Histopathology Flashcards

Question

Why might paediatric jaundice be normal?

Answer 1

Only normal if unconjugated is raised since it may be due to liver immaturity coupled with fall in haemoglobin

Answer 2

Recessive - 50% carry genes

Answer 3

5-6% of the population | 1 in 20

Answer 4

UDP glucuronyl transferase activity is reduced to 30% - unconjugated bilirubin tightly albumin bound and does not enter urine

Answer 5

- Albumin - Clotting factors (PT, PTTK) - Bilirubin

Answer 6

Bilirubin - Normal results for a total bilirubin test are 1.2 milligrams per deciliter (mg/dL) for adults and usually 1 mg/dL for those under 18. Normal results for direct bilirubin are generally 0.3 mg/dL. ALP<130 AST<50 ALT<50

Answer 7

Hepatocyte damage

Answer 8

Obstructive jaundice

Answer 9

Pre-hepatic - Gilberts, haemolysis Hepatic - viral, autoimmune, alcoholic, cirrhosis Post-hepatic - gallstones, pancreatic cancer

Answer 10

- Virus in faeces - 2-6 weeks - IgM - 3.5-13 weeks - IgG - 5 weeks

Answer 11

HBs Ag HBe Ag Anti-HBe Anti-HBs - vaccinated If both anti-HBe and anti-HBs = present infection

Answer 12

Liver cell damage: ballooning degeneration, Mallory-Denk bodies Inflammation Fibrosis

Answer 13

- Supportive - Stop alcohol - Nutrition - Vitamins - Occasionally steroids

Answer 14

Chronic stable liver disease

Answer 15

Visible veins Splenomegaly Ascites

Answer 16

- Oesophageal varices - Rectal varices - Umbilical vein recanalising - Spleno-renal shunt

Answer 17

Courvoisier's law; if gallbladder is palpable in a jaundiced patient, it is unlikely to be due to gallstones, because stones would have given rise to chronic inflammation and subsequently fibrosis of gallbladder therefore, rendering it incapable of dilatation.

Answer 18

1. Hepatic portal vein | 2. Hepatic artery

Answer 19

1. Hepatocytes 2. Bile ducts 3. Blood vessels 4. Endothelial cells 5. Kupffer cells 6. Stellate cells

Answer 20

- Loss of microvilli - Stellate cells are activated --> become myofibroblasts and make collagen --> invade endothelium - Kupffer cells get activated

Answer 21

1. Whole liver involved 2. Fibrosis 3. Nodules of regenerating hepatocytes 4. Distortion of liver vascular architecture: intra- and extra- hepatic (e.g. gastro- oesophageal) shunting of blood

Answer 22

a) According to nodule size: Micronodular or macronodular b) According to aetiology: 1) Alcohol / insulin resistance 2) Viral hepatitis etc.

Answer 23

1. Portal hypertension 2. Hepatic encephalopathy 3. Liver cell cancer

Answer 24

Spotty necrosis

Answer 25

1. Viral hepatitis 2. Drugs 3. Auto-immune

Answer 26

MUST be greater than 6 months Severity of inflammation = Grade (portal tract inflammation, interface hepatitis, lobular inflammation) Severity of fibrosis = Stage (collagen is blue in stain --> intrahepatic shunting of blood)

Answer 27

Intrahepatic shunt: blood goes to liver, but is unfiltered and toxic blood when it returns to heart Extrahepatic shunt: blood bypasses liver and goes straight to heart as unfiltered and toxic blood

Answer 28

1. Viruses (e.g. A and E) | 2. Drugs

Answer 29

1) Fatty liver 2) Alcoholic hepatitis 3) Cirrhosis

Answer 30

* Ballooning ( +/- Mallory Denk Bodies) * Apoptosis * Pericellular fibrosis * Mainly seen in Zone 3

Answer 31

Three zones can be distinguished: 1) Periportal zone 2) Intermediary zone 3) Perivenous, pericentral, or centrilobular zone.

Answer 32

* Histologically looks like alcoholic liver disease * Due to insulin resistance associated with raised BMI and diabetes * Becoming recognised as one of the commonest causes of liver disease, world-wide

Answer 33

* Previously primary biliary cirrhosis * F> M * Bile duct loss associated with chronic inflammation (with granulomas) * Diagnostic test is detection of anti-mitochondrial antibodies

Answer 34

* M>F * Periductal bile duct fibrosis leading to loss * Associated with ulcerative colitis * Increased risk of cholangiocarcinoma * Diagnostic test is bile duct imaging

Answer 35

* Genetically determined increased gut iron absorption * Gene on chromosome 6 (HFe) * Parenchymal damage to organs secondary to iron deposition (bronzed diabetes)

Answer 36

The accumulation of iron in macrophages which may be due to multiple blood transfusions

Answer 37

* Accumulation of copper due to failure of excretion by hepatocytes into the bile * Assessed by biopsy or biochemistry * Genes on chromosome 13 * Accumulates in the liver and CNS (hepato- lenticular degeneration) including Kayser- Fleishcer rings

Answer 38

Rhodanine stain for copper

Answer 39

* F>M * Active chronic hepatitis with plasma cells * Anti-smooth muscle actin antibodies in the serum * Responds to steroids

Answer 40

* Failure to secrete alpha-one antitrypsin * Intra-cytoplasmic inclusions due to misfolded protein * Hepatitis and cirrhosis

Answer 41

10% of drug reactions involve the liver | May be dose-related or idiosyncratic

Answer 42

Specific causes: • PBC • drugs General causes • TB • Sarcoid etc

Answer 43

1) Liver cell adenoma 2) Bile duct adenoma 3) Haemangioma

Answer 44

1. hepatocellular carcinoma 2. hepatoblastoma 3. cholangiocarcinoma 4. haemangiosarcoma

Answer 45

Associated with: • PSC • Worm infections • Cirrhosis Can arise from: • intrahepatic ducts • extrahepatic ducts (including gall bladder)

Answer 46

Epidermis Dermis Subcutaneous tissue (fat)

Answer 47

Thicker keratin layer

Answer 48

- More sebaceous glands | - More hair follicles

Answer 49

- Epidermis thinner | - Quality of elastic fibres and collagen bundles is decreased

Answer 50

* Vesiculobullous * Spongiotic * Psoriasiform * Lichenoid * Vasculitic * Granulomatous

Answer 51

Forms tense bullae particularly in flexural surfaces particularly in the elderly. Dermo-epidermal junction affected

Answer 52

IgG and C3 attack the basement membrane Detected by immunofluorescence IgG anti-hemidesmosome Eosinophils recruited to release elastase Elastase damages the anchoring proteins Fluid fills up gap between BM and epithelium

Answer 53

Flaccid blisters, rupture easily | Epiderma-epidermal junction affected (within epidermis)

Answer 54

IgG attacks between the keratin layers (acantholysis) I.E. Loss of intracellular connections (desmosomes) Common for many conditions; Nikolsky’s sign positive Need immunofluorescence to confirm

Answer 55

Top layer is very thin so never blisters IgG-mediated – outer layer of stratum corneum shears off Diagnose with immunofluorescence

Answer 56

A common type of eczema/dermatitis defined by scattered, well-defined, coin-shaped and coin-sized plaques of eczema. Causes involve elements of barrier dysfunction, alterations in cell mediated immune responses, IgE mediated hypersensitivity, and environmental factors. Flexor surfaces Very itchy; plaques form

Answer 57

``` Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale Dermis Hypodermis ```

Answer 58

Itchy; latex and nickel Itchy --> hyperparakeratosis (thickening) Epidermis gets thicker --> lichenification

Answer 59

Epidermis gets thicker Eczema is spongiotic because there is oedema in between the keratinocytes T cell mediated and eosinophils are recruited A differential for an eczematous reaction pattern is a drug reaction

Answer 60

``` Psoriasiform reaction pattern; extensor surfaces Silver plaques (similar to discoid eczema) ```

Answer 61

Normal keratinocyte turnover time = 56 days Psoriasis keratinocyte turnover time = 7 days Rapid turnover --> epidermis thicker A layer of parakeratosis forms at the top Stratum granulosum disappears as not enough time to form it; and dilated vessels form Munro's microabscesses form, made up from recruitment of neutrophils

Answer 62

T-cell mediated; itchy Papules and plaques of purplish-red colour on the wrists and arms In mouth it presents as white lines (Wickham striae)

Answer 63

T-lymphocytes have destroyed bottom keratinocytes Creates band-like inflammation Cannot see where dermis finished, and epidermis starts

Answer 64

Vasculitis (not actually gangrenous) Presents as non-healing ulcer Often, first manifestation of a systemic disease E.G. colitis, hepatitis, leukaemia

Answer 65

“Cauliflower”, pigmented, gets caught on clothing (and taken off) Stuck-on appearance, harmless and benign Lots of growth and ordered proliferation Ordered and benign growth “Horn cysts” – epidermis entrapping keratin

Answer 66

Transluminates, central punctum, circumscribed, hot | Squamous cell lining surrounding the cyst

Answer 67

Rolled, pearly-edge, central ulcer, telangiectasia “Rodent ulcer” as it burrows away Benign but can disfigure Occurs in sun-exposed areas Dysplastic change Cancer from keratinocytes at bottom of epidermis Cannot break through the BM --> cannot metastasise

Answer 68

Squamous cell carcinoma in situ [i.e. pre-cancerous] Keratinocytes become more pleiomorphic and larger with mitotic figures Bowen’s disease name changes depending on location (i.e. anal vs. cervix) Dysplasia can be 1, 2 or 3 (low, moderate or high grade)

Answer 69

Subdivided into level of differentiation: Poorly to well differentiated Poorly differentiated means you cannot determine origin cell lineage Peri-neural invasion can occur (i.e. local invasion)

Answer 70

A form of melanocytic naevus

Answer 71

1) Cafe-au-lait spots 2) Junctional nevus = melanocytes nest in the epidermis Flat and coloured Normally, melanocytes sit in the basal layer of the epidermis Melanocytes can, however, physiologically exist in the dermis As you age, melanocytes usually drop into the dermis 3) Compound nevus = nests in epidermis and dermis Raised area Surround by flat pigmented area   4) Intradermal naevus = nests in the dermis Raised area Skin-coloured or pigmented

Answer 72

Irregular border Variable pigmentation Bleeding Itchy Growing

Answer 73

The junctional melanocytes are not normally maturing and dropping out of the dermis – they are moving up through the dermis instead = “Pagetoid spread” this is NOT normal Melanocytes also display mitotic figures (abnormal unless in pregnancy)

Answer 74

Melanoma is staged by “Breslow Thickness” | A melanoma with a thickness >4 mm, it has a very high mortality (> 50%)

Answer 75

Stage I - through skin to epidermis - <1mm Stage II - through skin, to epidermis and a bit of dermis - <1-2mm Stage III - through skin, epidermis, more of dermis - <2-4mm Stage IIII - through skin, epidermis, dermis and reaches SC fat - over 4mm

Answer 76

``` Asymmetry Border Colour Diameter Elevation Firm Growing ```

Answer 77

Type I: Facilitate gas exchange Maintain ion and fluid balance within the alveoli Communicate with type II pneumocytes to secrete surfactant in response to stretch. Type II: Produce and secrete pulmonary surfactant - surfactant is a vital substance that reduces surface tension, preventing alveoli from collapsing. Expression of immunomodulatory proteins that are necessary for host defense Transepithelial movement of water Regeneration of alveolar epithelium after injury

Answer 78

A condition in which breathing periodically rendered difficult by widespread narrowing of the airways that changes in severity over short periods of time. Severe attacks = status asthmaticus

Answer 79

``` Allergens and atopy Pollution Drugs - NSAIDs Occupational–inhaled gases/fumes Diet Physical exertion–“cold” Intrinsic Underlying genetic factors ```

Answer 80

IMMEDIATE: Mast cells degranulate on contact with antigen Mediators released cause vascular permeability, eosinophil and mast cell recruitment, and bronchospasm LATE: Tissue damage Increased mucus production Muscle hypertrophy

Answer 81

Mucus plug Overinflated lung Mucus plug in-situ

Answer 82

- Hyperaemia - Hypertrophic constricted muscle - Eosinophilic inflammation and goblet cell hyperplasia - mucus

Answer 83

– Chronic cough productive of sputum | – Most days for at least 3 months over at least 2 consecutive years

Answer 84

* Smoking * Air pollution * Occupational exposures

Answer 85

Dilatation of airways Goblet cell hyperplasia Hypertrophy mucous glands

Answer 86

* Repeated infections (most common cause of hospital admission and death) * Chronic hypoxia and reduced exercise tolerance * Chronic hypoxia results in pulmonary hypertension and right sided heart failure (cor pulmonale) * Increased risk of lung cancer independent of smoking

Answer 87

Permanent abnormal dilatation of bronchi

Answer 88

Congenital Inflammatory – Post-infectious (especially children or cystic fibrosis patients) – Ciliary dyskinesia 1o [Kartagener’s] and 2o – Obstruction (extrinsic/intrinsic/middle lobe syn.) – Post-inflammatory (aspiration) – Secondary to bronchiolar disease (OB) and interstitial fibrosis (CFA, sarcoidosis) – Systemic disease (connective tissue disorders) – Asthma

Answer 89

* Recurrent infections * Haemoptysis * Pulmonary Hypertension and right sided heart failure * Amyloidosis

Answer 90

* Affects 1 in 2,500 live births | * Autosomal recessive (approx 1/20 of population are heterozygous carriers)

Answer 91

* Chr 7q3 = CFTR gene (Cystic Fibrosis Transmembrane Conductance Regulator) = ion transporter protein * Abnormality leads to defective ion transport and therefore excessive resorption of water from secretions of exocrine glands * Results in abnormally thick mucus secretion - affects all organ systems

Answer 92

Lung --> airway obstruction, respiratory failure, recurrent infection GI tract --> meconium ileus, malabsorption Pancreas --> pancreatitis, secondary malabsorption Liver --> cirrhosis Male reproductive system --> infertility

Answer 93

* Pulmonary oedema and diffuse alveolar damage (includes Acute respiratory distress syndrome and HMD) * Infections * COPD - Emphysema * Granulomatous diseases * Fibrosing interstitial lung disease and occupational lung disease

Answer 94

Accumulation of fluid in alveolar spaces as consequence of “leaky capillaries” or “back pressure” from failing left ventricle.

Answer 95

– Left heart failure – Alveolar injury – Neurogenic – High altitude

Answer 96

– Acute : heavy watery lungs, intra- alveolar fluid on histology – Chronic: Iron laden macrophages, fibrosis Poor gas exchange therefore hypoxia and respiratory failure

Answer 97

“Heart failure cells” – iron laden macrophages

Answer 98

Pattern of acute diffuse lung injury in which patients present with rapid onset of respiratory failure, requiring ventilation on ITU. CXR shows “white out” all lung fields Pathogenesis : Acute damage to endothelium and/or alveolar epithelium leading to exudative inflammatory reaction.

Answer 99

Adults – Acute respiratory distress syndrome “shock lung” • Numerous causes in adults: – Infection (local or generalised sepsis), aspiration, trauma, inhaled irritant gases, shock, blood transfusion, DIC, drug overdose, pancreatitis, idiopathic. – Common on ITU Neonates - Hyaline membrane disease of newborn • Insufficient surfactant production leading to stiff lungs and secondary alveolar epithelial damage. • Premature babies

Answer 100

X-ray: fluffy white infiltrates in all lung fields (“white out”) Lungs are expanded and firm Plum coloured, airless Often weigh >1kg

Answer 101

1) Capillary congestion 2) Exudative phase 3) Hyaline membranes 4) Organising phase

Answer 102

* Death ~ 40% of cases * Superimposed infection * Resolution: lung returns to normal * Residual fibrous scarring --> chronic impairment

Answer 103

Variety of patterns of lung involvement depending upon organism and other co-factors: – Bronchopneumonia – Lobar pneumonia – Abscess formation – Granulomatous inflammation

Answer 104

Compromised host defense - Elderly

Answer 105

Often low virulence organisms - Staphylococcus, Haemophilius, Streptococcus, Pneumococcus, Pathology - Patchy bronchial and peribronchial distribution, often lower lobes

Answer 106

* Peribronchial distribution | * Acute inflammation surrounding airways and within alveoli

Answer 107

Acute bacterial infection of a large portion of a lobe or entire lobe. * Infrequent with advent of antibiotics * Widespread fibrinosuppurative consolidation

Answer 108

High virulence organism: 90-95% pneumococci (S. pneumoniae)

Answer 109

1. Congestion – hyperaemia, intra-alveolar fluid 2. Red hepatization - hyperaemia, intra-alveolar neutrophils 3. Grey hepatization - intra-alveolar connective tissue 4. Resolution - restoration normal architecture

Answer 110

* Abscess formation * Pleuritis and pleural effusion * Infected pleural effusion (EMPYEMA) * Fibrous scarring * Septicaemia

Answer 111

Emphysema is a permanent loss of the alveolar parenchyma distal to the terminal bronchiole

Answer 112

Damage to alveolar epithelium: – SMOKING – Alpha1 antitrypsin deficiency – Rare – IVDU, connective tissue disease

Answer 113

Cigarette smoke --> neutrophil activation + macrophage activation --> proteases (elastase) --> tissue damage (emphysema)

Answer 114

Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by low serum levels of alpha-1 antitrypsin (AAT). Loss of AAT disrupts the protease-antiprotease balance in the lungs, allowing proteases, specifically neutrophil elastase, to act uninhibited and destroy lung matrix and alveolar structures.

Answer 115

Smoking - loss centred on bronchiole - CENTRILOBULAR Alpha 1 antitrypsin deficiency - diffuse loss of alveolae - PANACINAR

Answer 116

* Large air spaces (bullae) – rupture - pneumothorax * Respiratory failure: loss of area for gas exchange - compression of adjacent normal lung * Pulmonary hypertension and cor pulmonale

Answer 117

- Collection of histiocytes/macrophages +/- multinucleate giant cells - Necrotising or non necrotising

Answer 118

``` – Infection – Sarcoidosis – Foreign body – aspiration or IVDU – Drugs – Occupational lung disease ```

Answer 119

– Idiopathic pulmonary fibrosis (Cryptogenic fibrosing alveolitis) – Extrinsic allergic alveolitis - “farmers lung” – Industrial lung diseases – “pneumoconiosis”

Answer 120

* Also known as cryptogenic fibrosing alveolitis * Chronic - SOB and cough * Over 50 years, male predominance

Answer 121

* Progressive disease | * Over 50% die in 2-3 years

Answer 122

* Macro – Basal and peripheral fibrosis and cyst formation | * Micro - interstitial fibrosis at varying stages

Answer 123

Diagnosis by HRCT +/- biopsy

Answer 124

Virchows triad: – factors promoting blood stasis: obesity, immobility, cardiac failure, pregnancy, abdominal masses – damage to endothelium: local trauma, cannulation – increased coagulation: malignancy, haemoconcentration, polycythaemia, DIC, contraceptive pill, cannulation, anti-phospholipid syndrome

Answer 125

* Small peripheral pulmonary arterial occlusion * Haemorrhagic infarct * Repeated emboli cause increasing occlusion of pulmonary vascular bed and pulmonary hypertension * Patients present with pleuritic chest pain, acute SOB and/or chronic progressive shortness of breath

Answer 126

* Large emboli can occlude the main pulmonary trunk (saddle embolus) * Sudden death, acute right heart failure, or cardiovascular shock occurs in 5% of cases when >60% of pulmonary bed is occluded * If patient survives, the embolus usually resolves * 30% develop second or more emboli

Answer 127

``` Bone marrow Amniotic fluid Trophoblast Tumour Foreign body Air ```

Answer 128

PHBP = mean pulmonary arterial pressure > 25mmHg at rest

Answer 129

Pulmonary circulation normally low pressure (mean PAP 12mmHg)

Answer 130

Precapillary ``` Vasoconstrictive – Chronic hypoxia – Hyperkinetic congenital heart disease – Unknown (Primary pulmonary hypertension) – Chronic liver disease, HIV infection, Connective tissue disease Embolic – Thromboembolic – Parasitic (schistosomal) – Tumour emboli ``` Capillary Widespread pulmonary fibrosis - mechanical vascular distortion and chronic hypoxia Postcapillary Veno-occlusive disease Left-sided heart disease

Answer 131

Arise from a variety of cell types: epithelial, mesenchymal (soft tissue), lymphoid

Answer 132

Arise at a variety of sites: airways, seromucinous glands, alveolar parenchyma, vessels, pleura

Answer 133

Chondroma | Can cause local complications - airway obstruction

Answer 134

Commonest are epithelial tumours and of these main types (90-95%)

Answer 135

NON-small cell carcinoma • Squamous cell carcinoma (30%) • Adenocarcinoma (30%) • Large cell carcinoma (20%) SMALL cell carcinoma • Small cell carcinoma (20%)

Answer 136

SMOKING 25% of lung ca in non-smokers attributed to passive smoking Strongest association with squamous cell carcinoma and small cell carcinoma

Answer 137

SMOKING 25% of lung ca in non-smokers attributed to passive smoking Strongest association with squamous cell carcinoma and small cell carcinoma

Answer 138

* Tumour initiators: Polycyclic aromatic hydrocarbons * Tumour promotors: N Nitrosamines, Nicotine, Phenols * Complete carcinogens: Nickel, Arsenic

Answer 139

10-20% in non-smokers – Asbestos exposure (Asbestos + smoking = 50 fold increase risk) – Radiation (Radon exposure, theraputic radiation, uranium miners) – Air pollution – Other: Heavy metals (Chromates, arsenic, nickel)\ Genetics - Familial lung cancers rare Susceptibility genes - Chemical modification of carcinogens - Polymorphisms in genes for cytochrome p450 (CYP1A1) and glutathione S transferases which play a role in eliminating carcinogens - Susceptibility to chromosome breaks and DNA damage - Nicotine addiction

Answer 140

Normal epithelium --> hyperplasia --> squamous metaplasia --> dysplasia --> carcinoma in situ --> invasive carcinoma

Answer 141

Site – Traditionally centrally located arising from bronchial epithelium, however increasing number of peripheral squamous cell carcinomas Behaviour – Local spread, metastasise late

Answer 142

Precursor lesion: Atypical adenomatous hyperplasia Proliferation of atypical cells lining the alveolar walls. Increases in size and eventually can become invasive. AAH --> Non-mucinous Adenocarcinoma-in-situ --> Mixed pattern invasive adenoCa (acquires invasive phenotype)

Answer 143

Adenocarcinoma

Answer 144

Site – Peripheral and more often multicentric Behaviour – Extrathoracic metastases common and early Histology – Histology shows evidence of glandular differentiation – Variety patterns relate underlying molecular abnormalities and prognosis

Answer 145

Poorly differentiated tumours composed of large cells No histological evidence of glandular or squamous differentiation BUT on electron microscopy many show some evidence of glandular, squamous or neuroendocrine differentiation i.e are probably very poorly differentiated adeno/squamous cell carcinomas Poorer prognosis

Answer 146

Site Often central near bronchi Behaviour 80% present with advanced disease Although very chemosensitive, have an abysmal prognosis Paraneoplastic syndromes Histology Small poorly differentiated cells p53 and RB1 mutations common

Answer 147

Small cell lung carcinoma – Survival 2-4 months untreated – 10-20 months with current therapy ``` Non-small cell lung carcinoma Early Stage 1: 60% 5yrs Late Stage 4: 5% 5yrs Less chemosensitive 20-30% have early stage tumours for surgical resection ```

Answer 148

Some adenocarcinomas show a variety molecular changes which can be targeted by specific therapies EFGR ALK Ros1 In contrast some patients with squamous cell carcinoma develop fatal haemorrhage with some drugs (Bevacizumab)

Answer 149

X-ray Cytology - bronchial washings/sputum, endoscopic fine needle aspiration of tumour/lymph nodes Histology - biopsy, percutaneous CT, mediastinoscopy, open biopsy, resection specimen

Answer 150

TKI regulates several pathways including transcription, proliferation, migration and angiogenesis. TKI therapy (gefitinib) --> targets EGFR pathway in EGFR +ve lung cancers. ALK translocation - responds to crizotinib Ros1 translocation

Answer 151

High levels of PD1 or PDL1 protein expression (IHC) may inhibit Immune response. Blocking this will allow PDL1 immune damage to tumour.

Answer 152

``` Adenocarcinoma/NSCLC • EGFR mutation • Responder mutation • Resistance mutation • Alk translocation • Ros1 translocation • PD-L1 expression ``` Squamous cell carcinoma • PDL1 expression

Answer 153

Pathology: cytopathology/biopsy | Lesion aspirated by a 16/18gauge needle

Answer 154

``` Aspirates of breast lumps are coded C1-5: C1 = inadequate C2 = benign C3 = atypia, probably benign C4 = suspicious of malignancy C5 = malignant ```

Answer 155

Intact tissue removed, fixed in formalin, embedded in paraffin wax, thinly sliced, stained with H&E Core biopsies, surgical excisions Takes 24 hours to process. Architectural & cellular detail

Answer 156

Inflammation and dilation of large breast ducts Aetiology unclear Usually presents with nipple discharge Sometimes causes breast pain, breast mass and nipple retraction Cytology of nipple discharge shows proteinaceous material and inflammatory cells only Benign condition with no increased risk of malignancy

Answer 157

``` Acute inflammation in the breast Often seen in lactating women due to cracked skin and stasis of milk May also complicate duct ectasia Staphylococci the usual organism Presents with a painful red breast Drainage & antibiotics usually curative ```

Answer 158

An inflammatory reaction to damaged adipose tissue Caused by trauma, surgery, radiotherapy Presents with a breast mass Benign condition

Answer 159

A group of alterations in the breast which reflect normal, albeit exaggerated, responses to hormonal influences. Very common. Presents with breast lumpiness. No increased risk for subsequent breast carcinoma.

Answer 160

A benign fibroepithelial neoplasm of the breast. Common. Presents as a circumscribed mobile breast lump in young women aged 20-30. Simple “shelling out” curative.

Answer 161

A benign fibroepithelial neoplasm of the breast. Common. Presents as a circumscribed mobile breast lump in young women aged 20-30. Simple “shelling out” curative.

Answer 162

A group of potentially aggressive fibroepithelial neoplasms of the breast. Uncommon tumours. Present as enlarging masses in women aged over 50. Some may arise within pre-existing fibroadenomas. Vast majority behave in a benign fashion but a small proportion can behave more aggressively.

Answer 163

A benign papillary tumour arising within the duct system of the breast. Arise within small terminal ductules (peripheral papillomas) or larger lactiferous ducts (central papillomas).

Answer 164

Common. Seen mostly in women aged 40-60. Central papillomas present with nipple discharge. Peripheral papillomas may remain clinically silent if small. Excision of involved duct is curative.

Answer 165

A benign sclerosing lesion characterised by a central zone of scarring surrounded by a radiating zone of proliferating glandular tissue. Range in size from tiny microscopic lesions to large clinically apparent masses. Lesions >1 cm are sometimes called “complex sclerosing lesions”.

Answer 166

Reasonably common lesions. Thought to represent an exuberant reparative phenomenon in response to areas of tissue damage in the breast. Usually present as stellate masses on screening mammograms which may closely a carcinoma. Excision is curative.

Answer 167

Reasonably common lesions. Thought to represent an exuberant reparative phenomenon in response to areas of tissue damage in the breast. Usually present as stellate masses on screening mammograms which may closely a carcinoma. Excision is curative.

Answer 168

A diverse group of intraductal proliferative lesions of the breast associated with an increased risk, of greatly different magnitudes, for subsequent development of invasive breast carcinoma. Microscopic lesions which usually produce no symptoms. Diagnosed in breast tissue removed for other reasons or on screening mammograms if they calcify.

Answer 169

Emerging genetic data suggests FEA may represent the earliest morphological precursor to low grade ductal carcinoma in situ. 4 times relative risk of developing cancer

Answer 170

Current evidence suggests that in situ lobular neoplasia is a risk factor for subsequent invasive breast carcinoma in either breast in a minority of women. The relative risk is quoted as between 7-12 times that expected in women without lobular neoplasia.

Answer 171

A neoplastic intraductal epithelial proliferation in the breast with an inherent, but not inevitable, risk of progression to invasive breast carcinoma. Common. Incidence has markedly increased since the introduction of breast screening programmes.

Answer 172

85% are detected on mammography as areas of microcalcification. 10% produce clinical findings such as a lump, nipple discharge, or eczematous change of the nipple (Paget’s disease of the nipple). 5% are diagnosed incidentally in breast specimens removed for other reasons. Subclassified histologically into low, intermediate and high grade.

Answer 173

Treatment is surgical excision. Complete excision with clear margins is curative. Recurrence is more likely with extensive disease and high grade DCIS.

Answer 174

A group of malignant epithelial tumours which infiltrate within the breast and have the capacity to spread to distant sites. The most common cancer in women with a lifetime risk of 1 in 8. Incidence rates rise rapidly with increasing age, such that most cases occur in older women.

Answer 175

Early menarche, late menopause, increased weight, high alcohol consumption, oral contraceptive use, and a positive family history are all associated with increased risk. About 5% show clear evidence of inheritance. BRCA mutations cause a lifetime risk of invasive breast carcinoma of up to 85%.

Answer 176

Most cases present symptomatically with a breast lump. An increasing proportion of asymptomatic cases are detected on screening mammography.

Answer 177

Recently described type of carcinoma following genetic analysis of breast carcinomas Histologically characterised by sheets of markedly atypical cells with a prominent lymphocytic infiltrate Central necrosis is common Immunohistochemically characterised by positivity for “basal” cytokeratins CK5/6 and CK14 Often associated with BRCA mutations Seem to have particular propensity to vascular invasion and distant metastatic spread

Answer 178

All invasive breast cancers are graded histologically by assessing: 1) tubule formation 2) nuclear pleomorphism 3) mitotic activity Each parameter is scored from 1-3 and the three values are added together to produce total scores from 3-9. 3-5 points = grade 1 (well differentiated). 6-7 points = grade 2 (moderately differentiated). 8-9 points = grade 3 (poorly differentiated).

Answer 179

``` Oestrogen receptor (ER) Progesterone receptor (PR) Her2 status ``` - Low grade tumours tend to be ER/PR positive and Her2 negative - High grade tumours tend to be ER/PR negative and Her2 positive - Basal-like carcinomas are often ER/PR/Her2 negative (“triple negative”)

Answer 180

The single most important prognostic factor is the status of the axillary lymph nodes Other important factors include tumour size, histological type, and histological grade

Answer 181

- The aim of screening is to pick up DCIS or early invasive carcinomas - Women aged 47-73 are invited for screening every three years - The screening test is a mammogram which looks for abnormal areas of calcification or a mass within the breast

Answer 182

Core biopsies taken from the breast as part of the screening programme are given a B code from 1-5: ``` B1 = normal breast tissue B2 = benign abnormality B3 = lesion of uncertain malignant potential B4 = suspicious of malignancy B5 = malignant (B5a = DCIS B5b = invasive carcinoma) ```

Answer 183

Refers to enlargement of the male breast Pubertal boys and older men aged over 50 Idiopathic or associated with drugs (both therapeutic and recreational) Histologically the breast ducts show epithelial hyperplasia with typical finger-like projections extending into the duct lumen The periductal stromal is often cellular and oedematous Benign, no risk of malignancy

Answer 184

Carcinoma of the male breast is rare (0.2% of all cancers) Median age at diagnosis 65 years old Most present with a palpable lump Histologically the tumours show similar features to female breast cancers

Answer 185

33% - 1.8 billion

Answer 186

Non-motile rod-shaped bacteria Relatively slow-growing compared to other bacteria Long-chain fatty (mycolic) acids, complex waxes & glycolipids in cell wall - structural rigidity, staining characteristics Acid alcohol fast

Answer 187

Water Soil

Answer 188

``` AKA Environmental Atypical Ubiquitous in nature Varying spectrum of pathogenicity Little risk of person-to-person transmission Commonly resistant to classical anti-TB Rx May be found colonizing humans ```

Answer 189

``` Mycobacterium avium complex Immunocompetent - May invade bronchial tree - Pre-existing bronchiectasis or cavities Immunosuppressed - Disseminated infection Mycobacterium chimera - Associated to cardiothoracic procedures M. marinum - Swimming pool granuloma M. ulcerans - Skin lesions e.g. Bairnsdale ulcer, Buruli ulcer - Chronic progressive painless ulcer ```

Answer 190

M. abscessus, M. chelonae, M. fortuitum Skin & soft tissue infections - tattoo associated outbreaks In hospital settings, isolated from BCs - vascular catheters & other devices, plastic surgery complications CF and bronchiectasis

Answer 191

``` BTS guidelines 2017 American Thoracic Society/IDSA guidelines 2020 Lung disease Clinical: pulmonary symptoms, nodular/cavitary opacities, multifocal bronchiectasis with multiple small nodules Exclusion of other diagnoses Microbiologic: Positive culture >1 sputum samples OR +ve BAL OR +ve biopsy with granulomata ```

Answer 192

Susceptibility testing results may not reflect clinical usefulness ``` MAC Clarithromycin/azithromycin Rifampicin Ethambutol +/- Amikacin/streptomycin ``` Rapid-growing NTM Based on susceptibility testing Usually macrolide-based

Answer 193

Multisystem disease Common worldwide Most common cause of death by infectious agent – pre COVID-19 ~2 million deaths each year Increasing incidence since 1980s Most common opportunistic infection in HIV Immigration

Answer 194

``` Droplet nuclei/airborne <10µm particles Suspended in air Reach lower airway macrophages Infectious dose 1-10 bacilli 3000 infectious nuclei - cough, talking 5 mins Air remains infectious 30 mins ```

Answer 195

``` Primary TB Usually asymptomatic Ghon focus/complex Limited by CMI Rare allergic reactions include EN Occasionally disseminated/miliary Latent TB Reactivation ```

Answer 196

``` Reactivation or exogenous re-infection 5-10% risk per lifetime Risk factors for reactivation Immunosuppression Chronic alcohol excess Malnutrition Ageing Clinical presentation Pulmonary or extra-pulmonary ```

Answer 197

Caseating granulomata Lung parenchyma Mediastinal LNs Commonly upper lobe

Answer 198

- Lymphadenitis - Gastrointestinal - Peritoneal - Genitourinary - Bone and joint - Miliary TB - Tuberculous meningitis

Answer 199

``` Sputum 60% sensitivity Increased 10% & 2% with 2nd & 3rd sputa Gastric aspirates in kids Other specimens centrifuged Rapid Operator dependent ```

Answer 200

Rapid diagnosis of smear +ve | Drug resistance mutations

Answer 201

Detection of antigen-specific IFN-γ production ELISpot Quantiferon No cross-reaction with BCG Cannot distinguish latent & active TB Similar problems with sensitivity & specificity

Answer 202

First-line medication: Rifampicin Isoniazid Pyrazinamide Ethambutol ``` Second-line medication: Quinolones (Levofloxacin) Injectables Capreomycin, kanamycin, amikacin Ethionamide/Prothionamide Cycloserine PAS Linezolid Clofazimine Beta-lactams Bedaquiline Delamanid ```

Answer 203

Rifampicin - raised transaminases & induces cytochrome P450, orange secretions Isoniazid (H) - peripheral neuropathy (pyridoxine 10mg od), hepatotoxicity Pyrazinamide (Z) - hepatotoxicity Ethambutol (E) - visual disturbance

Answer 204

Directly observed therapy (DOT) | Video observed therapy (VOT)

Answer 205

Directly observed therapy (DOT) | Video observed therapy (VOT)

Answer 206

Multi-drug resistant tuberculosis

Answer 207

Resistant to rifampicin & isoniazid Extremely drug-resistant TB (XDR) Also resistant to fluoroquinolones & at least 1 injectable Spontaneous mutation + inadequate treatment 4/5 drug regimen, longer duration - quinolones, aminoglycosides, PAS, cycloserine, ethionamide

Answer 208

``` Previous TB Rx HIV+ Known contact of MDR TB Failure to respond to conventional Rx >4 months smear +ve/>5 months culture +ve ```

Answer 209

``` Disturbance of normal function (diarrhoea, constipation) Bleeding Perforation/fistula formation Obstruction +/- Systemic illness ```

Answer 210

Atresia/stenosis Duplication Imperforate anus

Answer 211

Intestinal atresia is a broad term used to describe a complete blockage or obstruction anywhere in the intestine.

Answer 212

Absence of ganglion cells in myenteric plexus Distal colon fails to dilate 80% male Constipation, abdominal distension, vomiting, ‘overflow’ diarrhoea Associated with Down’s syndrome (2%) RET proto-oncogene Cr10 + others

Answer 213

Clinical impression Biopsy of affected segment. Hypertrophied nerve fibers but no ganglia. Treatment: resection of affected (constricted) segment (frozen section)

Answer 214

``` Obstruction: Adhesions Herniation Extrinsic mass Volvulus ``` Diverticular disease

Answer 215

``` Complete twisting of a loop of bowel at mesenteric base, around vascular pedicle intestinal obstruction +/- infarction small bowel (infants) sigmoid colon (elderly) ```

Answer 216

``` High incidence in West Low fibre diet High intraluminal pressure ‘Weak points’ in wall of bowel 90% occur in left colon ```

Answer 217

``` Pain Diverticulitis Gross perforation Fistula (bowel, bladder, vagina) Obstruction ```

Answer 218

``` Acute colitis Infection (bacterial, viral, protozoal etc.) Drug/toxin (esp.antibiotic) Chemotherapy Radiation ``` Chronic colitis Crohn’s Ulcerative colitis TB

Answer 219

``` Secretory diarrhoea (toxin) Exudative diarrhoea (invasion and mucosal damage) Severe tissue damage + perforation Systemic illness (biopsy) ```

Answer 220

Antibiotic associated colitis Acute colitis with pseudomembrane formation Caused by protein exotoxins of C.difficile

Answer 221

Histology: Characteristic microscopic features on biopsy Laboratory: C. difficile toxin stool assay Therapy: Metronidazole or Vancomycin

Answer 222

Acute or chronic Most common vascular disorder of the intestinal tract Usually occurs in segments in “watershed” zones, e.g. splenic flexure (SMA and IMA) and the rectosigmoid (IMA and internal iliac artery) Mucosal, mural, transmural (perforation)

Answer 223

Arterial Occlusion: atheroma, thrombosis, embolism Venous Occlusion: thrombus, hypercoagulable states Small Vessel Disease: DM, cholesterol emboli, vasculitis Low Flow States: CCF, haemorrhage, shock Obstruction: hernia, intussusception, volvulus, adhesions

Answer 224

?Genetic predisposition (familial aggregation, twin studies, HLA) ?Infection (Mycobacteria, Measles etc.) ?Abnormal host immunoreactivity ->Inflammation

Answer 225

``` Western populations Occurs at any age but peak onset in teens/twenties White 2-5x > non-white Higher incidence in Jewish population Smoking Whole of GI tract can be affected (mouth to anus) ‘Skip lesions’ Transmural inflammation Non-caseating granulomas Sinus/fistula formation ‘Fat wrapping’ Thick ‘rubber-hose’ like wall Narrow lumen ‘Cobblestone mucosa’ Linear ulcers Fissures Abscesses ```

Answer 226

``` Arthritis Uveitis Stomatitis/cheilitis Skin lesions Pyoderma gangrenosum Erythema multiforme Erythema nodosum ```

Answer 227

``` Slightly more common than Crohn’s Whites > non-whites Peak 20-25 years but can affect any age Involves rectum and colon in contiguous fashion May see mild ‘backwash ileitis’ and appendiceal involvement but small bowel and proximal GI tract not affected. Inflammation confined to mucosa Bowel wall normal thickness Shallow ulcers ```

Answer 228

Severe haemorrhage Toxic megacolon Adenocarcinoma (20-30 x risk)

Answer 229

``` Arthritis Myositis Uveitis/iritis Erythema nodosum, pyoderma gangrenosum Primary Sclerosing Cholangitis (5.5% in pancolitis) ```

Answer 230

Non-neoplastic polyps Neoplastic epithelial lesions: adenoma, adenocarcinoma, carcinoid tumour Mesenchymal lesions: stromal tumours, lipoma, sarcoma Lymphoma

Answer 231

1) Polyps - Non-neoplastic (Hyperplastic) Inflammatory (“pseudo-polyps”) Hamartomatous (juvenile, Peutz Jeghers) 2) Polyps - Neoplastic Tubular adenoma Tubulovillous adenoma Villous adenoma

Answer 232

Excess epithelial proliferation + dysplasia 20-30% prevalence before age 40 40-50% prev. after age 60

Answer 233

Tubular Villous Tubulovillous

Answer 234

Size of polyp (> 4 cm approx 45% have invasive malignancy) Proportion of villous component Degree of dysplastic change within polyp

Answer 235

(Peutz Jeghers) Familial adenomatous polyposis: Gardner’s, Turcot Hereditary non polyposis colon cancer

Answer 236

Autosomal dominant - average onset is 25 years old Adenomatous polyps, mostly colorectal Minimum 100 polyps, average ~1,000 polyps Chromosome 5q21, APC tumour suppressor gene Virtually 100% will develop cancer within 10 to 15 years; 5% periampullary Ca

Answer 237

Same clinical, pathological, and etiologic features as FAP, with high Ca risk Distinctive extra-intestinal manifestations: - multiple osteomas of skull & mandible - epidermoid cysts - desmoid tumors - dental caries, unerrupted supernumery teeth - post-surgical mesenteric fibromatoses

Answer 238

Uncommon autosomal dominant disease 3-5% of all colorectal cancers 1 of 4 DNA mismatch repair genes involved (mutation) Numerous DNA replication errors (RER) Onset of colorectal cancer at an early age High frequency of carcinomas proximal to splenic flexure Poorly differentiated and mucinous carcinoma more frequent Multiple synchronous cancers Presence of extracolonic cancers (endometrium, prostate, breast, stomach)

Answer 239

98% are adenocarcinoma Age: 60-79 years If < 50yrs consider familial syndrome Western population

Answer 240

``` Grade = level of differentiation Dukes’ staging A = confined to wall of bowel B = through wall of bowel C = lymph node metastases D = distant metastases TNM (tumour, nodes, metastases) ```

Answer 241

Acute inflammation of the pancreas caused by aberrant release of pancreatic enzymes

Answer 242

- Duct obstruction - gallstones, trauma, tumours - Metabolic/toxic - alcohol, drugs, high Ca, high lipids - Poor blood supply - shock, hypothermia - Infection/inflammation - viruses - Autoimmune - Idiopathic

Answer 243

Gallstone stuck distal to where the common bile duct and pancreatic ducts join leads to: reflux of bile up the pancreatic duct followed by damage to acini and release of proenzymes which then become activated

Answer 244

Alcohol leads to spasm/oedema of Sphincter of Oddi and the formation of a protein rich pancreatic fluid which obstructs the pancreatic ducts

Answer 245

Acinar cells

Answer 246

Periductal - necrosis of acinar cells near ducts (usually secondary to obstruction) Perilobular – necrosis at the edges of the lobules (usually due to poor blood supply) Panlobular – develops duct obstruction or direct acing injury

Answer 247

Activated enzymes --> acinar necrosis --> enzyme release etc.

Answer 248

Lipases -> fat necrosis (calcium ions bind to free fatty acids forming soaps which are seen as yellow- white foci)

Answer 249

Complications Pancreatic : pseudocyst, abscess Systemic: shock, hypoglycaemia, hypocalcaemia Prognosis Overall mortality up to 50% for haemorrhagic pancreatitis

Answer 250

Relapsing or persistent, associated with acute pancreatitis in half of cases. Relatively uncommon Mortality 3% per year

Answer 251

Metabolic/toxic - Alcohol, Haemochromatosis Duct obstruction - Gallstones Tumours, Abnormal pancreatic duct anatomy, Cystic fibrosis (“mucoviscoidosis”) Idiopathic - Autoimmune

Answer 252

Alcohol - 80%

Answer 253

Chronic inflammation with parenchymal fibrosis and loss of parenchyma Duct strictures with calcified stones with secondary dilatations

Answer 254

Chronic inflammation with parenchymal fibrosis and loss of parenchyma Duct strictures with calcified stones with secondary dilatations

Answer 255

* Malabsorption * Diabetes mellitus * Pseudocyts * Carcinoma of the pancreas

Answer 256

• Associated with acute and/ or chronic pancreatitis • Lined by fibrous tissue (no epithelial lining), contain fluid rich in pancreatic enzymes or necrotic material • Connect with pancreatic ducts • May resolve, compress adjacent structures, become infected or perforate

Answer 257

Characterised by large numbers of IgG4 positive plasma cells. May involve the pancreas, bile ducts and almost any other part of the body.

Answer 258

Carcinomas Ductal Acinar Cystic neoplasms Serous cystadenoma Mucinous cystic neoplasm Pancreatic neuroendocrine tumours (Islet cell tumours)

Answer 259

Carcinoma - ductal (85% of all neoplasms)

Answer 260

* Smoking * BMI and dietary factors * Chronic pancreatitis * Diabetes

Answer 261

Arise from dysplastic ductal lesions: Pancreatic Intraductal Neoplasia (PanIN) Intraducal Mucinous Papillary Neoplasm K-Ras mutations in 95% of cases

Answer 262

Macroscopic Appearance Gritty and grey Invades adjacent structures Tumours in the head present earlier Microscopic Appearance Adenocarcinomas: mucin secreting glands set in desmoplastic stroma

Answer 263

* Head (60%) * Body * Tail * Diffuse

Answer 264

* Direct: Bile ducts, duodenum * Lymphatic: Lymph nodes * Blood: Liver * Serosa: Peritoneum

Answer 265

Due to spread Chronic pancreatitis Venous thrombosis (“migratory thrombophlebitis”)

Answer 266

* Contain serous or mucin secreting epithelium (cf. ovarian tumours) * Usually benign

Answer 267

* Usually non-secretory * Contain neuroendocrine markers e.g. chromogranin * Behaviour difficult to predict, * May be associated with the Multiple Endocrine Neoplasia (MEN) 1 syndrome

Answer 268

* Insulinomas (derived from beta cells) | * Commonest type of secretory tumour

Answer 269

20% of adults in the West

Answer 270

Age and gender: increasing age, F>M Ethnic and geographic: e.g. Native Americans Hereditary: e.g. disorders of bile metabolism Drugs e.g. oral contraceptive Acquired disorders e.g. rapid weight loss

Answer 271

* Cholesterol (more than 50% cholesterol) - may be single, mostly radiolucent * Pigment (contain calcium salts of unconjugated bilirubin) - multiple, mostly radio-opaque

Answer 272

* Bile duct obstruction * Acute and chronic cholecystitis * Gall bladder cancer * Pancreatitis

Answer 273

Acute cholecystitis • Acute inflammation • 90% associated with gall stones ``` Chronic cholecystitis • Chronic inflammation • Fibrosis • Diverticula – Rokitansky-Aschoff sinuses • 90% contain gall stones ```

Answer 274

* Adenocarcinomas | * 90% associated with gall stones

Answer 275

* Pneumocystis jiroveci: pneumonia * CMV: especially retina and GIT * Candida * Tuberculosis and atypical mycobacteria * Cryptococcus: meningitis * Toxoplasma gondii: encephalitis and mass lesions * JC papovavirus: progressive multifocal leukoencepalopathy * Herpes simplex * Cryptosporidium, Isospora belli, microsporidia: GIT

Answer 276

Oesophageal ulcer

Answer 277

CMV nuclear inclusion

Answer 278

Kaposi’s sarcoma: HHV-8 Lymphoma: systemic, CNS or body cavity based B cell lymphomas EBV Others: Squamous cell carcinoma Anus and cervix HPV

Answer 279

A. The dermis is expanded by a solid tumour B. Fascicles of relatively monomorphic spindled cells, with slit-like vascular channels containing erythrocytes C. The nuclei of the tumour cells demonstrate immunoreactivity for HHV-8

Answer 280

Progressive encephalopathy = AIDS dementia complex CNS lymphoma - perivascular lymphomatous infiltrate

Answer 281

Caseating granulomas Demonstration of acid fast bacilli Cavitating TB Granuloma with caseous necrosis

Answer 282

``` Lung Lymph node Bone: e.g. vertebra Heart: e.g. pericarditis GIT: e.g. peritonitis CNS: e.g. meningitis etc. ```

Answer 283

Giant cells on the outside | Epithelioid cells inside

Answer 284

* Lung: scattered granulomas, heal with fibrosis * Lymph nodes: usually hilar and mediastinal * Spleen * Liver * Heart * Joints * Bone marrow * Skin: nodules, plaques or macules * Eyes: iritis, choroid retinitis, lacrimal glands * CNS * Salivary glands

Answer 285

Inflammation dominated by IgG4 antibody producing plasma cells Fibrosis, obliteration of veins

Answer 286

Plasma cell rich, inflammatory infiltrate | Immunohistochemistry for IgG4

Answer 287

* Salivary and lacrimal glands: Mikulicz syndrome * Thyroid: Riedel thyroiditis * Peritoneum: Retroperitoneal fibrosis * Liver: Biliary obstruction * Pancreas: Autoimmune pancreatitis * Mass lesions: Inflammatory pseudotumour

Answer 288

• Liver: fatty change (steatosis), fatty liver hepatitis (steatohepatitis), cirrhosis, liver cell cancer (hepatocellular carcinoma) • GI Tract: acute gastritis, oesophageal varices • Nervous system: peripheral neuropathy, Wernicke-Korsakoff syndrome etc. • Cardiovascular system: dilated cardiomyopathy, hypertension, atheroma (and decreases it!) • Pancreas: acute pancreatitis, chronic pancreatitis • Fetal alcohol syndrome • Cancer: oral cavity, pharynx. oesophagus, liver and breast

Answer 289

Normal liver --> steatosis --> steatohepatitis --> fibrosis --> cirrhosis --> hepatocellular

Answer 290

* Pancreas: duct obstruction, exocrine atrophy * Salivary glands: duct obstruction, atrophy * Intestine: meconium ileus * Liver: biliary obstruction, cirrhosis * Lung: bronchial obstruction, superimposed infection with abscess formation (Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa) * Male genital tract: infertility, absence of the vas

Answer 291

Deposition of an abnormal proteinaceous substance in non branching fibrils, 7.5-10nm diameter Always contains P component Beta-pleated sheet structure Resistant to enzymic degradation

Answer 292

AA - derived from serum amyloid A e.g. Crohn’s Disease, Rheumatoid arthritis AL - derived from light chains e.g. multiple myeloma, B Cell lymphoma Transthyretin e.g. mutation Beta2-macroglobulin – peritoneal dialysis Abeta2 protein - Alzheimer’s Insulin, calcitonin – endocrine tumours

Answer 293

* Proteinuria, renal failure * Restrictive cardiomyopathy, arrhythmias * Autonomic neuropathy * Carpal tunnel syndrome * Macroglossia * Bleeding on injury * Also deposited in blood vessels, endocrine organs, liver, spleen

Answer 294

Z-line - squamo-epithelial junction | Epithelium, submucosa, muscularis extra

Answer 295

Body: gastric mucosa (foveolar, mucin secreting), specialised glands in lamina propria, muscularis mucosae NO goblet cells Duodenum Glandular epithelium with goblin cells (intestinal-like) Villous architecture - ratio of 2:1 of villous to crypt

Answer 296

- Ulceration - Haemorrhage - Perforation - Stricture - Barrett's oesophagus

Answer 297

Metaplasia: squamous epithelium by metaplastic columnar epithelium 2 types: - w/o goblet cells: gastric metaplasia - with goblet cells: intestinal type metaplasia

Answer 298

Adenocarcinoma

Answer 299

Alcohol | Smoking

Answer 300

Inflammation of gastric mucosa: Acute Chronic

Answer 301

Chemical - aspirin/NSAIDs - alcohol - corrosives Infection - H. pylori

Answer 302

Autoimmune: anti parietal antibodies Bacterial: H. pylori Chemical: NSAIDs, bile reflux, antrum

Answer 303

CLO-IM-dysplasia Adenocarcinoma Lymphoma (MALToma)

Answer 304

Bleeding: anaemia, shock (massive haemorrhage) Perforation: peritonitis

Answer 305

Has some of the cytological and histological features but has not invaded the basement membrane

Answer 306

``` Japan Chile Italy China Portugal Russia ``` Survival is 15%

Answer 307

95% adenocarcinoma 5%: - squamous cell carcinoma - MALToma - gastrointestinal stromal tumour - neuroendocrine tumour

Answer 308

Intestinal - well differentiated Diffuse - poorly differentiated (Linitis plastic), signet ring cell carcinoma

Answer 309

- Chronic inflammation - chronic immune stimulation - B cell (marginal zone) lymphocytes Treatment: treat H. pylori

Answer 310

Increased acid production in the stomach - spills over to duodenum. Chronic inflammation and gastric metaplasia with helicobacter infection --> erosive duodenitis

Answer 311

- Immunosuppressed - CMV - Cryptosporidiosis - Giardia lamblia infection - Whipple's disease - Tropheryma whippelii

Answer 312

- Villous atrophy - Crypt hyperplasia - Increased intraepithelial lymphocytes (normally around 20%)

Answer 313

Endomysial antibodies and tissue transglutaminase antibodies Duodenal biopsies: gluten rich diet shows villous atrophy, glutin showing normal villi

Answer 314

Coeliac disease - T-cell origin, enteropathy associated T-cell lymphoma

Answer 315

Tumours of the Central Nervous System: - Brain and coverings - Spinal cord and coverings - Pituitary gland Tumours of the Peripheral Nervous System: - Small nerves in any organ – usually neurofibromas of soft tissue or skin - Large nerves: cranial and spinal nerve schwannomas (acoustic neuroma most common) - Most are benign tumours

Answer 316

Primary CNS tumours are rare in adults (1-2%) | In children, most common tumours (25%) and most common cause of cancer death

Answer 317

EXTRA-AXIAL (COVERINGS) Tumours of bone, cranial soft tissue, meninges, nerves INTRA-AXIAL (PARENCHYMA) Derived from the normal cell populations of the CNS: glia, neurons, neuroendocrine cells... Derived from other cells types lymphomas, germ cell tumours…

Answer 318

Less than 5%

Answer 319

Neurofibromatosis 1 (17q11) Neurofibromatosis 2 (22q12) Schwannomatosis (22q11) Tuberous Sclerosis 1 (9q34) and 2 (16p13) Brain tumour polyposis syndrome 1 (PMS2 7p22, MSH6 2p16) and 2 (APC 5q21) Li-Fraumeni (p53 17p13) Cowden syndrome (PTEN,10q23.3) Gorlin syndrome (PTCH1, 9q31) Von Hippel Lindau (3p25) Rhabdoid tumour predisposition (SMARCB1, 22q11)

Answer 320

Intracranial hypertension Headache, vomiting Change in mental status Supratentorial Focal neurological deficit Seizures Personality changes Subtentorial Cerebellar Ataxia Long tract signs Cranial nerve palsy

Answer 321

RADIOTHERAPY Low and high-grade gliomas, metastases, selected benign tumours External fractionated RT, stereotactic radiosurgery CHEMOTHERAPY Mainly for high-grade gliomas (temozolomide) and lymphomas Biological agents (EGFR inhibitors, PD-L1 inhibitors etc)

Answer 322

Craniotomy for debulking –subtotal and complete resections (as much tumour as possible) Open biopsy – inoperable but approachable tumours (about 1cm) – usually representative Stereotactic biopsy – if open biopsy not indicated (about 0.5cm tissue) – tissue may be insufficient

Answer 323

Tumour type: putative cell of origin or lineage of differentiation Tumour grade: tumour aggressiveness/malignancy degree Molecular profile: expanded compared to previous 4th edition (genetics, methylome), most tumour types have molecular markers INTEGRATED HISTOLOGICAL AND MOLECULAR DIAGNOSIS No staging (TNM)

Answer 324

Astrocytes - astrocytoma (glioma) Oligodendrocytes - oligodendroglioma (glioma) Ependyma – ependymoma Neurons - neurocytoma Embryonal cells -medulloblastoma Meningothelial cells – meningioma Schwann cells – schwannoma, neurofibroma

Answer 325

Diffuse gliomas - grades ≥ 2 - malignant progression Circumscribed gliomas - grades 1-2 - rare malignant transformation

Answer 326

Diffuse gliomas - adults Circumscribed gliomas - children

Answer 327

Diffuse gliomas Astrocytomas (grades 2-4) Oligodendrogliomas (grades 2-3) ``` Circumscribed gliomas Pilocytic astrocytoma (grade 1) Pleomorphic xanthoastrocytoma (grade 2) Subependymal giant cell astrocytoma (grade 1) Ependymomas (usually) ```

Answer 328

DIFFUSE GLIOMAS IDH1/2 mutations (30%) H3 mutations (1%) CIRCUMSCRIBED GLIOMAS MAPK pathway mutations (BRAF, NF1, FGFR1)

Answer 329

Usually 1st and 2nd decade - 20% of CNS tumours below 14 years Often cerebellar, optic-hypothalamic, brainstem

Answer 330

MRI: well circumscribed, cystic, enhancing lesion Histology: piloid “hairy” cell Very often Rosenthal fibres Slowly growing: low mitotic activity Genetic profile: BRAF mutation (KIAA1549-BRAF fusion) in 70% of PA

Answer 331

IDH mutation is associated with longer survival and a better response to chemotherapy and radiotherapy

Answer 332

Young adults 20-40, cerebral hemispheres MRI: T1 hypointense, T2 hyperintense, non-enhancing lesion Low choline/creatinine ratio at MRSpec Histology: low to moderate cellularity Mitotic activity is low No vascular proliferation and necrosis Genetic profile: point mutation in IDH1/2

Answer 333

Most patients >50 years, cerebral hemispheres Most aggressive and most frequent glioma; incidence ↑ with age

Answer 334

MRI: heterogeneous, enhancing post-contrast Histology: high cellularity and high mitotic activity, microvascular proliferation, necrosis Genetic profile: IDH1 wildtype. Common mutations in TERT, PTEN, EGFR and EGFR ampl

Answer 335

38% of primary CNS tumours Rare in patients < 40, incidence ↑ with age Originate from meningothelial cells of the arachnoid mater Any site of craniospinal axis, can be multiple (NF2) MRI: extraxial, isodense, contrast-enhancing 80% Grade 1: benign, recurrence <25% 20% Grade 2: atypical, recurrence 25-50% 1% Grade 3: malignant, recurrence 50-90%

Answer 336

Crucial: determines grade mitoses / 10HPF (of 0.16mm2) and how fast it can proliferate <4 = grade 1 4-20 = grade 2 > 20 = grade 3

Answer 337

Lung ca, breast ca, melanoma, renal cell ca

Answer 338

CNS tumour which originates from neuroepithelial cells/neuronal precursors of the cerebellum or dorsal brainstem Rare (2 per 1,000,000 year), but second most common brain malignancy in children; also in young adults

Answer 339

4 histological subtypes: classic, nodular/desmoplastic, extensive nodularity, large cell anaplastic

Answer 340

4 histological subtypes: classic, nodular/desmoplastic, extensive nodularity, large cell anaplastic

Answer 341

3 molecular subtypes by transcriptome or methylome profiling: WNT-activated, SHH-activated, nonWNT/nonSHH

Answer 342

Most tumours have characteristic patterns of DNA methylation of CpG islands The methylation signature is stable and reflects the tumour cell of origin or early transformed cells - Gives information on tumour type not progression/grade The DNA methylation status of a subset of CpG islands is assessed with DNA arrays and compared to a reference dataset (“Classifier”)

Answer 343

Vasogenic – disruption of the blood brain barrier Cytotoxic – secondary to cellular injury e.g. hypoxia/ischaemia

Answer 344

Cerebrospinal Fluid (CSF) flows through the four ventricles and then flows between the meninges in an area called the subarachnoid space. CSF cushions the brain and spinal cord against forceful blows distributes important substances and carries away waste products.

Answer 345

Non-communicating involves obstruction of flow of CSF Communicating involves no obstruction but problems with reabsorption of CSF into venous sinuses

Answer 346

7–15mmHg

Answer 347

Enclosed bony box- pressure can increase because of localised (space occupying) lesions, oedema or both Increased pressure forces brain against unyielding bony wall of skull and inflexible dural folds This results in herniation of brain structures where space is available

Answer 348

- subfalcine - transtentorial - uncal - tonsillar

Answer 349

A stroke is a clinical syndrome characterised by rapidly developing clinical symptoms and/or signs of focal, and at times global loss of cerebral function, with symptoms lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin This definition includes stroke due to cerebral infarction, primary intracerebral haemorrhage, intraventricular haemorrhage and most cases of subarachnoid haemorrhage It excludes subdural haemorrhage, epidural haemorrhage, intracerebral haemorrhage (ICH) or infarction caused by infection or tumour

Answer 350

TIA is a warning stroke that should be taken very seriously TIA is caused by a clot; the blockage is temporary Most TIAs last less than five minutes; the average is about a minute. Unlike a stroke, when a TIA is over, there is usually no permanent injury to the brain

Answer 351

1/3 of those with TIA get significant infarct within 5 years

Answer 352

Occur anywhere in the CNS Become symptomatic between 2nd and 5th decade (mean age 31.2 years) Present with haemorrhage, seizures, headache, focal neurological deficits High pressure – MASSIVE BLEEDING

Answer 353

Seen on angiography Morbidity after rupture 53-81% - high in eloquent areas Mortality 10-17.6% Treatment: surgery, embolization, radiosurgery

Answer 354

Well-defined malformative lesion composed of closely packed vessels with no parenchyma interposed between vascular spaces. Can be found anywhere in the CNS, usually symptomatic after age 50.

Answer 355

Present with headache, seizures, focal deficits, haemorrhage Low pressure – recurrent bleeds Treatment: surgery

Answer 356

Rupture of a berry aneurysm; present in 1% of general population 80 % - internal carotid artery bifurcation, 20% occur within the vertebro-basilar circulation 30% of patients have multiple aneurysms Greatest risk of rupture when 6-10mm diameter Present with sudden onset of severe headache, vomiting, loss of consciousness

Answer 357

Tissue death due to ischaemia Commonest form of cerebrovascular disease 70-80% of strokes

Answer 358

Cerebral atherosclerosis most common cause: hypertension, diabetes, smoking are major risks factors

Answer 359

a) Focal cerebral ischaemia: defined vascular territory | b) Global cerebral ischaemia: systemic circulation fails

Answer 360

Worst atherosclerosis in larger vessels (extracerebral arteries) – thrombosis, often near carotid bifurcation or in basilar artery Other cause - emboli (intracerebral arteries) Usually from heart or atherosclerotic plaques Embolic occlusion usually in middle cerebral artery branches

Answer 361

- Fractures (may extend to base. of skull --> otorrhea, rhinorrhea - Contusions --> brain collides with skull and surface bruising, Pia mater torn and becomes laceration - Diffuse axonal injury --> Shear & tensile forces affecting axons, commonest cause of coma (when no bleed), midline structures particularly affected e.g. corpus callosum, rostral brainstem and septum pellucidum

Answer 362

A series of diseases with common molecular pathology Transmissible factor No DNA or RNA involved Prion (proteinaceous infectious only)

Answer 363

``` Sporadic neuropsychiatric disorder Patients <45 yrs old Cerebellar ataxia Dementia Longer duration than CJD Linked to BSE ```

Answer 364

Extracellular plaques Neurofibrillary tangles Cerebral amyloid angiopathy (CAA) Neuronal loss (cerebral atrophy)

Answer 365

APP is an integral membrane protein expressed in many tissues, especially in the synapses of neurons: APP consists of a single membrane-spanning domain, a large extracellular glycosylated N-terminus and a shorter cytoplasmic C-terminus.

Answer 366

A-beta --> oligomers --> protofibrils --> fibrils

Answer 367

Hippocampus --> temporal lobe --> parietal lobes

Answer 368

α-synuclein immunostaining is considered as the diagnostic gold standard

Answer 369

Lewy bodies accumulate for a while before symptomatic - so if spotted early can be treated

Answer 370

Multiple system atrophy Progressive supranuclear palsy Corticobasal degeneration

Answer 371

Fronto-temporal atrophy Marked gliosis and neuronal loss Balloon neurons Tau positive Pick bodies

Answer 372

Single gene on 17q21 16 exons Alternative splicing gives rise to 6 isoforms 3R or 4R-tau (microtubule-binding domains) Two further inserts with unknown function Shortest form (3R/0N) foetal

Answer 373

Characterized by atheromatous deposits in and fibrosis of the inner layer of the arteries - atheroma (plaque) is one which protrudes into the vessel lumen

Answer 374

1) Smooth endothelium damaged 2) Platelets stick to damaged tissue. Proliferation of endothelium. Fibrous cap forms on top of endothelium. Deposition of cholesterol (in core). 3) Plaque enlarges, blocking artery. Fatty core.

Answer 375

Raised lesion Soft lipid core White fibrous cap

Answer 376

2 risk factors increase the risk fourfold 3 risk factors increase the risk sevenfold

Answer 377

Constitutional: Age Gender Genetics ``` Modifiable: Hyperlipidaemia Hypertension Cigarette smoking Diabetes ``` Other: inflammation, hyperhomocyteinaemia, metabolic syndrome, lipoprotein, haemostats, lack of exercise, stress, obesity

Answer 378

Chronic inflammatory and healing response of arterial wall to endothelial injury ``` Endothelial injury Lipoprotien accumulation (LDL) Monocyte adhesion to endothelium Monocyte migration into intima -> macrophages & foam cells Platelet adhesion Factor release Smooth muscle cell recruitment Lipid accumulation -> extra & intracellular, macrophages & smooth muscle cells ``` ``` Smooth muscle proliferation Intimal smooth muscle proliferation Some from circulating precursors – (have synthetic & proliferative phenotype) ECM matrix deposition Fatty streak -> mature atheroma & growth PDGF, FGF, TGF-alpha implicated ```

Answer 379

Herpes, CMV, Chlamydia pneumonia

Answer 380

1) Fatty streak: earliest lesion, lipid-filled foamy macrophages, no flow 2) Atherosclerotic plaque: patchy; local flow disturbed, only involve portion of wall, appear eccentric, composed of - cells, lipid, matrix 3) Atheromatous plaque: obstruct, rupture, stenosis, erosion (exposing prothrombin sub endothelial BM)

Answer 381

Lots foam cells or extracellular lipid Thin fibrous cap Few smooth muscle cells Clusters inflammatory cells Adrenalin increases blood pressure & causes vasoconstriction Increases physical stress on plaque Hence emotional stress increases risk of sudden death Circadian periodicity to sudden death (6am-noon)

Answer 382

Leading cause of death worldwide for men and women (7million/year) 90% myocardial ischaemia due to reduced blood flow due to atherosclerosis Long silent progression prior to symptoms Imbalance of supply to demand for oxygenated blood Also less nutrients & less waste removal Therefore less well tolerated than pure hypoxia

Answer 383

``` Sudden change to plaque Platelet aggregation Vasospasm Coagulation Thrombus evolves ```

Answer 384

LAD – 50%, ant wall LV, ant septum, apex RCA - 40%, post wall LV, post septum, post RV LCx - 20%, lat LV not apex

Answer 385

Under 6 hours – normal by histology (CK-MB also normal) 6–24 hrs loss of nuclei, homogenous cytoplasm necrotic cell death 1-4 days – infiltration of polymorphs then macrophages (clear up debris) 5-10 days removal of debris 1-2 weeks granulation tissue, new blood vessels, myofibroblasts, collagen synthesis Weeks-months strengthening, decellularising scar Order of cells: neutrophils, macrophages, angioplasty, fibroblasts and collagen

Answer 386

Clinical importance uncertain Due to oxidative stress, Ca overload, inflammation Arrhythmias common Biochemical abnormalities last days -> weeks Thought to cause “stunned myocardium” – reversible cardiac failure lasting several days

Answer 387

A state when some segments of the myocardium exhibit abnormalities of contractile function - reversed with revascularisation

Answer 388

Contractile dysfunction – 40% infarct-> cardiogenic shock with 70% mortality rate Arrhythmia due to myocardial irritability & conduction disturbance Myocardial rupture - free wall most common, septum less common, papillary muscle least common (at mean 4-5days, range 1-10 days) Pericarditis (Dressler syndrome) 2nd or 3rd day RV infarction Infarct extension – new necrosis adjacent to old Infarct expansion – necrotic muscle stretches ->mural thrombus Mural thrombus Ventricular aneurysm, late -> thrombus, heart failure, arrhythmia, do not rupture Papillary muscle rupture Chronic Ischaemic Heart Disease

Answer 389

Progressive loss of myocytes Dilated heart Causes: Idiopathic Infective – viral myocarditis Toxic: alcohol, chemotherapy (adriamycin, daunorubicin), cobalt, iron Hormonal – hyper-, hypo- thyroid, diabetes, peri-partum (?) Genetic – haemochromatosis, Fabry’s, McArdle’s Immunological – myocarditis incl. Viral (hypersensitivity component)

Answer 390

Left ventricular hypertrophy Familial in 50% (autosomal dominant, variable penetrance) Beta-myosin heavy chain Thickening of septum narrows left ventricular outflow tract

Answer 391

Impaired ventricular compliance Idiopathic or secondary to myocardial disease eg amyloid, sarcoidosis Normal size heart – big atria

Answer 392

Predominantly left-sided valves (almost always mitral) Mitral > Aortic > Tricuspid > Pulmonic Mitral alone 48%, Mitral + aortic 42% Thickening of valve leaflet, especially along lines of closure Fusion of commissures Thickening, shortening and fusion of chordae tendineae

Answer 393

``` Commonest cause aortic stenosis 70s or 80s: calcified aortic stenosis Calcium deposits outflow side cusp Impairs opening Orifice compromised Outflow tract obstruction ```

Answer 394

``` Rigidity - rheumatic, degenerative Destruction - microbial endocarditis Disease of aortic valve ring - dilatation - valve insufficient to cover increased area Marfan's Syndrome Dissecting aneurysm Syphilitic aortitis Ankylosing spondylitis ```

Answer 395

True - all layers wall False – extravascular haematoma Causes: Weak wall Congenital eg Marfans Atherosclerosis Hypertension

Answer 396

- Duplication | - Agenesis

Answer 397

``` Vulva: vulvitis Vagina: vaginitis Cervix: cervicitis Endometrium: endometritis Fallopian tube: salpingitis Ovary: oopheritis ```

Answer 398

Candida: Diabetes mellitus, oral contraceptives and pregnancy enhance development of infection Tichomonas vaginalis: protozoan Gardenerella: gram negative bacillus causes vaginitis

Answer 399

Chlamydia: major cause of infertility Gonorrhoea: major cause of infertility Mycoplasma: causes spontaneous abortion and chorioamnionitis HPV: implicated in cancer

Answer 400

Gonococci, chlamydia, enteric bacteria usually starts from the lower genital tract and spreads upward via mucosal surface Staph, strept, coliform bacteria and clostridium perfringens secondary to abortion usually start from the uterus and spread by lymphatics and blood vessels upwards deep tissue layer involvement

Answer 401

Peritonitis Bacteraemia Intestinal obstruction due to adhesions Infertility

Answer 402

Salpingitis is inflammation of the fallopian tubes, caused by bacterial infection. ``` Usually direct ascent from the vagina Depending on severity and treatment may result in: Resolution Complications: Plical fusion Adhesions to ovary Tubo-ovarian abscess Peritonitis Hydrosalpinx Infertility Ectopic pregnancy ```

Answer 403

2nd most common cancer affecting women worldwide Mean age 45-50yrs 95% of cases HPV-positive

Answer 404

``` Normal epithelium HPV infection: abnormal cells CIN 1 CIN 2 CIN 3 Carcinoma ``` Borderline -> mild -> moderate -> severe -> dyskaryosis From low to high grade squamous intraepithelial lesions

Answer 405

Invasion through the basement membrane defines change from CIN to invasive carcinoma

Answer 406

Squamous cell carcinoma (80%) Adenocarcinoma (20% of all invasive cases) - HPV dependent or independent

Answer 407

Two proteins E6 and E7 encoded by the virus have transforming genes E6 and E7 bind to and inactivate two tumour suppressor genes: 1) Retinoblastoma gene (Rb) (E7) 2) P53 (E6)

Answer 408

HPV DNA continues to reside in the basal cells Infectious virions are not produced Replication of viral DNA is coupled to replication of the epithelial cells occurring in concert with replication of the host DNA Complete viral particles are not produced The cellular effects of HPV infection are not seen Infection can only be identified by molecular methods

Answer 409

HPV DNA continues to reside in the basal cells Infectious virions are not produced Replication of viral DNA is coupled to replication of the epithelial cells occurring in concert with replication of the host DNA Complete viral particles are not produced The cellular effects of HPV infection are not seen Infection can only be identified by molecular methods

Answer 410

25 - First invitation 25 - 49 - 3 yearly 50 - 64 - 5 yearly 65+ - If one of the last 3 tests was abnormal Cervical cytology has a sensitivity ranging between 50% - 95% and specificity of at most 90% in detecting high grade CIN and SCC. Now screening is focusing on detection of high risk HPV by molecular genetic approaches.

Answer 411

Girls and boys aged 12 to 13 years are offered the HPV vaccine as part of the NHS vaccination programme In England, they are routinely offered the 1st dose when they're in school Year 8, and the 2nd dose is offered 6 to 24 months after the 1st dose.

Answer 412

Endometrium: Glands Stroma Myometrium

Answer 413

Endometrial epithelial tumours and precursors Tumour like lesions; e.g. endometrial polyp Mesenchymal tumours specific to the uterus Mixed epithelial and mesenchymal tumours Miscellaneous tumours

Answer 414

``` Perimenopause Persistent anovulation Polycystic ovary (PCO) Ovarian Granulosa cell tumours ov Oestrogen therapy May be associated with atypia ```

Answer 415

Endometrial cancer is the most common gynaecological malignancy in developed countries, causing 6% of new cancer cases in women. ``` Risk factors: Nulliparity Obesity Diabetes mellitus Excessive oestrogen stimulation ```

Answer 416

Are oestrogen dependent Often associated with atypical endometrial hyperplasia Low grade and high grade tumours Develop through the accumulation of mutations of different genes Genetic Mutations – need accumulation ≥4 different mutations PTEN PI3KCA K-Ras CTNNB1 FGFR2 p53

Answer 417

Older, postmenopausal Less oestrogen dependent Arise in atrophic endometrium High grade, deeper invasion, higher stage

Answer 418

Endometrial serous carcinoma P53 mutations in 90% PI3KCA mutations in 15% Her-2 amplification Clear cell carcinoma PTEN mutation CTNNB1 mutation Her-2 amplification

Answer 419

Serous, clear cell, mixed, undifferentiated, dedifferentiated and carcinosarcoma are considered high grade. Endometrioid carcinoma: FIGO 3 tier system: grade 1, 2 and 3 depending on: Architecture: % of gland formation Cytological atypia Stage I Tumour confined to the corpus uteri IA No or less than half myometrial invasion IB Invasion equal to or more than half of the myometrium Stage II Tumour invades cervical stroma Stage III Local and/or regional spread of the tumour IIIA Tumour invades the serosa of the corpus uteri and/or adnexa IIIB Vaginal and/or parametrial involvement IIIC Metastases to pelvic and/or para-aortic lymph nodes IIIC1 Positive pelvic nodes IIIC2 Positive para-aortic lymph nodes with or without positive pelvic lymph nodes Stage IV Tumour invades bladder and/or bowel mucosa, and/or distant metastases IVA Tumour invasion of bladder and/or bowel mucosa IVB Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes

Answer 420

``` Exome sequencing Somatic copy number alteration Whole genome sequencing DNA methylation mRNA expression Protein expression microRNA expression ```

Answer 421

Smooth muscle tumour of myometrium Commonest uterine tumour May be intramural, submucosal or subserosal Rarely turns into leimyosarcoma in post-menopause (local invasion and blood stream spread: 5 yr survival 20-30%)

Answer 422

Presence of endometrial glands and stroma outside the uterus Metaplasia of pelvic peritoneum Implantation of endometrium, retrograde menstruation Ectopic endometrial tissue is functional and bleeds at time of menstruation > pain, scarring and infertility Can develop hyperplasia and malignancy

Answer 423

- Follicular and luteal cysts - Polycystic ovarian disease: 3-6% of reproductive age women, patients have persistent, anovulation, obesity and hirsutism/virilism - Endometrioitc cyst

Answer 424

Epithelial tumours - serous, mutinous, endometroid, clear cell, transitional, mixed types Germ cell tumours - bimodal distribution Sex cord-stromal tumours Miscellaneous tumours

Answer 425

Serous Cystadenomas Cystadenofibromas Mucinous cystadenomas Brenner tumour

Answer 426

Up to 10% of epithelial ovarian cancer cases are familial 3 familial syndromes: All are transmitted in an autosomal dominant fashion 1) familial breast-ovarian cancer syndrome 2) site-specific ovarian cancer 3) cancer family syndrome (Lynch type II) - endometriosis and clear cell types BRCA --> serous tumours HNPCC --> mucinous tumours, endometrioid carcinomas

Answer 427

Most common type of malignant tumours (80%) Aggressive Alteration in P53, in virtually all BRCA1 or BRCA2 abnormalities (germline and somatic mutations; BRCA1 promoter methylation) These genes encode proteins that play important roles in DNA repair (homologous recombination) - PARP inhibitors can target this, BRAC2 advantage to BRCA-negtaive or 1

Answer 428

Distinct pathogenesis from high grade serous carcinoma. Low grade, relatively indolent, arise de novo or from borderline ovarian tumours. Mutations in KRAS, BRAF. No association with BRCA mutations.

Answer 429

Ampulla of Fallopian tube

Answer 430

Type I - endometrioid, mucinous and secretory adenocarcinoma (atypical EH) Genetic Mutations – need accumulation ≥4 different mutations PTEN PI3KCA K-Ras CTNNB1 FGFR2 p53 Type II - serous and clear cell tumours (high grade and atrophic endometrium) Serous Carcinoma: p53 (90%) PI3KCA (15%) Her 2 amplification Clear Cell Carcinoma: PTEN CTNNB1 Her-2 amplification

Answer 431

Complete (2.5% --> malignancy; 10% --> invasive moles) and partial (0% --> malignancy) mole Incidence: 1 in 20,000-30,000 pregnancies Rapidly invasive, widely metastasising (lung, vagina, brain, liver, kidney) Responds well to chemotherapy 50% arise in moles 25% arise in previous abortion 22% arise in normal pregnancy

Answer 432

Complete = empty egg fertilised by 2 sperm (or 1 which duplicates DNA) 46 XY or 46 XX (paternal origin only) Partial = normal egg fertilised by 2 sperm (or 1 which duplicates DNA) 69 XXX or 69 XXY (1x maternal and 2x paternal origin)

Answer 433

Spontaneous abortion USS – snowstorm, cluster of grapes Very high hCG

Answer 434

Strongly --> clear cell (mesonephroid/epithelial) ovarian cancer Less strongly --> endometroid (epithelial) ovarian cancer

Answer 435

TWO vaccines available Bivalent (16 + 18) Quadrivalent (6, 11, 16, 18) The vaccine offers no reduction in disease in women who are already infected National vaccination programme for girls aged 12 + boys aged 13

Answer 436

``` Fibromas (arising from fibroblasts): Benign No endocrine production   Granulosa cell tumour: Variable behaviour May produce oestrogen   Thecoma (arising from thecal cells): Benign Fibrous tissue containing spindle cells and lipid May secrete oestrogen (rarely secretes androgens)   Sertoli-Leydig Cell Tumour Variable behaviour May be androgenic ```

Answer 437

Dygerminoma (no differentiation, germ cells mixed with lymphocytes) Teratoma: mature, immature, mature cystic Choriocarcinoma --> trophoblastic cells Extraembryonic --> endodermal sinus tumour

Answer 438

Bilateral metastases composed of mucin-producing signet ring cells Most often from gastric or breast cancer

Answer 439

``` Lichen sclerosus   Papillary Hidradenoma (benign tumour)   Malignant Tumours: Squamous cell carcinoma (85%) – risk factors… HPV or lichen sclerosus VIN (vulval intraepithelial neoplasia) ``` Invasive adenocarcinoma or adenocarcinoma in situ (Paget’s disease) Malignant melanoma BCC

Answer 440

``` • Duct obstruction Gall stones (50%) Trauma Tumours • Metabolic/toxic Alcohol (33%) - 5% of alcoholics develop acute pancreatitis Drugs (e.g. thiazides) Hypercalcaemia Hyperlipidaemia • Poor blood supply Hypothermia Shock • Infection/ inflammation Viruses (e.g. mumps) • Autoimmune • Idiopathic (15%) ```

Answer 441

- Gallstones: can lead to damaged acini and release of proenzymes - Alcohol: spasm/oedema of Sphincter of Oddi (leads to protein rich pancreatic fluid)

Answer 442

Periductal - necrosis of acinar cells near ducts (usually secondary to obstruction) Perilobular – necrosis at the edges of the lobules (usually due to poor blood supply) Panlobular

Answer 443

Pancreatic : pseudocyst, abscess Systemic: shock, hypoglycaemia, hypocalcaemia

Answer 444

Lipases --> fat necrosis (calcium ions bind to free fatty acids forming soaps which are seen as yellow- white foci)

Answer 445

Overall mortality up to 50% for haemorrhagic pancreatitis

Answer 446

* Relapsing or persistent, associated with acute pancreatitis in half of cases * Relatively uncommon * Mortality 3% per year

Answer 447

Metabolic/toxic Alcohol (80%) Haemochromatosis Duct obstruction Gallstones Abnormal pancreatic duct anatomy Cystic fibrosis (“mucoviscoidosis”) Tumours Idiopathic Autoimmune

Answer 448

Pathogenesis of chronic pancreatitis As for acute pancreatitis Pattern of injury Chronic inflammation with parenchymal fibrosis and loss of parenchyma Duct strictures with calcified stones with secondary dilatations

Answer 449

* Malabsorption * Diabetes mellitus * Pseudocyts * Carcinoma of the pancreas (?)

Answer 450

* Associated with acute and/or chronic pancreatitis * Lined by fibrous tissue (no epithelial lining), contain fluid rich in pancreatic enzymes or necrotic material * Connect with pancreatic ducts * May resolve, compress adjacent structures, become infected or perforate

Answer 451

* Characterised by large numbers of IgG4-positive plasma cells * May involve the pancreas, bile ducts and almost any other part of the body

Answer 452

• Carcinomas Ductal (85% of all neoplasms) Acinar • Cystic neoplasms Serous cystadenoma Mucinous cystic neoplasm • Pancreatic neuroendocrine tumours (Islet cell tumours)

Answer 453

* Smoking * BMI and dietary factors * Chronic pancreatitis * Diabetes

Answer 454

• Arise from dysplastic ductal lesions: Pancreatic Intraductal Neoplasia (PanIN) Intraducal Mucinous Papillary Neoplasm • K-Ras mutations in 95% of cases

Answer 455

Macroscopic Appearance Gritty and grey Invades adjacent structures Tumours in the head present earlier Microscopic Appearance Adenocarcinomas: mucin secreting glands set in desmoplastic stroma

Answer 456

* Head (60%) * Body * Tail * Diffuse * Direct: Bile ducts, duodenum * Lymphatic: Lymph nodes * Blood: Liver * Serosa: Peritoneum

Answer 457

* Contain serous or mucin secreting epithelium (cf. ovarian tumours) * Usually benign

Answer 458

* may be associated with the Multiple Endocrine Neoplasia (MEN) 1 syndrome * usually non-secretory * contain neuroendocrine markers e.g. chromogranin * behaviour difficult to predict

Answer 459

* Insulinomas (derived from beta cells) | * the commonest type of secretory tumour

Answer 460

• Cholesterol (more than 50% cholesterol) May be single, mostly radiolucent • Pigment (contain calcium salts of unconjugated bilirubin) Multiple, mostly radio-opaque

Answer 461

* Chronic inflammation * Fibrosis * Diverticula – Rokitansky-Aschoff sinuses * 90% contain gall stones

Answer 462

* Adenocarcinomas | * 90% associated with gall stones

Histopathology Flashcards

(497 cards)