HW path notes Flashcards
POLYCYTHAEMIA VERA is
A myeloproliferative neoplasm that results in an excess of red blood cells
Typically presents in older patients, with slight male predilection
Varied presentation, most serious being venous and arterial thrombosis and transformation into acute myeloid leukaemia
Features:
Hypertension
Unbearable pruritis
Venous thrombosis
Arterial thrombosis
Conjunctival injection
Facial plethora
Gout
JAK2 mutation, found in >95% of people
MULTIPLE MYELOMA is
monoclonal gammopathy, the most common primary malignant bone neoplasm
Arises from red marrow due to the monoclonal proliferation of plasma cells
Four main patterns are recognised:
- Disseminated - multiple well defined, punched out lytic lesions
- Disseminated - diffuse skeletal osteopenia
- Solitary plasmacytoma - single large lesion
- Osteosclerosing myeloma
A common malignancy in patients >40yo
Clinical presentation
Bone pain - intermittent and then constant
Anaemia - normochromic, normocytic
Renal failure
Proteinuria
Hypercalcaemia
Complications :
Pathological fracture
Amyloidosis
Recurrent infection
Plasmacytomas typically progress to multiple myeloma
MULTIPLE MYELOMA path
Monoclonal proliferation of malignant plasma cells which produce immunoglobulins (commonly IgG) and infiltrate haemopoietic locations (red marrow)
Renal involvement is common and renal failure is multifactorial :
- Obstructive casts in the renal tubules
- Direct nephrotoxicity of Bence Jones proteins on the epithelial cells of the renal tubules
- Hypercalcaemia and dehydration
- Amyloidosis
- Increased risk of renal infection
PLASMACYTOMA is
Discrete, solitary tumours of neoplastic monoclonal plasma cells in either bone or soft tissue (extramedullary)
No/minimal systemic bone marrow involvement
Two groups:
Solitary bone - 70%
Extramedullary plasmacytoma - 30%
Usually in adults age 40-80yo
Can arise in any part of the body
LYMPHOMA is
A malignancy arising from lymphocytes or lymphoblasts
Can present as nodal or extranodal disease
Nodal: Hodgkin and low-grade NHL
High grade NHL: SVC, cauda equina
Often present with B symptoms: fever, night sweats and weight loss
Unknown aetiology, but potential lymphomatogenic risk factors:
- Viral infection - EBV, HIV, HCV
- Bacterial infection - Helicobacter pylori
- Chronic immunosuppression - post transplant
- Prior chemotherapy and drug therapy e.g. digoxin
Classification
Hodgkin lymphoma 40%
Non-Hodgkin lymphoma 60%
- Mature B-cell lymphoma - 85%, the remainder are T-cell
- Mature T-cell and NK-cell lymphoma
- Post-transplant lymphoproliferative disorders
HODGKIN LYMPHOMA is/path
Spreads contiguously along lymphatic pathways
Curable in ~90% of cases
Bimodal distribution, young 15-34, and older >55
Typically presents with painless lymphadenopathy
Pathology:
- Characterised by the presence of Reed-Sternberg cells (a type of B cell)
- These occupy a very small proportion of the overall cell population of the affected lymph node
Contiguous spread is another feature
EBV infection is present in 40-80%
5 subtypes, divided into two groups - classical and non-classical
Classical
- Positive for CD15/CD30 and negative for CD20/45/EMA
- Nodular sclerosing - 70%
- Mixed cellularity - 25%
- Lymphocyte rich - 5%
- Lymphocyte depleted - <5%
Worst prognosis
Non-classical
- Positive for CD 19, 20, 22, 79a/EMA and negative for CD15/CD30
- Nodular lymphocyte predominant - best proggy
HODGKIN LYMPHOMA location
Typically entirely confined to the lymph nodes, and starts in the upper body
Extranodal manifestations are uncommon, but can be found in any organ system
Spine
- Erosion of the anterior/anterolacteral aspect of the vertebral body - from enlarged lymph nodes
- Nodular sclerosing - diffusely increased density with or without anterior erosion, vertebral body heigh is unaffected
- Single, dense vertebra is suggestive in adults
Long bones - frequently lytic
NON-HODGKIN LYMPHOMA is
Catch all phase for any non-hodgkin lymphoma
- burkitt
- marginal zone
- follicular
- waldenstrom macroglobulinaemia
BURKITT LYMPHOMA is
An aggressive B-cell lymphoma predominantly affecting children
The most common NHL in children, ~40%
Median age is 8yo
Risk factors:
HIV/AIDs
Post transplant immunosuppression
Presentation:
- Extranodal involvement is common ~30%, most often as an abdominal or pelvic mass
- Most patients present with widespread disease
BURKITT LYMPHOMA pathology
Three forms are described:
- Endemic - linked to EBV and malaria
- Sporadic - aetiology unknown
- Immunodeficiency associated - occur in patients with HIV, post transplant or congenital immunosuppression
An aggressive tumour with a doubling time of 24hrs
Can present in a wide variety of locations:
- Head and neck
- Pleural space ~70%
- GIT, esp ileocaecal
- Mesentery, peritoneum, retroperitoneum
- Kidneys
- Gonads ~75%
Nodal involvement is more common in adults than children
MARGINAL ZONE LYMPHOMA is
A group of NHL
Three types, depending on the site of origin
Mucosa-associated lymphoid tissue (MALT), splenic and extranodal marginal lymphoma
The marginal zone in the germinal follicles undergoes hyperplasia in response to infection or antigen
The most common type of NHL, often in the stomach (associated with H-pylori infection) and thyroid
Genetic abnormalities: t(11, 18) and trisomy 3 are reported
FOLLICULAR LYMPHOMA is
subtype of NHL
Accounts for ~45% of all NHL
Markers:
CD10 positive
CD5 negative
CD20 positive
Translocation t(14;18) is found in majority of patients with follicular lymphoma
Can transform into a more aggressive type
WALDENSTROM MACROGLOBULINAEMIA
A lymphoplasmacytic lymphoma
rare
SICKLE CELL DISEASE is
A hereditary autosomal recessive condition resulting in the formation of abnormal haemoglobin, which manifests as multisystem ischemia and infarction, as well as haemolytic anaemia
No gender predilection
The highest incidence is in individuals of african descent > eastern mediterranean
Close relationship with malaria
Early manifestation in early childhood, commonly with a painful vaso-occlusive crisis - sudden onset bone or visceral pain due to microvascular occlusion and ischaemia, often in the setting of sepsis or dehydration
Presentation:
Bone pain - infarction, osteomyelitis
Pulmonary - acute chest syndrome, recurrent pneumonia, chronic lung disease
Abdominal - vaso-occlusive crises, sequestration syndrome (rapid pooling of blood in the spleen, leading to intravascular volume depletion)
Haemolytic anaemia and extra-medullary haematopoiesis
Impaired immunity from autosplenectomy
Multiple renal manifestations resulting in renal failure
Cerebral - stroke, cognitive impairment
Ocular and orbital complications - central retinal artery occlusion
SPLENIC SIDEROTIC NODULES
Splenic siderotic nodules - Gamna-gandy bodies of the spleen, most commonly encountered in portal hypertension. The pathological process is the result of microhaemorrhage resulting in haemosiderin and calcium deposition followed by fibroblastic reaction
SPLENOMEGALY
Massive splenomegaly: longer than 18cm, or extending into the pelvis or across the midline
Pathology:
Haematological disease
Haemodynamic
Infectious
Storage Diseases/metabolic/infiltrative disorders
Neoplastic - non haemorrhagic
Traumatic
Connective tissue disordERS
Massive: Chronic myeloid leukaemia, myelofibrosis, gaucher disease, lymphoma, Kala-azar, malaria, beta-thalassemia major, AIDs with mycobacterium, Sarcoidosis
Moderate :Rickets, hepatities, hepatic cirrhosis, lymphoma/leukaemia, EBV, pernicious anaemia, amyloidosis, abscess
LEUKAEMIA is
A haematological neoplasm characterised by the overproduction of immature (blasts) or abnormally differentiated cells of the haematopoietic system in bone marrow that often, but not always, extends into peripheral blood
Divided according to the percentage of blasts in the bone marrow or peripheral blood
Acute - when there is proliferation of mostly immature/poorly differentiated cells (blasts) in the bone marrow
- >20%
- Clonal cells build-up crowds out of the marrow in detriment of healthy blood lineage cells
- Disease becomes symptomatic early
Chronic - proliferation of mostly mature but abnormal leukocytes with or without cytopenia
LEUKAEMIA classification
Acute lymphoblastic leukaemia
- Commonly affecting children - ~80%
- Usually severely symptomatic
Chronic lymphocytic leukaemia
- Commonly affecting elderly patients >75yo
Acute myeloid leukaemia
- Commonly seen in adults, but also the second most common form in children
- Male predominance
Chronic myeloid leukaemia
- Male adults
- Philadelphia chromosome is present in 90%
CML is
Overproduction of granulocytes with fairly normal differentiation
Typically age 50-60
Risk factors - high-dose radiation exposure
Bloods: leucocytosis with a predominance of the neutrophil lineage
Genetics:
Chromosomal abnormality of the haematopoietic stem cell: where translocation between chromosomes 9 and 22 creates the fusion gene BCR-ABL1
The shortened chromosome 22 contains the fusion gene Philadelphia chromosome
Imaging:
Splenomegaly and diffuse marrow infiltration
VITAMIN K DEFICIENCY
A clotting dyscrasia, vital as a cofactor for the enzymatic activation of several key components of the clotting pathway, including the prothrombogenic proteins, prothrombin, factors VII, IV and X, and the anticoagulant molecules: proteins C, S and Z
Presents with bleeding tendency:
Spontaneous haematomas
Mucosal bleeding
Haematochezia and melena
Haematuria
Menorrhagia
Anaemia
Aetiology:
Fat malabsorption
Chronic broad spectrum antibiotics
Dietary fat insufficiency
EPSTEIN-BARR VIRUS
Exposure is widespread, 90% of adults are seropositive
When acquired in childhood it remains subclinical. If acquired as a young adults, 25% are symptomatic
In 5%, CMV is the causative pathogen
Clinical presentation
Fever/tonsillitis
Lymphadenopathy and splenomegaly - occasionally hepatosplenomegaly
Fatigue
Rash
Complications:
Splenic rupture - may be spontaneous
Splenic infarction
Pathology:
A herpesvirus - herpesvirus 4
Thought to be person-to-person spread, through salivary secretions
Infects B-cells in the lymphoid tissue
Becomes a chronic infection with periodic shedding of virus
May have elevated transaminases
Imaging
Splenomegaly
Lymphadenopathy
Tonsillar enlargement
Possible hepatomegaly
Complications
Myocarditis rarely seen
CNS infection, rarely seen
INVASIVE LOBULAR CARCINOMA general
The most common type of invasive breast cancer after invasive breast carcinoma of no special type
They represent 5-10% of all breast cancer
Association:
- Greater likelihood of contralateral breast cancer in invasive lobular carcinoma, with a 5yr rate of bilateral cancer of 8%
- 4% synchronous and 4% metachronous
INVASIVE LOBULAR CARCINOMA pathology/markers
Pathology:
Characterised by malignant monomorphic cells that form loosely dispersed linear columns that invade the normal tissues and encircle ducts.
Invasive carcinoma of no specific type more commonly presents as a mass with vigorous desmoplastic response
The cells often preserve the architecture of the ducts, which limits the sensitivity of detection using mammography
Markers:
- Loss of E-cadherin is a specific biomarker for invasive lobular carcinoma as opposed to invasive breast carcinoma of no special type
- Although 15% of ILC are positive for E-cadherin
- The majority of invasive lobular carcinomas have the following receptor profile:
- Oestrogen receptor +
- Progesterone receptor +
- HER2 amplification -
Variants:
Tubulolobular
Solid
Alveolar
Pleomorphic
Mixed
INVASIVE LOBULAR CARCINOMA imaging
Imaging
Often multicentric and bilateral 10-15%
Imaging of the contralateral breast is crucial
Can be subtle changes e.g. progressive shrinkage/enlargement or reduced compressibility of the involved breast
Mammography:
Sensitivity 57-81%
Spiculated mass lesion - most common
Asymmetrical densities 3-25%
Opacities or architectural distortion 10-25%
Microcalcifications <10%
16% are occult or benign
Ultrasound
Heterogenous, hypoechoic mass with angular or ill-defined margins and posterior acoustic shadowing
Characteristic: heterogenous infiltrating area of low echogenicity with disproportionate posterior shadowing
MRI is recommended due to propensity for multicentricity
ATYPICAL LOBULAR HYPERPLASIA
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)
LOBULAR CARCINOMA IN SITU
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
MEDULLARY CARCINOMA OF THE BREAST
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
MEDULLARY CARCINOMA OF THE BREAST imaging
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
PAGET DISEASE OF THE BREAST/NIPPLE is
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
PAGET DISEASE OF THE BREAST/NIPPLE path
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
PAGET DISEASE OF THE BREAST/NIPPLE imaging
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
GYNAECOMASTIA is/path./causes
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
LYMPHOCYTIC MASTITIS is
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.
PLASMA CELL MASTITIS is and imaging
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
FAT NECROSIS IS
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
FAT NECROSIS PATH
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
FAT NECROSIS IMAGING
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
RADIAL SCAR is
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
RADIAL SCAR path
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
RADIAL SCAR imaging
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
DCIS IS
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
DCIS path
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
DCIS imaging
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
JUVENILE PAPILLOMATOSIS is, path, imaging
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
TUBULAR CARCINOMA is
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
TUBULAR CARCINOMA path
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
TUBULAR CARCINOMA imaging
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
Diabetic mastopathy also known as
Sclerosing lymphocytic lobulitis
SCLEROSING ADENOSIS is
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
SCLEROSING ADENOSIS path
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
SCLEROSING ADENOSIS imaging
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
DIABETIC MASTOPATHY is and path
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
PSEUDOANGIOMATOUS STROMAL HYPERPLASIA is
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
PSEUDOANGIOMATOUS STROMAL HYPERPLASIA path
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
PSEUDOANGIOMATOUS STROMAL HYPERPLASIA imaging
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
MUCINOUS BREAST CARCINOMA is
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
MUCINOUS BREAST CARCINOMA path
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
MUCINOUS BREAST CARCINOMA imaging
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
MALE BREAST CANCER is
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
MALE BREAST CANCER path, risk factors, imaging
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
ANGIOSARCOMA is
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
ANGIOSARCOMA path and imaging
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
BREAST LYMPHOMA is
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
BREAST LYMPHOMA path
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
PAPILLARY CARCINOMA breast IS AND IMAGING
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
PAPILLARY CARCINOMA breast PATH
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
PAPILLOMA is
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
PAPILLOMA path
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
PAPILLOMA imaging
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
HEREDITARY BREAST AND OVARIAN CANCER SYNDROME
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
PHYLLOIDES is and imaging
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
PHYLLOIDES path
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
INFLAMMATORY BREAST CANCER is
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
INFLAMMATORY BREAST CANCER imaging
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
TAKAYASU ARTERITIS general
“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
TAKAYASU ARTERITIS path
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
TAKAYASU ARTERITIS classification
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
POLYARTERITIS NODOSA general
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%
POLYARTERITIS NODOSA path
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
GIANT CELL ARTERITIS general
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
GIANT CELL ARTERITIS path
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
FIBROMUSCULAR DYSPLASIA general
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
GRANULOMATOSIS WITH POLYANGIITIS general
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%
EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS | CHURG-STRAUSS SYNDROME general
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%
EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS | CHURG-STRAUSS SYNDROME dx criteria
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
EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS | CHURG-STRAUSS SYNDROME pathology
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
BEHCETS general
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
BEHCETS assoc and clinical
Associations:
- HLA-B51
- Factor V Leiden mutation
- Superficial thrombophlebitis
The classic clinical triad:
- Oral ulceration
- Genital ulceration
- Ocular manifestation
BEHCETS distribution
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
VARICOSE VEINS general
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
VARICOSE VEINS pathology
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
MARFAN SYNDROME general
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
MARFAN SYNDROME pathology
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
FIBRINOID NECROSIS
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
AORTIC DISSECTION pathology
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
HYPERALDOSTERONISM is and path
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
PHEOCHROMOCYTOMA assoc
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
PHEOCHROMOCYTOMA path
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
CUSHING SYNDROME is
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
CUSHING SYNDROME path
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
ADRENAL INSUFFICIENCY is and path
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
RENAL PAPILLARY NECROSIS is path and causes
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
RENAL CORTICAL NECROSIS is and path
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
ARPKD is
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
ARPKD path
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
ADPKD is
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
ADPKD path
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
ALLAGILIE SYNDROME is
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
MCDK is and assoc
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
MCDK path
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
MEDULLARY SPONGE KIDNEY is
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
TUBEROUS SCLEROSIS IS/PATH
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
TUBEROUS SCLEROSIS manifestations
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
VON HIPPEL LINDAU is
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
VON HIPPEL LINDAU manifestations
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
ANGIOMYELOLIPOMA is./path/assox
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.
ONCOCYTOMA is and path
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
CLEAR CELL RCC is and path
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
PAPILLARY RCC is and path
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
CHROMOPHOBE RCC is
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”
MEDULLARY RCC
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
BLADDER ADENOCARCINOMA (?bladeno?) is and path
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
BLADDER SCHISTOSOMIASIS (schistosomiapiss?) is and path
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
BLADDER SCC is
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
BLADDER TCC is n path
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
BLADDER RHABDOMYOSARCOMA is n path
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
Barrett’s oesophagus:
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
OESOPHAGEAL VARICES are
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
OESOPHAGEAL VARICES path
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
OESOPHAGEAL WEB is, path and assoc
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
BARRETS OESOPHAGUS is and path
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
MALToma is and path
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
MEN 1
Pituitary adenoma, parathyroid adenoma, pancreatic neuroendocrine tumour
MEN 2A
medullary thyroid cancer, pheochromocytoma, parathyroid hyperplasia
MEN 2B
Medullary thyroid cancer, pheochromocytoma, mucosal neuromas/gangliomas, marfanoid habitus
OESOPHAGEAL CARCINOMA is and risk factors
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
OESOPHAGEAL CARCINOMA path
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
OESOPHAGEAL CARCINOMA staging
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
GASTRIC CANCER is and path
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
GIST - GASTROINTESTINAL STROMAL TUMOUR is and assoc
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
GIST - GASTROINTESTINAL STROMAL TUMOUR path
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
LEIOMYOMA is and light path
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
MALTOMA is and light path
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
SMALL BOWEL CARCINOMA path
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
MUCINOUS NEOPLASM OF THE APPENDIX is and light path
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
COLORECTAL CARCINOMA is, risk factors and assoc
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
COLORECTAL CARCINOMA path
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
RECTAL CA IS AND STAGIGN
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
ANAL CANCER IS
Relatively uncommon, <2% of large bowel malignancies
Most are SCC
Typically originates between the anorectal junction above and the anal verge below
POLYPOSIS LOCATION
Stomach - cronkite-canada
Small bowel - Peutz Jegher
Large bowel - Juvenile polyposis, Lynch, Cowden, Turcot, FAP, cronkite-canada
CRONKITE-CANADA IS AND PATH
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
PEUTZ-JEGHER IS AND PATH
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
TURCOT IS AND PATH
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
GARDNER SYNDROME is and path
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
FAMILIAL ADENOMATOUS POLYPOSIS is and path
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
COWDEN SYNDROME is and path
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
LYNCH is and path
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
JUVENILE POLYPOSIS SYNDROME is and path
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
