3:1 Diagnosed age 30-50yo Presentation: Hypertension, renal impairment – renal artery stenosis CNS symptoms Angina/MI/sudden death due to coronary artery Symptoms of mesenteric ischaemia Exact cause is unknown Any layer of vessel wall can be affected – intima, media or adventitia There is an absence of inflammatory cells 5 categories, according to vessel wall layer involvement: Intima 5% Intimal fibroplasia Media 90-95% Medial dysplasia ~70%, most common Perimedial (subadventitial) fibroplasia 15-20% Medial hyperplasia 8-10% Adventitia – rare, Adventitial fibroplasia 1% The outcome is arterial stenoses Typically a string of beads appearance Weakens the vessel and predisposes to dissection Location: Renal arteries Cervicoencephalic arteries Iliac arteries Coeliac trunk and mesenteric arteries Subclavian and axillary arteries

Answer 59

a multisystem necrotising non-caseating granulomatous c-ANCA positive vasculitis affecting small – medium sized arteries, capillaries and veins Predilection for the respiratory system and kidneys Slight male predilection, and onset approximately 50yo Diagnostic criteria: at least two of the following - Positive biopsy for granulomatous vasculitis - Urinary sediment with red blood cells - Abnormal chest radiograph - Oral or nasal inflammation An immune-mediated vascular injury In 90% of cases, cANCA is positive and levels correlate with disease activity. The classic triad of organ involvement: - Lung – 95% - upper respiratory tract/sinuses - 75- -90% Kidneys – 80%

Answer 60

Small to medium vessel necrotising pulmonary vasculitis Also classified under the spectrum of eosinophilic lung disease Incidence typically ~3rd - 4th Almost all patients have asthma and eosinophilia. Markers: p-ANCA ~75%

Answer 61

Requires a positive biopsy for vasculitis, and at least 4/6 criteria: Asthma Blood eosinophilia Mono/polyneuropathy Transient pulmonary infiltrates Paranasal sinus abnormalities - pain or radiographic abnormality Presence of extravascular eosinophils on a biopsy specimen

Answer 62

Can be histologically identical to classic polyarteritis nodosa or microscopic polyangiitis Around 25% will have renal disease Biopsy of parenchymal opacities may show a mixture of necrotising granulomas, eosinophilic pneumonia and granulomatous vasculitis

Answer 63

A multisystemic and chronic inflammatory vasculitis of unknown aetiology Mean age 20-30yo Most prevalent in the Mediterranean region, middle east and east Asia The highest incidence is in turkey Men 2-5x: 1 female The underlying process is vasculitis and perivascular inflammatory infiltrates affecting vessels of differing sizes in various organs

Answer 64

Associations: - HLA-B51 - Factor V Leiden mutation - Superficial thrombophlebitis The classic clinical triad: - Oral ulceration - Genital ulceration - Ocular manifestation

Answer 65

Cardiovascular manifestations 5-30% of cases - Thickening of the aorta and SVC - Inflammation of the veins leads to thrombosis, while arterial involvement includes arterial narrowing and aneurysmal dilatation Thoracic manifestations 1-8% - Pulmonary artery aneurysm: fusiform to saccular - Subpleural infiltrates GI manifestations 10-50% CNS 10-50% MSK > 50% develop articular disorders or arthralgia

Answer 66

Dilated tortuous superficially located venous channels that accompany the superficial veins of the upper or lower limbs More common in women than men, and usually lower limb Risk factors: - Pregnancy - Older age - Female - Prolonged standing

Answer 67

Incompetent saphenofemoral junction resulting from saphenofemoral valve insufficiency Results in regurgitation of blood during expiration and consequently raises the venous pressure in the great saphenous and other superficial veins Incompetent perforators are another causative factor when destruction of the valves inside the perforators allow the blood to move from the deep to superficial system and consequently increases the superficial venous pressure

Answer 68

A multisystem connective tissue disease caused by a defect in the protein fibrillin 1 - encoded by the FBN1 gene No recognised gender or racial predilection Clinically: General Tall stature, long arm span, joint laxity Spine High arched palate, scaphocephaly, kyphoscoliosis Hands Arachnodactyly Pelvis Pes planus, hallux valgus, club foot Chest wall deformity Pectus excavatum, pectus carinatum Ocular Ectopia lentis, myopia Cardiovascular Aortic regurgitation or mitral regurgitation, dolichoectasia

Answer 69

A multisystem connective tissue disease caused by a defect in the protein fibrillin 1 - encoded by the FBN1 gene Majority are autosomal dominant, with high genetic penetrance and variable expression Microscopic: the arterial walls may show cystic medial necrosis

Answer 70

Also known as lipohyalinosis A disease affecting the small cerebral arteries associated with lacunar infarction and deep white matter changes related to small vessel chronic ischaemia Histopathological landmarks: Irregular fibrosis and hyaline of small cerebral arteries associated with leakage of plasma proteins Often caused by chronic hypertension Fibrinoid necrosis and/or endothelial dysfunction causing local inflammation leading to vascular narrowing

Answer 71

When blood enters the medial layer of the aortic wall through a tear or penetrating ulcer in the intima and tracks longitudinally along the media Majority occur in elderly hypertensive patients Pathology: The normal lumen lined by intima (true lumen) and blood channel in the media (false lumen) Causes: Hypertension - medial degeneration Inherited connective tissue disorders - medial degeneration Atheroscerlosis - penetrating ulcer Vasculitis - inflammation Pregnancy - unknown

Answer 72

Primary hyperaldosteronism: excess aldosterone production Occurs secondary to: - Adrenal cortical adenoma ~35% - Bilateral adrenal hyperplasia ~60%, or - Adrenal carcinoma - rare Conn syndrome: when primary hyperaldosteronism is due to an aldosterone-producing adenoma Presentation: - Diastolic hypertension - Metabolic alkalosis - Hypokalaemia - Others: muscular weakness, paraesthesias, headache, polyuria and polydipsia Pathology: Differentiated from secondary hyperaldosteronism by measuring serum renin - Primary - low renin levels - Secondary - high renin levels

Answer 73

Associations: majority are sporadic. 5-10% have an underlying condition Multiple endocrine neoplasia type II - both MEN IIa and IIb - Account for 3%, almost never extra-adrenal, always bilateral Von Hippel-Lindau disease Neurofibromatosis type I Sturge-weber syndrome Carney triad Tuberous sclerosis

Answer 74

A type of paraganglioma Catecholamine-secreting tumours derived from chromaffin cells Typically demonstrate a nesting (Zellballen) pattern on microscopy Composed of well-defined clusters of tumours cells containing eosinophilic cytoplasm separated by a fibrovascular stroma Various scores are used (PASS/GAPP) to predict differentiation and likelihood of metastases Location: most frequently arise from the chromaffin cells of the adrenal medulla - 10% are not located in the adrenal glands - Extra-adrenal tumours are more likely to be malignant and metastasise - Can be found along the sympathetic chain, as well as in the urinary bladder and Organ of Zuckerkandl A rare but classical cause of uncontrolled secondary hypertension Investigate with collection of urinary catecholamines

Answer 75

Due to the effects of excessive glucocorticoids, which may be exogenous or endogenous Cushing disease: glucocorticoid excess solely due to an adrenocorticotropic hormone-secreting pituitary adenoma Cushing syndrome: encompasses all aetiologies of glucocorticoid excess Presentation: Round 'moon-shaped' face Progressive centripetal obesity and weight gain Prominent supraclavicular and dorsocervical fat pads "buffalo hump" Purple skin striae Easy skin bruising Acanthosis nigricans Proximal myopathy Depression and other mood disorders Osteoporosis Hypertension Hyperglycaemia and development of overt diabetes mellitus Immunosuppression and recurrent infections Signs of androgen excess: hirsutism/acne/changes in libido etc in females, but no so in men since the adrenal glands aren't a major source of androgens Investigation requires measurement of both cortisol and ACTH over a 24hr period - cortisol release is intermittent Complications: bilateral adrenalectomy in a patient with Cushing disease can lead to development of Nelson syndrome

Answer 76

Due to the effects of excessive glucocorticoids, which may be exogenous or endogenous Source - Adrenal adenoma 20% - ACTH-secreting tumour 80% - Pituitary adenoma 85% - Ectopic production 15% - Lung cancer - small cell lung cancer, broncial carcinoid - Small cell cancers of the thymus - Pancreatic neuroendocrine tumour - Phaeochromocytoma - Benign ovarian tumours - Primary pigmented nodular adrenal dysplasia (PPNAD) - rare - Adrenocorticotropin-independent macronodular adrenocortical hyperplasia (AIMAH) - rare - Corticotropin-releasing hormore-secreting tumour - very rare - Hypothalamic tumours - Ectopic production

Answer 77

Inadequate secretion of corticosteroids (glucocorticoids and mineralocorticoids) Two types: - Primary adrenal insufficiency - Addisons disease. From partial or complete destruction of the adrenal cortex - Secondary adrenal insufficiency - due to lack of stimulation of the gland Presentation: - Acute - fever, backpain, hypotension, weakness - Chronic - progressive lethargy, weakness, cutaneous pigmentation, weightloss Biochemistry: Low sodium, potassium, azotemia, hypercalcaemia, hypoglycaemia Pathology: Primary Idiopathic autoimmune disorders - 80% - Most common in developed countries Granulomatous disease: TB and sarcoid

Answer 78

Ischaemic necrosis of the renal papillae Necrosis occurs in the medullary pyramids Can present acutely or chronically Calyceal or ureteral obstruction by sloughed papillae manifests with flank pain, haematuria and varying degrees of renal impairment Anuria or oliguria may be present in the fulminant stage if renal failure develops Pathology: Characterised by necrosis and sloughing of papillary tissues which may result in a substantial loss of renal function Causes: NSAID NSAID Sickle cell disease Acetaminophen (paracetamol) and phenacetin Infection e.g. pyelonephritis, tuberculosis Diabetes mellitus or dehydration

Answer 79

Occurs as a result of severe systemic illness in a variety of settings, and can result in permanent renal impairment Pathology: Aetiology: Severe haemodynamic shock Microangiopathic haemolysis - Haemolytic uraemic syndrome Renal transplantation

Answer 80

Enlarged echogenic kidneys with multiple small cysts One of the commonest inheritable infantile cystic renal diseases No gender or racial predilection Age of presentation is variable and divided into perinatal, neonatal, infantile and juvenile forms Inverse relationship with the liver: The worse the kidneys, the better the liver The younger the presentation, the more the renal disease predominates

Answer 81

Results from a mutation in the PKHD1 (polycystic kidney and hepatic disease) gene located on chromosome 6p Results in bilateral symmetric microcystic disease occurring in the distal convoluted tubules and collecting ducts The number of ducts involved determines the age of presentation Perinatal type - most common Oligohydramnios and pulmonary hypoplasia 75% die within 24hrs of delivery Minimal hepatic fibrosis Neonatal type - minimal hepatic fibrosis Infantile type - moderate periportal fibrosis Juvenile type - gross hepatic fibrosis Portal hypertension with splenomegaly and portosystemic varices Associations: Caroli disease Multiple biliary hamartomas Congenital hepatic fibrosis

Answer 82

The most common hereditary cause of ESRF A number of conditions are recognised as being associated with ADPKD: Cerebral berry aneurysms - 6-16% - 16% if a family history of aneurysms, 6% if no family history Intracranial dolichoectasia 2-3% Hypertension - up to 80% Colonic diverticulosis Small bowel diverticula Bicuspid aortic valve Mitral valve prolapse Aortic dissection Multiple biliary hamartomas Cysts in other organs - Liver - most common, 75% by age 60 - Ovaries - Spleen - Seminal vesicles - 60% by age 40 - Prostate - Pancreas - more common in VHL Complications Renal: ESRF Recurrent UTIs Cyst haemorrhage Cyst rupture No increased risk of RCC, unless related to dialysis Distant complications: SAH Aortic dissection

Answer 83

Macroscopically demonstrated cysts of variable size in both the cortex and medulla Autosomal dominant pattern of inheritance Three genes with slightly different phenotypes: PKD1 Chromosome 16p 85% of cases Encodes polycystin-1 Presentation is earlier and more likely to progress to end stage renal failure PKD2 Chromosome 4q 15% of cases Encodes polycystin-2 Less severe GANAB - rare Chromosome 11q13 Liver cysts are common +/- hepatic dysfunction Mild renal disease, ESRF unusual The main abnormality is in the cilia-centromere complex of tubular epithelial cells The defect results in cystic dilatation of the renal tubules (of all parts of the nephron) in a minority of nephrons The cysts are variable in size, and result in compression of the remainder of the kidney, resulting in increased renin and erythropoietin secretion and gradual renal dysfunction

Answer 84

Arteriohepatic dysplasia A congenital genetic multisystem disorder Infants typically present with symptoms relating to the liver - one of the most common causes of hereditary cholestasis Genetics: Inherited in an autosomal dominant fashion, with a mutation of the JAG1 (90%) and NOTCH2 genes (1-2%), located on the short arm of chromosome 20 There is a diverse spectrum of disease: Hepatic Paucity +/- stenosis of the intrahepatic ducts that can lead to cirrhosis and hepatic failure Renal Variable, including cystic kidney disease, small kidneys, echogenic kidneys and nephrocalcinosis Ocular Posterior embyotoxon Otic Hypoplasia of the posterior semicircular canal Skeletal Butterfly type vertebrae (~50%) Facial Triangular facial Cardiovascular Coarctation of the aorta Peripheral pulmonary artery stenosis

Answer 85

A type of non-heritable paediatric cystic renal disease Results in multiple cysts being formed in utero in the affected kidney Typically unilateral, with a predisposition for the left kidney. Bilateral has a higher incidence in females Can be a common cause of agenesis, following complete involution during childhood Associations: Vesicoureteric reflux - most common, seen in up to 20% Pelviureteric junction obstruction Ureteral ectopia Vesicoureteric junction obstruction Ureterocele

Answer 86

No functioning renal tissue, but replacement with multiple cysts Two types have been described: Pelvi-infundibular Most common Multiple small non-communicating renal cysts - representing the dilated calyces Atresia of the ureter and renal pelvis May sometimes regress spontaneously Hydronephrotic-obstruction Dominant cyst present in the renal pelvis

Answer 87

A sporadic condition where the medullary and papillary portions of the collecting ducts are dysplastic and dilated Most patients are asymptomatic during life, incidentally diagnosed Alternatively, patients may present with a complications, including: - Urinary tract infection - Haematuria - Urolithiasis/ureteric calculi Represents a developmental defect affecting the formation of collecting tubules and resulting in cystic dilatation of medullary and papillary portions of the collecting ducts Associations: - Ehlers-Danlos syndrome - Congenital hemihypertrophy/ Beckwith-Wiedemann syndrome - Caroli disease Medullary nephrocalcinosis occurs in the majority of cases - May be unilateral or bilateral and affect a single or multiple pyramids

Answer 88

Phakomatosis characterized by the development of multiple benign tumours of the embryonic ectoderm Most are sporadic The pathognomonic triad – only seen in 30% Seizures: absent in ¼ of individuals Intellectual disability: up to half have normal intelligence Adenoma sebaceum: only present in ~¾ of patients Pathology: Spontaneous mutations account for 50-66%, the rest are inherited as an autosomal dominant condition Two tumour suppressor genes are involved: TSC1 – encoding hamartin, on chromosome 9q32-34 TSC2 – encoding tuberin, on chromosome 16p13.3

Answer 89

Neurology: Cortical/subcortical tubers: 50% in the frontal lobe - High T2, low T1 – 10% enhance, frequently calcify Subependymal hamartomas – 88% associated with calcification - Variable signal, high T1, iso-high T2 - Variable enhancement - Only serial growth is reliable to differentiate from SEGA Subependymal giant cell astrocytomas - Peak occurrence 8-18yo White matter abnormalities -Radial bands – specific for TS - Variable appearance – nodular, ill-defined, cystic and band-like lesions seen Retinal phakomas Rarer findings: Cerebellar atrophy Infarcts Arachnoid cysts Chordoma Abdominal Renal angiomyolipomas - TS accounts for 20% - Seen in 55-75% of patients with TS - Tend to be multiple, large and bilateral - Fat may not be visible in up to 4.5% Renal cysts: TSC2 gene is located adjacent to the PCKD1 gene - 18-53% of patients with TS Renal cell carcinoma and oncocytomas - RCC tends to occur earlier Retroperitoneal lymphangiomyomatosis - Histologically identical to pulmonary LAM - Retroperitoneal cystic lesions - Chylous ascites, enlarged lymph nodes, dilatation of the thoracic duct GI polyps Pancreatic neuroendocrine tumours Hepatic angiomyolipomas Thoracic Lymphangioleiomyomatosis (LAM) - Rare - 25-40% of female pts with TS - Indistinguishable from sporadic LAM - Pneumothorax and chylous pleural effusions are common - ~80% 10yr survival Multifocal micronodular pneumocyte hyperplasia (MMPH) - Rare - Multicentric, well-demarcated nodular proliferation of type II pneumocytes - Benign, non-progressive - Differentials: miliary opacities Cardiac rhabdomyomas - Benign striated muscle tumour characterised by the presence of spider cells - Seen in 50-65% of pts with TS - 40-80% of patients with cardiac rhabdomyomas have TS - Multiple or single - Typically involve the ventricular septum - Occur before the age of 1yo (75%) - Spontaneous regression in 70% of children by age 4 Thoracic duct and aortic/pulmonary artery aneurysm Myocardial fatty foci MSK Sclerotic bone lesions 46-66% Hyperostosis of the inner table of the calvaria Periosteal new bone Scoliosis Bone cyst Skin Cutaneous lesions in ~95% of cases Facial angiofibromas Hypopigmented macules – ash leaf spots Fibrous plaques on forehead Confetti lesions

Answer 90

Numerous benign and malignant tumours in different organs, due to mutations in the VHL tumour suppressor gene on chromosome 3 Most are diagnosed with their first tumour in early adulthood Classi Can be according to the clinical phenotypes Type 1 – low risk pheo, but higher risk CNS haemangioblastoma, RCC, pancreatic cyst and pNET Type 2A – high risk pheo, low risk RCC Type 2B – high risk pheo and RCC Type 2C – high risk pheo only

Answer 91

Abdominal: Renal cell carcinomas - Usually clear cell and bilateral - 70% lifetime risk - Present earlier in pts with VHL Renal cysts - Often bilateral and multiple - Can be simple, complex or cystic RCC Renal angiomyolipomas Adrenal: Phaeochromocytomas 25-30% Extra-adrenal phaeochromocytoma/paraganglioma Pancreas – may be the earliest manifestation - Pancreatic cysts ~40% - Pancreatic neuroendocrine tumours - ~12.5% of patients - Usually non-functional - Frequently multiple - Pancreatic serous cystadenomas: ~12.5% of patients - Pancreatic adenocarcinomas Liver Liver cysts Urogenital - Epididymal cysts - Papillary cystadenoma of the epididymis - Broad ligament cystadenomas CNS Haemangioblastomas ~70% - Cerebellar ~60% - Spinal cord ~30% - most commonly in the cervical and thoracic cord - brainstem Choroid plexus papilloma Head and neck Retinal haemangioblastoma - Most common presenting feature - Vision loss Endolymphatic sac tumours - Bilateral in 30%, pathognomonic for vHL

Answer 92

Sporadic, or as part of a phakomatosis 80:20% respectively Also associated with: TS – predominantely Von Hippel-Lindau syndrome Neurofibromatosis type 1 These usually larger, earlier and more numerous More likely to be fat-poor Often incidentally found Symptomatic presentaiton is with spontaneous retroperitoneal haemorrhage Pathology: - Perivascular epithelioid cells tumour group (PEComas) and are composed of variable amount of three components: - blood vessels lacking elastic tissue, - Plump spindle cells, and - Adipose tissue Variants: - Typical – triphasic - Atypical – monophasic or epithelioid - Epithelioid AML often with nuclear atypia – may mimic RCC Larger AMLs resect of embolise.

Answer 93

Relatively benign renal tumours 6th-7th decade presentation, with a 2:1 male predilection Pathology: Macroscopic: = Macroscopically tan in colour, similar to renal cortex, or dark brown = A rim of compressed normal renal parenchyma is sometimes seen, forming a pseudocapsule Microscopic = Thought to originate from the intercalated tubular cells of the collecting tubules = Composed of large, swollen eosinophilic cells of protuberant mitochondrial components = Necrosis is usually absent Associations: Birt-Hogg-Dube Tuberous sclerosis

Answer 94

The most common type of RCC Usually ~60yo, but younger onset with von-Hippel Lindau. Pathology: - 75-80% of RCC cases. - Sporadic in >95%, but 5% are familial - VHL - Loss of sequences on the short arm of chromosome 3, usually by deletion or unbalanced translocation resulting in loss of 3p12-3p26 - The region containing the sequence for the VHL gene (a tumour suppressor gene) - The gene increases expression of proteins of the ubiquitin ligase complex - Ubiquitin ligase complex normally identifies and tags proteins for destruction - Ubiquitin mediated degradation of hypoxia inducible factor 1 (HIF-1) - A proangiogenic factor normally expressed in hypoxic environments - So, the loss of the VHL allele results in increased levels of HIF-1 and resulting increase in pro-angiogenic factors such as VEGF, PDGF, TGF-alpha, TGF-beta, leading to cellular dysplasia and ultimately neoplasia Macroscopic: yellowish, golden appearance due to high lipid content Microscopic: characterised by - - Large cells with uniform appearance - Abundant clear cytoplasm rich in glycogen and lipid - High vascularity Compared to other forms of RCC, it is said to have: - An exophytic appearance - A greater degree of enhancement on the corticomedullary and nephrographic phases on multiphasic CT (compared to papillary cell carcinoma) - A more heterogenous appearance (due to multiple areas of internal necrosis, cystic change or haemorrhage

Answer 95

The second most common histological subtype of RCC May account for 13-20% of all RCC - slightly increased male predilection Associations: - Hereditary leiomyomatosis and RCC - Hereditary papillary renal cell cancer type 1 Two subtypes: Type 1 - Papillae covered by a single layer of cuboidal or low columnar cells with scanty cytoplasm and low grade nuclei - Carry a better prognosis than type II tumours Type 2 - higher nuclear grade and contain more than one layer of cells with abundant eosinophilic cytoplasm - Mostly unilateral, the subtype is considered most common to result in bilateral RCCs Less vascular than the more common clear cell subtype, showing overall hypoenhancement compared to the adjacent normal renal cortex - particularly in the corticomedullary phase Can be difficult to differentiate from hyper-attenuating cysts

Answer 96

One of the less common subtypes of renal cell carcinoma The least common major subtype of RCC, occurring 5% of the time Arises from intercalated cells of collecting ducts - called chromophobe because the tumour cells are less translucent than clear cell renal cell carcinomas during staining Similar origin to oncocytomas. "spoke wheel pattern of enhancement"

Answer 97

Rare and highly aggressive variant Centered in the renal medulla Occurs almost exclusively in adolescent and young adult blacks with sickle cell trait or haemoglobin SC disease - But not with homozygous haemoglobin SS sickle cell disease Typically affects patients around the age of 20yo, range of 10-39yo Pathology: - Epithelial origin - Thought to arise at the renal pelvic-mucosal interface - The tumour quickly grows to fill the renal pelvis, and invade vascular and lymphatic structures

Answer 98

Rare, accounts for ~1% of bladder cancers. 90% are TCC Metaplasia of the urinary bladder induced by chronic irritation or infection can lead to adenocarcinoma Pathological types of adenocarcinoma of the urinary bladder: - Mucinous adenocarcinoma - Signet-ring types - Papillary adenocarcinoma - Not otherwise specified (NOS) Can be subclassified as primary (2/3 are non-urachal, 1/3 is urachal) or secondary (metastases) Aetiology: - Persistent urachal remnant is most common - Cystitis glandularis (secondary to bladder outlet obstruction, chronic infection and/or bladder calculi - Schistosomiasis, - Associated with bladder exstophy Appearance: - Non-urachal: diffuse bladder wall thickening - Urachal: midline, infraumbilical soft tissue mass with peripheral calcification

Answer 99

An infection caused by the Schistosoma flukeworm Predisposes individuals to bladder SCC Very common, particularly in Africa Pathology: - 5 species of the blood fluke that cause disease in humans - Larvae are released from snails into water and penetrate human skin exposed to the infected water - These travel to the lungs and liver of the human host, where they reside until they mature - After maturation, the adult worms travels to the pelvic veins. - Eggs are deposited in the bladder wall vessels and incite a granulomatous response that results in polypoid lesions - The eggs may go on to incite a chronic inflammatory response and fibrosis, which is an important predisposing factor for SCC Features: - Acute - nodular, bladder wall thickening is observed - Chronic - contracted, fibrotic, thick-walled bladder with calcifications - Calcifications are typically curvilinear and represent the large numbers of calcified eggs in the bladder wall - A mass may be secondary to inflammation or complicating carcinoma, typically SCC - Calcifications can extend to the ureters

Answer 100

Rare, accounts for only 3-8% of all bladder cancers The most common type of non-TCC bladder cancer Most commonly seen in the setting of chronic irritation, e.g. from bladder stones Tend to be solitary and large at the time of detection, with muscular wall invasion reported Risk factors: - Antecedent infection with Schistosomiasis - Chronic irritation e.g. indwelling catheter, bladder calculi - Chronic infection - Intravesical BCG

Answer 101

The most common primary malignancy of the urinary tract May be found along its entire length, from renal pelvis to the bladder Urothelial cell carcinoma can be used to described malignant bladder carcinomas of epithelial origin, since 25-37% of transitional cell carcinomas contain a mixture of histologic tissue types Typically a tumour of older patients, with the average age being ~65 and typically >60 Strong male predilection Chemical compounds implicated: - Smoking - Azo dye/pigment manufacturing - Cyclophosphamide - also haemorrhagic cystitis and bladder fibrosis - Thorotrast - Phenacetin - Aristolochic acid - typically results in upper urinary tract tumours - Heavy caffeine consumption and artificial sweeteners Additionally, stasis acts to prolong exposure of the urothelium to any carcinogens in the urine - so horseshoe kidney/calculi/ureteral pseudodiverticulosis/ureteritis cystica Distribution: - Renal pelvis - uncommon ~2-3% - Ureter - least common ~1% - Bladder - most common ~97% Pathology: Two main morphological patterns: Papillary - Broad base with many frond-like papillary projections - Tend to be low grade and invasion beyond the mucosa is a late feature Non-papillary - Sessile or nodular tumours - Tend to be high grade with early invasion beyond the mucosa

Answer 102

Uncommon tumours occuring in pelvic organs A disease nearly exclusive to the paediatric population Peak incidence is 3-6yo, with a slight male predominance 2-3:1 Prostatic origin is the most common in males, and the bladder is most frequent in both Vagina, cervix and uterus ma all be involved in females The vagina is the most prevalent Paratesticular tumours are the only GIT rhabdomyosarcomas that tend to occur in older children - typically adolescents Pathology: As with other rhabdomyosarcomas, there are 4 major subtypes: - Embryonal - Most common - Botryoid variant of embryonal type - Most frequent to affect the bladder - Alveolar - Undifferentiated

Answer 103

Distal stratified squamous mucosa is replaced by metaplastic specialised (intestinalised columnar epithelium) 30x risk of developing oesophageal adenocarcinoma The annual risk of developing adenocarcinoma depends on the degree of histological dysplasia

Answer 104

Dilated submucosal veins of the oesophagus An important portosystemic collateral pathway Epidemiology: - Present in ~50% of pts with portal hypertension - Occur with greater frequency in pts with more severe cirrhosis - ~40% Child Pugh A patients - ~85% Child Pugh C patients Presentation: - Asymptomatic until a variceal heamorrhage - yearly rate of 5-15% - Present with upper GI haemorrhage: haematemesis, melaena - The primary predictor is variceal wall tension: diameter and pressure - Patients will have stigmata of portal hypertension and cirrhosis Treatment: - Primary prevention is the mainstay - pharmacological (beta blockers) or endoscopic variceal ligation

Answer 105

Uphill varices - the most common form - Typically from portal hypertension, as a collateral between the portal vein and SVC - Typically occur in the lower third of the oesophagus - Commonly co-occur with gastric varices (less common) - There is extension of the oesophageal varices along the lesser curvature - Can also have paraoesophageal varices - varices of the adventitial oesophageal veins Aetiology: - Cirrhosis - Budd-Chiari syndrome - Primary biliary cholangitis - Primary sclerosing cholangitis Downhill varices - relatively rare - Due to SVC obstruction, as part of the superior vena cava syndrome - Typically in the upper 1/3, although can span the entire oesophagus - Do not co-occur with gastric varices due to a different pathophys - Relatively lower bleeding risk

Answer 106

An oesophageal constriction caused by a thin mucosal membrane projecting into the lumen Tend to affect middle-aged females Pathology: - More commonly occur in the cervical esophagus near cricopharyngeus muscle than in the thoracic oesopahgus - Anterior wall, never posterior wall Associations: - Plummer-Vinson syndrome - Graft-vs-Host disease - GORD Treatment: - Balloon dilatation - Bougienage during endoscopy

Answer 107

A term for intestinal metaplasia of the oesophagus Considered a precursor lesion for adenocarcinoma Epidemiology: - Thought to have a prevalence of 3-15% in patients with reflux oesophagitis - Mean age at diagnosis 55y Risk factors: - Male - Tobacco intake - Central obesity - White race - Scleroderma - ~37% of patients Asymptomatic, discovered in the workup for GORD Pathology: - Progressive metaplasia of oesophageal stratified squamous cell epithelium to columnar epithelium - 90-100% of adenocarcinomas are thought to arise from the metaplasia - 30x risk of developing oesophageal adenocarcinoma, but the annual risk depends on the degree of histological dysplasia Management: - Considered a premalignant lesion - upper endoscopy and biopsy is warranted - If confirmed, aggressive therapy for GORD +/- endoscopic surveillance

Answer 108

An extranodal marginal zone B-cell lymphoma Represents 7% of non-Hodgkin lymphoma Average age of presentation is 60yo, with slight female predominance Pathology: - Arise in epithelial tissues where lymphoid cells are not usually found - Chronic infection/inflammation has been implicated in the pathogenesis - Less than 10% transform from low-grade to high-grade disease

Answer 109

Pituitary adenoma, parathyroid adenoma, pancreatic neuroendocrine tumour

Answer 110

medullary thyroid cancer, pheochromocytoma, parathyroid hyperplasia

Answer 111

Medullary thyroid cancer, pheochromocytoma, mucosal neuromas/gangliomas, marfanoid habitus

Answer 112

Relatively uncommon, tends to present with increasing dysphagia, initially to solids and progresses with obstruction of the lumen Epidemiology: - <1% of all cancers, 4-10% of all GI malignancies - Male preponderance 4: 1F Predisposing factors: - Alcohol and smoking - for squamous cell carcinoma and adenocarcinoma - Achalasia - Asbestosis - Barrett oesophagus - for adenocarcinoma - Coeliac disease - Ionising radiation - Obesity - adenocarcinoma - Plummer-Vinson syndrome - HPV Treatment/outcome - Localised disease ~40% 5yr survival - Distant metastasis ~5% 5yr survival Complications: - Fistula formation to the trachea 5-10%, bronchi or mediastinum

Answer 113

Histological subtypes - Squamous cell carcinoma of the oesophagus 81-95% - Adenocarcinoma of the oesophagus 4-19% - Arising from the mucosal/submucosal glands, heterotopic gastric mucosa or columnar-lined epithelium - >90% relate to Barrett oesophagus - Tend to occur at the GOJ - In the western world, adenocarcinoma is as common, or slightly more common than squamous cell carcinoma Macroscopic appearance - Polypoid/fungating (most common) - Sessile/pedunculated - Lobulated surface protruding - Irregular, polycyclic, overhanging - Ulcerating - large ulcer niche in a bulging mass - Infiltrating - gradual narrowing with a smooth transition - Superficial spreading carcinoma

Answer 114

Tumour 0 No evidence of primary tumour, Tis: high grade dysplasia 1 - Tumour invades the lamina propria, muscularis mucosae or submucosa 2 - Tumour invades the muscularis propria 3 - Tumour invades the adventitia 4 - Tumour invades adjacent structures Nodes 0- No lymph nodes 1- 1-2 regional lymph nodes 2- 3-6 regional lymph nodes 3 - >7 regional lymph nodes Stage of disease: 1 - T1 N0 M0 2 - 3: Any combination of T and N that adds up to the stage 4: M1 Metastases: Haematogenous: lung, liver, adrenal glands

Answer 115

Adenocarcinoma, the most common gastric malignancy Third most common GI malignancy following colon and pancreatic cancer Epidemiology: - Rare before age 40. Climbs and peaks in the 7th decade of life - 2:1 male predominance Non-specific symptoms Nodal metastases: - Sister Mary Joseph's node - umbilical - Virchow's node - left supraclavicular - Drains the thoracic duct - Krukenberg's tumour - ovary - Irish node - enlarged axillary lymph node Aetiology: - Association with H-pylori - Most are sporadic in occurrence, 8-10% have an inherited gastric component Risk factors: - Pernicious anaemia - Adenomatous gastric polyps - Atrophic gastritis - Bilroth II partial gastrectomy for benign disease - Type A blood group - Smoking Prognosis: - 20% 5yr survival rate Differentials: - Gastric lymphoma - Gastric metastases - GIST

Answer 116

The most common mesenchymal tumour of the GIT Account for ~5% of all sarcomas Most frequently found within the stomach and mid-distal small bowel Used to be called Leiomyomas/etc but differentiated by an expression of c-KIT and CD34 antigens Epidemiology: - Uncommon compared to gastric carcinoma - Age ~40+ - Possible slight male predilection Location: - Oesophagus - uncommon (vs leiomyomas) - Stomach - most common, 70% - Small bowel - #2, 20-25% - Colon/rectum - most common rectal sarcoma - 7% at the rectum, then colon - Can also occur in the mesentery, omentum and retroperitoneum Associations: Majority are sporadic, but can also occur with: - Carney triad - extra-adrenal paraganglioma, GIST, pulmonary chondroma - NF1 - Carney-Stratakis syndrome - autosomal dominant condition comprising of familial paragangliomas and gastric stromal sarcoma Treatment - Resection - 50% will have metastasized at the time of presentation - Adjuvant chemotherapy is given

Answer 117

Typically submucosal tumours Often the overlying mucosa remains intact on pathological and imaging assessment Arise from the Interstitial cells of Cajal 95% stain positive for cd117 (C-KIT) and 70% for CD34 - a tyrosin kinase growth factor receptor and target of ST-571 Grading requires assessment of both tumour size and mitotic index - Smaller lesions have less aggressive biological behaviour, as do stomach GISTs compared to tumours elsewhere Macroscopic: - Rounded with frequent haemorrhage - Larger tumours may demonstrate necrosis and cystic change - Size is variable, 1-30cm Histology: - A relatively cellular tumour composed of spindle cells 70-80% and plump epithelioid cells 20-30% - They appear to arise from the muscularis propria layer

Answer 118

A benign smooth muscle neoplasm of the oesophagus, the most common benign tumour of the oesophagus Epidemiology: most frequently presents in young and middle aged groups 20-50yo Pathology: like other leiomyomas, they comprise of smooth muscle overgrowth Location: mid-distal oesophagus No treatment necessary if <5cm and asymptomatic, otherwise resected

Answer 119

Extranodal marginal zone B-cell lymphoma, low grade Represents ~7.5% of non-Hodgkin lymphomas Average age ~60yo with female predominance Pathology: - Arise in the epithelial tissues where lymphoid cells aren't usually found - Chronic infection/inflammation has been implicated in the pathogenesis - e.g. H pylori in gastric MALT, Sjogren syndrome in salivary gland MALT Less than 10% transform from low-grade to high grade disease Considered indolent disease with good prognosis. Treatment is tailored to the affected organ, and may consist of: surgery, chemotherapy and/or radiation therapy - Antibiotics are used to treat gastric MALToma

Answer 120

50% less common than colonic carcinoma Pathology: Almost 50% are found in the duodenum, especially near the ampulla. Of the remaining, the jejunum is more commonly involved than the ileum Risk factors: - Crohn disease - Sprue - Peutz-Jeghers syndrome - Lynch syndrome II - Congenital bowel duplication - Ileostomy or duodenal or jejunal bypass surgery More distal adenocarcinomas tend to be annular, duodenal adenocarcinomas tend to be papillary/polypoid

Answer 121

Epithelial tumours of the appendix that produce mucin Represent a spectrum of malignant potential, and the most common cause of pseudomyxoma peritonei Pathology: - Classified as premalignant, uncertain malignant potential or malignant Defined as mucinous when extracellular mucin corresponds to more than 50% of the lesion

Answer 122

The most common cancer of the GIT, tends to be a disease of the elderly, with median age of diagnosis between 60-80yo Slight male predilection Risk factors: - Low fibre/high fat/animal protein diet - Obesity - IBD - Asbestos exposure - Family history of benign/malignant colorectal tumours Associations: - Seen in 6% of CRC - Familial adenomatous polyposis syndrome - Gardner and Turcot syndrome variants - Peutz-Jeghers syndrome - Hereditary non-polyposis colon cancer syndrome - Juvenile polyposis syndrome - MUTYH-associated polyposis Location: - Rectosigmoid 55% - Caecum and ascending colon ~20% - Ileocaecal valve 2% - Transverse colon ~10% - Descending colon ~5% Treatment/prognosis: - Local resection for all - Adjuvant chemotherapy for stage III - 40-50% 5yr survival, with stage at operation the single most important factor affecting prognosis - BRAF-mutated CRC has a poorer prognosis with a median survival of <12mo - Recurrence is common - Local recurrence - 80% within 2yrs - CEA is used for detecting early recurrence - inappropriate for screening - Higher levels are associated with higher grade tumours, higher stage of disease and visceral metastases

Answer 123

Most arise from pre-existing colonic adenomas (neoplastic polyps) which undergo malignant transformation as they accumulate additional mutations Morphology can be anything Rarely will there be wide invasion of the submucosa (e.g. like linitis plastica of the stomach) These are typically scirrhous adenocarcinomas

Answer 124

Shares many features with CRC Requires an MRI for local staging Epidemiology: >50yo, and male predilection Similar path to other adenocarcinomas T stage - Confined to or extends through the muscularis propria - Extent of extramural spread and whether the peritoneum or other organs are invaded N stage - Size isn't a reliable indicator of nodal involvement - Number of nodes, irregular or spiculated margin and heterogenous signal intensity Surgical resection with either radiotherapy alone or combined chemo/ray in T3 and/or N1 disease A circumferential resection margin of <1-2mm confers a poorer prognosis Staging: T1: invades the submucosa T2: invades muscularis propria T3: invades through the muscularis propria into the subserosa or non-peritonealised perirectal tissues without reaching the mesorectal fascia or adjacent organs - A - <1mm, b 1-5mm, C 5-15mm, D >15mm T4: invades directly into other organs or structures and/or perforates visceral peritoneum

Answer 125

Relatively uncommon, <2% of large bowel malignancies Most are SCC Typically originates between the anorectal junction above and the anal verge below

Answer 126

Stomach - cronkite-canada Small bowel - Peutz Jegher Large bowel - Juvenile polyposis, Lynch, Cowden, Turcot, FAP, cronkite-canada

Answer 127

Non neoplastic, non-hereditary hamartomatous polyposis syndrome Characterized by rash, alopecia and watery diarrhoea Epidemiology: - 3 male : 2 female - Patients are typically middle age 50-60yo Clinical presentation: - Watery diarrhoea and a protein-losing enteropathy with associated nail atrophy, brownish skin pigmentation and alopecia Pathology: - Numerous hamartomatous polyps in the digestive tract - Predominant involvement of the stomach, large intestine and to a lesser extent, small bowel - The exact etiology is unknown - Polyps are similar to those of juvenile polyposis syndrome, except the mucosa in CCS polyps is oedematous and inflammation of the lamina propria is usually present - In juvenile polyposis syndrome, the mucosa between polyps is normal

Answer 128

Autosomal dominant polyposis syndrome Characterized by: - Multiple hamartomatous polyps - Mucocutaneous melanin pigmentation involving the mouth, fingers and toes Locations: - Small intestines, predominantly the ileum - Colon and stomach - Mouth and esophagus are spared Pathology: - Non-neoplastic hamartomas due to the proliferation of all three layers of the mucosa, - Polyps have a characteristic feature of a smooth muscle core continuous with muscularis mucosa in a tree-like branching pattern - Distinguishes them from the hamartomatous polyps of CCS, JP and cowden disease - Patients are at increased risk of intussusception - GI tract adenocarcinoma, although the polyps aren't premalignant Stomach 29% lifetime risk Small intestines 13% lifetime risk Extraintestinal malignancy: Adenomal malignum (subtype of the cervix) Breast 45-50%, usually ductal Pancreas 11-36% Ovary 18-21% uterus Cervix Testes Lung Genetics: - Attributed to mutations in tumour suppressor genes, most commonly STK11 Due to the increased risk of malignancy, screening is generally recommended

Answer 129

A variation in polyposis syndromes Characterized by multiple colonic polyps and an increased risk of colon and primary brain cancers Epidemiology: - A rare disease - Typically presents by the second decade Pathology: - Intestinal polyposis - CNS: typically glioblastoma or medulloblastoma Genetics: - Autosomal recessive inheritance - 2/3 of patients have mutations in the APC gene, the same genetic defect as in FAP - these patients have multiple colonic adenomas and virtually all develop colorectal carcinoma by age 40 - The common intracranial tumour in this subtype is medulloblastoma - The other 1/3 have mutations in the HNPCC genes - Colonic malignancy is not as common in this type, but tends to develop at a younger age - Most develop glioblastomas

Answer 130

One of the polyposis syndromes, characterized by: - Familial adenopolyposis - Multiple osteomas - especially of the mandible, skull and long bones - Epidermal cyst - Fibromatoses - Desmoid tumours of mesentery and anterior abdominal wall Other abnormalities include: - Supranumerary teeth, odontomas, dentigerous cysts - Duodenal tumours/ampullary carcinoma - Papillary thyroid carcinoma Autosomal dominant inheritance in the FAP gene (chromosome 5q) in a majority of patients, but with 20% of cases resulting from new mutations Extracolonic features often precede the diagnosis of colonic polyps

Answer 131

Characterized by the presence of hundreds of adenomatous polyps in the colon The most common of the polyposis syndromes Familial polyposis coli, attenuated familial adenomatous polyposis and Gardner syndrome are all variants of the same disease and FAPS is used to describe the entire spectrum The average age of presentation is 16yo Associations: - Colorectal carcinomas - Hepatoblastoma - Extracolonic polyps - stomach, duodenum - Desmoid tumours - Osteomas - Dental anomalies - Congenital hypertrophy of the retinal pigment epithelium - Papillary thyroid carcinoma Pathology: - Hundreds/thousands of colonic adenomatous polyps, usually tubular or tubulovillous - The rectum is occasionally spared - Less commonly they affect the small bowel and stomach Genetics: - Due to a mutation of the tumour suppressor adenomatous polyposis coli gene (APC) located on chromosome 5q21-2. - 1/3 are thought to be sporadic, 2/3 familial - MUTYH gene has been associated with APC-negative FAPS: this has autosomal recessive inheritance Total colectomy with ileoanal anastomosis is generally considered the surgical treatment of choice

Answer 132

Multiple hamartoma syndrome - characterized by multiple hamartomas throughout the body, and increased risk of several cancers Type 2 segmental Cowden syndrome is the association of Cowden syndrome with a Cowden naevus when it is considered a type of epidermal naevus syndrome Pathology: Characterized by: - Mucocutaneous lesions - present in >90% - GI hamartomatous polyps (small and large bowel) - Glycogenic acanthosis - Thyroid abnormalities - Thyroid adenomas - Multinodular goitre - Fibrocystic disease of the breast Increased risk for cancers: - Breast 30% - Thyroid 5%, usually follicular - CNS dysplastic cerebellar gangliocytoma, occurs when in association with Lhermitte-Duclos disease Syndromic associations - PTEN-related diseases: - Lhermitte-Duclos disease - Bannayan-Riley-Ruvalcaba syndrome Genetics: Autosomal dominant inheritance, with -variable penetrance A gene locus for the disease has been identified on chromosome 10q22-23, a mutation of the pTEN gene

Answer 133

Hereditary non-polyposis colorectal cancer Autosomal dominant condition which predisposes to a host of malignancies, including colorectal carcinoma Epidemiology: - Typically presents age 40-50 with colorectal cancer or an associated malignancy - 5x more common than familial adenomatous polyposis syndromes - The most common hereditary cause of endometrial cancer Pathology: - Mutation in DNA mismatch repair (MMR) genes, resulting most frequently in colorectal carcinoma as well as extracolonic malignancies GU - Endometrial carcinoma 15-60%, most often endometrioid type - Ovarian tumour 4-12% - Prostate cancer 30% - Urothelial tract cancer 1-7% Small bowel cancer ~5% - Duodenum 45% - Jejunum 29% - Ileum 12% - Gastric cancer 6-13% Hepatobiliary tract malignancy 1-4% Pancreatic malignancy 1-6% CNS tumours: most often glioblastomas Variants: - Muir-Torre syndrome: HNPCC-variant with sebaceous tumours and keratoacanthocytomas Radiographic features - Related to underlying conditions: - Colorectal cancer - more frequently right sided, 70% proximal to the splenic flexure - Arise from adenomatous polyps - Diffuse polyposis is characteristically absent - Small bowel adenocarcinoma: most commonly duodenal - Endometrial carcinoma - Ovarian tumours - urinary tract malignancy Frequent screening +/- colectomy

Answer 134

Consists of hundreds of juvenile polyps Presentation is in the second decade Present with rectal bleeding, bowel obstruction and intussusception Hundreds of hamartomatous polyps containing fluid/mucous Both the tumour suppressor gene SMAD4 on chromosome 10q and BMPR1A gene have been implicated Associations: - Intestinal malrotation - Meckel diverticulum - Hydrocephalus - Congenital heart disease - Mesenteric lymphangioma - Pulmonary AVM

Answer 135

More common in males 3:1, and usually the older population Risk factors: - Helicobacter pylori infection - Confirmed on biopsies obtained at endoscopy and urea breath test - NSAIDS - Corticosteroids - Stress - Zollinger-Ellison syndrome - Hypercalcaemia Ulceration is the end point, after acid resulting in inflammation, superficial erosions and eventually frank ulceration H Pylori: a spiral gram-negative bacterium has been identified as the leading cause of duodenal ulceration

Answer 136

frequent complication, often involving the GIT, skin and liver. A disease of allogenic bone marrow transplant or haematopoietic stem cell transplantation Can present early/acute (<100 days) or late/chronic (>100 days) post allogeneic haematopoietic stem cell transplantation and is one of the major complications of this treatment The skin, GIT (esp small bowel) and liver are the principal affected organs End organ damage is the result of the recipient's immune system (mainly antigen presenting cells) interacting with donor T-cell, leading to the latters activation with a resultant cell-mediated and inflammatory cascade Bowel: "ribbon" appearance, with fold thickening - Oedema of the mucosal folds in the ileum and jejunum - Effacement of the folds towards the ileum: can give featureless (atrophic) loops - Thickening of the bowel walls - Spasms and stenosis with prestenotic dilatation - In the active phase, the bowel can appear shortened CT: - Bowel wall thickening, small/large or both (most common) - Bowel dilatation - Engorgement of the vasa recta adjacent to the affected bowel segments - Mucosal enhancement - Mesenteric stranding ~60% - Ascites - Biliary abnormalities

Answer 137

The presence of a fistulous tract across/between/adjacent to the anal sphincter Usually an inflammatory condition Male predilection 2-4:1 Associations: Spontaneous: - Diverticulitis - Crohn disease - Other bowel or pelvic infections - Tuberculosis Iatrogenic - Post surgical complication Pathology: - Cryptoglandular hypothesis: obstruction of the deep submucosal glands results in infection and abscess formation in the inter-sphincteric space, which consequently drains inferiorly between the sphincters opening onto the skin surface or, less commonly, erodes through both the internal and external sphincters into the ischiorectal space, then onto the skin surface - Transsphincteric fistulae are secondary to ischiorectal abscesses with a resultant extension of the tract through the external sphincter - Intersphincteric fistulae are due to perianal abscesses - Suprasphincteric fistulae are due to supralevator abscesses

Answer 138

Radiological grading: based on landmarks in the axial plane and incorporates abscesses and secondary extensions Grade 1 - simple linear intersphincteric Grade 2 - intersphincteric with abscess or secondary tract Grade 3 - transsphincteric Grade 4 - transsphincteric with abscess or secondary tract within the ischiorectal fossa Grade 5 - supralevator and translevator extension

Answer 139

Acute inflammation of the vermiform appendix Pathology: Typically caused by obstruction of the appendiceal lumen, with resultant build-up of fluid, suppurative inflammation, secondary infection, venous congestion, ischaemia and necrosis Obstruction may be caused by: - Lymphoid hyperplasia ~60% - Appendicolith ~33% - Foreign body ~4% - Crohn disease

Answer 140

When there is abnormal accumulation of mucin causing abnormal distention of the vermiform appendix due to various neoplastic or non-neoplastic causes Benign or malignant lesions, categorised into 4 histologic types: - Mucous retention cyst due to obstruction - usually appendicolith - Mucosal hyperplasia - Mucinous cystadenoma of the appendix (most common) - Mucinous adenocarcinoma of the appendix Curvilinear mural calcification suggests the diagnosis Intraluminal bubbles of gas, or a gas-fluid level within a mucocoele indicates the presence of superinfection Mural nodularity and irregular mall thickening are suggestive of a malignant process

Answer 141

Idiopathic thickening of the gastric pyloric musculature which then results in progressive gastric outlet obstruction Relatively common, male predilection 4:1 Risk factor: first born, maternal history of pyloric stenosis Typically manifests 6-12 weeks of age Pathology: - The result of both hyperplasia and hypertrophy of the pyloric circular muscle fibres Four theories: - Immunohistochemical abnormalities - Genetic abnormalities - Infectious cause - Hyperacidity theory Associations: - Turner syndrome - Tracheo-oesophageal fistula - Oesophageal atresia - Trisomy 18

Answer 142

The most common cause of neonatal colonic obstruction 15-20% Commonly characterized by a short segment of colonic aganglionosis affecting neonates, esp boys In short segment disease there is a male predilection, which reduces with increasing length of involvement Almost never seen in premature infants Characterised by aganglionosis in the distal colon and rectum Thought to occur from either a failure of neuroblasts in neural crest cells to migrate into bowel segments or degeneration of already migrated neuroblasts Affects cells in the myenteric and submucosal plexuses Functional obstruction develops as a result of a spasm in the denervated colon Anatomically divided into four types according to the length of the aganglionic segment: - Short segment ~75%: rectal and distal sigmoid colon only - Long segment ~15%: typically extends to the splenic flexure/transverse colon - Total colonic aganglionosis ~7.5% - Also known as Zuezler-Wilson syndrome - Occasional extension of aganglionosis into the small bowel - Ultrashort segment disease - 3-4cm of internal anal sphincter only Associations: - Down syndrome ~10% - Neurocristopathy syndromes - Waardenburg-Shah syndrome - MEN Iia - Neuroblastoma

Answer 143

The most common gastrointestinal condition in premature neonates Characterized by inflammation, ischemia and permeability of the neonatal bowel wall to bacteria Potentially life threatening with significant associated morbidity Usually develops 2-3 days after birth, 90% within the first 10 days Pathology: - Usually idiopathic and multi-factorial - A combination of ischaemic and infective aetiology with contributive factors e.g. immature immunity - No causative organ has been isolated - Inflammation starts from the mucosal surface and progresses to haemorrhagic and coagulative necrosis - There is ensuing loss of mucosal integrity, transmural necrosis and perforation - Can affect any part of the large or small bowel, but most commonly involves the terminal ileum - The right colon is occasionally involved Management: - Medically and surgically - Medical: supportive measures and cessation of oral feeding, broad spectrum antibiotics and gastric aspiration - Surgery: reserved for patients with evidence of perforation, entails resection of the necrotic bowel High mortality, and surviving patients often go on to develop a stricture

Answer 144

Uncommon benign hepatic lesions mostly seen in children under 2 Considered to be developmental anomalies rather than cystic neoplasia Lesions are characterised by an admixture of ductal structures (blood vessels, small groups of hepatocytes and bile ducts) within a copious loose/oedematous connective tissue stroma Rarely calcify Typically there are multiple cysts in an oedematous stroma The cysts vary in size Histologically: a series of histologic modifications including progressive loss of hepatocytes, degeneration of bile duct epithelium and cystic changes of the mesenchymal component Genetics: attributed to abnormal expression of the chromosome 19 microRNA cluster

Answer 145

loss of parietal cells and intrinsic factor disables ileal vitamin B12 absorption Typically spares the antrum and induces hypergastrinaemia (compared to H-pylori) Characterized by antibodies to parietal cells and intrinsic factor that can be detected in serum and gastric secretions Reduced serum pepsinogen levels Antral endocrine cell hyperplasia B12 deficiency (pernicious anaemia/megaloblastic) Defective gastric acid secretions (achlorydia) Associated with Hashimotos and addisons disease

Answer 146

A rare infectious multi-system disorder caused by the actinobacteria Tropheryma Whipplei Incidence is unknown Peak age for presentation is the 5th decade of life, men 8: 1 women More common in farmers/those who work with soil and livestock Pathology: - Periodic acid-Schiff-positive granular foamy macrophages in a sampled tissue Location: - Small bowel classically, as well as a multitude of other organ systems with or without small bowel involvement: - Skin - Joints, - CNS - Mediastinum GIT: - Extensive infiltration of the lamina propria with large macrophages infected by intracellular T-whipplei causes marked swelling of intestinal villi and thickened irregular mucosal folds primarily in the duodenum and proximal jejunum - When they become large enough to be macroscopically visible, they may appear as innumerable small filling defects superimposed on irregularly thickened folds "sand-like nodules" Imaging: - Diffuse 1-2mm micronodules in the jejunum - Thickened mucosal folds: esp jejunum - Small bowel calibre: normal or slightly dilated - Mesenteric lymphadenopathy: nodes of very low (near fat) density

Answer 147

Infectious: - Preferentially right colon, appendix and ileum: yersinia, salmonella - Diffuse colon: CMV, E-coli - Most severe at the left colon: Shigella, schistosomiasis - Rectosigmoid: gonorrhoea, herpes, C-trachomatis Ischaemia: Location relates to the anatomy - SMA: right colon to splenic flexure - IMA: left colon from splenic flexure Watershed areas: - Splenic flexure - Griffiths point - Rectosigmoid junction - Sudeck point Pathology: - Diminished/absent blood flow > bowel wall ischaemia and secondary inflammation - Bacterial contamination may produce superimposed pseudomembranous inflammation - If necrosis develops, then ulceration or perforation can occur - Fibrosis may lead to stricture Aetiology: - Arterial occlusion - arteriosclerosis, vasculitis, emboli - Venous thrombosis - Low flow states - Others - sickle cell disease,

Answer 148

A chronic condition of autoimmune and non-autoimmune aetiology Two types: A - Autoimmune - Gastric body and fundus atrophy secondary to antiparietal cell antibodies - Decreased secretion of acid and intrinsic factor, with the latter leading to vitamin B12 deficiency B - non-autoimmune (more common) - Gastric antrum atrophy secondary to H-pylori infection (most common), alcohol, NSAIDs Associations: - Vitamin B12 deficiency - Pernicinous anaemia- megaloblastic - Subacute combined degeneration of the cord - Gastric carcinoid tumours

Answer 149

Predominantly affects the colon, with extraintestinal manifestations Typically manifests in young adults, age 15-40yo Pathology: - Limited to the mucosa and submucosa - Crohns is a transmural disease Associations: - Primary sclerosing cholangitis (PSC) 70-80% of patients with PSC develop IBD 87% UC - Moya moya phenomenon - Ankylosing spondylitis - Colorectal carcinoma Extraintestinal manifestations: -Uveitis, iritis - Thrombotic complications - Fatty liver - Seronegative spondyloarthropathy - Chronic active hepatitis

Answer 150

An idiopathic inflammatory bowel disease characterised by widespread discontinuous GIT inflammation The terminal ileum and proximal colon are most often affected Epidemiology: typically diagnosed age 15-25yo Pathology: - Idiopathic - Higher incidence in people with first degree relatives with IBD - Initially the disease is limited to the mucosa, with neutrophilic cryptitis and lymphoid hyperplasia, lymphoedema and shallow aphthoid ulceration - The entire bowel wall becomes involved as the disease progresses, with linear longitudinal and circumferential ulcers extending into the mesentery - Chronic fibrotic change occurs over time, with stricture formation - Inflammation can occur anywhere along the digestive tract Extraintestinal manifestations: - Enterocutaneous fistulas - Joints: sacroiliitis, seronegative spondyloarthritides - Eyes: episcerlitis, iritis, uveitis - Liver: pericholangitis, PSC, autoimmune hepatitis, cirrhosis, gallstones, hepatic abscess, - Renal: renal calculi, - Lung: bronchiectasis, mosaic perfusion, chronic bronchitis, COP

Answer 151

A chronic autoimmune disease Small bowel mucosa is primarily affected, resulting in progressive degrees of villous inflammation nad destruction Tends to start in the duodenum and extend towards ileum, resulting in induction crypt hyperplasia Loss of villi, which absorb fluid, and hypertrophy of crypts which produce fluid, resulting in excess fluid in the small bowel lumen Associations: - Idiopathic pulmonary haemosiderosis - iGa Deficinecy - Small bowel lymphoma

Answer 152

Autosomal recessive disorder of copper metabolism affecting multiple systems. Pathology: A disorder that results from abnormal caeruloplasmin metabolism, as a result of a variety of mutations in the ATP7B gene Total body copper is elevated - has toxic effects on hepatocytes with copper deposition and resulting damage to a variety of organs e.g. liver and brain Three pathways are most affected: - Dentatorubrothalamic tract - Pontocerebellar tract - Corticospinal tract Markers: - Serum caeruloplasmin reduced - Serum copper reduced - Free serum copper increased Urinary copper increased Hepatobiliary manifestations vary, from fatty changes to cirrhosis and occasionally fulminant hepatic necrosis - Due to the accumulation of copper in the liver - Usually the presentation at 10-13yo NB: cant be seen on MR, so the commonest change is contour/cirrhotic abnormalities

Answer 153

An iron overload disorder, characterised by a progressive increase in total body iron stores and deposition of iron in some non-reticuloendothelial system (RES) body organs which results in some organ dysfunction Primary haemochromatosis: 90% due to an abnormal HFE gene - the protein product of which regulates iron absorption from the GIT - The two most common HFE gene mutations are c282y AND h63d Equally distributed incidence between men and women, but menstruation is protective and presentation is delayed until after menopause. Secondary haemochromatosis Rare and seen in association with disease that chiefly cause hemosiderosis The distribution of iron in RES and non-RES tissue can aid differentiation Aetiology: - Frequent transfusion - High erythrogenic requirements Radiographic features: Primary haemochromatosis: Predominant liver involvement without spleen/bone marrow deposition - non-RES iron deposition Secondary haemochromatosis: spleen and bone marrow, and liver - RES deposition, most likely from haemosiderosis

Answer 154

Hepatic venous outflow obstruction, where there is partial or complete obstruction of the hepatic veins The acute presentation: - Ascites - Hepatomegaly - Abdominal pain The acute form results from an acute thrombosis of the main hepatic veins, or IVC The chronic form is related to fibrosis of the intrahepatic veins, presumably related to inflammation Aetiology: Majority result from thrombosis within the hepatic veins 25% arise from external compression that results in obstruction May be associated with concurrent portal vein thrombosis Idiopathic Congenital - Hepatic vein or IVC webbing - Interruption of the diaphragm Venous thrombosis secondary to: - Dehydration - Sepsis - Polycythemia rubra vera - Antiphospholipid syndrome - Sickle cell disease Injury and/or inflammation: - Phlebitis: bone marrow transplant and chemotherapy - Behcets disease - Tumour invasion

Answer 155

A hereditary metabolic disorder The most common genetic cause of emphysema and metabolic liver disease in children Accumulation of altered alpha-1-antitrypsin in hepatocytes incites an inflammatory response and chronic liver disease Pathology: - Alpha-1-antitrypsin is a protein that prevents enzymes e.g. elastase from degrading normal host tissue - 90% of the alpha-1-antitrypsin protein is produced in hepatocytes by codominant gene expression on chromosome 14 - Alpha-1-antitrypsin protein inhibits neutrophil elastase - The neutrophil elastase acts unopposed resulting in damage to the lower respiratory tract - the damage distribution is predominantly basal due to gravitational distribution of pulmonary blood flow Associations: - Asthma - Pancreatitis - Aneurysms Hepatic manifestation: cirrhosis, and increased risk of HCC

Answer 156

Multiple strictures of the biliary tree, liver damage and eventual cirrhosis Strongly associated with IBD, especially ulcerative colitis Associations: - Ulcerative colitis - Autoimmune hepatitis - Sjogren syndrome - Retroperitoneal fibrosis - Mediastinal fibrosis - Riedel thyroiditis - Orbital pseudotumour Pathology: - No histological findings are pathognomonic Frequent findings include: - Periductal fibrosis - Periportal eosinophilic infiltrate - Paucity of ducts Markers: antibody titres are usually absent or low LFTs will have a cholestatic pattern with elevated ALP and bilirubin Intra and extra hepatic involvement - In 20% only the intrahepatic and proximal extrahepatic bile ducts are involved - Cirrhosis of the whole liver, with the exception of the caudate lobe - Other causes of cirrhosis will often involve hypertrophy of the left lobe A risk factor for gallbladder cancer, so polyps should be considered malignant until proven otherwise Complications: - Hepatic osteodystrophy - Cholangiocarcinoma - Colorectal cancer - Hepatocellular carcinoma - Gallbladder carcinoma

Answer 157

A chronic progressive cholestatic liver disease that is the cause of 1-2% of deaths from cirrhosis and constitutes the third most common indication for liver transplantation in adults Typically middle aged women with symptoms of fatigue and pruritis Associations: - Cholelithiasis ~40% - Other autoimmune diseases: Sjogren syndrome 75%, autoimmune thyroiditis 25%, systemic sclerosis 10% - Interstitial lung disease 15% - Hepatocellular carcinoma ~5% - Hepatic osteodystrophy Characterised by the destruction of small intrahepatic bile ducts, portal inflammation and progressive scarring The cause is unknown Serum anti-mitochondrial antibody (AMA) tests are highly sensitive and specific for PBC

Answer 158

1 - fusiform dilation of the extrahepatic bile duct 2 - saccular outpouchings from the supraduodenal extrahepatic bile duct or intrahepatic bile duct 3 - focal dilation of the distal common bile duct into the duodenum (choledochocele) 4 - multiple communicating intra- and extra-hepatic duct cysts 5 - caroli disease

Answer 159

Absence or severe deficiency of the extrahepatic biliary tree. Complete or partial obstruction of the lumen of the extrahepatic biliary tree within the first 3mo of life.

Answer 160

Benign, generally hormone-induced, liver tumours Usually solitary, with a predilection for haemorrhage Epidemiology: - OCP - Anabolic steroids - typically young men - Glycogen storage diseases - Type 1 - Von Gierke disease - Type 3 - Cori or Forbes disease - Obesity Pathology: Usually solitary 70-80% of cases, and large at the time of diagnosis 5-15cm Most frequently seen at the subscapular location in the right lobe of the liver and are often round, well-defined pseudo-encapsulated masses May have dystrophic calcification Hepatic adenomatosis - the presence of numerous (10+) hepatic adenomas Patients often have an associated risk factor, like glycogen storage disease type 1 Histologically characterized by proliferation of pleomorphic hepatocytes without normal lobular architecture - Frequently have abundant glycogen Described as being devoid of bile ducts and Kupffer cells

Answer 161

Inflammatory hepatic adenoma - Most common - Highest bleed rate - Different appearance from the other subtypes - The most common subtype 40-50% - Occur in OCP setting, or older patients with hepatic steatosis or metabolic syndrome - Clinical presentation: fever, leucocytosis, elevated CRP, elevated LFTs - MRI - Unlike the others, these can show enhancement after PRIMOVIST (HB contrast) since they express the hepatospecific receptor - No drop out on the out of phase HNF-1 alpha mutated hepatic adenoma - Second most common subtype 30-35% - Only in female with history of OCP use - Often multiple (50%) - MRI - T1 iso/hyper relative to liver - Moderate arterial enhancement - No continuity of enhancement - Drop out on out of phase - Iso – mildly high T2 Beta catenin-mutated hepatic adenoma - Least common subtype 10-15% - Highest risk in men on anabolic steroids and patients with glycogen storage disease, familial adenomatous polyposis - Usually regresses with ceasation of hormone administration Unclassified hepatic adenoma - Lack known genetic abnormalities

Answer 162

A regenerative mass lesion of the liver and the second most common benign liver lesion Most frequently found in young-middle-aged adults, with a strong female predilection Usually isolated occurrence is the commonest, but up to 20% may be multiple Associations: - Hepatic haemangiomas - Hereditary haemorrhagic telangiectasia - Arteriovenous malformations (AVM) - Anomalous venous drainage - Hepatic adenoma - Budd-Chiari syndrome Pathology: - Thought to be due to a hyperplastic growth of normal hepatocytes with a malformed biliary drainage system, possibly in response to a pre-existent AVM - Arterial supply - hepatic artery - Venous drainage - hepatic veins - No portal venous supply Two types: Typical 80% Atypical 20% - Lacks a central scar and central artery

Answer 163

The most common primary malignancy of the liver Strongly associated with cirrhosis, of both alcoholic and viral aetiologies Risk factors: Hepatitis B, C Biliary cholangitis Congenital biliary atresia Inborn errors of metabolism - Haemochromatosis - Alpha-1-antitrypsin deficiency - Type 1 glycogen storage disease - Wilson disease - Tyrosinaemia type 1 - Porphyrias Obesity and diabetes Pathology: - The origin is believed to be related to repeated cycles of necrosis and regeneration, irrespective of the cause - HBV/HCV may contain genetic material that may predispose cells to accumulate mutations or disrupt growth control Three types of macroscopic growth: - Nodular - Massive - Infiltrative Markers: AFP are elevated in 50-75%

Answer 164

A distinct histological variant of HCC Characterized on microscopy by laminated fibrous layers between tumour cells Typically occur in young adults 20-40yo Not associated with cirrhosis, alcoholism or hepatitis B/C infection Pathology: - Well differentiated and well circumscribed, with a dense fibrotic background - The tumour cells are arranged in cords that are separated by sheetlike fibrous bands arranged in a parallel or lamellar distribution Often these don’t produce AFP The central scar is typically low on all sequences, can be T2 bright, mimicking FNH

Answer 165

A primary epithelial malignancy arising from the gallbladder, in which the majority (90%) are adenocarcinomas and the remainder are squamous cell carcinomas More prevalent in elderly women, and in most cases are only symptomatic when in advanced stages Risk factors: - Chronic cholecystitis - Gallstones are present in 70-90% of cases - FAP - IBD - Porcelain gallbladder - Gallbladder polyps >1cm - Primary sclerosing cholangitis Majority are related to chronic inflammatory metaplasia and dysplasia Three morphologies: - Intraluminal mass - Diffuse mural thickening - Mass replacing the gallbladder

Answer 166

Risk factors: - Caroli disease/choledochal cysts - Choledocholithiasis - Primary sclerosing cholangitis - Recurrent pyogenic cholangitis - Cirrhosis - Toxins - Viral infection - IBD - Fibropolycystic liver disease - Hepatolithiasis Location -Intrahepatic - 10% - Extrahepatic - Perihilar 70% - Klatskin tumour - Distal 20% (Distal to the cystic duct insertion ) Typically sclerotic masses without haemorrhage or macroscopic necrosis The active tumour is at the periphery, with central portions replaced by fibrosis: accounting for the capsular retraction Three macroscopic descriptions are used: - Mass-forming: definite mass in the liver parenchyma - Periductal-infiltrating: extends longitudinally along the bile duct, often causing peripheral bile duct dilatation - Intraductal growth - proliferates in the lumen of the bile duct like a papilla or tumour thrombus - Characterised by alterations in duct calibre, usually duct ectasia with or without a visible mass - If the mass is visible, it may be mural or polypoid in shape - The duct dilatation is thought to be due to abundant mucin production - similar to IPMN Histologically divided into well, moderately and poorly differentiated adenocarcinomas. - Biliary intraepithelial neoplasia is a common finding, considered to be a precursor lesion of cholangiocarcinoma - Typically a microscopic lesion with a flat or micropapillary dysplastic epithelium - Synonymous with carcinoma in situ.

Answer 167

Mass-forming: - Non contrast: Homogenously low in attenuation - Arterial - heterogenous minor peripheral enhancement with gradual centripetal enhancement - The rate and extent depends on the degree of central fibrosis - Capsular retraction may be evident - The distal bile ducts are typically dilated - Narrowing of the portal veins, less frequently hepatic veins, can also be seen, but cholangiocarcinoma rarely forms a tumour thrombus - Lobar or segmental hepatic atrophy is usually associated with vascular invasion Periductal infiltrating - Intrahepatic tumours appear as regions of duct wall thickening or of the periductal parenchyma, with altered calibre of the involved duct (usually narrowed) - These are most common at the hepatic hilum - Tend to be longer than benign strictures (approximately 20mm in length), and show contrast enhancement - There is usually some proximal (peripheral) dilatation of the biliary tree Intraductal tumours - Characterised by alterations in duct calibre, usually duct ectasia with or without a visible mass

Answer 168

The presence of bile duct stones within the intra-hepatic bile ducts, specifically proximal to the confluence of the right and left hepatic ducts Associations: - Primary sclerosing cholangitis - Post-operative biliary strictures - Caroli disease Pathology: - Can occur with or without the concomitant presence of cholelithiasis or choledocholithiasis

Answer 169

A disorder of pregnancy involving new-onset hypertension (systolic BP >140 or diastolic >90) and involvement of one other organ system Affects up to 8% of pregnancies Risk factors: - Diabetes mellitus - Chronic hypertension - Family history - Nulliparity - Advanced maternal age (>40yo) - Obesity - Anti-phospholipid syndrome (9x) - Pre-eclampsia in prior pregnancy (7x) After 20 weeks with: - Proteinuria - Thrombocytopenia - Renal impairment (doubling of creatinine) - Liver impairment (doubling of hepatic transaminases) - Pulmonary oedema - Headache or visual disturbance - If they seizure = eclampsia Pathology: incompletely understood Defective development of spiral placental arteries and subsequent placental ischaemia is thought to be key

Answer 170

An acute inflammation of the pancreas Two subtypes: Interstitial oedematous pancreatitis 90-95% Necrotising pancreatitis Pathology: Debate over the precipitating factor leading to acute pancreatitis Duct occlusion is an important factor, but not necessary or sufficient Activation of pancreatic enzymes in the pancreas rather than the bowel leads to inflammation of the pancreatic tissue, disruption of small pancreatic ducts and leakage of pancreatic secretions The pancreas lacks a capsule, so the juices have ready access to surrounding tissues Pancreatic enzymes digest fascial layers, spreading the inflammatory process to multiple anatomic compartments Aetiology: - Gallstone passage/impaction - most common - Idiopathic 20%, most are associated with congenital duct abnormalities - Alcohol abuse – most common cause of chronic pancreatitis - Metabolic disorders – hypertriglyceridaemia-induced - Most common cause in pregnancy - Hypercalcaemia - Autoimmune pancreatitis - Penetrating peptic ulcer - Trauma – most common in children - Blunt abdominal trauma - Surgery - Malignancy - Pancreatic adenocarcinoma - Lymphoma - Hereditary pancreatitis - Malnutrition - Infection - Viral – mumps, Coxsackievirus, hepatitis, i- fectious mononucleosis, HIV/AIDS - Parasitic – ascariasis, clonorchiasis - Structural – not a cause,

Answer 171

A form of chronic pancreatitis associated with autoimmune manifestations Rare, incidence is ~5-11% of chronic pancreatitis cases Variable age of presentation, male predilection Clinical presentation: - Jaundice, weight loss - New onset diabetes mellitus - Extra-pancreatic manifestations with lymphocytic infiltration: - Inflammatory bowel disease - Pulmonary involvement - Renal involvement - Biliary tree - Salivary glands - Elevated IgG and antinuclear antibody levels >50% of cases - Abdominal pain and acute pancreatitis - Serum amylase and lipase can also be raised Characterised by a heterogenous autoimmune inflammatory process where prominent lymphocytic infiltration with associated fibrosis of the pancreas causes organ dysfunction The cause is unknown, though an autoimmune process with antibody reaction to carbonic anhydrase and lactoferrin has been postulated Macroscopic appearance: diffusely indurated and firm pancreas, with some demonstrating a focal mass Microscopic: - Collar-like periductal infiltrates composed of lymphocytes and plasma cells, with the lymphocytes being CD8+ and CD4+ T lymphocytes - Clusters of inflammatory cells are also seen in the walls of small veins and nerves, as well as medium and large-sized vessels - Interlobular septa are thickened by a proliferation of myofibroblasts and infiltrated by lymphocytes and plasma cells - Other organs can be involved with a lymphocyte infiltrate: gallbladder, biliary tree, kidney, lung and salivary gland Associations: - IgG4- related sclerosing disease - Rheumatoid arthritis - Sjogren syndrome - Inflammatory bowel disease - IgG4-related sclerosing cholangitis

Answer 172

Arise from the pancreatic islet cells and include some distinct tumours that match the cell type of origin Overall have an incidence of 0.001%, and account for 1-2% of pancreatic neoplasms They occur most commonly at ages 30-60, with no clear gender predilection Associations - Most are isolated - 1-2% are associated with multiple endocrine neoplasia type I (MEN I) which is characterised by the triad of parathyroid, pituitary and pancreatic lesions - Pancreatic endocrine tumours - Von Hippel-Lindau disease - Tuberous sclerosis Syndromes: Insulinoma: Whipple triad - Fasting hypoglycaemia - Symptoms of hypoglycaemia - Immediate relief with administration of glucose Gastrinoma: Zollinger-Ellison syndrome - Diarrhoea - Gastritis - Severe GORD - Peptic ulcer disease Glucagonoma: 4D syndrome - D - dermatitis - D - mild diabetes mellitus - D - deep vein thrombosis - D - depression Non-functioning: tend to present late and often larger in size

Answer 173

Insulinoma - Most common - Develop from ductal pluripotent cells into unregulated cells secreting insulin - The beta cells of the islet of Langerhans normally secrete insulin -10% of insulinomas are multiple, and 10% malignant - Equally distributed throughout the pancreas Gastrinomas - Usually multiple - Typically located in the duodenum (more commonly) or pancreas (less commonly) - Secrete gastrin that results in hypersecretion of gastric acid - Marker: Chromogranin A levels may be elevated Glucagonoma - Most are malignant - Most are large and have metastasised at the time of diagnosis - Most are located in the distal pancreas and tend to demonstrate significant hypervascularity

Answer 174

Epithelial pancreatic cystic tumours of mucin-producing cells that arise from the pancreatic ducts Most commonly seen in elderly patients Characterised by single or multiple unilocular or septated pancreatic cystic lesions communicating with the pancreatic ducts Typically 50-60yo can be main or side branch Main duct lesions present a decade earlier than branch type Can be further divided histologically with respect to their macroscopic appearances Uncommon ductal epithelial tumours comprising of 10-15% of cystic pancreatic neoplasms

Answer 175

Main duct - Reminiscent of chronic pancreatitis - Segmental or diffuse distribution - Highest malignant potential ~60% Branch type - Most seen in the head and uncinate process - More localised and mass-like - Multi-focal - May be macro or microcystic in appearance - Typically indolent behaviour ~5% are malignant Divided into: - Adenoma - Borderline-malignant - Intraductal papillary mucinous adenocarcinoma Markers: Abnormal pancreatic enzyme markers (amylase/lipase) are associated with malignant IPMN

Answer 176

An uncommon type of benign cystic pancreatic neoplasm Strong female predilection, and usually present in middle age to elderly patients >60yo Association: - Von hippel lindau - can be multiple or diffuse and present at a younger age Pathology: - Benign neoplasms composed of numerous small cysts arrayed in a honeycomb-like formation - Can be significant variation in locule size 1-20mm - Most are typically <10mm - Three morphological patterns: - Polycystic 70% - Honeycomb 20% - Oligocystic <10% - Cysts are lined by glycogen-rich flat or cuboidal epithelium separated by fibrous septa that radiate from a central scar and may by calcified - Tend to be large at presentation Location: - Head/uncinate process 40%, body 34% and tail 26%

Answer 177

The most common pancreatic cystic lesion Middle aged females exclusively Pathology: - A large uni/multilocular cystic pancreatic neoplasm lined by columnar mucinous epithelium - Infrequently communicate with the pancreatic duct, but can cause partial pancreatic ductal obstruction - Considered premalignant/malignant: usually with an elevated CEA and CA19-9 Cant differentiate on CT between adenoma and adenocarcinoma

Answer 178

Rare, account for 1-2% of exocrine pancreatic lesions Tend to present in young non-Caucasian females ~2nd-3rd decades of life Associations: pancreatic dorsal agenesis Pathology: - Frequently contain varying amounts of necrosis, haemorrhage and cystic change - Can be large at the time of diagnosis Greater predilection to occur at the tail

Answer 179

Risk factors: - Cigarette smoking - Chronic pancreatitis - Obesity - Diabetes mellitus - Family history - Hereditary syndromes: - BRCA2 mutations are the most frequent cause of familial pancreatic cancer - HNPCC - Familial breast cancer - Familial atypical multiple mole melanoma - Hereditary pancreatitis - Ataxia-telangiectasia - Peutz-jegher syndrome Serum markers: - CEA - CA19-9 Pathology: Precursors: - Pancreatic intraepithelial neoplasia - 90% - Intraductal papillary mucinous neoplasm (IPMN) - Mucinous cystic neoplasm Pathogensis: - The most prevalent molecular changes responsible are: - KRAS - the most commonly mutated oncogene 90% - TP53 70-75% - SMAD4 - inactive 55% - CKN2A altered 30%

Answer 180

Most common cause of fatal sporadic fulminant necrotising viral encephalitis Two subgroups: - Neonatal - typically HSV2 - Childhood and adult – typically HSV 1 (90%) There is no particular age, sex or seasonal predilection Diagnosis: PCR of CSF – pleocytosis and elevated protein Pathology: - Obligatory intracellular virus - Enters via infecting nasopharyngeal cells into the sensory branch of the lingual nerve, ascending to trigeminal ganglion where it remains latent for a lifetime - Reactivation occurs with immunosuppression, trauma, or other stressors - Can result in fulminant hemorrhagic necrotising encephalitis - High affinity for limbic systems with bilateral but asymmetric involvement Micro: - Perivascular cuffs of lymphocytes, large inclusions in neurones and glial cells - "owl eyes"

Answer 181

An infection of the CNS with the yeast-like fungus Cryptococcus neoformans The most common fungal infection Predominantly immunocompromised patients, Pathology: - Typically haematogenous spread from the lungs - usually the primary site - In HIV/AIDs patients, the infection occurs when the CD4+ count drops below 100 cells/uL - Can have either meningeal or parenchymal involvement, meningeal being the primary manifestation - Grey mucinous exudate accumulates over the involved brain surface Three forms: - Meninges = meningitis - Parenchyma = cryptococcomas - Perivascular spaces = gelatinous pseudocysts. Usually only immunocompromised

Answer 182

An opportunistic infection caused by the parasite Toxoplasma gondii Typically affects patients with HIV/AIDs, and is the most common cause of cerebral abscess in these patients An intracellular parasite that infects birds and mammals Transferred via excrements into food, leading to infection Pathologically, the lesions have three distinct zones: - A central avascular zone of coagulative necrosis - An intermediate vascular zone containing numerous organisms - An outermost zone of encysted organisms These lesions don’t have a capsule Manifest as multiple lesions, with a predilection for the basal ganglia, thalami and corticomedullary junction

Answer 183

A transmissible spongiform encephalopathy resulting in rapidly progressive dementia and death, usually within a year of onset The vast majority are sporadic, but familial and acquired forms are occasionally encountered Four types: - Sporadic - 85-90% of cases - Variant - bovine transmission - Familial - 10% -PRPc mutation - Iatrogenic Diagnostic markers - EEG - S100 - CSF 14-3-3 protein - a positive marker Pathology: - Mediated via prions, a type of protein - Considered infectious, in that they can alter the structure of neighbouring proteins - Leads to spongiform degeneration of the brain - Caused by the conversion of normal prion protein to proteinaceous infectious particles that accumulate in and around neurones and lead to cell death

Answer 184

Can result from either haematogenous spread from distant infection or direct extension from local infection Protean infection, can affect all compartments Extra-axial - TB meningitis : leptomeningitis - pachy is rare Intra - Tuberculoma (tuberculous granuloma) - Focal tuberculous cerebritis - Intracranial TB abscess - TB rhombencephalitis - TB encephalopathy Seen in all age groups, with a predilection for younger patients Haematogenous spread from the lungs or GIT is most common, leading to small subpial or subependymal infective foci These are called Rich foci and form a reservoir from which intracranial manifestations may arise Either during primary infection (uncommon) or reactivated later

Answer 185

A parasitic infection caused by ingestion of tapeworm eggs through faecal-oral transmission A pork tapeworm: Taenia solium No gender or race predilection, most symptomatic patients are aged 15-40yo Pathology: - Infection by contaminated food/water Four stages: - Vesicular - variable parasite with intact membrane, and no host reaction - Cyst with a dot sign - Colloidal vesicular - parasite dies within 4-5yrs untreated, or earlier with treatment and the cyst fluid becomes turbid - As the membrane becomes leaky oedema surrounds the cyst - Oedema, cyst and the wall become thickened and brightly enhance - Granular nodular - oedema decreases as the cyst retracts further, enhancement persists - Oedema decreases, cyst retracts and becomes a small enhancing nodule - Nodular calcified - end stage quiescent calcified cyst remnant, no oedema Location can be both intra and extra-axial. The most common locations are: - Subarachnoid space over the cerebral hemispheres - Parenchyma - most frequent - Basal cisterns - 'grape-like' "racemose" - Ventricles - Usually a solitary cyst - 4th ventricle is most common - Spinal forms - Concomitant intracranial involvement - Subarachnoid and interventricular cysts don't typically have a visible scolex - Look for ventriculitis

Answer 186

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy An autosomal dominant microvasculopathy characterised by recurrent lacunar and subcortical white matter ischaemic strokes and vascular dementia in young and middle-aged patients without known vascular risk factors Typically symptomatic in adulthood, 30-50yo Present with TIA/strokes in multiple areas Mutation of chromosome 19p13.12, involving the NOTCH3 gene Results in small vessel and arteriole stenosis secondary to fibrotic thickening of the basement membrane of the vessels - The pathological hallmark is the deposition of granular osmiophilic material in close relation to the vascular smooth muscle cells Anterior temporal lobe and external capsule Relative sparing of subcortical U-fibres and the cortex, as well as occipital/ orbitofrontal subcortical white matter

Answer 187

Cerebrovascular disorder caused by the accumulation of cerebral amyloid-B in the tunica media and adventitia of the leptomeningeal and cortical vessels of the brain The resultant fragility manifests in normotensive elderly patients as lobar intracerebral hemorrhage Can be sporadic or familial - Sporadic - higher rates in Alzheimers - Familial - rare, autosomal dominant conditions Pathology - Deposition of amyloid in the tunica media and/or tunica adventitia of small and medium-sized arteries of the cerebral cortex and leptomeninges - There is associated fibrinoid degeneration with separation of the tunica media and tunica intima and microaneurysm formation - Different proteins can lead to intravascular amyloid deposition Associations - Alzheimer disease - Down syndrome - Chronic traumatic encephalopathy - Spongiform encephalitis Imaging - Intracerebral haemorrhage - usually cortico-subcortical - Micro-haemorrhage - Tend to spare the basal ganglia and pons - Convexity SAH - Cortical superficial siderosis Cerebellar superficial siderosis Ischemia

Answer 188

Primarily affects the grey matter structures - Basal ganglia - Thalami - Cerebral cortex - esp sensorimotor and viscual cortices - Cerebellum - Hippocampi Grey matter involvement due to high metabolic requirement for oxygen and glucose to supply a large number of synapses - Makes the grey matter more susceptible to hypoxic-ischaemic injury MRI: DWI is the first to change

Answer 189

Thiamine (vitamin B1) deficiency Typically seen in alcoholics Triad of presentation: - Acute confusion - Ataxia - Ophthalmoplegia Can evolve into a chronic form: korsakoff psychosis - Memory loss - Confabulation Aetiology: - Malnutrition and malabsorption, which can occur for a number of reasons - Alcohol abuse - Starvation/fasting - Chronic dialysis - GI malignancy Acutely: haemorrhage, necrosis and oedema may be present Chronic: atrophy, especially involving the mamillary bodies MRI Symmetrically increased signal intensity in the: - Mamillary bodies - Dorsomedial thalami - Tectal plate - Periaqueductal grey matter - Around the third ventricle - Can have contrast enhancement in the same region - Restricted diffusion may be seen Differential: - Leigh syndrome - child

Answer 190

May result in anoxic-ischaemic encephalopathy, with acute as well as delayed effects Acute: headache, dizziness, altered conscious state, seizure Cardiac arrest may occur Chronic: cognitive decline, abnormal gait, faecal incontinence Pathology: Two fold pathophysiology: - CO binds strongly to haemoglobin and the resultant carboxyhaemoglobin in the bloodstream can cause profound hypoxic/anoxic injury - A respiratory chain metabolism toxin that interferes with mitochondrial oxidative phosphorylation and activates polymorphonuclear leucocytes > delayed brain lipid peroxidation Tend to be bilateral, with the globus pallidus most affected

Answer 191

Subacute necrotising encephalomyelopathy A mitochondrial disorder with progressive neurodegeneration leading to death, usually in childhood Symptoms are evident by age 2 - Psychomotor delay/regression - Superimposed signs of basal ganglia and brainstem dysfunction - Ataxia - Ophthalmoplegia - CN palsies Pathology - One of many mitochondrial disorders, due to a broad range of genetic mutations in either nuclear or mitochondrial DNA - Nuclear DNA mutations are more common - AR, and X-linked Chronic energy deprivation leads to histological features such as: - Spongiform degeneration - Capillary proliferation - Demyelination - Neuronal loss - Gliosis Markers: CSF lactate may be elevated MRI - Brainstem - Periaqueductal grey matter - Medulla - Midbrain - Putamen

Answer 192

Autosomal recessive disorder of copper metabolism Abnormal caeruloplasmin metabolism, as a result of a variety of mutations in the ATP7B gene Total body copper is elevated - toxic effects on hepatocytes with copper deposition and resulting damage to a variety of organs e.g. liver and brain Three pathways are most affected: - Dentatorubrothalamic tract - Pontocerebellar tract - Corticospinal tract Basal ganglia - especially putamen, followed by midbrain, pons and thalamus Distribution is bilateral and symmetric CT - May see atrophic changes in the basal ganglia, cortical and cerebellar regions - Non-enhanced: copper deposition doesn't increase density on CT - Post contrast: lesions don’t enhance MRI - Abnormal T2 high signal in the putamen - Predominantly the deep grey nuclei - "face of the giant panda sign" - midbrain tegmentum involvement

Answer 193

"eye of the tiger sign": symmetrical bilateral abnormal low signal on T2 Accumulation of iron in the globus pallidus with central high signal

Answer 194

end stage eye An atrophic scarred and disorganised non-functioning globe, that may result from a variety of occular insults Typicaly elderly patients Small globe with thickened/folded posterior sclera Dysmorphic calcification is common, osseous metaplasia may occur Aetiology - Trauma - Infection - Other inflammatory process' - Radiation - Chronic retinal detachment - retinoblastoma

Answer 195

Deficiency or resistance to the hormone vasopressin (antidiuretic hormone) which results in polyuria and polydipsia Central/neurogenic/hypothalamic - vasopressin deficient (most common) Peripheral/nephrogenic - vasopressin resistant Aetiology: Central - reduced secretion - Trauma, NSx - Malignancy - craniopharyngioma, germinoma, mets - Autoimmune - lymphocytic hypophysitis - Inflammatory disease - sarcoid, LCH, IgG4 - Infection - TB - Pregnancy - Familial, - Idiopathic Peripheral - increased end-organ resistance to vasopressin - Congenital renal insensitivity to vasopressin (rare) - Long term lithium use (~15% of patients) - Metabolic - hypokalaemia, hypercalcaemia - Chronic kidney disease - pregnancy

Answer 196

An autosomal dominant trinucleotide repeat neurodegenerative disease Characterised by a loss of GABAergic neurones of the basal ganglia, especially atrophy of the caudate nucleus and putamen - Atrophic caudate nucleus > concomitant enlargement of the frontal horns of the lateral ventricles Typically diagnosed age 30-50yo, equal incidence in both genders Presentation is progressive rigidity, choreoathetosis, dementia, psychosis and emotional lability Genetics: autosomal dominant with complete penetrance and genetic anticipation - The next generation with have more repeats of CAG and a more severe course of the disease/earlier symptoms - Chromosome 4p16:3, a CAG trinucleotide repeat - Microscopically: Huntington nuclear inclusion bodies Both deep grey matter, and white matter (to a lesser degree) are involved

Answer 197

A neurodegenerative disease and one of the tauopathies characterised by the accumulation of Pick bodies Typically manifests between age 40-60, with a male predilection Characteristic features: - Pick bodies - Swollen chromatolytic neurones - Loss of large pyramidal neurones - Astrocytic gliosis Imaging: cortical atrophy of the frontal and temporal lobes - Can be markedly asymmetrical and affect one area more than another - Caudate head volume can also be reduced Differential: - Other varieties of frontotemporal lobar degeneration - Alzheimer disease - parietal lobe is more pronounced

Answer 198

A common neurodegenerative disease, responsible for 60-80% of all dementias A result of accumulation and deposition of cerebral amyloid-B, the most common cerebral amyloid deposition disease Typically 85-90yo Risk factors: - Advanced age - Female gender - Current smoker - Family history - Down syndrome - Psoriatic arthritis - chronic inflammation etc. The accumulation of cerebral amyloid-beta forms neuritic plaques, neurofibrillary tangles and eventually progressive loss of neurones Increasing evidence suggests that chronic inflammation is at least partially responsible Imaging: - Diagnosis should be made based on two features: - Mesial temporal lobe atrophy - particularly the hippocampus, entorhinal cortex and perirhinal cortex - Assessment of volumes should be done accurately, not by eyeballing - Additionally often have white matter high T2 signal - chronic small vessel ischaemic changes - SPECT/PET: detect regional hypoperfusion/hypometabolism in a biparietal and bitemporal distribution, while amyloid and tau accumulate in the grey matter and medial temporal lobes respectively

Answer 199

A neurodegenerative disease and movement disorder characterised by resting tremor, rigidity and hypokinesia due to progressive degeneration of dopaminergic neurones in the substantia nigra The most common cause of the parkinsonian syndrome - accounts for 80% of cases The remainder are others, e.g. Lewy body dementia The most common form s in elderly patients, and usually sporadic Clinically: -Resting pill rolling tremor - Cog-wheel rigidity - Bradykinesia - Postural instability Pathology: - The dopaminergic tract is predominantly affected - Nigrostriatal dopaminergic degeneration > neuronal loss in the substantia nigra pars compacta - Other areas: basal ganglia, brainstem, autonomic nervous system and cerebral cortex Imaging: Loss of the normal swallow tail appearance of susceptibility signal pattern in the substantia nigra on axial imaging

Answer 200

Primary neuroendocrine tumours that occur in the pituitary gland, one of the most common intracranial neoplasms Classified into micro (<10mm) and macro (>10mm) Associations: A small number are associated with: - MEN 1 - MEN 4 - Carney complex - McCune-Albright syndrome Presentation: either hormonal imbalance or mass effect - esp the optic chiasm

Answer 201

Cystic masses with peripheral calcification Far more common than papillary, and identified in all age groups with peaks in child hood and age 40-60 Primarily suprasellar, with a small intrasellar component present in 20-25% Purely intrasella is uncommon Presentation: - Headache and raised ICP - Visual symptoms - Hormonal imbalances - Short stature and delayed puberty - Amenorrhoea - Diabetes insipidus - Behavioural change due to frontal or temporal extension Pathology: - Palisading peripheral columnar epithelium, wet keratin and stellate reticulum that have appearances reminiscent of the enamel pulp of developing teeth - similar to ameloblastomas - May be a single or multiple cysts filled with thick oily fluid, rich in protein, blood products and/or cholesterol - Calcification is usually present ~90%

Answer 202

WHO grade 1, typically presenting as mostly solid masses Far less common than adamantinomas, and rare before middle age Most commonly between 40-60yo No race or sex has been identified Primarily suprasella, with a small intrasellar component present in a minority Purely intrasellar is uncommon Occasionally appear as masses within the third ventricle Presentation: - Headache, raised ICP - Visual symptoms - Hormonal imbalances: - Decreased libido - Amenorrhoea - Diabetes insipidus Formed of mases of monomorphic squamous epithelium with a fibrovascular core and scattered immune cells "wet keratin" and calcifications are absent - seen in adamantinomatous Usually solid

Answer 203

Loss of normal myelin around axons in the CNS Different from dysmyelination: where the formation of normal myelin is absent Primary demyelinating disorders: - Clinically isolated syndrome: may not progress to MS - Multiple sclerosis - Variants: - Tumefactive - Acute malignant Marburg type - Neuromyelitis optica (Devic disease) - Schilder type (diffuse cerebral sclerosis) - Balo concentric sclerosis - Acute disseminated encephalomyelitis (ADEM) - Transverse myelitis - Chronic inflammatory demyelinating polyneuropathy - Guillain-Barre syndrome Infective: - Progressive multifocal leukoencephalopathy - HIV encephalitis Toxic: - Osmotic demyelination syndrome - Posterior reversible encephalopathy syndrome Metabolic/genetic - Leukodystrophies

Answer 204

An acquired chronic relapsing demyelinating disease involving the CNS Disseminated in space and time Presents between adolescence and the 6th decade, with a peak around 35yo Strong female predilection Presentation depends on the area of involvement - Common - optic neuritis, internuclear ophthalmoplegia Several patterns of longitudinal disease - Relapsing-remitting ~70% - Secondary progressive - 85% of those with RR MS eventually enter this phase - Primary progressive 10% - Progressive with relapses - Benign 15-50% Investigations - History - Oligoclonal bands in CSF - Immunoglobulin G in serum - Abnormal visual evoked potential Pathology: - Poorly known - An infectious agent is suspected - A cell mediated autoimmune response against one's own myelin components, with loss of oligodendrocytes, with little or no axonal degeneration in the acute phase - In the later stage, loss of oligodendrocytes results in axonal degeneration - Each lesion/plaque undergoes three stages: Early acute - active - Active myelin breakdown - Plaques are pink and swollen Subacute - Abundant macrophages - Plaques are paler in colour Chronic stage - inactive plaques/gliosis - Little or no myelin breakdown - Gliosis with associated volume loss - Appear grey/translucent

Answer 205

A severe demyelinating disease caused by an autoantibody to the aquaporin-4 water channel The classic presentation is: optic neuritis, longitudinally extensive myelitis and positive anti-AQP4 antibody Slightly older group than MS

Answer 206

A rounded lesion with alternating layers of high and low signal intensity on MRI "bulls-eye or onion-bulb" appearance T1/2: irregular concentric areas

Answer 207

A monophasic acute inflammation and demyelination of white matter, typically 1-2weeks following a viral infection or vaccination Grey matter, especially basal ganglia, is often involved. Spinal cord to a lesser extent Thought to occur from a cross-reactivity in immunity to viral antigens, triggering a subsequent autoimmune attack on the CNS Half of the confirmed cases have anti-MOG (myelin oligodendrocyte glycoprotein) Markers - CSF pleocytosis - CSF may show increase in myelin basic protein - Anti-MOG antibodies Involvement of the callososeptal interface is unusual

Answer 208

An inflammatory condition affecting both halves of the spinal cord Typically long segment of greater than 2/3rds of the cross-sectional area of the cord with variable enhancement and no diffusion restriction CSF: need to demonstrate inflammation = pleocytosis or increased IgG index or enhancement Aetiology: - Acute infection - most commonly viral - Post infection - Autoimmune - Post vaccination - Systemic malignancy - Atopy and allergy

Answer 209

Acute demyelination in the setting of osmotic changes - typically the rapid correction of hyponatraemia Classic trident shaped appearance. Can also involve the basal ganlia The peripheral fibres (corticospinal tracts, ventrolateral longitudinal fibres) as well as periventricular and subpial regions are typically spared

Answer 210

The most common Chiari variant Characterised by the caudal descent of the cerebellar tonsils through foramen magnum Underlying cause: a mismatch between size and content of the posterior fossa Four groups: - Abnormal skull base - e.g. short clivus - Cervical segmentation anomalies e.g. Klippel-Feil syndrome - Small cranial vault and/or posterior fossa and consequent overcrowding - Excessive brain tissue Has to protrude >5mm to count Associations: - Cervical cord syrinx ~35% - Hydrocephalus - Skeletal anomalies - Platybasia/basilar invagination - Atlanto-occipital assimilation - Sprengal deformity - Syndrome associations: - Klippel-Feil syndrome - Crouzon syndrome - Hajdu-Cheney syndrome Look for features of intracranial hypertension as a differential Perform CSF flow studies

Answer 211

Myelomeningocele (lumbosacral spina bifida aperta) with a small posterior fossa, with descent of the brainstem and cerebellar tonsils and vermis Due to in utero malformation of the spine and cranial structures resulting in characteristic displacement of the medulla, 4th ventricle and cerebellum through foramen magnum Thought to be due to open spinal dysraphism Associations Spinal - Syrinx - Scoliosis - Segmentational anomalies 50% - Klippel-Feil syndrome - Diastematomyelia Cerebral - Corpus callosum dysgenesis - Absent septum pellucidum - Obstructive hydrocephalus Skeletal - Club foot

Answer 212

A spectrum of posterior fossa malformation, characterised by: - Hypoplasia of the vermis and cephalad rotation of the vermian remnant - Cystic dilatation of the 4th ventricle, extending posteriorly - Enlarged posterior fossa with trocular-lambdoid inversion

Answer 213

Cerebral cavernous venous malformations A slow flow venous malformation Typically presents ~40-60yo, most with a single lesion Multiple lesions may be familial - familial cavernous malformation syndrome Risk of haemorrhage is 1% per patient year for familial, lower for sporadic "mulberry-like' clusters of hyalinised dilated thin-walled capillaries with surrounding haemosiderin - These vessels are thrombosed to varying degrees - There is no normal brain between the interstices of these lesions - unlike AVMs Associations: - Developmental venous anomaly Tend to be supratentorial ~80% of cases, but can be found anywhere, including the brainstem

Answer 214

Diffuse axonal injury is characterised by multiple focal lesions with a characteristic distribution: typically located at the grey-white matter junction, in the corpus callosum and in more severe cases in the brainstem. A classification : Grade 1: microscopic-only evidence of axonal damage in the white matter of the cerebral hemispheres including corpus callosum, in the brainstem, and, occasionally, in the cerebellum Grade 2: focal lesion in the corpus callosum, in addition to diffuse axonal damage Grade 3: focal lesions in both the corpus callosum and dorsolateral quadrant of the rostral brainstem, in addition to diffuse axonal damage

Answer 215

Common tumour of parotid gland with double layer of epithelial cells resting on dense lymphoid stroma 2nd most common benign salivary gland tumour Almost always is the parotid gland, 10% of parotid tumours. Often in the tail 70% of bilateral salivary glands are warthin tumours Usually male smokers age 40+ Associations: - Smoking, irradiation, TB May occur synchronous with pleomorphic adenoma and salivary duct carcinoma Malignant change 1% - to lymphoma, Merkel cell carcinoma, adenocarcinoma etc. Pathology: Encapsulated, lobulated, mulitcystic with mucinous/serous secretions Presence of a mural nodule is highly suggestive. solid cystic.

Answer 216

Benign mixed tumours Well-circumscribed rounded masses, most commonly within the parotid gland 70-80% of benign salivary gland tumours Mixed histology Contain both epithelial and myoepithelial (mesenchymal) tissues, with mixed histology Appear encapsulated, well circumscribed, however the pseudocapsule is incomplete

Answer 217

A malignant glandular epithelial neoplasm characterised by mucous, intermediate and epidermoid cells, with columnar, clear cell or oncocytoid features Most common salivary gland neoplasm in adults and children Occurs in major > minor salivary glands Possibly associated with ionising radiation Pathology: A mixture of: - Mucous secreting cells - Squamous cells - Lymphoid infiltrate Histology: - Clear mucin-containing cells, which stain reddish pink with the mucicarmine stain Histologically classified as: - Low – well differentiated with little cellular atypia - High proportion of mucous cells - Prominent cyst formation - Intermediate - High – poorly differentiated with cellular pleomorphoism - High proportion of squamous cells - Solid with few, if any, cysts heterogenous enhancement

Answer 218

A carcinoma of the primary salivary glands characterised by its biphasic ductal and myoepithelial differentiation May occur in major and minor salivary glands - Most commonly the parotid Grows in tubular, cribriform and/or solid patterns Epidemiology: - M=F - Mean age ~57 Locally aggressive, propensity for perineural spread homogenous enhancement

Answer 219

A histological subtype of adenocarcinoma Generally considered low grade, Characterised by serous acinar cell differentiation in at least some of the neoplastic cells Essential features: - Parotid is the most common - Favourable prognosis – low local recurrence, distant mets 10-17% of primary salivary gland malignancies 2nd most common in children, 3rd in adults: mucoepidermoid carcinoma > adenoid cystic carcinoma

Answer 220

Epithelium-lined connection between the foramen caecum and the thyroid that forms during the descent of the thyroid during embryological development Arises from the proximal primitive foregut between the first and second pharyngeal pouches Passes anterior to the body of the hyoid bone, curving backwards and superiorly to reach behind the bone, before turning inferiorly and continuing to the isthmus of the thyroid The pyramidal lobe, if present marks this point The tip of the duct bifurcates, forming the two lobes of the gland

Answer 221

Autoimmune disease with goiter, elevated circulating antithyroid peroxidase and antithyroglobulin antibodies 90-95% in women, usually 45-65yo May coexist with other conditions – SLE, RA, Sjogren syndrome, MALT lymphoma etc. Associated with well differentiated thyroid cancer, and may evolve into thyroid lymphoma Autoantibodies include: - Anti-TSH: specific for hashimoto's and grave's disease - Antithyroglobulin - Antithyroid peroxidase Pathology: - Diffuse enlargement of the thyroid gland with intact capsule - May have adhesions, but easily separated from other structures - Surface resembled lymph nodes with tannish yellow colour - May have increased interlobular fibrosis, or be fibrotic - Occasionally gland in nodular or asymmetric - No necrosis of calcification - Histologically, extensive lymphocytic infiltrate with germinal centre formation

Answer 222

The most common thyroid malignancy Typically middle ages, ~3-4th decades More common in women Associations: - Gardner syndrome - Cowden syndrome - FAP Tendency to metastasise early to local lymph nodes - check ipsilateral jugular chain, level III + IV Distal haematogenous dissemination is less common than with follicular cancer Lymphatic spread is more common Histopath: - Delicate stalks of epithelial cells - Characteristic orphan annie eye nuclear inclusions and psammoma bodies

Answer 223

Typically occurs in women, and an older age group than papillary It metastasises late to lymph nodes, but only 5-10% have nodal mets at the time of diagnosis - Haematogenous spread is more common – 20% at the time of presentation Genetics: RAS oncogene is positive Variants: - Classic follicular thyroid carcinoma - Insular variant Cytology required, FNA can't differentiate between follicular thyroid adenoma and follicular thyroid carcinoma

Answer 224

Non-familial case – typically peaks in the 3rd - 4th decades Associations: - MEN 2 – both A and B - VHL - NF1 Arises from the parafollicular C cells of the thyroid Amyloid components are seen on histology Characterised by consistent production of a hormonal marker (calcitonin), calcification of both primary and metastatic sites Mets up to 50% of the time

Answer 225

A highly aggressive form of thyroid cancer Typically occurs in the elderly, with peak incidence in the 6th-7th decades A significant proportion may have a history of concurrent multinodular goitre Tend to present late with symptoms of neighbouring structure compression US – may show microcalcifications Highly infiltrative mass

Answer 226

A subacute granulomatous thyroiditis – self limited, subacute thyroiditis Inflammation of the thyroid gland that includes granulomas 75% in women, usually 30-50yo - Associated with HLA-B35 Aetiology may be systemic viral infection, Self-limited, usually resolves in 6-8 wks, with only 1% having permanent hypothyroidism - May have transient hypothyroidism at 2-8 wks Focal – diffuse enlargement of the thyroid gland >2x normal size - May be asymmetric with nodules of variable size, - May be firm, but does not adhere to surrounding structures Microscopic - Early – neutrophils and destruction of follicles with colloid depletion - Later – non-caseating granulomas surrounding follicles and engulf colloid

Answer 227

Diffuse enlargement of the parathyroid glands A less common cause of primary HPTH Female predilection ~50% have asymmetric enlargement of the parathyroid glands Aetiology: primary - Sporadic 80% - radiation and lithium exposure - Familial 20% - MEN 1 and 2a Secondary - Renal failure

Answer 228

Increased parathyroid hormone leads to increased osteoclastic activity Results in bone resorption and cortical thinning + osteopenia subtypes Primary - Parathyroid adenoma 80% - Parathyroid hyperplasia 10-15% - Parathyroid carcinoma 1-5% Secondary - Chronic hypocalcaemia with renal osteodystrophy being the most common cause - Results in parathyroid hyperplasia

Answer 229

The most common intraocular neoplasm found in childhood Characterised by a heterogenous retinal mass with calcifications, necrotic components and increased vascularisation May be sporadic or secondary to a germline mutation of the retinoblastoma protein tumour suppressor gene (RB), which is usually inherited Can be: Bilateral (30-40%) = definitely have a germline mutation Unilateral 60-70% of cases, 15% of these have a germline mutation So around 55% The mutation is inherited in an autosomal dominant fashion, with 90% penetrance Most cases are diagnosed within the first 4yrs of life, typically ~18-24yo A germline mutation also means increased risk of developing trilateral retinoblastoma (unilateral or bilateral retinoblastoma and pineoblastomas Also osteosarcoma Pathology: Three patterns of growth: - Endophytic - Growth occurs inwards into the vitreous - Cell clusters may detach and float in the vitreous - Exophytic - Growth occurs outwards - Associated with non-hematogenous retinal detachment - Combined endophytic and exophytic May metastasise via direct spread into the orbit, along the optic nerve into the brain, or into the subarachnoid space = leptomeningeal metastases It can also haematogenously metastasise preferentially to the bone, bone marrow and liver Rarely it will spread to regional lymph nodes Histology: - A small round-cell tumour of neuroepithelial origin - Flexner-Wintersteiner rosettes (relatively specific for retinoblastoma) and Homer-Wright pseudo-rosettes (also found in other PNETs)

Answer 230

Rare benign cystic lesions involving the mandible or maxilla Locally aggressive and tend to recur after excision Predominantly in younger patients (2nd and 3rd decades) May be seen in either the body or ramus of the mandible (~70%) or maxilla May be a male predilection Typically incidental Pathology: - Thin walled, friable cyst containing fluid and debris - Viscosity of the contents ranges - They originate from epithelial cell rests found along the dental lamina and periodontal margin of the alveolus of the mandible - Inflammation may impede histologic characterisation Associations - Basal cell naevus syndrome - strong association - Gorlin syndrome - Marfan syndrome - Noonan syndrome OPG - Solitary, radiolucent, unilocular, expansile with smooth, corticated borders - Often scalloped around the roots of the teeth - In the maxilla, they expand into the maxillary sinus - Appearance and location can vary MRI - T1 - high - T2 - heterogenous - DWI - restricts, due to presence of keratin - Peripheral enhancement, no nodular component Differentials: - Dentigerous cyst - both can be positioned pericoronally/ Tend to attach to the cemento-enamal junction of teeth - Radicular cyst - doesn't scallop, septate and is more expansile - Ameloblastoma - multilocular, more expansile with a soap-bubble appearance. Tends to be more aggressive with more significant tooth resorption

Answer 231

Slow growing benign and non-inflammatory odontogenic cysts Well-defined and unilocular radiolucency surrounding the crown of an unerupted or impacted tooth within the mandible Second most common odontogenic cyst - After periapical Typically seen in the 2nd-4th decades of life Formed by the hydrostatic force exerted by the accumulation of fluid between reduced enamel epithelium and the tooth crown of unerupted teeth The cyst encloses the crown and is attached to the neck at the cementoenamel junction Almost exclusively occur in permanent dentition Stratified squamous non-keratinising epithelium lines the cyst Over 75% of all cases are located in the mandible Associations - Mucopolysaccharidoses - Basal cell naevus syndrome Imaging: - a cystic expansile pericoronal lesion - Contains the crown of an impacted tooth projecting into a cystic cavity - No further imaging is required - Thin regular sclerotic margin - Expand the overlying cortex without breach - The roots of the teeth are often outside the cyst MRI - T1 low - T2 high - No solid component or enhancement

Answer 232

Locally aggressive benign tumours that arise from the mandible, less commonly the maxilla Usually present as a slowly but continuously growing lesion near the angle of the mandible in the 3rd - 5th decade Second most common tumour - odontoma is the most common Arise from ameloblasts, which are part of the odontogenic epithelium, responsible for enamel production and eventual crown formation Four forms are described: - Unicystic - Solid (multi-cystic) - Desmoplastic - Peripheral (extra-osseous) There are no histo features to differentiate between craniopharyngiomas Imaging: - Multicytic, expansile "soap bubble" lesions, with well-demarcated borders and no matrix calcifications - Resorption of adjacent teeth and root blunting is often a feature MRI - mixed solid and cystic pattern, with thick irregular wallls Differential: - ABC - Other odontogenic cysts

Answer 233

Most common odontogenic tumour Can occur at any age, typically diagnosed ~2nd decade of life "tooth hamartoma" - consists of various tooth components Complex - irregular calcified lesions with no distinct tooth components Compound - identifiable tooth components Associations: - 1/2 will be associated with an unerupted tooth - A feature of Gardner syndrome Imaging: - Initially lucent, develops small calcifications which eventually coalesces to form a radiodense lesion with a lucent rim - Epithelial components may occasionally give rise to a dentigerous cyst

Answer 234

The most frequent cystic lesion related to teeth and result from infection of the tooth Typically seen in middle to older 3rd-6th Results from infection of the tooth, which spreads to the apex Usually <1cm in diameter and bordered by a thin rim of cortical bone Differentials: - Periapical abscess - Periapical granuloma - Dentigerous cyst - Keratocystic odontogenic tumour

Answer 235

Rare benign, but locally aggressive, vascular tumours Occur almost exclusively in males, typically adolescence Benign but highly vascular tumours May be locally aggressive Exact site is variable, but thought to arise from the posterior choanal tissues in the region of the sphenopalatine foramen Imaging: - Arise in the region of the sphenopalatine foramen, usually sizeable at diagnosis and frequently extend medially into the nasopharynx, laterally into the pterygopalatine fossa, eventually going into the orbit, paranasal sinuses, intracranial cavity and infratemporal fossa - Bony remodelling/resorption rather than destruction - Majority are supplied by the ECA, ICA less common MRI - T1 intermediate - T2 heterogenous – dark flow voids - Prominent enhancement

Answer 236

A spectrum of infection and inflammation of the upper female genital tract, resulting in a range of abnormalities Highest incidence is sexually active women, 75% < 25yo Presentation: - Acute pelvic pain, cervical motion tenderness, vaginal discharge, fever, dyspareunia and leucocytosis - Right upper quadrant pain - perihepatitis in Fitz-Hugh-Curtis syndrome Pathology: - Ascending spread of micro-organisms, unrelated to pregnancy or surgery - Generally ascends from the vagina/cervix to the endometrium, then fallopian tubes +/- contiguous structures e.g. tubo-ovarian abscess, peritonitis - Can result from a number of causative organisms Common: - Chlamydia trachomatis - pelvic chlamydial infection - Neisseria gonorrhoeae - pelvic gonococcal infection - Polymicrobial infection ~35% - Less common: TB, actinomyces Usually bilateral, except when caused by the direct extension of an adjacent inflammatory process e.g. appendiceal, diverticular or post-surgical abscesses Often non-specific features, but disproportionate to what may be apparent from the symptoms Complications: - Tubo-ovarian abscess - Pyosalpinx - Infertility due to tubal adhesions - Ectopic pregnancy - Chronic pelvic pain - Peritonitis - Ovarian vein thrombosis - Peritoneal adhesion formation causing bowel obstruction - Fitz-Hugh-Curtis syndrome

Answer 237

Congenital abnormalities that occur when the Mullerian ducts don't develop correctly May be as a result of complete agenesis, defective vertical or lateral fusion or resorption failure Occur in 1-5% of women Majority are asymptomatic Subtypes: - Uterine agenesis 10% - Arcuate uterus ~7% - Unicornuate uterus ~15% - Uterine duplication anomalies - Uterus didelphys ~7.5% - Bicornuate uterus ~25% - Septate uterus ~45% - Subseptate uterus The shape of the external uterine contour is crucial to differentiate a septate uterus from a bicornuate uterus

Answer 238

A common uterine condition of ectopic endometrial tissue in the myometrium Classically, affects multiparous women of reproductive age Most patients are asymptomatic, but can cause dysmenorrhoea, menorrhagia, dysparenunia etc. Histologically defined as the presence of ectopic endometrial tissue within the myometrium The exact cause is unknown, but thought that the endometrial glands directly invade the myometrium resulting in spiral vessel angiogenesis and adjacent smooth muscle hyperplasia and hypertrophy Postulated that the dysfunctional hypertrophied muscular tissue surrounding the ectopic endometrial glands prevents uterine contractions from tamponading bleeding myometrial arterioles, hence these patients frequently present with dysfunctional uterine bleeding or menorrhagia Associations: - Co-existent endometriosis 20% - Leiomyomas 50% - Endometrial hyperplasia - Endometrial polyps Three forms: - Diffuse adenomyosis - most common - Focal adenomyosis and adenomyoma (term used for focal adenomyosis) - Cystic adenomyosis and adenomyotic cyst Typically relatively generalised, affecting large portions of the uterus, but sparing the cervix

Answer 239

Endometrial hyperplasia - Defined as diffuse smooth thickening >15mm premenopause, >5mm post menopause. - An increased proliferation of the endometrial glands relative to the stroma, resulting in an increased gland-to-stroma ratio when compared with normal proliferative endometrium. Now classified as non-atypical hyperplasia and atypical hyperplasia - Non atypical rarely progress to adenocarcinoma 1-3% - Atypical hyperplasia - have a lot of overlap with well-differentiated endometrioid adenocarcinoma and accurate distinction without hysterectomy isn't possible. 23-48% are found to have carcinoma when a hysterectomy is performed Associations: - Obesity - PCOS - Pregnancy - including ectopic - Oestrogen-secreting ovarian tumours - granulosa cell tumour of the ovary - Tamoxifen

Answer 240

he most common gynecological malignancy, with peak incidence ~6th decade Risk factors: Anything that leads to increased oestrogen exposure - Oestrogen replacement therapy - PCOS - Tamoxifen - Obesity - Early menarche or late menopause - Nulliparity - Oestrogen producing tumours e.g. g-ranulosa cell cancer = Diabetes mellitus Smoking may be protective Associations: = HNPCC, 30-50x increased lifetime risk Two subtypes Type 1: 80% = In the setting of unopposed hyperoestrogenism and endometrial hyperplasia = Most commonly obese women, age 55-65 = Tamoxifen = Well differentiated tumour with relatively slow progression, and a more favourable outcome = PTEN gene mutation occurs in 30-80% Type 2: 20% = In the setting of endometrial atrophy, females 65-75 = P53 mutation occurs in up to 50% = Tend to be less differentiated and spread early via lymphatics or through Fallopian tubes into the peritoneum = poorer prognosis

Answer 241

FIGO 1. confined to uterus a;less than half myome b; outer half myomet 2. extends to cervical stroma 3. beyond uterys a; serosa or adneza b; vagina or parametrium c pelic or paraaortic nodes c1 pelvic c2 parasortic 4. bladder/rectal or distant a; bladder/bowel b; distant mets

Answer 242

Benign tumours of myometrial origin, and the most common solid benign uterine neoplasm Commonly an incidental finding on imaging Occur in ~25% of women of reproductive age, particularly common in the African population Responsive to hormones e.g. stimulated by oestrogen, so growth is accelerated during pregnancy and involution occurs with menopause Pathology - Benign monoclonal tumours, predominantly composed of smooth muscle cells with variable amounts of fibrous connective tissue - Commonly multiple ~85%, and range significantly in size Numerous locations Intrauterine - Intramural - most common - Subserosal - may be pedunculated and simulate an adnexal mass - Submucosal - least common, 10-15% Extrauterine - Broad ligament leiomyoma - Cervical leiomyoma - Parasitic leiomyoma - Diffuse uterine leiomyomatosis Can undergo - Hyaline degeneration - Cystic degeneration ~5% - Myxoid degeneration - Red degeneration - due to haemorrhagic infarction, esp in pregnancy

Answer 243

The most common location for a leiomyosarcoma Irregular margins of a uterine leiomyoma on MRI is suggestive of sarcomatous transformation, but not specific Mostly arise de novo from uterine musculature or the connective tissue of uterine blood vessels, but can rarely arise from a pre-existing leiomyoma The pattern of tumour spread is myometrium > pelvic blood vessels and lymphatics > contiguous pelvic structures, abdomen, and distantly often to the lungs Differentiated histologically from a leiomyoma by the presence of infiltrative margins, nuclear atypia and increased mitotic figures

Answer 244

A chronic anovulation syndrome associated with androgen excess The Rotterdam criteria is used to make the diagnosis and requires any two of the following three criteria for the diagnosis - Ovulatory dysfunction (oligo- and/or anovulation) - Clinical and/or biochemical signs of hyperandrogenism - Polycystic ovarian morphology on US The classic triad is: - Oligomenorrhoea and/or anovulation - Hirsutism - Obesity Pathology Markers - Anti-Mullerian hormone (AMH) levels are generally increased - Measure free testosterone, free androgen index, or calculated bioavailable testosterone, androstenedione Associations: - Subfertility and recurrent pregnancy loss Long term increased risk of: - T2DM - Dyslipidaemia - Cardiovascular disease - Endometrial cancer - High prevalence of anxiety and depression - Increased risk of OHSS when undergoing IVF US criteria: - In patients >8yrs post menarche, with transvaginal images: - Follicle number >20 per ovary and/or - Ovarian volume >10ml - No corpora lutea, cysts or dominant follicles are present Not part of the criteria: - Hyperechoic central stroma - Peripheral location of follicles - Follicles of similar size, 2-9mm

Answer 245

The commonest of the epithelial ovarian tumours More prevalent than mucinous Subdivided into benign 60%, borderline 15% and malignant 25% - Malignant tend to be older - Benign: no cellular proliferation - Borderline: cellular proliferation + minor nuclear atypia without invasion - Malignant: cellular proliferation + nuclear atypia + stromal invasion Pathology: - Defined by a histological resemblance to normal fallopian tubal epithelium Imaging: - Typically smaller than mucinous - Typically unilocular and homogenous - Often bilateral, esp if maligannt - Psammoamtous calcification is a feature, not seen in mucinous Features favouring malignant: - Large cystic mass - Thick irregular walls and septa - Papillary projections - Large soft tissue component - Ascites - Evidence of invasive spread or adenopathy Differentials: - Functional cyst - tend to change or resolve in the next menstrual cycle - Paraovarian cyst - ovary is separate from the cyst - Mucinous cyst - tend to be multiseptated, often larger than serous tumours - Monolateral rather than bilateral - Cystic loculi with variable signal intensities on MR

Answer 246

A subgroup of epithelial tumours Represent 10-15% of all ovarian tumours, 10% of malignant ovarian tumours Typically women 20-40yo (benign) Borderline and malignant tumours tend to be an older age range Pathology - Multiple cysts lined by mucinous epithelium, often resembling gastrointestinal-type epithelium - KRAS mutations are a common feature Subtypes: - Cystadenoma 80% - Borderline 10-15 - Cystadenocarcinoma 5-10% Imaging: - Often larger than serous counterparts - Tend to be more multilocular with small cystic components +/- honeycomb-like locules - Calcification is comparatively rare, and tends to be linear - Usually unilateral - Peritoneal carcinomatosis is less common compared with serous tumours - May have accompanying pseudomyxoma peritonei MRI - T1 - depends on the mucin concentration - T2 - high Differentials: Serous tumour - Calcification - Smaller - More frequently bilateral Haemorrhagic cyst - Smaller - Unilocular Endometrioma - High signal on T1, with T2 shading

Answer 247

Ovarian teratomas are associated with limbic encephalitis True - paraneoplastic limbic encephalitis. Mature (benign) teratomas - cystic and often referred to as dermoid cysts. Usually found in young women during the active reproductive years. 1% of dermoids undergo malignant transformation, most commonly to SCC Specialised/monodermal teratomas - struma ovarii and carcinoid. Always unilateral. Carcinoid can cause carcinoid syndrome. They usually arise from intestinal tissue found in teratomas. Metastatic intestinal carcinoid is virtually always bilateral. Primary ovarian carcinoid is not. Immature malignant teratomas - rare. Grow rapidly and frequently penetrate the capsule, spread either locally or distally.

Answer 248

The most common group of ovarian germ cell tumours Can be divided into 3 main subtypes Mature - Also called a dermoid cyst - Slow growing elements from multiple germ cell layers - Dermoid: only dermal and epidermal elements (both ectodermal) - Teratoma: mesodermal and endodermal - Encapsulated tumours with mature tissue or organ components - Composed of well-differentiated derivations from at least 2 of 3 germ cell layers - Typically smaller than 10cm - Bilateral in 10-15% - US: - Tip of iceberg sign - Rokitansky nodule - Don’t metastasise Immature - Uncommon, differ histologically and clinically - more malignant - Affect a younger age group, usually in the first two decades of life - The proportion of immature tissue elements correlates with the tumour grade - Large, encapsulated masses with a prominent solid component - May have features of a mature teratoma - hair/cartilage/bone/calc - Associations: - Ipsilateral mature cystic teratoma 25% - Contralateral immature teratoma 10% - Markers - Doesn't produce b-HCG - Serum AFP elevation in 50% - Imaging - A large, heterogenous mass with a prominent solid component - Tend to be larger than mature cystic teratomas Specialised - Struma ovarii

Answer 249

Defined as the presence of ascites and pleural effusion in associated with a benign, usually solid ovarian tumour In the vast majority of cases, the primary tumour is an ovarian fibroma Less than 1% present with this syndrome Other primary tumours: - Fibrothecoma - Thecoma - Granulosa cell tumour - Brenner - rare Usually ~7th decade of life, rare <30yo Speculative pathophysiology of ascites Plural fluid tends to be right sided Benign and resolves after resection of the primary tumour

Answer 250

Results from the abnormal proliferation of trophoblastic tissue, and encompasses a spectrum of diseases Hydatidiform mole: complete/partial/coexistent Gestational trophoblastic neoplasia - Invasive mole ~10% - Choriocarcinoma 1% - Placental site trophoblastic tumour - Epithelioid trophoblastic tumour Typically women >40, and <20 are at higher risk Presentation: - Uterus larger than pregnancy age - Abnormally high B-HCG - Hyperemesis - Hypertension - Theca-lutein cysts Pathology: all characteristically are an abnormal proliferation of trophoblasts, but different components predominate in different tumours Hydatidiform mole Complete - commonest ~80% - 46 XX or 46 XY: paternal chromosomes only - No fetus - BHCG markedly elevated - Atypia of cells present - May progress to an invasive mole ~15%, or choriocarcinoma ~5% Partial - 69XXX or 69XXY: paternal and maternal chromosomes - May have fetus or fetal components - BHCG moderately elevated - No cellular atypia Gestational trophoblastic neoplasia Invasive mole - Distorts uterine zonal structures - Boundaries between a tumour and myometrium are irregular and indistinct - May invade parametrial tissue and blood vessels Gestational choriocarcinoma - May look identical to a hydatidiform mole - Arises following: - Molar pregnancy 50% - Miscarriage 30% - Normal pregnancy 20% - Can appear less vascular than a complete mole - Tends to invade myometrium through venous plexuses - Patients often present with multiple metastases without an easily identified primary

Answer 251

An uncommon surface epithelial tumour of the ovary Account for ~3% of ovarian epithelial neoplasms Typically women in their 5th-7th decades of life Pathology: transitional cells covered by fibrous stroma, similar to neoplasms of the urothelium Associations: - Another epithelial ovarian neoplasm of either the ipsilateral or contralateral ovary in ~30% of cases - Bilateral in 6-7%

Answer 252

A subtype of epithelial ovarian tumours Majority are malignant and invasive Usually characterised as complex non-specific solid-cystic masses and found associated with endometriosis The second commonest malignant ovarian neoplasm Similar path to other tumours, with variable solid and cystic components Benign is rare Associations: - Synchronous endometrial carcinoma or endometrial hyperplasia may be present in up to 1/3 of cases - Endometrioid carcinoma is the most common malignant neoplasm arising within an endometioma Bilateral in 25-40% Look for endometrial thickening, evidence of endometriosis or a contralateral mass

Answer 253

A rare subtype of ovarian germ cell tumour Account for <1% Occur in prepubertal girls and post menopausal women May occur during or outside of pregnancy Can represent metastasis from uterine choriocarcinoma, or arise from an ectopic pregnancy Serum BHCG is elevated A vascular solid tumour with cystic, haemorrhagic and necrotic areas

Answer 254

A rare type of mixed ovarian tumour with both epithelial and stromal components Biphasic tumours with both carcinomatous (epithelial) and sarcomatous (stromal) elements

Answer 255

Classified as ovarian sex cord/stromal tumours Typically occur in premenarchal girls and young women, ~13yo Precocious puberty as a consequence of oestrogen secretion Associations: - Maffucci syndrome - Ollier disease Vary varied appearance.

Answer 256

A subtype of ovarian sex cord stromal tumour Rare, typically <30yo Most are unilateral and confined to the ovaries Characterized by the presence of testicular structures that produce androgens Only 30% are hormonally active Typically a solid/cystic mass

Answer 257

Benign sex cord/stromal origin tuours Secrete oestrogen = described as functional ovarian tumours Typically present in older women, >80% post menopausal Pathology: - Same histopath spectrum as fibroma/fibrothecoma Associations: - Most have a mixture of fibroma and thecoma components - More than 20% have concurrent endometrial carcinoma

Answer 258

A form of myopathy: a broad range of diseases which lead to dysfunction of skeletal muscle Wide range of differentials: - Inflammatory - Infectious - Drug related - Trauma MRI is the gold standard, demonstrating oedema in the affected muscle Inflamed muscles demonstrate contrast enhancement If chronic, T1 will show fat replacement and atrophy

Answer 259

An inflammatory myositis, often considered the most common acquired myopathy in patients > 50yo Tends to present in older individuals, with greater occurrence in males 3:1 Clinical onset is gradual: months - years. - Weakness peripherally of the wrist and fingers - Dysphagia in approximately 50% Pathology: - Chronic, progressive muscle inflammation accompanied by muscle weakness - Inflammation isn't considered a dominant component of the disease - Pathognomonic is the presence of inclusion bodies in the nucleus and cytoplasm of affected muscle cells Can affect both proximal and distal muscles, usually bilateral, although weakness may affect only one side of the body Recognized associations: - Diabetes mellitus ~20% - Other autoimmune conditions ~15% No response to steroids etc. Mangagement is essentially suportive

Answer 260

A wide range of soft tissue lesions that share an underlying histopathologic pattern of fibrous tissue proliferation They occur in a variety of anatomic sites, and also vary in their behaviour Ranging from indolent/benign lesions to metastatic/malignant

Answer 261

A rapidly growing non-neoplastic soft tissue lesion which is frequently located in the deep subcut region or in the fascia The most common locations are the volar aspect of the forearm, the lower extremity (16%), chest and back (20%), head and neck (18%) Typically manifests as a rapidly growing mass Often in patients 20-40yo, but children may also be affected Pathogenesis is poorly understood, possible reaction to trauma Location: Three subtypes based on involvement location - Subcutaneous - Intramuscular - Fascial Microscopic: - Benign proliferation of fibroblasts and myofibroblasts, typically mistaken for a sarcomatous lesion due to rapid growth, abundant spindle-shaped cells and mitotic activity Imaging: - Tend to be small - Categorized as myxoid/cellular or fibrous Verify with an excisional biopsy

Answer 262

Previously malignant fibrous histiocytoma The most common type of soft tissue sarcoma Aggressive biological behaviour and poor prognosis Usually affects the extremities, but can involve the retroperitoneum Typically in adults, age 32-80 with a slight male predominance The most frequent soft tissue sarcoma to occur as a result of radiotherapy, and also seen on a background of Paget disease Secondary transformation has been reported in fibrous dysplasia, giant cell tumour, enchondroma, chronic myelitis and osteonecrosis Usually confined to the soft tissue but occasionally may arise in or from bone Macroscopically: typically large, well circumscribed but unencapsulated with a grey firm heterogenous cut surface, sometimes with areas of necrosis Histopath: - Heterogenous fibroblastic tumours made up of poorly differentiated fibroblasts, myofibroblasts, histocyte-like cells with significant cellular pleomorphism, storiform architecture and bizarre multi-nucleated giant cells High grade and aggressive Frequently metastasis (30-50% at diagnosis), and locally recur. Survival 25-70% over 5yrs Prognostic factors: - Tumour size - smaller is better - Location - superficial is better - Histological grade: myxoid is better than stooriform-pleomorphic

Answer 263

Rare malignant soft tissue neoplasms representing a vascular tumour which occurs in patients with chronic lymphoedema Affects females > males - Esp post-mastectomy lymphoedema Arises from the vascular channels, pathogenesis is unclear Look for enhancing vascular nodular soft tissue tumour involving soft tissue and skin of the involved limbs associated with signs of oedema within the subcutaneous tissue

Answer 264

Originate from smooth muscle cells Can potentially occur anywhere with smooth muscle Uterus = 1/3, retroperitoneum = most common non-uterus site These tend to be large, with central necrosis and no calcification

Answer 265

Malignant counterpart to lipoma Second most common type of soft-tissue sarcoma Found in adults, age 40-60 Presentation varies according to the tumour location Histological subtypes: - Well differentiated liposarcoma, most common 50% - Myxoid liposarcoma - 2nd most common, chromosomal translocation t(12,16) - Dedifferentiated liposarcoma - high grade, aggressive - Pleomorphic liposarcoma - least common, high grade, frequent mets - Mixed Usually seen in the extremities, most commonly the thigh. Less common in the retroperitoneum

Answer 266

Common intermediate-to-high grade malignant soft tissue tumours Most commonly involving the soft tissue surrounding the knee Typically adolescents - young adults, age 15-40 May be a mild male predilection Pathology: - Resembles normal synovium, but stains for epithelial markers (e.g. epithelial membrane antigen and cytokeratin) which synovium does not - Can be found in locations without synovium - Most commonly near large joints e.g. popliteal fossa. Four subtypes: - Biphasic 20-30% - Monophasic fibrous 50-60% - Monophasic epithelial: very rare - Poorly differentiated 15-25% Cytogenetic aberation of t(X; 18) translocation is highly specific, seen in >90% of cases Very suspicious if dystrophic calcification is present - non specific within the periphery of the lesion Very heterogenous "triple sign" on T2

Answer 267

Arise from vascular structures Difficult to differentiate Tend to be multicentric tumours with haemorrhage and necrosis

Answer 268

Chronic autoimmune multisystemic inflammatory disease that affects many organs, but predominantly attacks the synovial tissues and joints Overall prevalence, 0.5-1%, and 2-3x more common in women Onset is generally ~4th-5th decades Risk factors: - Smoking - seropositive RA - Obesity - Low socioeconomic status Aetiology is probably multifactorial Thought to be a genetic predisposition (HLA-DR B1), with an environmental trigger e.g. EBV, leading to an autoimmune response against synovial structures Activation of B cell lymphocytes to produce antibodies, including rheumatoid factor, which makes immune complexes that deposit in different tissues and contribute to further injury Activation of endothelial cells > increased adhesion and accumulation of inflammatory cells Produce RANKL which in turn activates osteoclasts causing subchondral bone destruction The inflammatory response leads to pannus formation - Pannus: oedematous thickened hyperplastic synovium infiltrated by lymphocytes, plasmocytes, macrophages and osteoclasts - Pannus will gradually erode bare areas, followed by articular cartilage - It causes fibrous ankylosis which eventually ossifies Markers: Rheumatoid factor: an IgM antibody against the FC portion of the IgG antibodies - A traditional marker, but non-specific - Associated with several autoimmune and chronic infectious diseases Anti-cyclic citrullinated peptide (Anti-CCP)/ACPA) - More than 80% sensitive, more than 95% specific Elevated CRP or ESR

Answer 269

Pulmonary - Interstitial lung disease - Pulmonary nodules - Pleural effusion - Caplan syndrome - rheumatoid arthritis and pneumoconiosis Cardiovascular involvement - Accelerated/premature coronary artery atherosclerosis - Pericarditis Cutaneous involvement - Rheumatoid nodules - usually in pressure areas, in RF-positive patients - Rheumatoid vasculitis - classically deep cutaneous ulcers in the lower limbs Haematological involvement - Anaemia of chronic disease - Felty syndrome - syndrome characterised by the triad of rheumatoid arthritis, splenomegaly and neutropenia - Large granular lymphocyte leukaemia Ocular involvement - Episcleritis - Keratoconjunctivitis sicca

Answer 270

The most common chronic arthritic disease of childhood By definition, symptoms must start before 16 years of age Females are more affected 2:1 Oligoarticular or polyarticular arthritis of a duration of 6wks + Can present with systemic onset (Still disease) - Intermittent spiking fevers are typically noted, which helps distinguish JIA from other diseases e.g. infection, other inflammatory diseases and malignancy Pathology: Several subtypes: - Oligoarticular - Polyarticular - Systemic onset

Answer 271

The most common form of arthritis, affecting ~25% of adults Prevalence increases with age – more in men <50yo, more in women >50yo Pain, instability and stiffness – worsened by activity and decreases at rest Pathology: - Incompletely understood - Emphasis is placed on articular cartilage degeneration, but the remainder of the joint is involved Classification: - Primary – idiopathic - No antecedent insult - Strong genetic component - Secondary – abnormal mechanical forces e.g. occupational stress, obesity - Previous joint injury - Post-traumatic OA - Prior surgery - Crystal deposition e.g. gout, CPPD - Inflammatory arthritis e.g. RA, seronegative spondyloarthritis - Haemochromatosis Risk factors: - Obesity - Increasing age - Female sex, esp age 50-80

Answer 272

The cooccurrence of arthritis with evidence of CPPD deposition within the articular cartilage CPPD: occurrence of calcium pyrophosphate crystals +/- symptoms Asymptomatic CPPD: chondrocalcinosis +/- changes of osteoarthritis, but clinically asymptomatic Acute CPPD crystal arthritis (pseudogout): self limiting synovitis in the setting of CPPD OA with CPPD – typical changes of OA in the setting of CPPD Commonest in patients >50yo, and equally men and women Presentation resembles a gout attack, but commonly involves the knee and upper joints, or pubic symphysis Pathology: - Weakly positively birefringent on polarised microscopy - Rhomboid or rod shape Aetiology: - Idiopathic - Hereditary – AD, ANKH gene Secondary - Haemochromatosis - Hyperparathyroidism - Hypothyroidism - Hypomagnesemia - Previous joint injury - Ochronosis

Answer 273

Features of OA with an unusual distribution e.g. symmetrical, non-weightbearing joints OA in joints not commonly affected: - Wrist: radiocarpal and scapholunate joints - SLAC wrist in advanced cases - Metacarpophalangeal joints - 2nd and 3rd preferentially - Hook like osteophytes - Patellofemoral joint - Shoulder and elbow Chondrocalcinosis in many locations: - Knee – medial meniscus and patellofemoral joint - Wrist – TFCC, lunotriquetral - Pubic symphysis - Spine - Chronic retro-odontoid pseudotumour - Crowned dens syndrome - Intervertebral discs

Answer 274

A crystal arthropathy due to deposition of monosodium urate crystals in and around the joints Typically occur in those 40+yo, with a strong male predilection 20:1 - The male predilection is more pronounced in younger and middle-aged adults - Estradiol has a urate-lowering effect = uncommon in premenopausal women Pathology: - Characterised by monosodium urate crystal deposition in periarticular soft tissues - Needle-shaped and strongly negative birefringent in plane-polarised light - The synovial fluid is a poor solven for monosodium urate, and therefore crystallisation occurs at low temperatures - Crystals are chemotactic and active complement There are 5 recognised stages: - Asymptomatic hyperuricaemia - Acute gouty arthritis - Intercritical gout – between attacks - Chronic tophaceous gout - Gouty nephropathy The primary risk factor is hyperuricaemia, but only a small proportion of patients with hyperuricaemia develop gout – often taking 20-30yrs to develop Aetiology: Primary RF is hyperuricaemia, only a small proportion of whom develop gout. often taking 20-30ys. Undersecretion of uric acid by the kidneys 90% - Chronic kidney disease - Hypertension - Hyperparathyroidism - Alcohol - Drugs - Lead poisoning - Obesity Overproduction of uric acid 10% - Myeloproliferative disorders - Haemolysis - Extreme exercise - Lesch-Nyhan syndrome Location: - Usually asymmetrical polyarticular distribution - 1st MTP joint, hands and feet - Less common: bones, tendons and bursae - Chondrocalcinosis is present in ~5% Tophi: - T1 iso, T2 variable, characteristically heterogenously hypointense - Often enhance - Hyperdense heterogenous on US, with poorly defined contours Look for synovial thickening Management: - NSAIDs acutely - Xanthine oxidase inhibitors e.g. allopurinol, to reduced urate levels and prevent further acute flares

Answer 275

A disease of uncertain aetiology, characterised by periarticular and intra-articular deposition of hydroxyapatite crystals The shoulder is the most frequently involved site Most commonly found in middle-aged individuals Pathology: - Believed that HADD will begin to accumulate in damaged tendons (secondary to trauma) via fibrocartilaginous metaplasia - Characterised by calcium apatite crystal deposition in periarticular soft tissues – esp in the tendons - Most frequently involves the shoulder joint, where crystal deposition occurs in the supraspinatus tendon, but can affect numerous other sites as well - Calcific enthesitisis the most appropriate term - Can involve other sites e.g. gluteus medius tendon, or femur etc. - Variable size and shape of calcifications, - Mono- or polyarticular Three phases: - Formative, resting and resorptive - Formative and resting – round –to-ovoid calcification in the soft tissue with well-defined borders - Resorptive – ill-defined with a comet tail-like appearance - May mimic a periosteal reaction Treatment: NSAIDs, When intra-articular, crystals can cause joint destruction - Milwaukee shoulder - Advanced articular surface destruction - Intra-articular loose bodies - Subchondral sclerosis - Soft tissue swelling - Rotator cuff disruption

Answer 276

Seronegative spondyloarthropathy resulting in fusion of the spine and sacroiliac joints Thought to be male predominant 3:1, manifesting in young adults by the 3rd decade Associations: - Anterior uveitis 25-40% - Psoriasis - Inflammatory bowel disease - Osteopenia - Cardiovascular disease - Apical/UL predominant ILD with small cystic spaces - Aortic valve disease/aortitis Pathology: - Rheumatoid factor negative - HLA-B27 is the gene with the strongest association : 90% - 5% of people with the gene develop ankspon

Answer 277

Sterile, inflammatory, monoarticular or oligoarticular arthritis that follows an infection at a different site – typically enteric or urogenital A type of seronegative spondyloarthropathy Formerly known as Reiter syndrome – urethritis, arthritis and conjunctivitis Most commonly occurs in males ages 15-35yo - 1 in 100 following enteric infections Usually transient and involving one or two large joints Other extra-articular manifestations: cardiac conduction abnormalities and aortic regurgitation Pathology: - Joint inflammation, bone proliferation, periostitis and enthesitis Aetiology: - Enteric – yersinia, salmonella, shigella, campylobacter and less commonly E-COLI - Sexually transmitted – chlamydia - Other – brucellosis Markers: - HLA-B27 positive in ~80% of patients - A proportion have serum rheumatoid factor

Answer 278

Symmetrical polyarthritis, varying degrees Deforming non-erosive arthropathy, due to ligamentous laxity (not articular destruction) Classically seen on Norgaard views, but absent on PA views = reducible deformities - Deformity without erosion differentiates if from rheumatoid Hands and feet: - Symmetrical interphalangeal joint involvement: swan neck and boutonniere deformity, subluxation with ulnar deviation of the 1st MCP joint, a widened forefoot and hallux valgus - Joint space narrowing is uncommon - Can develop hook erosions of the MCP heads, more on the radial side

Answer 279

An inflammatory arthritis associated with psoriasis Usually negative for rheumatoid factor Affects up to ~25% of patients with psoriasis – median age of diagnosis 48yo Associations: - Obesity - Hypertension - T2DM - Hyperlipidaemia - Dermatological features precede arthritis in ~65% - Asymmetrical oligoarthritis with spondylitis Pathology: - Up to 60% are HLA-B27 positive - A proportion have a positive serum RF Extra-articular manifestations are common: - Ocular – uveitis, conjunctivitis - GI – IBD - Cardiac – rhythm disturbances: LBBB - Urogenital – urethritis, prostatitis, cervicitis, vaginitis Imaging: - Combined erosion and bone proliferation, predominantely distal distribution - Hands and feet: symmetric polyarthropathy, or asymmetric oligoarthropathy with distal predominance - Enthesitis and marginal bone erosions: "pencil-in-cup" deformities - Bone proliferation results in an irregular "fuzzy" appearance of the bone - Periostitis – rregular thickening of the cortex - Dactylitis – sausage digit - Acro-osteolysis - Arthritis mutilans – osteolysis and articular collapse - Ivory phalanx - Sacroiliitis – often asymmetrical

Answer 280

Destructive arthropathy caused by intra-articular infection that is usually related to severe symptoms and reduced range of motion Risk factors: - Bacteraemia, advanced age, immunocompromised, RA, itra-articular injection, prosthetic joint - Usually secondary to haematogenous seeding - Staph aureus is most common - Gonococcal is not uncommon Large joints are most prone, IVDU: sternovclavicular and SIJ are more frequently affected

Answer 281

Permanent joint disease as a long-term consequence of repeated haemarthrosis Around50% of haemophilia will develop this Haemophilia: X-linked recessive disease, mainly affecting males - Haemarthroses are usually in the same joint, age 2+ to adolescence - Less common in adulthood - Proliferative chronically-inflammed synovium results in the development of haemophiliac arthropathy Haemarthrosis results in iron deposition in the synovium > neoangiogenesis and ultimately damage to both the articular cartilage and subchondral bone Arthropathy: - Synovial hyperplasia, chronic inflammation, fibrosis and haemosiderosis - The synovium mass erodes cartilage and subchondral bone leading to subarticular cyst formation Location: - Knee > elbow > ankle > hip > shoulder

Answer 282

Joint effusion Periarticular osteoporosis – from hyperaemia Epiphyseal enlargement with gracile diaphysis – from hyperaemia Symmetrical degenerative changes Knee: - Widened intercondylar notch - Squared inferior margin of patella - Bulbous femoral condyles - Flattened condylar surfaces Elbow: - Enlarged radial head - Widened trochlear notch Ankle: - Talar tilt

Answer 283

Benign proliferative condition affecting synovial membranes of the joints, bursae or tendons resulting from possible neoplastic synovial proliferation with villous and nodular projections and haemosiderin deposition Most commonly monoarticular ~70% knee Can be oligoarticular Predominantely early – middle age No gender predilection for intra-articular disease, extra-articular disease has a slight female predilection. Associations: - Cherubism - Extremity lymphedema - Mandibular lesion - Noonan syndrome - Vascular lesions Synovium is diffusely thickened, dark brown/heterogenous with areas of yellow discolouration

Answer 284

Benign sclerosis of the ilium, adjacent to the SIJ, typically bilateral and triangular in shape More common in women, primarily pregnancy and puerperium Usually asymptomatic Unknown aetiology Lack of sacral or joint space involvement is diagnostic

Answer 285

aka reichel syndrome disorder characterised by loose cartilaginous bodies which may be calcified/ossified can be primary or secondary - priary; monoarticular, unknown aetiology - secondary; loose bodies from trauma, OA, neuropathic arthropathy in secondary, articular nodules are large, vary in size and frequently ossify in primary smaller and more uniform.

Answer 286

Lung disease characterised by abnormal intra-alveolar accumulation of surfactant-derived lipoprotienaceous material Rare, usually presents in young and middle aged adults 20-50yo Smoking is strongly associated When it presents before the age of 1yo there is an association with thymic alymphoplasia Pathology: Multiple causes: Autoimmune - 90% - Adult/acquired - IgG antibodies to GM-CSF Secondary 5-10% presents in individuals with other precipitating illness - Hematological malignancies - most commonly myeloid origin - CML > AML - Inhalational lung disease - Silica - Titanium oxide - Immunosuppression Congenital 2% - Presents in the neonatal period in term babies - Poor prognosis if left untreated Histopath: amorphous periodic acid-Schiff (PAS) stain lipoproteinaceous material filling the alveoli with relatively normal background lung architecture Markers: - Elevated acute inflammatory markers e.g. lactate dehydrogenase - + BAL or serum anti-GM-CSF antibodies Complications: - Superimposed infection - Pulmonary fibrosis in 30%

Answer 287

A group of immune-mediate pulmonary disorders characterised by an inflammatory and/or fibrotic reaction affecting the lung parenchyma and small airways Aetiology: more than 200 different antigens are involved The triggering particles are usually in the range of 1-5micrometres in size. In ~40% the inciting agent may not be identified Histopathology: - Chronic inflammation of the bronchi and peribronchiolar tissue, often with poorly defined granulomas and giant cells in the interstitium or alveoli - Fibrosis and emphysema may develop later on - Most cases involve 4 histologic features in variable amounts and combinations: - Cellular bronchiolitis - Diffuse chronic interstitial inflammatory infiltrates - Poorly circumscribed interstitial non-necrotising granulomas - Individual giant cells in the alveoli or interstitium Smoking is protective Subtypes: - Non-fibrotic - purely inflammatory - Fibrotic - mixed inflammatory/fibrotic or purely fibrotic

Answer 288

Rare benign pleural-based tumours that account for <5% Usually presents are 6th-7th decades, with no gender predilection Associations: - Hypoglycaemia 2-4%: thought to be due to the production of insulin-like growth factor 2 - Hypertrophic pulmonary osteoarthropathy ~20% - due to abnormal production of hyaluronic acid - Asbestos exposure is not an association Irregularly arranged fascicles consisting of spindle cells separated by collagen 80% arise from the visceral pleura Myxoid or cystic degeneration can occur Approximately 30% are malignant Location: - Predilection for the mid-lower zones of the chest Variants: - Lipomatous haemangiopericytoma - a fat-forming variant Imaging: - Pleural based, may be pedunculated - Calcification, rib destruction and pleural effusions aren't typically associated - Tends to have soft tissue attenuation MRI: - T1 typically low - intermediate - T2 typically low

Answer 289

Defined as the presence of a productive cough for 3mo in two successive years in a patient in whom other causes of a chronic cough has been excluded Often results from overproduction and hypersecretion of mucous by goblet cells The mechanism isn't entirely clear, but linked to both hypertrophy of submucosal glands and increased number of goblet cells which are thought to be the protective reaction to tobacco smoke or other pollutants It can lead to worsening airflow obstruction by luminal obstruction of small airways, epithelial remodelling and alteration of airway surface tension predisposing to collapse

Answer 290

Abnormal and permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of the alveolar wall and without obvious fibrosis Predominantly a disease of middle - late life, owing to the cumulative effect of lifelong tobacco smoking Risk factors: - Smoking ~90% of cases - Alpha-1-antitypsin deficiency - Ritalin lung Clinical: pink puffers, often hypocapnic Pathology: - A heterogenous group of pathological processes forming COPD Morphological subtypes - Centrilobular emphysema - Panlobular emphysema - Paraseptal emphysema - Paracicatricial emphysema

Answer 291

A hereditary metabolic disorder, the most common genetic cause of emphysema and metabolic liver disease in children Results in the un-opposed action of the neutrophil elastase

Answer 292

A fibrotic pneumoconiosis caused by the inhalation of fine particles of crystalline silicon dioxide Occurs in two forms, subdivided by their temporal relationship to the exposure to silica - Acute - alveolar silicoproteinosis - Classic - chronic interstitial reticulonodular disease Imaging: - Nodules 1-10mm in diameter - Predominately upper lobe and posterior - Calcification of nodules, eggshell calcification of node - Perilymphatic distribution

Answer 293

Three main effects from carbon on the lungs: - Anthracosis - harmless deposition of carbon dust - Simple CWP - Complicated CWP Along with silicosis, asbestosis, berylliosis and talcosis, CWP is a fibrotic pneumoniosis Not easily distinguished on imaging from silicosis Imaging: - Nodules tend to be less well-defined and more granulated - Increased risk of tuberculosis

Answer 294

An aggressive malignant tumour of the mesothelium Most tumours arise from the pleura ~90% Accounts for 5-28% of all malignancies that involve the pleura There is a strong association between asbestos fibre exposure and mesothelioma - Crocidolite is the most causative fibre type Increased risk for those with household exposure Clinically: - Pleural effusions are seen in the vast majority of patients at some stage - 25% are metastatic at presentation Aetiology: - Asbestos fibre exposure - Erionite fibre exposure - Simian virus 40 - Radiation exposure Histology: Three types: - Epithelial ~60% - Mixed ~25% - Sarcomatoid 15% The cytological and histological diagnosis can be difficult, with mesothelial hyperplasia and metastatic adenocarcinoma appearing similar Specific markers: - Calretinin - Epithelial membrane antigen - Cytokeratin - Mesothelin Subtypes e.g. multicystic/cystic are rarer and less aggressive

Answer 295

A collective term for conditions caused by infection with a fungus of the Aspergillus species Multiple forms: - Aspergilloma - Allergic bronchopulmonary aspergillosis - Invasive aspergillosis - Obstructive bronchopulmonary aspergillosis There are a variety of species. If the lungs are normal and host immunity is intact, this shouldn't cause pathology Both heightened (hypersensitivity) and reduced immunity predisposes

Answer 296

Mass-like fungal balls: mycetoma is an incorrect term Underlying conditions: - Pulmonary TB - Sarcoidosis - Bronchiectasis - Pulmonary cavities: - Bronchogenic cyst - Pulmonary sequestration - Pneumocystis pneumonia associated pneumatoceles Haemoptysis may be present due to the surrounding reactive vascular granulation tissue An eroded bronchial artery can lead to life-threatening haemoptysis Pathology: a mass-like collection of fungal hyphae, mixed with mucous and cellular debris within a cavity, the walls of which demonstrate vascular granulation tissue Commonly in the posterior upper lobes and superior lower lobes Monod sign. can have calcs. bronchial arteries can be enlarged. pleura can be thickened

Answer 297

Mostly patients with longstanding asthma, occasionally with cystic fibrosis Generally patients are young and diagnosed before the age of 40 Major and minor criteria: Major - Clinical - asthma - Radiographic: - Pulmonary opacities - Central bronchiectasis - Immune system - Blood eosinophilia - Elevated IgG and/or IgE against A.fumigatus - Increased serum IgE Minor criteria - Fungal elements in the sputum - Expectoration of brown plugs/flecks - Delayed skin reaction to fungal antigens Pathology: A hypersensitivity reaction towards aspergillus spp. Which grows in the lumen of the bronchi without invasion The hypersensitivity initially causes bronchospasm and bronchial wall oedema - IgE mediated Ultimately there is bronchial wall damage with loss of muscle and bronchial wall cartilage resulting in bronchiectasis (typically central bronchiectasis) Both types I and III allergic reactions have been implicated Bronchocentric granulomatosis often occurs - characterised by necrotising granulomatous inflammation that destroys the walls of the small bronchi

Answer 298

A life threatening condition, seen in patients who are profoundly immunosuppressed Pathology: Spores of Aspergillus spp are inhaled and proliferate in the alveoli The hyphae are able to invade the pulmonary arteries resulting in pulmonary necrosis and haemorrhage May gain access to the systemic circulation and disseminate If the neutrophil count recovers the central necrotic area of lung demarcates, shrinks and separates from the adjacent viable tissue = the air crescent sign

Answer 299

Can be divided into two groups depending on location: - Bronchial carcinoid tumours: central lesion - Peripheral pulmonary carcinoid tumours: peripheral lesions Can also be divided into typical and atypical by histology Bronchial: - Occur in relation to a bronchus - usually segmental or larger - Typically affects patients from the 3rd-7th decades, with a mean age ~45 - Most are central - Associations: - Multiple endocrine neoplasia type 1 - Cushing syndrome - ACTH producing carcinoid tumour types Peripheral: - A subtype, less common than centrally-located bronchial carcinoids - Most are discovered incidentally - Many have a lobulated margin

Answer 300

Abnormal accumulation of fluid within the pleural space Pathology: transudate vs exudate Transudate - when there is an increase in hydrostatic pressure or a decrease of capillary oncotic pressure - cardiac failure - Cirrhosis - Nephrotic syndrome - Dressler syndrome - Biochemical analysis: - Protein concentration <30 - Lactate dehydrogenase <20 Exudate - occurs due to the increase in permeability of the microcirculation or alteration in the pleural space drainage to lymph nodes - bronchial carcinoma - Pulmonary embolism and infarction - Pneumonia - Tuberculosis - Biochemical analysis - Protein >30 - Lactate dehydrogenase >20

Answer 301

Virtually never present in immunocompetent individuals Typically occurs at CD4 counts <200 cells/mm An atypical yeast-like fungus of the genus Pneumocystits, previously thought to be a protozoan Ground glass pattern, predominantly perihilar or mid zones Reticular opacities or septal thickening Pneumatoceles Differentials: - Viral pneumonia - similar, but cysts are absent - Mycobacterium TB when upper zone cysts are prominent - Angio invasive aspergillosis

Answer 302

May be seen as part of widespread involvement or distinct entity in young adult smokers Usually young adults, 20-40yo A history of current or previous cigarette smoking is identified in up to 95% of cases Associations: - Haematopoietic neoplasms - ALL - AML Can present with a pneumothorax Proliferate in the bronchiolar and bronchial epithelium, forming granulomas These evolve, peripheral fibrosis forms, resulting in traction on the central bronchiole which becomes cyst-like So evolution nodule > cyst Electron microscopy: Birbeck granules

Answer 303

Non caseating granulomatous multisystem disease with a wide range of clinical and radiographic manifestations Most commonly presents in the 2nd-4th decades of life No significant gender predominance Pathology: - A multisystem disorder of unknown aetiology characterized by the formation of inflammatory non-caseating granulomas within affected tissues - Histologically, the lesions characteristically demonstrate an absence of a necrotic component, except in rare cases - The granulomas may resolve spontaneously or progress to fibrosis - Thought to represent a disorder of immune regulation, particularly of cell-mediated immunity - Mycobacterium and propionibacterium RNA and DNA have been detected in sarcoidosis lesions - raising the possibility of an infectious trigger Microscopic: - Non-caseating granulomas - Schaumann bodies - Asteroid bodies - Necrosis is atypical and may suggest another aetiology Biochemical markers - Elevated ACE - Hypercalcaemia, hypercalciuria - A positive Kveim-Siltzbach skin test helps to confirm the diagnosis

Answer 304

Benign asbestos - induced pleural effusions: 20%, exudative - Usually occur within 10yrs of exposure Pleural plaques - Almost always involve the parietal pleura Visceral pleural involvement is usually at the lower and lateral aspect - May be calcified, non-calcified or mixed - Tend to spare the apices and costophrenic angles Diffuse pleural thickening ~15%

Answer 305

The leading type of cancer in the world, accounting for ~20% of deaths Major risk factor is smoking, and increased risk can be divided by histological subtypes Other risk factors: - Asbestos - Occupational exposure - Diffuse lung fibrosis - Chronic obstructive pulmonary disease Associations: Paraneoplastic: Endocrine/metabolic - SIADH causing hyponatreamia - ACTH secretion (cushing syndrome) - Carcinoid syndrome - Gynaecomastia - Adrenal insufficiency (addison) - from bilateral metastases - Hyperparathyroidism - Hypocalcaemia - PTH-related peptide causing hypercalcaemia Neurological - Polyneuropathy - Myelopathy - Limbic encephalitis - Cerebellar degeneration - Lambert-Eaton myasthenia syndrome Other - Finger clubbing - Hypertrophic pulmonary osteoarthropathy - squamous cell carcinoma - Nephrotic syndrome - Polymyositis - Dermatomyositis - Eosinophilia Pathology: Non-small cell lung cancer 80% - Adenocarcinoma 35% - Most common, especially women, peripheral - Squamous cell cancer 30% - Smoking, most common to cavitate, poor prognosis - Large cell carcinoma 15% - Peripheral, large, usually >4cm Small cell lung cancer 20% - Almost always in smoking, metastasizes early - Most common primary lung malignancy to cause paraneoplastic syndromes and SVC obstruction - Worst prognosis Markers - PDL1 - TTF-1: expressed in most except squamous cell cancer Genetics - ROS1 mutation - ALK mutation

Answer 306

Staging: - Limited - Confined to one hemithorax - Inclusive of hilar/supraclavicular lymph nodes - Suitable for radiotherapy and chemotherapy - Extensive - Extends beyond one hemithorax - Only chemotherapy - 70% of cases 90-95% occur centrally, arising adjacent to a lobar or main bronchus Serology: - Lactate dehydrogenase is a non-specific marker of survival The most common cause of SVC obstruction

Answer 307

Second only to adenocarcinoma as the most commonly encountered ~30-35% of cancers Associated with smoking, more common in male smokers, adenocarcinoma is more common in female smokers Presentation depends on location of the tumour - Central > invasion and obstruction of the bronchi - Peripheral > invade the chest wall e.g. pancoast tumour Pathology: - Invade the surrounding parenchyma and extend into the chest wall - Have a tendency to undergo central necrosis - Characterised by intercellular bridging and/or keratinisation of the individual cells or squamous pearls Degree of differentiation classifies it into 4 subtypes: - Papillary - Clear cell - Small cell - Basaloid Immunohistochemistry: - P63, negative for TTF1

Answer 308

The most common histologic type of lung cancer Pathology: Preinvasive - Atypical adenomatous hyperplasia - Adenocarcinoma in situ Minimally invasive - Lepidic growth pattern Invasive >5mm invasion AAH <5mm. adeno in situ <3cm, lepic pattern. absence of stromal vascular or pleural invasion minimally invasive described small solitary adenocarcinomas with either pure lepidic or lepidic preominant and <5mm stromal invasion. invasive >5mm invasion. further subcat according to dominant histo pattern. EGFR and KRAS are becoming increasingly important for consideration of therapy

Answer 309

rare thymic epithelial lesion. Over 30 conditions are associated with a thymoma - Myasthenia gravis - most common - Pure cell aplasia - Hypogammaglobinaemia SLE Pathology: - Macroscopically of variable shape - typically rounded with a bosselated outer surface - Both non-invasive and invasive thymomas may appear to have an intact capsule - Larger tumours are more likely to demonstrate cystic changes as well as haemorrhage and calcification Imaging: - Calcification is frequently seen in thymic carcinoma

Answer 310

Rheumatoid nodules tend to be located in the periphery of the upper and middle zones.” Most commonly UIP, with peripheral and basilar predominance of fibrosis, indistinguishable from idiopathic pulmonary fibrosis Can have bronchiectasis Bronchiolitis may be due to chronic infection or constrictive bronchiolitis Rheumatoid nodes are rare. May be single or multiple, can become large and cavitate Rheumatoid nodules may be complicated by bronchopleural fistula

Answer 311

Surplus iron deposition in the lungs can be primary or secondary - primary - goodpastures - heiners - idiopathic - secondary; usually MS Characterised by: - Small, ill-defined pulmonary nodules or - Coarse reticular areas of increased opacity with a bias for middle and lower lung regions - Not actually calcified, tend to be large nodular opacities - Pulmonary ossification - dense nodules with a tenduancy for confluence

Answer 312

A rare idiopathic condition characterised by widespread intra-alveolar deposition of spherical calcium phosphate microliths Slight female predilection Associations: testicular microlithiasis Pulmonary alveolar microlithiasis is believed to be due to a mutation in the SLC34A2 gene that causes inactivation of a sodium-dependent phosphate cotransporter, which is found mainly in alveolar type II cells. This cotransporter normally clears phosphate from degraded surfactant, and when inactivated there is accumulation of phosphate in the alveolus, and calcium phosphate microliths are then thought to form 9. An autosomal recessive inheritance pattern has been proposed given familial occurrence in a majority of cases 2,3,9. Usually, there is no abnormal calcium metabolism.

Answer 313

Benign neoplasms composed of cartilage, connective tissue, muscle, fat and bone May be chondromatous (most common), leiomyomatous or a mixture Usually found in the 4th-5th decade, uncommon in children Majority are located peripherally within the lungs (>90%), endobronchial hamartomas represent 5% of lesions 60% have fat, 20-30% have calcification - popcorn like Pulmonary carcinoid: - Higher attenuation - More lobulation - More distal nodularity - Distal hyperlucency - Atelectasis - More bronchial extension and involvement - Marked homogenous contrast enhancement

Answer 314

A wide disease spectrum, predominantly caused by the organism mycobacterium tuberculosis ulmonary manifestations depend on whether the infection is primary or post-primary Primary: - Usually asymptomatic - Although a small number go on to have symptomatic haematological dissemination = miliary TB - 5%, usually with impaired immunity, go on to have progressive primary tuberculosis - May present with a chronic dry cough +/- haemoptysis - ghon lesion; clacified fdocus - ranke complex; focus and calcified node post primary - recurs years latyer, decreased immaune status Location: - Primary - anywhere in children, upper or lower zone predilection in adults - Post primary - strong predilection for the upper zones - Miliary - evenly distributed

Answer 315

An autosomal recessive genetic disease that affects the exocrine function of the lungs, liver, pancreas, small bowel, sweat glands and male genital system Due to homozygous defect of the CFTR gene located on chromosome 7q31.2 - Encodes for the transmembrane protein "cystic fibrosis transmembrane regulator" responsible for regulating chloride passage across cell membranes - Also encodes for the indlux of chloride and increases the sodium channel activity in the skin = increase in salt content in the skin of pts with CF Atleast 6 classes of mutations

Answer 316

Broadly categorised into: - Dizygotic 70% - Monozygotic 30% DIZYGOTIC - Independent fertilisation of two ova, and always results in dichorionic-diamniotic pregnancies - 20% of monozygotic pregnancies will be dichorionic-diamniotic - Documentation of different sex fetus' is the most reliable sign of dizygotic Risk factors: - IVF - Advanced maternal age - Advanced parity - Maternal family history - Ethnicity MONOZYGOTIC - Due to fertilisation of a single ovum that then separates into two - Unlike dizygotic pregnancy, monozygotic pregnancies do not have maternal age, family history or ethnic predisposition - The time of separation determines the chorionicity and amnionicity of the pregnancy - 1-2 days: DCDA - 4-8 days: MCDA - 1-2 weeks: MCMA - >2 weeks: conjoined twins Complications - The risk depends on chorionicity - prognosis is worse for mono-mono and best for di-di - Mono-mono: >50% perinatal mortality Monochorionic complications - ~30% of pregnancy related complications - Share a single placenta, so prone to haemodynamic complications e.g. - Twin-twin transfusion - Twin anaemia polycythaemia sequence - Twin reversed arterial perfusion sequence - Acardiac twin - Demise of co-twin - Twin embolisation syndrome Monoamniotic complications - Share the amniotic sac - Prone to entangled cords, as well as all the monochorionic complications - Conjoined twins can only occur in monoamniotic pregnancies US Dichorionic - Separate gestational sacs with chorion extending between them <10 wks - Twin-peak sign - Separate placental masses - May be of different genders Monochorionic diamniotic - Single gestational sac - Two yolk sacs - T sign: thin intertwin membrane - Single placental mass Monoamniotic - No intertwin membrane - Usually one yolk sac - Entangled cords are common

Answer 317

A potential complication that can occur in a monochorionic twin pregnancy Results from unbalanced vascular (arteriovenous and arterioarterial) anastomoses in the placenta So the placental circulation is directed predominantly towards one twin and away from the other The resultant hypovolaemia and hypoperfusion in one twin and hypervolaemia and hypertension in the other create a cascade of hormonal changes including the renin-angiotensin system Leads to chronic tubulopathy and oliguria in the hypovolaemia twin, with consequent oligohydramnios, and polyuria and subsequent polydramnios in the hypervolaemic twin

Answer 318

twin reversed arterial perfusion rare comp of MC preganncies lack of a well formed heart in one twin "acardiac". superficial artery to artery placental anatomosis providing perfusion of the acardiac twin by the "donor" twin reversel of the acardiac twin umbilical artery doppler; flow toward fetus

Answer 319

acardiac - severely abnormal - morph types; acardius, anceps, amorphus, acormus - heart absent or abnormal - head and upper extremities underdeveloped due to perfusion to iliacs - severe anasarca and cystic hydromas - single UA common pump - often normal, but can have anomalies - ridk of high output heart failure - complications = HOCF = cerebral ischaemia = preterm = FDIU

Answer 320

A rare cause of pituitary apoplexy and hypopituitarism Only occurs in postpartum females who experience large volume haemorrhage and hypovolaemic shock, either during delivery or afterwards with resultant necrosis of the anterior pituitary cells Clinical presentation: Pituitary failure - Can be silent, with delayed hypopituitarism - Agalactorrhoea - Amenorrhoea - Oligomenorrhoea - Adrenal insufficiency Optic chiasm compression - Visual field loss - Headache - Ophthalmoplegia Pathology Hyperplasia of pituitary cells occurs in the weeks preceding delivery resulting in increased metabolic demand, without a concomitant increase in blood supply The anterior pituitary blood supply is under relatively low pressure, making these cells susceptible to ischaemia The posterior pituitary has its blood supply under higher pressure, not usually affected

Answer 321

Excessive extravasation of fluid into the third space in a fetus which could be due to heart failure, volume overload, decreased oncotic pressure, or increased vascular permeability Defined as the accumulation of fluid +/- oedema involving at least two fetal components, which may manifest as: - Pleural effusion - Pericardial effusion - Ascites - Generalised body oedema: - Fetal anasarca - Subcutaneous skin thikening to more than 5mm - Nuchal oedema - swollen neck >3mm up to the 14th week, >4-6mm later. No septations - Cystic hydroma - Placental enlargement - Polyhydramnios - Hepatomegaly Considered a prenatal form of cardiac failure Divided into two broad groups: Immune hydrops - Minority ~10% - Fetomateral blood group incompatibility Non-immune hydrops - Chromosomal anomalies - Turner syndrome - Trisomies - 13, 18, 21 - Cardiac - tachyarrhythmias - Twin pregnancy complications - In-utero infections - Parvovirus B19 is most common infectious cause, secondary to anaemia - Fetal tumours capable of producing AV shunts

Answer 322

A general term applied to abnormal placental adherence The placental villi extend beyond the confines of the endometrium and attach to the superficial aspect of the myometrium, but without deep invasion Risk factors: - Placenta previa - Prior caesarean section - Uterine anomalies - Previous uterine surgery - Dilation and curettage - Myomectomy - Maternal age >35 - Multiparity Abnormal implantation is thought to result from a deficiency in the decidua basalis, where the decidua is partially or completely replaced by loose connective tissue Chorionic villi directly attach to the myometrium with little or no intervening decidua Lab investigations: = Elevated alpha-fetoprotein = Elevated BHCG

Answer 323

Intermediate level, with placental villi extending beyond the confines of the endometrium and invading the myometrium

Answer 324

Transmural extension of placental tissue across the myometrium with a serosal breach

Answer 325

Low lying placenta - close to, or covering the internal cervical os The most common cause of antepartum haemorrhage Cant make the diagnosis before 20 weeks Classification: 1 - low lying placenta Lies in the lower uterine segment, but lower edge 0.5 - 2.0cm from the internal os 2 - marginal placenta Tissue reaches the margins of the internal cervical os, but doesn’t cover it 3 - partial previa Partially covers the internal cervical os 4 - complete previa Placenta completely covers the internal cervical os

Answer 326

Premature separation of the normally implanted placenta after the 20th week of gestation, and before the 3rd stage of labour Risk factors - Pre-eclampsia and maternal hypertension - Previous placental abruption - Prolonged rupture of membranes - Maternal age - Maternal trauma - Cigarette smoking Clinical presentation - Increased abdominal tone, contractions - Pathology - unknown, likely rupture of a spiral artery with haemorrhage into the decidua basalis leading to separation of the placenta - The small vessel disease seen in abruptio placentae may also result in placental infarction Can be classified as: - Marginal placental abruption - Retroplacental abruption - Preplacental abruption

Answer 327

A disorder of pregnancy involving new-onset hypertension and involvement of one or more other organ systems - Systolic >140, diastolic >90 Affect up to 8% of pregnancies Risk factors: - DM - Chronic hypertension - Family history - Nulliparity - Advanced maternal age - Obesity - Antiphospholipid syndrome - Pre-eclampsia in prior pregnancy Occurs after 20wks gestation, and up to 4-6 wks postpartum, with one or more of: - Proteinuria - Thrombocytopenia - Renal impairment - Liver impairment - Pulmonary oedema - Headache or visual disturbance The addition of tonic-clonic seizures = eclampsia US may demonstrate IUGR, and mean UA PI >95th centile

Answer 328

A metabolic bone disease characterised by decreased bone mass and skeletal fragility Defined as: - BMD T-score < -2.5 SD - Measured in post menopausal women and men at least 50yo - Reference standard is the femoral neck, but other sites e.g. lumbar spine can be used Essentially decreased bony tissue per unit volume of bone There is no microstructural or biochemical change - as in osteomalacia or rickets So the mineral-to-osteoid ratio is normal - Decreased in osteomalacia Can be localised or diffuse: Primary - no cause identified - Post menopausal (type 1): occurs in 50-65yo females, - Disproportionate loss of cancellous bone as compared to cortical bone - So more involvement of cancellous bone-rich areas e.g. vertebrae and ends of long bones - Senile (type 2): in the elderly - Proportionate loss of cortical and cancellous bones affecting long bones Secondary (type 3): due to a range of causes, including: - Endocrine disease - cushings, hyperthyroidism, hyperparathyroidism, DM - Chronic illness - COPD, chronic liver disease, multiple sclerosis, coeliac disease - Inflammation - Medications - steroids, phenytoin - Thalassaemia major - Nutritional disturbances - malnutrition, anorexia - Muscular dystrophies - duchenne muscular dystrophy

Answer 329

Excess parathyroid hormone in the body Can be primary, secondary or tertiary Supported biochemically by either an elevated serum parathyroid hormone level or an inappropriately normal level in the setting of hypercalcaemia Associations: - MEN 1, 2A Pathology: - Increased levels of parathyroid hormone lead to increased osteoclastic activity - The resultant bone resorption produces cortical thinning (subperiosteal resorption) and osteopenia Subtypes: Primary hyperparathyroidism - Parathyroid adenoma ~80% - Parathyroid hyperplasia 10-15% - Parathyroid carcinoma 1-5% Secondary hyperparathyroidism - Caused by chronic hypocalcaemia with renal osteodystrophy being the most common cause - Others - malnutrition, vitamin D deficiency - Results in parathyroid hyperplasia Tertiary hyperparathyroidism - Autonomous parathyroid adenoma, caused by the chronic overstimulation of hyperplastic glands in renal insufficiency

Answer 330

Subperiosteal bone resorption - Radial aspect of the proximal and middle phalanges of the 2nd and 3rd fingers - Medial aspect of the tibia/femur/humerus Subchondral resorption - Lateral end of the clavicles - Symphysis pubis - Sacroiliac joints Subligamentous resorption - Ischial tuberosity - Trochanters Intracortical resorption - cigar/oval shaped or tunnel shaped radiolucency in the cortex Terminal tuft erosion Rugger-jersey spine Osteopenia Brown tumours Salt and pepper sign in the skull Chondrocalcinosis

Answer 331

Bone softening due to insufficient mineralisation of the osteoid secondary to any process that results in vitamin D deficiency or defects in phosphate metabolism - High remodelling rate - excessive osteoid formation with normal/little mineralisation - Low remodelling rate - normal osteoid production with diminished mineralisation Aetiology: Vitamin D deficiency - most common - Inadequate intake or absorption - Dietary deficiency, lack of sunlight exposure, gastric surgery, small bowel disease - crohns/coeliac, or pancreatic insufficiency - Deficiency of vitamin d metabolism - Cirrhosis - Chronic kidney disease - Cytochrome P450 inducers Phosphate deficiency - Inadequate intake or absorption - Renal phosphate wasting - Hereditary hypophosphataemic rickets - Fanconi syndrome - Tumour induced osteomalacia - due to phsphaturic mesenchymal tumour Decreased deposition of calcium in bone - Bisphosphonates Markers: - 25(OH)D decreased - Serum calcium - slightly decreased/normal - Urinary calcium - decreased - Serum phosphorus - decreased - Serum alkaline phosphatase - elevated - Serum parathyroid hormone - elevated

Answer 332

An uncommon hereditary disorder that results from defective osteoclasts Bones become sclerotic and thick, but abnormal structure causes them to be weak and brittle Clinical: - Present with fractures, often with multiple areas of callous formation - Crowding of the marrow > bone marrow function is affected, resulting in myelopthisic anaemia, extramedullary haematopoiesis and splenomegaly - May terminate in acute leukaemia Pathology: - Localised chromosomal defects which result in defective osteoclasts and overgrowth of bone - Disordered architecture results in weak and brittle bones - Osteoclasts lack carbonic anhydrase, which may play a role in the pathophysiology Types: - Infantile autosomal recessive osteopetrosis - Benign adults autosomal dominant osteopetrosis Treatment: - Bone marrow transplant

Answer 333

A heterogenous group of congenital, non sex-linked, genetic disorders of collagen type I production, involving connective tissues and bones The hallmark is osteoporosis and fragile bones which fracture easily, as well as, blue sclera, dental fragility and hearing loss Occurs with equal frequency between males and females, races and ethnic groups Associations: - Congenital cataracts Pathology: - Disturbance in the synthesis of type I collagen, which is the predominant protein of the extracellular matrix of most tissues - In bone, it results in osteoporosis - It’s a major constituent of dentine sclerae, ligaments, blood vessels and skin Genetics: - A mutation in one of the two genes which carry instructions for making type 1 collagen - COL1A1 and COL1A2 genes which encode the alpha2 polypeptide chains, and are responsible for >90% of all cases - Depending on the type, the inheritance can be autosomal dominant (>95%), autosomal recessive (<10%) or by sporadic mutation Types - 1 - mild - 2 - perinatal lethal - 3 - progressive deforming - 4 - 8 vary in severity, these are uncommon

Answer 334

Non neoplastic, tumour like congenital process, manifested as a localised defect in osteoblastic differentiation and maturation, with replacement of the normal bone with large fibrous stroma and islands of immature woven bone 4 subtypes: - Monostotic - single bone - Polyostotic - multiple bones - Craniofacial fibrous dysplasia - skull and facial bones alone - Cherubism - mandible and maxilla alone - not true fibrous dysplasia 75% occur before the age of 30yo. The polyostotic form usually presents by age 10 Usually sporadic, but has a number of associations: - McCune-Albright syndrome: 2-3% of cases with the polyostotic form - Isolated endocrinopathy without the full McCune-Albright syndrome precocious puberty in girls - Mazabraud syndrome Pathology: - Due to developmental dysplasia and focal arrest in normal osteoblastic activity secondary to a non-hereditary mutation which results in the presence of all of the components of normal bone with a lack of normal differentiation into their mature structures Mono-ostotic: 70-80% of cases - Becomes inactive after puberty, and the monostotic form does not progress to polyostotic form - Location: - Ribs - 30%, most common - Proximal femur 25% - Tibia > craniofacial bones > humerus Polyostotic: - Often unilateral and monomelic: one limb - Femur 90%, tibia 80%, pelvis 80%, foot etc. Sarcomatous dedifferentiation: - Osteosarcoma - most common - Fibrosarcoma - Malignant fibrous histiocytoma - Rarely chondrosarcoma - More common in the polyostotic form

Answer 335

cafe au lait polyostotic fd endocrinopathy

Answer 336

polyostotic fd intramuscular myxomas

Answer 337

A common chronic bone disorder characterised by excessive abnormal bone remodelling Relatively common, may be male predilection Pathology: - The aetiology is not entirely known, but a disease of osteoclasts - Viral infection in association with genetic susceptibility has been postulated Three classically described stages, part of a continuous spectrum: - Early destructive stages (incipient active, lytic): predominanted by osteoclastic activity - Intermediate stages (active, mixed): osteoblastic as well as osteoclastic activity - Late stage (inactive, sclerotic/blastic) Markers: - Elevated serum alkaline phosphatase - Normal calcium and phosphorus levels - Increased urine hydroxyproline Complications: - Osseous weakening resulting in deformity and pathological fractures - Increased risk of osteoarthritis - Hearing loss - Sensorineural hearing loss - Conductive hearing loss - Neural compression - Basilar invagination may occur in advanced cases with hydrocephalus or brainstem compression - Secondary development of tumours - Osteosarcoma ~1% of cases, highly resistant to treatment - GCT of the skull - High output congestive cardiac failure - Hyperparathyroidism ~10% - Extramedullary haematopoiesis

Answer 338

A generic term referring to the ischemic death of the constituents of the bone A wide variety of causes, and can affect any bone in the body Historically - Subchondral (epiphyseal) ON was called ischaemic and AVN - Bone infarct - medullary (metaphyseal) ON - ON is a general, more inclusive term Pathology: - Infarction begins when the blood supply to a section of bone is interrupted - Once established, there is a central necrotic core surrounded by an ischaemic zone - with the inner portion being 'almost dead' and the outer portion being hyperaemic - Beyond this is normal viable marrow - Between the normal and ischaemic zone that demarcation occurs with the development of viable granulation separating dead tissue = double line sign on MRI - Double line: T2 low outer sclerosis, with T2 bright inner (granulation tissue) line - When the infarct is subcortical, a wedge of tissue is typically affected, the apex of which points towards the centre of the bone Aetiology - Trauma - Caisson disease - Haemoglobinopathies - sickle cell disease - Pregnancy related - Radiotherapy - Connective tissue disorders - Renal transplantation - Corticosteroid excess - Pancreatitis - Gaucher disease - Alcohol - Cirrhosis - Freiberg disease - Chemotherapy

Answer 339

Inflammation of the bone due to infection, typically bacterial Can occur at any age, particularly common age 2-12 and in males Pathology: - Results from haematogenous spread, or direct from trauma/ulcers etc. - Bacteria multiple, localised inflammatory reaction results in localised cell death - With time, the infection becomes demarcated by a rim of granulation tissue and new bone deposition - No organisms are recovered in up to 50% of cases - Staph Aureus is the most common Other scenarios: - E coli - IVDU and GIT infection - Pseudomonas - IVDU - Klebsiella - HIB - neonate, and GB step Location: - Lower limb most common - Vertebrae: lumbar > thoracic > cervical - Radial styloid - SI joints - Neonates: metaphysis and/or epiphysis - Children: metaphysis - Adults: epiphyses and subchondral regions

Answer 340

Vertberal body osteomyelitis and IV discitis Pathology: haematogenous spread via arteries and veins Anterior involvement: spread through the anterior arterial arcade that richly supplies the subchaondral paradiscal bone, resulting in infection anterosuperiorly and anteroinferior - adjacent to the disc - The disc is conspiciously spared due to sparse vascularity - Subligamentous spread - Gradual anterior collapse = acute kyphotic/gibbus deformity Central involvement: spread via the venous plexus of Batson, typically resulting in infection arising centrally within the vertebral body - More common in older patients Posterior involvement - appendiceal pattern due to venous haematogenous spread via the posterior venous plexus Cold abscess: large paraspinal abscess' can develop without severe pain or frank pus, prominent inflammatory signs and symptoms

Answer 341

Small airways obstruction and a chemical pneumonitis XRAY Increased lung volumes - Hyperinflated lungs with flattened hemidiaphragms - Secondary to distal small airway obstruction and gas trapping Asymmetric patchy pulmonary opacities - Due to subsegmental atelectasis Pleural effusions Pneumothorax and pneumomediastinum

Answer 342

Refers to the aberrant formation of segmental lung tissue with no connection to the bronchial tree or pulmonary arteries A bronchopulmonary foregut malformation Extralobular more commonly presents in newborns as respiratory distress, cyanosis, or infection - Venous drainage into systemic veins - Separated from any surrounding lung by its own pleura Intralobular presents in late childhood or adolescence with recurrent pulmonary infections - Majority - Venous drainage commonly occurs via the pulmonary veins, but can be through the azygos-hemiazygos system - Closely connected to adjacent normal lung, doesn't have a separate pleura Prefer the lower lobes - 60% affect the LLL, 40% the RLL - Extralobar is always the LLL, and 10% can be subdiaphragmatic Associations - CPAM - Congenital heart disease - Congenital diaphragmatic hernia - Scimitar syndrome May show cystic spaces if infected A triangular opacity in the affected segment

Answer 343

Results form insufficient production of surfactant in preterm neonates - Uncommon after 36wks gestation The lack of surfactant increases the surface tension in alveoli causing collapse. A diffuse type of adhesive atelectasis Reduced lung volumes are key on imaging. - Diffuse ground glass changes - bilateral and symmetrical +/- air bronchograms Treated with exogenous surfactant administration and supportive oxygen therapy There is deposition of a layer of hyaline proteinaceous material in the peripheral airspaces of infants who succumb to this condition Associations: male gender, maternal diabetes, and delivery by caesarean section Fundamentally a deficiency of pulmonary surfactant - Responsible for the reduction of surface tension - Surfactant is produced by type II alveolar cells, accelerated after the 35th week of gestation - Synthesis is modulated by a variety of hormones and growth factors. Prophylactic surfactant treatments are given, as well as antenatal glucocorticoid therapy

Answer 344

Multicystic mass of segmental lung tissue with abnormal bronchial proliferation Part of a spectrum of bronchopulmonary foregut malformations If large, can cause pulmonary hypoplasia with resultant poor prognosis Pathology: - Results from failure of normal bronchoalvoelar development with a hamartomatous proliferation of terminal respiratory units in a gland-like pattern (adenomatoid) without proper alveolar formation - Histologically characterised by adenomatoid proliferation of bronchiole-like structures and macro- or microcysts lined by columnar or cuboidal epithelium and absence of cartilage and bronchial glands - These have intracystic communications and, unlike bronchogenic cysts, can also have a connection to the tracheobronchial tree Subtypes 1 - 4 Type 1 is most common - 70% of cases - Large cysts, one or more dominant cyst 2-10cm in size 2 - 15-20% of cases - Cysts are <2cm in diameter - Associated with other abnormalities - Renal agenesis or dysgenesis - Pulmonary sequestration - Congenital cardiac anomalies 3 ~10% - Microcysts, typically involve an entire lobe 4 - unlined cyst, typically affects a single lobe 0 - rare, lethal Location - Unilateral, involve a single lobe, and less frequently in the middle lobe Associations: - Hybrid lesions - CPAM and sequestration - Renal agenesis - Polyhydramnios - Hydrops fetalis

Answer 345

84% left sided, 13% right sided, 2% bilateral Mortality is determined by the development of pulmonary hypoplasia due to mass effect on the developing lung Diaphragm development is complete ~9th week of gestation Pathology: - Bochdalek - most common - Posterolateral - Morgagni - Less common, anterior, presents later Associations: - Pulmonary hypoplasia - LV hypoplasia - Intestinal malrotation - Bronchopulmonary sequestration

Answer 346

Eagle Barrett syndrome or triad syndrome A rare anomy comprising of three major findings: - Gross pelvicalyceal and ureteric dilatation with renal dysplasia - Anterior abdominal wall underdevelopment - Bilateral undescended testes in males Associations: Aneuploidic syndromic associations - Trisomy 18, 13 Congenital cardiac anomalies - VSD - ASD - TOF Intestinal malrotation Imperforate anus Talipes equinovarus Urinary tract abnormalities include: - Bilateral hydroutereronephrosis - extremely dilated, tortuous ureters - Varying degrees of renal dysplasia - Enlarged urinary bladder, often with urachal diverticulum - VUR is common - Poor bladder contractility - Dilated posterior urethra without urethral obstruction

Answer 347

A malignant paediatric renal tumour The most common renal mass, typically occurs in childhood 1-11yrs, with peak incidence 3-4yrs Associations: Overgrowth syndromes - WT2 gene - Beckwith-Wiedemann syndrome - Perlman syndrome - Sotos syndrome Non-overgrowth - WT1 gene - WAGR syndrome - Denys-Drash syndrome - Fasier syndrome - Bloom syndrome Isolated abnormalities - Cryptorchidism - Hemihypertropy - Hypospadias - Sporadic aniridia Risk factors: nephroblastomatosis Pathology: - Typically arises from mesodermal precursors of the renal parenchyma - Implicated genes on chromosome 11

Answer 348

Risk factors: - Prematurity 50-80% - Congenital heart disease - Perinatal asphyxia - Decreased umbilical flow in utero Pathology: - Usually idiopathic and multi-factorial - A combination of ischaemic and infective aetiology - Inflammation starts from the mucosal surface and progresses to haemorrhagic and coagulative necrosis - Ensuing loss of mucosal integrity, transmural necrosis and perforation - Can affect any part of the large or small bowel, most commonly the terminal ileum

Answer 349

These account for 90% of primary testicular tumours The most common non-haematologic malignancy in men age 15-49yo Divided into: Testicular seminoma – 40% Non-seminomatous – 60% - Embryonal cell carcinoma - Choriocarcinoma - Yolk sac tumour - Testicular teratoma - Mixed germ cell tumour 15% Testicular non-germ cell tumours – 10% - leydig - sertoli

Answer 350

Age 15-49 Risk factors - Undescended testis 10-40x increased risk - Previous tumour in the contralateral testis - Family history Bilateral are rare ~2% and almost always asynchronous Pathology: pure seminoma on histo, and not associated with an elevated AFP Otherwise classified as non-seminomatous Three subtypes: Classic: 85%, - infrequent mitoses; monotonous sheet of large cells with abundant cytoplasm and round hyperchromatic nuclei, prominent nucleoli Anaplastic: 10%, - ≥3 mitotic figures per high-power field Spermatocytic: 5%, - older male patients above 60 years old, rarely metastasise; well-differentiated with cells resembling secondary spermatids On gross examination, these are pale grey – yellow nodules that are uniform or slightly lobulated and often bulge form the cut surface

Answer 351

Occur in younger patients, late teens - twenties The most common primary testicular malignancy Tend to be more aggressive than seminomas, and frequently metastasise Markers: 70% produce hormone markers - AFP – elevated in yolk sac - BHCG – elevated in choriocarcinoma - Lactate dehydrogenase Tend to be more heterogenous on US, and T2 – frequent cystic areas or calcification Subtypes: Embryonal cell carcinoma - rare - Age 25-30yo Choriocarcinoma - Age 20-30yo - Most commonly detected as a component of a mixed malignant germ cell tumour - The pure form is rare - BHCG elevated Yolk sac tumour - Most common childhood tumour 80%, most before 2yo - Pure is rare in adults, but mixed GCT is commonly seen - Aetiology: totipotent cells which later form extraembryonic fetal membranes give rise to yolk sac tumours - Markers: AFP elevated in >90% - Macroscopically, the testis is replaced by a gelatinous mass - US: diffusely enlarged, heterogenous testis - MRI: heterogenous testicular mass with post-contrast heterogenous enhancement, areas of haemorrhage/necrosis Teratoma - Often aggressive in its biological behaviour - Often exists as part of a testicular mixed GCT - Divided by the age of the patient and degree of differentiation - Mature – well-differentiated, biologically indolent - Consider aggressive in post-pubertal males - Prepubertal are usually benign - Immature are more common in the testis - US Cystic, heterogenous, mixed mucinous or sebaceous material, with or without hair follicles Mixed - Consist of two+ types of GCT

Answer 352

~90% are benign, but cannot be differentiated from testicular malignancies on imaging LEYDIG - Most common, ~30% hormonally active - Non-specific imaging, but serum hormone levels are abnormal - Hypoestrogenism + gynaecomastia - Virilisation - Tend to be bimodal, one peak in paeds ~5-10yo, and one in adults ~20-30yo. - Malignancy in ~10% of tumours Pathology - Arise from the interstitial cells of Leydig, adjacent to the seminiferous tubules SERTOLI - Less common than Leydig cell tumour Pathology - Large-cell calcifying - paeds - Intratubular large cell hyalinising sertoli cell neoplasia - Associated with paediatric males with Peutz-Jegher syndrome - Sclerosing Sertoli cell tumour - adults - Less likely to be hormonally active - Associated with the Carney complex

Answer 353

Lymphoblastic leukaemia (acute or chronic) Lymphoma (Non-hodgkins) - Primary testicular lymphoma is rare Metastases

Answer 354

The most common primary malignant tumour in men Adenocarcinoma is the most common histological type Primarily a disease of elderly men PSA >1-4ng/dL is abnormal Pathology - 95% develop from the acini of the prostatic ducts - Arise in the posterior/peripheral (70%) prostate gland more commonly than in the anterior gland and central zone (30%) - Can spread by local invasion – bladder and seminal vesicles, lymphatic (pelvic > para-aortic > inguinal), or haematogenous - Bone > lung > liver > pleura > adrenal glands Histology - Grading is using the Gleason score – the sum of the most prevalent and second most prevalent types of dysplasia, each on a scale of 1-5 - 5 is the most dysplastic

Answer 355

Infection or inflammation of the prostate gland A clinical diagnosis, but imaging is used for abscess formation Subtypes: - Acute bacterial - Chronic bacterial - Chronic prostatitis/chronic pelvic pain syndrome - Granulomatous

Answer 356

Benign, solid extratesticular lesions that can originate from the epididymis, tunica vaginalis or spermatic cord 3rd - 5th decade Mesothelial origin Most common extra testicular neoplasm, and the most common tumour of the epididymis - Occur more often in the lower pole than the upper pole – 4:1 Usually an incidental finding, manifest as a small (<2cm) scrotal mass - More frequently on the left

Answer 357

Hyperplasia of stromal and glandular components Predominantly located in the transitional zone of the prostate 50% prevalence in men age 51-60, increasing incidence with age Location: transition (periurethral) zone of the prostate Pathophysiology - Proliferation of both stromal and epithelial cells, leading to new glandular budding and branching, with formation of nodules - Central role of sex steroids and growth factors - Aetiology unknown Markers: - Prostate specific antigen (PSA): Elevated but non-specific

Answer 358

A rare manifestation of extrapulmonary tuberculosis Infection usually affects the epididymis first, then can affect the testis if not treated Believed to occur due to retrograde extension from the prostate and seminal vesicles, as well as haematogenous spread

Answer 359

Absence of a testis in the scrotal sac Testes develop in the abdomen, at 21 wks migrating towards the inguinal canal through the deep inguinal ring The migration is complete ~30wks The gubernaculum is the ligament which connects the testes to the scrotum Under hormonal influence, the gubernaculum contracts, and the testes descend into the scrotum Causes: - Premature birth - Intrauterine growth restriction - Associations with smoking, alcohol intake during pregnancy - Androgen insensitive syndrome - Congenital syndrome - Noonan syndrome - Prune belly syndrome - Gestational diabetes

Answer 360

The most common subtype of malignant melanoma, a malignant neoplasm that arises from melanocytes Melanocytes predominantly occur in the basal layer of the epidermis, but do occur elsewhere in the body While a less common skin cancer, it causes majority of the skin cancer related deaths due to tendency to metastasise Risk factors: - Exposure to high level UV - Genetic predisposition - More than 50 naevi - Immunosuppression, sun sensitivity and freckles may also confer a predisposition to development of malignant melanoma Pathology: - Melanocytes produce melanin - the pigment responsible for skin colour - Arise from the neural crest in the embryo and migrate throughout the body. - Majority end up in the dermo-epidermal junction of the skin, providing melanin for the epidermal keratinocytes - Those that undergo malignant change show varied architectural patterns of growth Metastatic melanoma: - The most frequent site of involvement of metastatic disease is the lymphatic system, particularly the local and regional nodes surrounding the primary. - Further LN involvement typically progresses in a contiguous fashion - Detection of spread in the LN is the most important predictor of survival

Answer 361

The most common phakomatosis Autosomal dominant disorder 1:2500 – 3000, half are inherited the other are de novo mutation Variable expression, but 100% penetrance by 5yo Diagnostic criteria: - >6 café au lait spots evident during one year - 2+ neurofibromas or 1 plexiform neurofibroma - Optic nerve glioma - Distinctive osseous lesion – e.g. sphenoid wing dysplasia or thinning of long bone cortex +/- pseudoarthrosis - 2+ iris hamartomas (Lisch nodules) - Axillary or inguinal freckling - A primary relative with NF1 with the above criteria 45% have learning disabilities 1% have hypertension due to renal artery stenosis NF1 onset is earlier than schwannomatosis and NF2 Pathology: - NF1 gene locus on chromosome 17q11.2. The gene product is neurofibromin – acts as a tumour suppressor of the RAS/MAPK pathway - Inactivation of the gene predisposes to tumour development - Primarily the disease is a hamartomatous disorder that involves the ectoderm and mesoderm Three types: - Localised - most common, dermis and subcut skin - Diffuse - subcutaneous, usually head and neck - Plexiform - considered pathognomonic, often neck, pelvis and extremities Inactivation of a tumour suppressor gene > increased incidence of numerous tumours: - Pheochromocytoma - Malignant peripheral nerve sheath tumour - Wilms tumour - Rhabdomyosarcoma - Renal AML - Glioma: - Juvenile pilocytic astrocytoma ~20% - Optic nerve glioma - Diffuse brainstem glioma - Spinal astrocytoma, spinal pilocytic astrocytoma - Carcinoid tumours - Leiomyomas - Leiomyosarcoma - Ganglioglioma - Leukaemia Other manifestations CNS - FASI - Optic nerve glioma - Sphenoid wing dysplasia - Lambdoid suture defects - Dural calcification at the vertex - Moya-moya phenomenon - Buphthlamos Skeletal - Kyphoscoliosis - Posterior vertebral scalloping - Hypoplastic posterior elements - Enlarged neural foramina - Ribbon rib deformity, rib notching and dysplasia - Dural ectasia - Tibial pseudoarthrosis, or ulnar pseudoarthrosis - Bony dysplasia's - esp of the tibia - Severe bowing, gracile bones - Multiple non-ossifying fibromas - Limb hemihypertrophy Thoracic - Mediastinal masses - Neurofibroma - Lateral thoracic meningocele - typically on the convex side of scoliosis

Answer 362

Autosomal dominant neurocutaneous disorder manifesting as a development of multiple CNS tumours Rare, prevalence ~1:50 000, usually presents in young adults, age 18-24 50% of patients have an affected parent, and 50% have a de novo mutation Pathology: - NF2 gene is located on the long arm of chromosome 22 (22q12) and encodes the merlin protein - schwannomin - Plays a role in contact inhibition of growth, with partial tumour suppressor function Associations: - Syringohydromyelia with lesions in the spine and cataracts Imaging: - Meningioma - Schwannoma - Usually from the inferior vestibular division of the vestibulocochlear nerve - Can also be the facial nerve - Ependymoma - usually spinal intramedullary

Answer 363

45XO, the most common of the sex chromosome abnormalities in females Associations: - Hypertension - Glucose intolerance - Inflammatory bowel disease - Hypothyroidism - Horseshoe kidney - Gonodal dysgenesis Pathology: - Absence of one X chromosome (45 XO), with the missing chromosome most frequently (2/3) being the paternal one - Most occur spontaneously Three main subtypes: - Complete monosomy ~60% - most will spontaneously abort: ~70% at 16+ weeks - Partial monosomy ~15% - Mosaicism ~30% There is no association with maternal age Markers - Serum AFP decreased - Beta HCG Elevated if hydrops is present, decreased if no hydrops - Serum inhibin Elevated if hydrops is present, absent if hydrops is absent Complications - In utero development of hydrops fetalis - usually secondary to lymphatic failure

Answer 364

Antenatal - Cystic hygroma - may appear septate - Increased nuchal thickness, increased nuchal translucency - Coarctation of the aorta 15-20% - Bicuspid aortic valve - Pelvic kidney - Mild IUGR - Short fetal limbs Postpartum MSK - Scoliosis - Short 4th MCP - Narrowed scapholunate angle - positive carpal sign - Abnormal medial femoral condyle - Decreased carpal angle - madelung deformity - Valgus deformity of the elbow Pelvis: - Streaky uterus - Streaky ovary Cardiovascular: - Aortic dissection GI - Pyloric stenosis

Answer 365

The most common trisomy, and commonest chromosomal disorder Risk factors: - Increased incidence with increasing maternal age - Translocation down syndrome gene carriers - Previous pregnancy with Down syndrome Often diagnosed antenatally Classic phenotype: - Depressed nasal bridge - Epicanthal folds - Abundant nasal skin - Macroglossia Pathology: - Chromosomal abnormality is trisomy of chromosome 21 due to meiotic non-disjunction (failure of a chromosome pair to separate) - So the total chromosome count is 47 - maternal non-disjunction accounts for ~95% of cases Neurology: - Cerebellar and vermian hypoplasia - Moyamoya syndrome - Alzheimer disease - Hippocampal volume loss - Hearing loss: semicircular canal dysplasia and dehiscence, narrowed IAC, cochlear nerve canal stenosis, enlarged vestibular aqueduct Cardiovascular: - Congenital heart disease in 40% - AVSD - most common - Secundum ASD - VSD Respiratory - Pulmonary hypoplasia - Pulmonary cyst - Pig bronchus GI - Anal, duodenal atresia - Coeliac disease - Hirschsprung disease - Omphalocele - Diaphragmatic herniation MSK - Eleven ribs - Hypersegmented sternum - Joint laxity/dislocations - DDH - Atlantoaxial subluxation and atlanto-occipital instability - Hypoplastic posterior arch of C1 - "mickey mouse" pelvis with flaring of iliac wings Endocrine - Thyroid dysfunction - mostly hypothyroidism Increased incidence of leukaemia

Answer 366

Phakomatosis characterized by the development of multiple benign tumours of the embryonic ectoderm Most are sporadic The pathognomonic triad – only seen in 30% - Seizures: absent in ¼ of individuals - Intellectual disability: up to half have normal intelligence - Adenoma sebaceum: only present in ~¾ of patients Pathology: - Spontaneous mutations account for 50-66%, the rest are inherited as an autosomal dominant condition Two tumour suppressor genes are involved: - TSC1 – encoding hamartin, on chromosome 9q32-34 - TSC2 – encoding tuberin, on chromosome 16p13.3

Answer 367

Neurology: - Cortical/subcortical tubers: 50% in the frontal lobe - High T2, low T1 – 10% enhance, frequently calcify - Subependymal hamartomas – 88% associated with calcification - Variable signal, high T1, iso-high T2 - Variable enhancement - Only serial growth is reliable to differentiate from SEGA - Subependymal giant cell astrocytomas - Peak occurrence 8-18yo - White matter abnormalities - Radial bands – specific for TS - Variable appearance – nodular, ill-defined, cystic and band-like lesions seen - Retinal phakomas Rarer findings: - Cerebellar atrophy - Infarcts - Arachnoid cysts - Chordoma Abdominal - Renal angiomyolipomas - TS accounts for 20% - Seen in 55-75% of patients with TS - Tend to be multiple, large and bilateral - Fat may not be visible in up to 4.5% - Renal cysts: TSC2 gene is located adjacent to the PCKD1 gene - 18-53% of patients with TS - Renal cell carcinoma and oncocytomas - RCC tends to occur earlier - Retroperitoneal lymphangiomyomatosis - Histologically identical to pulmonary LAM - Retroperitoneal cystic lesions - Chylous ascites, enlarged lymph nodes, dilataton of the thoracic duct - GI polyps - Pancreatic neuroendocrine tumours - Hepatic angiomyolipomas Thoracic - Lymphangioleiomyomatosis (LAM) - Rare - 25-40% of female pts with TS - Indistinguishable from sporadic LAM - Pneumothorax and chylous pleural effusions are common - ~80% 10yr survival - Multifocal micronodular pneumocyte hyperplasia (MMPH) - Rare - Multicentric, well-demarcated nodular proliferation of type II pneumocytes - Benign, non-progressive - Differentials: miliary opacities Cardiac rhabdomyomas - Benign striated muscle tumour characterised by the presence of spider cells - Seen in 50-65% of pts with TS - 40-80% of patients with cardiac rhabdomyomas have TS - Multiple or single - Typically involve the ventricular septum - Occur before the age of 1yo (75%) - Spontaneous regression in 70% of children by age 4 Thoracic duct and aortic/pulmonary artery aneurysm Myocardial fatty foci MSK - Sclerotic bone lesions 46-66% - Hyperostosis of the inner table of the calvaria - Periosteal new bone - Scoliosis - Bone cyst Skin - Cutaneous lesions in ~95% of cases - Facial angiofibromas - Hypopigmented macules – ash leaf spots - Fibrous plaques on forehead - Confetti lesions

Answer 368

Numerous benign and malignant tumours in different organs, due to mutations in the VHL tumour suppressor gene on chromosome 3 Most are diagnosed with their first tumour in early adulthood Abdominal: Renal cell carcinomas - Usually clear cell and bilateral - 70% lifetime risk - Present earlier in pts with VHL Renal cysts - Often bilateral and multiple - Can be simple, complex or cystic RCC Renal angiomyolipomas Adrenal: - Phaeochromocytomas 25-30% - Extra-adrenal phaeochromocytoma/paraganglioma Pancreas – may be the earliest manifestation - Pancreatic cysts ~40% - Pancreatic neuroendocrine tumours - ~12.5% of patients - Usually non-functional - Frequently multiple - Pancreatic serous cystadenomas: ~12.5% of patients - Pancreatic adenocarcinomas Liver - Liver cysts Urogenital - Epididymal cysts - Papillary cystadenoma of the epididymis - Broad ligament cystadenomas CNS Haemangioblastomas ~70% - Cerebellar ~60% - Spinal cord ~30% - most commonly in the cervical and thoracic cord - brainstem Choroid plexus papilloma Head and neck - Retinal haemangioblastoma - Most common presenting feature - Vision loss - Endolymphatic sac tumours - Bilateral in 30%, pathognomonic for vHL

Answer 369

Acute endocarditis - High virulent organisms (e.g. staph aureus) - Typically seeds a previously normal valve - Necrotizing, ulcerating and invasive infections - Clinical: rapid onset fever and constitutional symptoms Morphology: - Right heart valves more commonly affected than left valves in IV drug users - Bulky vegetations with underlying valve destruction - Invasion into adjacent myocardium or aorta can occur - Distal embolization with septic infarcts and mycotic aneurysms can occur Subacute endocarditis: - Moderate to low virulence organisms - Streptococcus viridans most common (50-60%) - Enterococci - HACEK group of oral comsensals: - Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella - Seeding of a previously abnormal or damaged valve - Less valvular destruction - Nonspecific clinical course, lower mortality rate than acute infective endocarditis Morphology: - Smaller vegetations - Less likely to cause distal embolic phenomena due to their small size Duke Criteria for infective endocarditis: For diagnosis require: 2 major and 1 minor criteria 1 major and 3 minor criteria 5 minor criteria Major criteria: - Positive blood cultures - Typical micro-organism cultured - Persistently positive cultures: 2 blood cultures greater than 12 hours apart - Evidence of endocardial involvement: - Positive echocardiogram - Oscillating intracardiac mass - Abscess - New partial dehiscence of a prosthetic valve - New valvular regurgitation Minor criteria: - Predisposing heart condition or IV drug use - Fever >38 degrees Vascular phenomena: - Major arterial emboli - Septic pulmonary infarcts - Mycotic aneurysm - Intracranial haemorrhage - Conjunctival haemorrhage - Janeway lesions Immunologic phenomena: - Glomerulonephritis - Osler nodes - Roth spots - Rheumatoid factore Microbiologic evidence: - Positive blood culture which does not meet major criteria - Serological evidence of active infection with consistent organism - Echocardiography findings consistent with infective endocarditis but not meeting major criteria

Answer 370

cryptococci with their thick gelatinous capsules May show encapsulated yeasts of Cryptococci on India Ink or Cryptococcal antigen, or in tissue sections by PAS, mucicarmine and silver stains (esp. frequent in debilitated or immunocompromised patients)

Answer 371

Focal growth, encapsulated Cystic degeneration, haemorrhage, xanthomatous change common Arise eccentrically from parent nerve Nerve fibres do not run through tumour Spindle cells (Antoni A) & looser myxoid stroma (Antoni B) schwann cells. nf2. common. cnviii and spinal nerves. no malignant degen.

Answer 372

Infiltrating growth Unencapsulated Necrosis & cystic change uncommon Nerve fibres run through tumour Spindle cells, with intercellular collagen fibrils in myxomatous matrix nf1. cutaneous and spinal. 5-10% malignant degen.

Answer 373

Neurologic manifestations of CMV thus include acute or chronic meningoencephalitis, cranial neuropathy, vasculitis, retinitis, myelitis, brachial plexus neuropathy, and peripheral neuropathy The pathologic hallmark of CMV is the "owl's eye," an enlarged cell with a distended nucleus containing eosinophilic viral inclusions, surrounded by a halo, resulting in the characteristic appearance The owl's eye appearance can be seen in ependymal cells, subependymal astrocytes, oligodendroglia, endothelial cells, and neurons. Ependymal involvement is quite common. Infrequently, CMV infection may result in extensive destruction of gray and white matter Other typical histopathologic findings in the CNS include well-circumscribed microglial nodules,