Histopath Flashcards

Question

Lymphocytic Dueodenitis

Answer 1

Distinct from coeliac disease but usually a continuum Increased intraepithelial lymphocytes = CD8+ T Cells (20: 100 lymphocytes: enterocytes) Architectural villous structure normal = normal villi, normal crypts

Answer 2

Coeliac disease --> chronic inflammation = EATL (Enteropathy associated T-cell lymphoma) Aggressive lymphoma Important to stick to gluten-free diet to prevent EATL

Answer 3

Congential Absence of ganglion in myenteric plexus Nerve fibres ARE present Distal colon fails to dilate --> obstructing point - constipation - distension Histopathology: hypertrophy of the nerve fibres and absence of ganglion

Answer 4

Acute: - Infection - Drugs (notably Abx) - Chemotherapy - Radiation Chronic Colitis (acute on chronic picture): - Crohn’s - UC - TB

Answer 5

Acute: Arterial occlusion: Atheroma, Thrombus, Embolism Venous occlusion: Thrombus, Hypercoagulable states Small vessel disease: DM, Vasculitis Low flow states: CCF, Shock Obstruction: Hernia, Volvulus, Intussusception Chronic: - PVD - Vasculitis

Answer 6

Non-neoplastic: - Hyperplastic polyps = folds of mucosa that have grown a bit much - Inflammatory pseudo-polyps - Hamartomatous polyps Neoplastic polyps: - Tubular adenoma - Tubulovillous adenoma - Villous adenoma (microscopically different)

Answer 7

Higher risk of cancer: - Larger polyps (>4cm) - More polyps - Higher villous component - Dysplastic features Normal --> Adenoma --> Adenocarcinoma Remove the adenoma--> reduce risk of cancer 98% of colorectal cancers are adenocarcinomas

Answer 8

Aggregates formed in the renal collecting ducts The most common sites: - Pelvi-ureteric (between renal pelvis and ureter) - Pelvic brim (where ureter crosses iliac blood vessels) - Vesico-ureteric (where ureter inserts into bladder) The most common stones: 1. Calcium oxalate 75% 2. Magnesium ammonium phosphate (struvite) 15% 3. Uric acid 5%

Answer 9

Precipitated by an increase in the concentration of calcium Absorptive hypercalciuria (50%) – Vitamin D Renal hypercalciuria Hypercalcaemia: primary hyperparathyroidism

Answer 10

Precipitated by alkaline urine | Infection with proteus species-->urease producing bacteria Cause staghorn calculi

Answer 11

Precipitated by an increase in “uric acid” or cell turn-over Gout Chemotherapy (usually for B-cell lymphoma or leukaemia) Acidic urine

Answer 12

<15mm, well-circumscribed Trisomy 7, Trisomy 17, loss of Y chromosome Frequent incidental finding in nephrectomies and at autopsy esp in CKD

Answer 13

Pink oncocytic cells. Macrocytically: well circumscribed, Mahogany-brown mass with central scar. Seen in Birt-Hogg-Dubé syndrome (note: oncocyte = epithelial cell characterized by an excessive number of mitochondria)

Answer 14

Perivascular epitheloid cells (vessel wall, muscle and fat) Mostly sporadic but can be seen in tuberous sclerosis (with phaeos and hydrocephalus) Large >4cm May present with flank pain May bleed dramatically

Answer 15

Malignant epithelial kidney tumour RFs: Smoking, HTN, long-term dialysis, obesity, von Hippel Lindau, PKD Presentation: painless haematuria, may have flank pain +/- abdo mass, may have weight loss and fever. May be detected incidentally on imaging. Highly metastatic – lungs, liver and bones Sub-types: - clear cell renal cell carcinoma (70%) - papillary renal cell carcinoma (15%) - chromophobe renal cell carcinoma (5%)

Answer 16

Epithelial cell Golden yellow with haemorrhagic areas Loss of chromosome 3p Risk progression index - Leibovich Risk Model

Answer 17

Papillary epithelial cell composed of papillae, >15mm in size Trisomy 7 and 17, and loss of Y chromosome 2 types: - type 1 = well defined, classic cytologically - type 2 = heterogenous microscopically and cytologically

Answer 18

Epithelial cell Sheets of large cells, distinct cell borders, reticular cytoplasm, thick-walled vascular network Grossly appears as well-circumscribed solid brown tumour Pale, eosinophilic cells

Answer 19

Transitional cell carcinoma Arise from: - Bladder - Renal pelvis - Ureters Common RFs: smoking, aromatic amines (dyes) Most present with haematuria Three main subtypes - Non-Invasive Papillary Urothelial Carcinoma - Infiltrating Urothelial Carcinoma - Flat Urothelial Carcinoma in-situ

Answer 20

Dual Blood Supply: 1. Portal vein 2. Hepatic artery Ischaemic disease of the liver is very rare. More commonly Iatrogenic.

Answer 21

Arranged into portal tracts surround a central vein (6:1) Blood from portal vein and hepatic artery = portal tract Trickles down the spaces between strands of hepatocytes into the central vein Divided into three zones 1, 2, 3 Hepatocytes originate near portal tract in zone 1 --> 2 mature --> 3 Zone 3 hepatocytes are the most metabolically active. Zone 3 is around central veins where oxygenation is poor. Endothelial cells are unique • Do not have a basement membrane • Discontinuous (no tight junctions)

Answer 22

SPOTTY NECROSIS, foci of inflammation & necrosis, inflammatory infiltrates Drugs, Hep A&E

Answer 23

Viruses not A/E Drugs Auto-immune Hepatitis Primary biliary cholangitis Primary sclerosing cholangitis (UC) Haemochromatosis (bronzed diabetes) “Prussian blue” Wilson’s Disease “Rhodanine” A1AT Def

Answer 24

Fibrosis = stage F0 – F4 F4: Compensated cirrhosis Inflammation = grade - Portal inflammation: inflammation confined within limiting plate - Interface hepatitis “piecemeal necrosis”: inflammation across the limiting plate - Lobular inflammation: inflammation across entire lobule

Answer 25

Changes that occur in liver inflammation --> Fibrosis -Loss of hepatocyte microvilli -Loss of fenestration of endothelium + -Stellate cell activation and deposition of ECM in space of Disse -Activation of Kupffer cells

Answer 26

Features: Whole liver fibrosis with nodules of regenerating hepatocytes and distortion of vascular architecture Structural changes in previous slide lead to --> Intra-hepatic shunting (blood flows straight through sinusoids) --> portal anastomoses e.g. oesophageal varices and haemorrhoids Complications - Hepatic encephalopathy - Liver cell cancer - Portal hypertension

Answer 27

1- Fatty Liver - fatty infiltrates 2- Alcoholic hepatitis 3- Cirrhosis - fibrosis, loss of parenchymal tissue

Answer 28

- Ballooning of cells (accumulation of proteins and water --> swelling) - Mallory Denk Bodies (dense pink material within cells - clumping of IFs) - Neutrophil polymorphs and scarring - Apoptosis - Pericellular fibrosis - Zone 3 – acetaldehyde highest, and relatively hypoxic Relatively irreversible 80% of pmts with alcoholic hep are cirrhotic

Answer 29

Very similar histological features as alcoholic liver disease Non-alcoholic fatty liver disease caused by increased IR -TIIDM -Obesity = Metabolic syndrome --> Non-alcoholic steatohepatitis (equivalence of alcoholic hepatitis) = NASH

Answer 30

Causes 1) Secondary metastatic disease (commonest) - Multiple in number - Discrete 2) Primary tumours - HCC - AFP tumour marker - Hepatoblastoma (tumours of primitive hepatocytes) - Cholangiocarcinoma - associated with PSC, histology - capillary ingrowth - Haemangiosarcoma

Answer 31

Endo - Islets of Langerhans: insulin, glucagon, somatostatin Exocrine- acini: protease, lipase, amylase

Answer 32

Aberrant release of pancreatic enzymes Causes by duct obstruction and reflux + direct acinar injury Reflux enzymes --> acinar necrosis --> release of more enzymes Release of lipases --> fat necrosis --> soaponification with calcium Causes (GETSMASHED): Duct obstruction: Gallstones (50%) and tumours, trauma Metabolic / Toxic: Alcohol (33%), drugs, hypercalcaemia/hyperlipidaemia Ischaemia: Shock Infection: Mumps Autoimmune Idiopathic

Answer 33

Peri-ductal = Obstructive cause - Acinar cells adjacent to the ducts undergo necrosis Peri-lobular = Vascular/ischaemic cause -Necrosis at the edges of the lobules (blood supply comes with ducts so periphery most affected) Pan-lobular: either peri-ductal or peri-lobular injury progressing Alcohol: spasm/oedema of Sphincter of Oddi and the formation of a protein rich pancreatic fluid which obstructs the pancreatic ducts

Answer 34

- Haemorrhagic pancreatitis (50% mortality) - Metabolic disturbances: shock, hypoglycaemia, hypocalcaemia - Psuedocyst (lacks epithelial lining - lined by necrotic and granulation tissue) --> may become infected to form abscess - Abscess

Answer 35

Dx: serum lipase - IV fluids (sequestration) - ABX not recommended unless necrotising pancreatitis - Electrolyte replacement

Answer 36

Relapsing or persistent pancreatitis Chronic inflammation with parenchymal fibrosis & loss of parenchyma. Islets look bigger as acini disappear. Duct strictures with calcified stones and secondary dilatations. Causes: Alcohol (80%) Gallstones + tumours Haemochromatosis Idiopathic Autoimmune (IgG4 Disease)

Answer 37

Carcinomas • Ductal 85% • Acinar Acinar-ductal metaplasia (most originate from acinar --> ductal carcinoma) Cystic neoplasms • Serous cystadenoma • Mucinous cystic neoplasm Neuroendocrine tumours

Answer 38

5YSR: 5% K-ras mutations 95% Peri-neural invasion very common Commonest in the head of pancreas (60%), progressively less common moving down to the tail (Opposite of neuroendocrine tumours) Pre-malignant Bridges – arise from ductal dysplastic lesions PANcreatic Intraductal Neoplasia = PanIN Microscopically adenocarcinomas therefore secrete mucin

Answer 39

Contain neuroendocrine markers (e.g. chromogranin, neurosecretory granules – can be measured in blood or used as generic stain for NETs) Commonest in the tail --> less common in the head Associated with MEN 1 (pituitary, pancreas, parathyroid) Most non-secretory (i.e. most common type) Commonest type of secretory tumour: Insulinoma (beta cells)

Answer 40

Incredibly common (20% of all people) Types: 1. Cholesterol (>50%; single, radiolucent) – cholesterol solitaires 2. Pigment (Ca salts of unconjugated bilirubin, multiple, radiopaque) Complications: Bile duct obstruction Acute cholecystitis - neutrophil polymorphs (may be acute on chronic) Gall bladder cancer - 90% adenocarcinomas Pancreatitis

Answer 41

``` Malabsoprtion Diabetes Mellitus Pseudocysts Pancreatic calcifications Carcinoma of pancreas ```

Answer 42

Acinar-ductal metaplasia - most originate from acinar --> ductal carcinoma Associated with an increase in serum lipase

Answer 43

* Chronic inflammation * Fibrosis * Diverticula – Rokitansky-Aschoff sinuses

Answer 44

- Kupfer Cells (macrophages) activate - Gaps in the ECs collapse - Collagen is deposited - Leads to inflammation/fibrosis

Answer 45

- Genetic condition – increased iron absorption - FHE Gene mutation on Chr6 - No special stain required Damage to organs secondary to iron deposition - Pancreas – "bronzed diabetes" - Joints – arthritis - Heart– arrythmias, cardiomyopathy - Liver damage Rx - venesection

Answer 46

Progressive autoimmune destruction of intrahepatic bile ducts Build up of bile and other toxins - cholestasis AMA positive (anti-mitochondrial antibody) Histology – destruction of bile ducts associated with CHRONIC INFLAMMATION (with granulomas)

Answer 47

Affects intra and extrahepatic bile ducts Characterised by bile duct fibrosis and sclerosis Associated with UC and increased risk of cholangiocarcinoma Concentric fibrosis – onion skinning fibrosis, chokes off and destroys bile duct. WITHOUT inflammation

Answer 48

- Accumulation of copper due to failure of excretion - Defect of transporter protein from hepatocytes into bile duct - Genes on chromosome 13 - Accumulates in the liver and CNS - Kayser Fleicher Rings – slit lamp - Rhodanine stain (turns copper golden-brown against blue counter stain)

Answer 49

Haemangioma - most common, often incidentally picked up Liver cell adenoma Bile duct adenoma

Answer 50

Collagen deposition

Answer 51

Branching ducts ending in terminal-duct lobular units = the functional unit of the breast Duct-lobular system lined by an inner glandular epithelium and an outer myoepithelium

Answer 52

Presents with nipple discharge Histology shows dilated ducts with peri-ductal inflammation filled with secretions Cytology shows macrophages and proteinaceous material

Answer 53

Presents with painful red breast Seen in lactating women- stasis of milk/cracked skin Staphylococci – most common organism Treatment is usually antibiotics/drainage Histology shows acute inflammation +/- abscess formation Cytology shows abundant neutrophils

Answer 54

Presents with firm breast lump Inflammatory reaction to damaged adipose tissue Tissue can become fibrosed and calcified Associated with trauma, surgery and radiotherapy Cytology shows degenerate fat, foamy macrophages and giant cells

Answer 55

Duct ectasia Mastitis Fat necrosis

Answer 56

``` Fibroadenoma Fibrocystic change Phyllodes Tumour Intraductal papilloma Radial scar ```

Answer 57

Presents as a mobile breast lump Benign fibroepithelial tumour of the breast Histology shows a multinodular mass of expanded intralobular stroma and compressed slit-like ducts

Answer 58

Cyclical breast lumpiness Very common – associated with exaggerated hormonal responses Histology shows cysts, adenosis, mild epithelial and stromal hyperplasia

Answer 59

Presents as a rapidly enlarging breast mass - Group of potentially aggressive fibroepithelial neoplasms of the breast - Usually in women > 50 - Majority are benign – small proportion can be more aggressive Histology shows overlapping cells (not a monolayer), “leaf like” architecture, stromal overgrowth – particularly next to epithelial components

Answer 60

Presents with nipple discharge/mass - Benign papillary tumour from the ductal system - Lactiferous ducts = central papilloma - Terminal ductules = peripheral papillomas Histology shows a papillary (finger like) mass within a dilated duct lined by epithelium and myoepithelium

Answer 61

Usually picked up incidentally - Benign sclerosing lesion of the breast - Usually presents as a stellate mass on mammography Histology shows a central, fibrous stellate area and proliferation of ducts and acini in the periphery

Answer 62

Ductal Carcinoma in Situ Basal Like Carcinoma Invasive Breast Carcinoma - ductal, lobular, tubular, mucinous

Answer 63

85% present on screening mammography - A neoplastic intraductal epithelial proliferation - Associated with an inherent, but not inevitable, risk of progression to invasive breast carcinoma Histology shows ducts filled with atypical epithelial calls – lumen is regular

Answer 64

Recently described type of carcinoma discovered following genetic analysis of breast carcinomas Immunohistochemically characterised by positivity for “basal” cytokeratins CK5/6 and CK14. Histologically characterised by sheets of markedly atypical cells with a prominent lymphocytic infiltrate This is a dangerous type of breast cancer because it has a propensity for vascular invasion and distant metastatic spread

Answer 65

Presents with firm breast mass -Malignant epithelial neoplasms which infiltrate the breast and have the capacity to metastasise Histological subtypes 1) Ductal carcinoma – cells are big and pleimorphic, invasive cells move to the stroma 2) Lobular carcinoma – linear arrangement with cells of the same size. "Indian file". 3) Tubular carcinoma – elongated, round tubules of cancerous cells 4) Mucinous carcinoma – empty looking spaces, containing mucin

Answer 66

Hyperplasia results from an increase in both glands and stroma of endometrium Driven by oestrogen – Persistent oestrogen states: Perimenopausal Persistent Anovulation Polycystic ovaries Oestrogen only therapy Granulosa cell ovarian tumours – produce oestrogen

Answer 67

80-85% endometrial cancer - Low grade tumours which are superficially invasive - Often associated with atypical endometrial hyperplasia - Subtypes – endometrioid, mucinous and secretory adenocarcinoma - Seen in younger patients - Associated with PTEN/KRAS mutations

Answer 68

15-20% - Serous and clear cell carcinomas - Seen in older, post menopausal women - Not oestrogen dependent - More aggressive – higher grade and deeper invasion

Answer 69

From the epithelial surface covering the ovary Can be benign, bordeline or malignant ``` Type 1 - Less Exciting More Cancers: Low- grade serous Endometriod Mucinous Clear Cell ``` Type 2: Mostly serous

Answer 70

MOST COMMON Usually cystic and unilocular Psammoma bodies seen

Answer 71

Mucin secreting tumours Kruckenburg Tumour – malignancy which has metastasised from (GI) primary Mucin producing signet ring cells

Answer 72

Co-existence with endometrioid carcinoma in uterus common Forms tubular glands Better prognosis than mucinous/serous

Answer 73

Strong asssociation with endometriosis | Abundant clear cytoplasm

Answer 74

Choriocarcinoma Teratoma - Mature, Immature Dysgerminoma Yolk-Sac Tumours

Answer 75

Malignant | Secretes hCG

Answer 76

Benign, solid/cystic | Mature adult tissue types - teeth/hair common

Answer 77

Malignant, usually solid Contains immature, embryonal tissue Secretes AFP

Answer 78

No differentiation | Secretes hCG

Answer 79

Most common in children and young women

Answer 80

Granulosa/Thecal Cell Tumours Fibromas Sertoli-Leydig Tumour

Answer 81

Produce Oestrogen Thecomas - benign Granulosa cell tumours – can recur/progress

Answer 82

From ovarian stroma No hormone production Meig’s Syndrome – ascites, pleural effusion

Answer 83

Secretes Androgens

Answer 84

``` Symptoms: Headache Seizures Visual disturbances Focal neurology – weakness and sensory changes ``` Investigations: CT/MRI head Stereotactic or intraoperative biopsy Genetic sequencing ``` Management: Tumour debulking Chemotherapy Radiotherapy Palliative care ```

Answer 85

Mets are the most common cause of brain tumour Melanoma, breast, lung (also large bowel and prostate)

Answer 86

- Benign (WHO grade I) - Most common brain tumour in children (20% of CNS tumours <14) - Common in neurofibromatosis 1 - Usually cerebellar - MRI: well circumscribed, cystic, enhancing lesion - Cystic and piloid ‘hairy’ cell, often Rosenthal fibres & granular bodies - Slow growing - low mitotic activity - BRAF mutation (KIAA1549-BRAF fusion) in 70% of PA (better prognosis)

Answer 87

- 25-30% primary tumours - 2nd after gliomas - Common in elderly (rare in pts <40) - Attached to meninges - Calcified with psammoma bodies - MRI: extraxial, isodense, contrast-enhancing 80% Grade I: benign, recurrence <25% 20% Grade II: atypical, recurrence 25-50% 1% Grade III: malignant, recurrence 50-90% May get psuedoinvasion along the Virchows-Robin Space

Answer 88

- Malignant - Lethal tumour with dismal prognosis (WHO grade 4) - Most pts >50 - Spontaneous (90%) or transforms from more indolent astrocytomas (10%) - MRI - heterogeneous, enhancing post-contrast - Multiple mitotic figures, microvascular proliferation and necrosis

Answer 89

- WHO grade 4 - Most common malignant brain tumour in children (but still rare) - Usually cerebellar - Homer-Wright Rosettes - EMBRYONAL TUMOUR: originates from neuroepithelial precursors of the cerebellum/dorsal brainstem - Outcome considerably improved with chemo/radiotherapy `Small round blue cell` tumour: high grade, poorly differentiated Molecular classification: WNT-activated, SHH-activated, group 3, group 4

Answer 90

Supplies: - Superior motor and sensory cortices - Frontal lobe Stroke deficits: - Contralateral paralysis and sensory loss of leg and foot - Frontal lobe symptoms e.g. personality change and urinary incontinence

Answer 91

Supplies: - Bulk of cerebral hemispheres - Broca’s area (speech production) - Wernicke’s area (speech comprehension) Stroke deficits: - Contralateral paralysis and sensory loss of face and arm - Aphasia - Facial droop

Answer 92

Supplies: - Occipital lobe, visual cortices and cerebellum Stroke deficits: - Contralateral visual loss - Faceblindness - Ataxia if cerebellar

Answer 93

Rupture of arteries between dura and skull Common after pterion trauma --> middle meningeal artery rupture Convex white region on CT

Answer 94

Rupture of veins between dura and arachnoid mater Common after falls in the elderly White, crescent shaped region on CT

Answer 95

Spontaneous rupture of berry aneurysms in the subarachnoid space (present in 1% of 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 - thunderclap, vomiting, loss of consciousness Endovascular treatments - coils

Answer 96

Loss of neurons, synapses and glia result from deposition of amyloid-β and tau in Alzheimer’s Pathology starts in the temporal lobe (hippocampus) and progressively spreads to the occipital lobe and throughout the cortices Key histopathology: amyloid-β plaques and tau neurofibrillary tangles (also Cerebral amyloid angiopathy (CAA, thickening of the vessels) and neuronal loss (cerebral atrophy)) Staging of tau pathology- Braak stages

Answer 97

Loss of dopaminergic neurons in the substantia nigra impairs basal ganglia function in Parkinson’s Pathology starts in the brainstem and spreads upwards into the cortices Key histopathology: Lewy bodies (neuronal inclusions of α-Synuclein) Staging - Braak staging Key differentials to rule out on autopsy: Multiple system atrophy Progressive supranuclear palsy Corticobasal degeneration

Answer 98

Selective atrophy of the frontal lobes --> personality changes, and the temporal lobes --> impaired memory 2 main subtypes – Pick’s disease and TDP-43 positive FTD (linked with ALS), also TDP-17 syndromes Can differentiate the different tauopathies based on their molecular characteristics - 3R/4R (microtubule binding sites) Key histopathology: Pick bodies (tau) or TDP-43 inclusions ``` Pick's disease: Fronto-temporal atrophy Marked gliosis and neuronal loss Balloon neurons Tau positive Pick bodies ```

Answer 99

Obstructive lung disorders characterised by decreased exercise tolerance, infective exacerbations and mucus plugging - 2 components – bronchitis and emphysema - Neutrophilic infiltration into airways - Loss of alveoli, elastic fibres and lung parenchyma - COPD in a non-smoker + cirrhosis = alpha-1 antitrypsin deficiency

Answer 100

Obstructive lung disorders characterised by decreased exercise tolerance, infective exacerbations and mucus plugging Airway remodelling with smooth muscle hypertrophy, goblet cell hyperplasia and an eosinophilia in severe cases.

Answer 101

- Autosomal recessive mutation in CFTR gene on chromosome 7 - Viscous mucus secretion leads to recurrent lung infections, pancreatic insufficiency and malabsorption - Mucus clogged airways and inflammatory cell infiltration

Answer 102

- Pathological airway dilation secondary to recurrent infections - Cystic fibrosis is a major risk factor - Dilated, fibrotic airways with mucus plugging

Answer 103

- Non-small cell lung cancer - Most common lung cancer in non-smokers - Tend to be located peripherally compared to other lung tumours --> originate from type II pneumocytes in alveolar walls - Atypical adenomatous hyperplasia eventually becomes invasive - Mutations in KRAS and EGFR - Extrathoracic metastases common and early Histology: - Histology shows evidence of glandular differentiation - Papillae - Mucin - Variety patterns relate underlying molecular abnormalities and prognosis

Answer 104

- Non-small cell lung cancer - Lung cancer with the strongest correlation with smoking - Originate from the bronchi (also increasing number of peripheral) - Mutations in p53 are the most common - Local spread, metastasise late

Answer 105

SIADH - Small cell lung cancer secretes ectopic ADH --> euvolemic hyponatraemia CUSHINGS - Small cell lung cancer secretes ectopic ACTH --> Cushing’s syndrome (does not suppress with high dose dexamethasone) LAMBERT-EATON - Small cell lung cancer secretes anti-VGCC abs --> acts on presynaptic membrane --> muscle fatiguability that improves with activity (unlike myasthenia gravis) HYPERCALCAEMIA OF MALIGNANCY - Squamous cell lung cancer secretes PTHrp --> hypercalcaemia and hypophosphatemia (& suppression of endogenous PTH)

Answer 106

- Thought to arise from bronchial neuroendocrine cells - Mutations in p53 and retinoblastoma protein (RB1) - Very strong smoking association - Highly malignant and has a high rate of metastasis - 80% present with advanced disease - Commonly spreads to brain, ribs and spinal column - Very chen-sensitive but abysmal prognosis - ‘Oat cells’ on microscopy - Small, poorly differentiated cells on histology - High incidence of paraneoplastic syndromes

Answer 107

- Endothelial injury - Cholesterol deposition and oxidation - Macrophage recruitment - Phagocytosis of lipids --> foam cell formation - Foam cell deposition and fibrous cap formation - Fibrous cap thinning and rupture - Thrombous formation and artery occlusion

Answer 108

- First 24 hours - loss of cell nuclei and necrosis - 1-4 days: neutrophilic infiltration - 5-10 days: macrophages recruit debris - Weeks-months: granulation tissue and fibrosis

Answer 109

VENTRICULAR RUPTURE - Damaged ventricle splits open following myocardial infarction and a cardiac tamponade forms - Chest pain, signs of shock and haemodynamic instability quickly develop DRESSLER'S SYNDROME - Myocardial infarction followed by pericarditis - Release of myocardial proteins during cell necrosis triggers an autoimmune reaction - Pan-ST elevation on ECG

Answer 110

Acute or subacute bacterial infection of the inner lining of the heart (endocardium) RFs: IVDU - Staph aureus or epidermidis Dental surgery- Strep viridans Immunocompromise e.g. alcohol or HIV Strep viridans infections present subacutely (>2 weeks) with splenomegaly and clubbing Vegetations eats into heart valves leading to regurgitation Any new murmur + fever must be investigated with a transthoracic echocardiogram

Answer 111

All 4 heart valves can become stenosed or can regurgitate following rheumatic fever STENOSIS: - Most common valve affected is the aortic valve - Advancing age is the single biggest risk factor --> calcification of the valve - Other risk factors include rheumatic fever and a bicuspid valve - Aortic stenosis presents with chest pain, syncope and an ejection systolic murmur REGURGITATION: - Most common valves affected are mitral and aortic - Infective endocarditis is a massive risk factor --> vegetations eat into valve - Connective tissue disease e.g. Marfan’s and Ehlers-Danlos can also predispose - Mitral regurgitation presents with shortness of breath, syncope and a pansystolic murmur

Answer 112

Hypertrophic - thick walls Dilated - thin walls Restrictive - stiff walls (most common cause is amyloidosis) ``` Causes: Genetic Chemo Acromegaly Haemochromatosis Amyloidosis ```

Answer 113

Appearance: Multilobed nuclei with granules Significance: Acute inflammation

Answer 114

Appearance: Little cytoplasm with big nucleus Significance: Chronic inflammation, lymphoma

Answer 115

Appearance: Bi-lobed nucleus with red granules Significance: Allergic, parasites, Hodgkin lymphoma

Answer 116

Appearance: Large and heavily granular Significance: Allergy (e.g. urticaria)

Answer 117

Appearance: Large with lots of cytoplasm Significance: Late acute inflammation, chronic inflammation (inc granuloma)

Answer 118

Histological features: Keratin production Intercellular bridges Sites of origin: Lung, skin, oesophagus, head&neck, anus, cervix, vagina

Answer 119

Histological features: Mucin production - stain turns mucin blue Glands Sites: Lung, breast, colon, pancreas, cervix, stomach

Answer 120

Sites: bladder, ureter, urethra

Answer 121

Histological features: Arises from mesenchymal cell Sites: Bone, cartilage, fat, vascular

Answer 122

Histochemical: - Chemical reaction between stain and a specific component of the tissue - e.g. H&E - everyday stain, Prussian Blue - Iron (haemochromatosis), Congo Red - Amyloid Immunohistochemical: - Antibodies bind to specific antigen in the tissue --> immunofluorescence/immunoperoxidase - e.g. cytokeratin ab - epithelial cells, CD45 - lymphoid marker

Answer 123

Store vitamin A | Become activated to my-fibroblasts (lay down collagen)

Answer 124

Micronodular tends to be associated with alcoholism. | Macronodular tends to be associated with viral infections

Answer 125

Caused by iron overload Accumulation of iron in macrophages Usually occurs after blood transfusions

Answer 126

- Very active form of hepatitis with lots of plasma cells - Anti-smooth muscle antibodies (ASMA) - Responds to steroids

Answer 127

Failure to secrete alpha-1 antitrypsin Misfolded protein cannot exit hepatocytes leading to accumulation Leads to emphysema and cirrhosis

Answer 128

PBC Drugs TB Sarcoidosis

Answer 129

Alcohol affects the protein content of the pancreatic duct fluid which predisposes to obstruction as the thickened fluid condenses out

Answer 130

HypERcalcaemia can cause acute pancreatitis but acute pancreatitis can cause hypOcalcaemia

Answer 131

Submucosal

Answer 132

Px: explosive watery diarrhoea, usually after a course of abx Ix: C. diff stool toxin assay Rx: metronidazole or vancomycin

Answer 133

Definition: inflammation and injury of the large intestine caused by an inadequate blood supply Watershed: area between the supply of the SMA and IMA --> splenic flexure ``` Causes: Arterial (e.g. thrombus) Venous (e.g. hypercoagulable) Small vessel disease (e.g. DM) Low flow (e.g. shock) Obstruction (e.g. hernia) ```

Answer 134

AD Mutation of APC tumour suppressor gene Large numbers of polyps, pretty much everyone gets cancer

Answer 135

Same features as FAP ``` Extra-intestinal manifestations: Osteomas Desmoid tumours - connective tissue tumour Dental caries Supernumerary teeth ```

Answer 136

AD Mutation in DNA mismatch repair genes High risk of cancer, no polyps

Answer 137

Risk Factors - HPV 16 and 18 - Multiple sexual partners - Smoking - Immunosuppression Tumourigenesis HPV 16 and 18 encode two proteins that inactivate tumour suppressor genes. E6 - p53, and E7 - retinoblastoma. Transformation zone is most common site.

Answer 138

Cervical Intraepithelial Neoplasia (CIN) Dysplastic changes within the epithelium with an intact basement membrane. Progress to SCC CGIN: cervical glandular intraepithelial neoplasia progresses to adenocarcinoma (20%)

Answer 139

- Autosomal dominant - Flank pain and haematuria + recurrent pyelonephritis and hypertension - Associated with liver cysts + berry aneurysms in the Circle of Willis --> subarachnoid haemorrhage - End-stage renal failure by age 40-60 - PKD1, PDK2 -genes

Answer 140

- X-linked deficiency of type 4 collagen - Sensorineural hearing loss from an early age with macroscopic haematuria - End-stage kidney disease and cataracts develop as the disease progresses

Answer 141

``` PRE-RENAL: Hypoperfusion - Dehydration - Shock - Renal artery stenosis ``` ``` RENAL: Interstial or tubular damage - NSAIDs - Gentamycin - ACE inhibitors - Contrast ``` ``` POST-RENAL: Outflow obstruction - Stones - Tumours - BPH ```

Answer 142

Hyperkalaemia Uraemia Metabolic acidosis

Answer 143

``` Normocytic anaemia (decreased EPO) Vitamin D deficiency (decreased 1aOHase) ``` Association with ischaemic heart disease- Hypertension, hyperlipidaemia, calcification of blood vessels Association with calcium and phosphate metabolic derangement- Hyperparathyroidism, osteomalacia, osteoporosis

Answer 144

Up to 2 days post-URTI Presents with abdominal pain and haematuria Associated with IgA vasculitis (Henoch-Schonlein purpura) IgA predominant mesangial immune complex deposition 30% develop end stage renal failure Oxford classification (MEST-C)

Answer 145

Up to 2 weeks post-strep throat Associated with Streptococcus pyogenes Presents with haematuria and oliguria - "coca cola urine"

Answer 146

Autoimmune crescentic glomerulonephritis - Antibody production against type 4 collagen - Anti-glomerular basement membrane abs detectable with serology - Linear deposition of IgG demonstrable on the glomerular basement membrane - Haemoptysis and progressive renal failure - Post-renal transplant in Alport’s

Answer 147

Pauci-immune crescentic glomerulonephritis - trigger neutrophil activation and glomerular necrosis Vasculitis Wegner’s: - granulomatosis with polyangiitis - c-ANCA - ENT problems - (‘saddle nose’) + renal failure Churg-Strauss: - eosinophilic granulomatosis with polyangiitis - p-ANCA - Atopic background + renal failure

Answer 148

4 Key Criteria: - Proteinuria >3.5g per day - Hypoalbuminemia <2.5g/dl - Oedema - Hyperlipidaemia Complications: - Loss of anti-thrombin III --> thrombophilia - Loss of immunoglobulins --> infections - Pulmonary oedema

Answer 149

- Primary glomerular disease, non-immune complex mediated - Most common cause of nephrotic syndrome in children - Normal histology on light microscopy - Effacement of podocyte foot processes on electron microscopy - Need biopsy to confirm - General responds to immunosuppression

Answer 150

- Primary glomerular disease, non-immune complex mediated - Most common cause of nephrotic syndrome in adults - Visible sclerosis of podocytes and bowman’s capsule - Associated with chronic glomerulonephritis e.g. SLE or vasculitis - Need biopsy to confirm

Answer 151

- Primary renal disease, immune complex mediated - Common cause of nephrotic syndrome in adults - Common as a paraneoplastic or co-morbid phenomenon - Associated with immune deposits on outside of glomerular basement membrane (subepithelial) - Production of anti-phospholipase A2 type M receptor (PLA2R) antibodies against podocytes in 75% of cases - Need biopsy to confirm

Answer 152

- 30-40% of diabetics - High glucose levels thought to be directly injurious - Typically starts as microalbuminuria before progression to proteinuria and nephrotic syndrome- Mesangial thickening followed by Kimmelstiel-Wilson nodule formation - Albumin: creatinine ratio is measured to monitor the severity of nephropathy - All diabetic patients should receive an ACEi (nephroprotective) Nodular Glomerulosclerosis Stage 1 – Thickening of basement membrane on EM Stage 2 – Increase in mesangial matrix, without nodules Stage 3 – Nodular lesions / Kimmelstiel-Wilson Stage 4 – Advanced glomerulosclerosis

Answer 153

- Renal disease in SLE progresses from glomerulonephritis to nephrotic syndrome - ‘Wire-loop glomeruli’ indicate antibody complex deposition - A high anti-dsDNA titre and low complement indicate an active lupus flare - ISM/RPS classification

Answer 154

- The ureters and bladder are lined by transitional epithelium --> most common type of bladder cancer - Associated strongly with smoking and exposure to chemicals e.g. dyes-->always ask about occupation - Macroscopic haematuria --> all haematuria is malignancy until proven otherwise - Diagnosis is with cystoscopy and tumour excision or cystectomy

Answer 155

- Much rarer subtype of bladder cancer - Develops at junction between bladder and urethra - Strongly associated with chronic parasitic worm infections e.g. schistosomiasis - Much more common in developing countries without access to anti-parasite medication

Answer 156

Concentric hyperplasia of the prostate secondary to prolonged testosterone exposure. Stromal proliferation. Storage sx- frequency, nocturne, urgency Voiding sx - hesitancy, poor stream, incomplete emptying Rx: - Alpha blockers e.g. tamsulosin - 5-alpha reductase inhibitors e.g. finasteride - Transurethral Resection of the Prostate (TURP)

Answer 157

- Total incidence - 1:8, Afro-Caribbean males – 1:4 - Similar storage and voiding symptoms as BPH - Red Flags: haematuria and back pain – don’t miss Cauda Equina! Vast majority are adenocarcinomas – most peripheral glands proliferate first Arises from Prostatic Intraepithelial Neoplasia Mutations in PTEN, AMACR, GST-pi, p27 and more… Gleason grading system – score up to 10. The higher the score, the greater the malignancy and the worse the prognosis.

Answer 158

- Dilated scrotal venous plexus - Heaviness in testicle and soft lump - ‘Bag of worms’ on palpation and scrotal ultrasound to confirm

Answer 159

- Smooth, symmetrical mass secondary to fluid accumulation - Due to intact embryological tract or failure of fluid resorption - Transilluminates

Answer 160

Vast majority are germ cell tumours (95%) – arising from spermatocyte precursors. Amplification of i12p. Typically present in men aged 20-45 RFs: undescended testes, low birth weight/SGA Symptoms include a painless, craggy, fixed mass on the testicle and back pain if metastasised Seminomas are the most common germ cell tumour (also embryonal carcinoma, post pubertal teratoma, yolk sac tumour, choriocarcinoma) Non-germ cell tumours include Lymphoma (highly aggressive, older men), Sertoli and Leydig cell malignancies (usually benign) Investigation and treatment is with ultrasound, biopsy and orchidectomy. Germ cell tumours highly sensitive to platinum-based chemo. Germ cell - 98% 5YSR

Answer 161

Iron - haemachromatosis

Answer 162

Amyloid Apple green birefringence under polarised light

Answer 163

Inspection and Evisceration Do an examination of the body first: - Hands – clubbing, scars, splinter haemorrhages - Scar from median sternotomy – measure it and document (indicates CABG) - Look at the legs for vein harvest scar – measure and document - Hip replacement - Any operations on neck, any cyanosis on face Check name tag and identification of patient Make an incision from Adams apple to pubis to examine organs --> must remove chest plate on top of heart and lungs Cut through ribs (pericardium adheres to chest plate) Cut through trachea and great vessels in neck --> Remove heart and lungs in one block. Detach back of aorta. Detach large intestine Take out liver, spleen, pancreas, small bowel in another block Kidneys, bladder, ureters, prostate come out (also look at vessels for ruptured aneurysms) Genitals (&hernia) Organs go back in body in plastic bag. All sown up with suture material and can be buried and cremated. Can take swabs or samples of collections to the lab.

Answer 164

black and necrotic

Answer 165

Wedge shaped white spaces

Answer 166

Thinning cortex

Answer 167

Section 1a, b, c – deals with cause of death: A: immediate B: led to A C: led to B Section 2: Contributory factor Did not directly cause death Example: 1a) MI 1b) coronary artery atheroma 2) Diabetes, hypertension

Answer 168

Brain and spinal cord

Answer 169

Any organ | Intracranial: vestibular schwannoma (acoustic neuroma)

Answer 170

Tumours of the "coverings" - bone, cranial soft tissue, meninges, nerves, metastatic deposits ``` Astrocytes - astrocytoma Oligodendrocytes - oligodendroglioma Ependyma – ependymoma Neurons - neurocytoma Embryonal cells – medulloblastoma ```

Answer 171

Tumours of the parenchyma Derived from the normal cell populations of the CNS - glia, neurons, vessels, connective tissue.. Derived from other cells types - metastases, lymphomas, germ cell tumours Meningothelial cells – meningioma Schwann cells – schwannoma

Answer 172

LARGELY UNKNOWN Radiation to head and neck: meningiomas, rarely gliomas Neurocarcinogens? Genetic predisposition <5% of primary brain tumours- Familiarity, Familial syndromes

Answer 173

NF1: NEUROFIBROMA, PILOCYTIC ASTROCYTOMA NF2: SCHWANNOMA, MENINGIOMA TS: HAMARTOMAS, SEGA VHL: HEMANGIOBLASTOMA (neurofibromatosis, tubers sclerosis, von hippel lindau)

Answer 174

Tumour type: putative cell of origin Tumour grade: tumour differentiation A subset of tumours are defined by diagnostic mutations: genetic profile INTEGRATED HISTOLOGICAL AND MOLECULAR DIAGNOSIS No staging (like TNM)

Answer 175

``` 4 tier system: Grade I - benign - long-term survival Grade II – more than 5 yrs Grade III – less than 5 yrs Grade IV – less than 1yr ``` Grade guides treatment! Some tumour types have only one possible grade, some have 2 or 3, and some have all 4

Answer 176

DIFFUSE GLIOMAS IDH1/2 mutations Positive prognostic factor CIRCUMSCRIBED GLIOMAS MAPK pathway mutations (BRAF)

Answer 177

``` Mitotic activity is crucial: determines grade mitoses / 10HPF (0.16mm2): <4 = grade I 4-20 = grade II > 20 = grade III ```

Answer 178

- WHO grade 2 - Patients usually 20-40 years - Cerebral hemispheres most common site - MRI: T1 hypointense, T2 hyperintense, non-enhancing lesion. Low choline / creatinine ratio at MRSpec. - Low to moderate cellularity. Mitotic activity is negligible or absent. Vascular proliferation and necrosis are absent - Mutation of IDH1/2: in >80% of cases - Progression to higher grade is the rule: astrocytomas (grade II-III) become eventually glioblastoma (grade IV)

Answer 179

- WHO grade 2-3 - 5% of all primary brain tumours - Patients usually 20-40 years - Presents with long history of neurological signs – seizure - MRI: no or patchy contrast enhancement; MRI and MRSpec are not predictive of transformation - Round cells with clear cytoplasm (“fried eggs”) - Mutation of IDH1/2 + codeletion 1p/19q: almost 100% Better prognosis than astrocytomas Slow growth – resection is important Better response to chemo and radiotherapy

Answer 180

Excess accumulation of fluid in the brain parenchyma Two main types: Vasogenic – disruption of the blood brain barrier Cytotoxic – secondary to cellular injury e.g. hypoxia/ischaemia Result is raised intracranial pressure CT - area of lucency or hypodense or hypoattenuation

Answer 181

Increased volume of CSF in the ventricular system Non-communicating involves obstruction of flow of CSF Communicating involves no obstruction but problems with reabsorption of CSF into venous sinuses

Answer 182

- ICP is measured in mmHg and, at rest, is normally 7–15mmHg for a supine adult - 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 --> subfalcine, transtentorial, tonsillar herniation

Answer 183

Rapidly developing clinical symptoms and/or signs of focal, and at times global loss of cerebral function, with symptoms lasting more than 24 hours, with no apparent cause other than that of vascular origin Includes stroke due to: cerebral infarction, primary intracerebral haemorrhage, intraventricular haemorrhage and most cases of subarachnoid haemorrhage Excludes: subdural haemorrhage, epidural haemorrhage, intracerebral haemorrhage (ICH) or infarction caused by infection or tumour

Answer 184

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 1/3 of those with TIA get significant infarct within 5 years REMEMBER: TIA important predictor of future infarct

Answer 185

- Haemorrhage into the substance of the brain - rupture of a small intraparenchymal vessel - Most common in basal ganglia - Hypertension in > 50% of bleeds - Presentation with severe headache, vomiting, rapid loss of consciousness, focal neurological signs

Answer 186

- 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!!! - Seen on angiography - Morbidity after rupture 53-81% - high in eloquent areas - Mortality 10-17.6% - Treatment: surgery, embolization, radiosurgery Blood passes quickly from artery to vein, bypassing the capillary network.

Answer 187

- “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 - Pathogenesis unknown - Present with headache, seizures, focal deficits, haemorrhage - Low pressure – recurrent bleeds - Treatment: surgery - Target sign on T2 MRI

Answer 188

- 70-80% stroke - Worse atherosclerosis in larger vessels - 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 189

``` Infarct: Tissue necrosis (stains) Rarely haemorrhagic Permanent damage in the affected area No recovery ``` ``` Haemorrhage: Bleeding Dissection of parenchyma Fewer macrophages Limited tissue damage (periphery) Partial recovery ```

Answer 190

Trauma single largest cause of death in people under 45 9 deaths from head injury per 100,000 Account for 25% of all trauma deaths High morbidity: 19% vegetative or severely disabled 31% good recovery

Answer 191

Non-missile vs missle (missle = penetrating e.g. gun shot --> rare in this country) Non-missile by far most common --> most common cause of this is acceleration/deceleration in RTAs, falls and assaults If it's rotational - tends to focus all of the damage on midline structures Result can be focal (fractures, contusions) or diffuse

Answer 192

- Fissure fractures often extend into base of skull - May pass through middle ear or anterior cranial fossa - may get CSF leakage --> Otorrhea or rhinorrhea - Infection risk Battle sign and periorbital haemorrhages (racoon eyes)

Answer 193

- Brain in collision with skull - Surface “bruising” - If pia mater torn then becomes laceration - Some regions for susceptible than others due to bone on brain action - Lateral surfaces of hemispheres, inferior surfaces of frontal and temporal lobes - Coup or contrecoup injuries - RTA, rapid deceleration --> brain hits front of the skull, then there's a rebound and it hits the back of the skull

Answer 194

- Occurs at moment of injury (but also secondary phase where axons become more susceptible to damage later on) - 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 Research that there may be evidence of cognitive decline a while after TBI

Answer 195

- Rapidly progressive neurodegenerative disease – death within about a year - A series of diseases with common molecular pathology - Transmissible factor - No DNA or RNA involved - Prion (proteinaceous infectious only) - Purely protein – protein interaction which causes the problem

Answer 196

“The shake”, motor/brain disease in Papua New Ginuea. Caused/perpetated by endocanabolism – tradition in the tribe to eat your deceased relatives. Largely ended in the 70s but has a long incubation period – still some new cases.

Answer 197

Creutzfeldt-Jakob disease Gerstmann-Straüssler-Sheinker syndrome (GSSS) - genetic Kuru Fatal familial insomnia - genetic (north america and italy), massive psychiatric consequences

Answer 198

Spongiform encephalopathies – brain full of holes on post-mortum due to vacuolization – holes formed in the tissue due to the disease process. Prion proteins - cause plaques – lumps of prion protein sitting in brain substance. Transmission entirely dependent on interaction with host protein. Abnormal protein interacts with normal host protein and converts it to pathological protein. Normal prion protein unfolds from a helical structure and refolds into beta pleated sheet (same formation as amyloid). --> prion protein plaque deposits --> at some point this becomes irreversible.

Answer 199

- Sporadic neuropsychiatric disorder - Patients <45 yrs old - Cerebellar ataxia - Dementia - Longer duration than CJD - Linked to BSE - same protein found in mad cow disease - Diagnosed at autopsy since 1990

Answer 200

Multiple system atrophy (MSA) – a synuclein gone wrong but in the glial cells, not the neurons so much (it’s an oligodendroglial pathology) PSP and CBD – tauopathies (different protein to parkinsons) - Corticobasal degeneration (CBD) – astrocytic plaques with abnormal tau protein (hyperphosphorylated) - Progressive Supernuclear Palsy (PSP) – tufted astrocytes and oligoinclusions (pat lantos bodies)- tau

Answer 201

Goblet cells

Answer 202

Columnar Lined Oesophagus

Answer 203

US - has to be INTESTINAL metaplasia i.e. columnar AND goblet cells UK - diagnose with just gastric metaplasia i.e. columnar, no goblet cells

Answer 204

Poor | Diagnosis of pre-invasive stage important

Answer 205

50% per bleed/rebleed

Answer 206

Treat early - lymphoma will go away, if you leave it too long then it won't

Answer 207

- Helicobacter infection is associated with an 8x increased risk of (non-cardia) gastric cancer - cag-A-positive H.pylori have a needle like appendage that injects toxin into intercellular junctions allowing the bacteria to attach more easily.--> most damaging form - This strain is associated with more chronic inflammation. - Treatment of the infection with antibiotics drastically reduces the risk of cancer.

Answer 208

Chronic ulcers are fibrosed

Answer 209

Worse than intestinal. Signet ring cells tend to spread everywhere throughout the stomach. Lauren classification --> Different aeitiologies, pathways of development and clinical implications

Answer 210

H pylori is the cause of almost all duodenal ulcers --> get acid in the duodenum which is is completely not used to --> gastric metaplasia (if you see this, you know there has been increased acid) ``` Others: Immunosuppressed CMV Cryptosporidiosis Giardia lamblia infection Whipple’s disease -Tropheryma whippelii. ```

Answer 211

Pancreatic calcifications are diagnostic on AXR Macroscopically - fat, fibrosis, strictures and duct dilatation Histo: no acini - replaced by fibrosis. Appear to have more islets of langerhans.

Answer 212

Pancreatic enzymes Necrotic material Connect with pancreatic ducts May resolve, compress adjacent structures, become infected or perforate

Answer 213

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

Answer 214

Mucin secreting glands set in desmoplastic (fibrous) stroma - makes them "gritty" and hard to cut out

Answer 215

pancreatic cancer

Answer 216

"migratory thrombophlebitis" | Secrete mucin --> activates clotting cascade

Answer 217

Cysts commonly develop in patients with end stage renal disease who are on dialysis- multiple, bilateral, Cortical and Medullary Increased risk of development of malignancy - 7% risk at 10 years. Papillary renal cell carcinoma.

Answer 218

Failure of Glomerular Filtration Blockage of tubules by casts --> Leakage of tubules to interstitial space --> Secondary haemodynamic changes

Answer 219

Immune injury to tubules and interstitium ``` Can also be due to infection and drugs: NSAIDs Antibiotics Diuretics Allopurinol Proton Pump Inhibitors ``` Heavy interstitial inflammatory infiltrate with tubular injury - can see eosinophils, granulomas

Answer 220

- Acute inflammation of glomeruli - Presents with oliguria with urine casts containing erythrocytes and leucocytes - When sufficient to cause acute renal failure, there are almost always crescents (proliferation of cells within Bowman’s space).

Answer 221

Deposition of extracellular proteinaceous material exhibiting β-sheet structure Commonest forms in kidney are: - AA, derived from serum amyloid associated protein (SAA), an acute phase protein; patients tend to have a chronic inflammatory state - AL, derived from immunoglobin light chains; 80% of patients have multiple myeloma

Answer 222

``` Diabetes – 27.5% Glomerulonephritis – 14.1% Polycystic Kidney Disease – 7.4% Pyelonephritis – 6.5% Hypertension – 6.8% Renal Vascular Disease – 5.9% Other / Uncertain – 31.7% ```

Answer 223

Pathophysiology is not fully understood - Narrowing of arteries and arterioles leading to scarring and ischaemia of glomeruli - Hypertension in glomeruli leading to altered haemodynamic environment, stress and segmental scarring Shrunken kidneys with granular cortices Histopathology may show “nephrosclerosis” --> Arteriolar hyalinosis, arterial intimal thickening, ischaemic glomerular changes, segmental and global glomerulosclerosis

Answer 224

- Wilm's tumour - Malignant triphasic kidney tumour of childhood - Blastema (small round blue cells), Epithelial, Stromal - Typically presents as an abdominal mass in children aged 2-5 years old - 1 in 8,000 – second most common childhood malignancy - 95% of cases show favourable histological features with excellent prognosis

Answer 225

- Appear as frond-like growths - Divided into low grade and high grade (WHO 2004) based on nuclear atypia - Low grade tumours have a low risk of progression to invasive disease (<5%) - High grade tumours carry a higher risk of progression to invasive disease--> Unstable, carry a number of genetic aberrations including in RB and TP53

Answer 226

Urothelial tumour displaying invasive behaviour Wide range of subtypes Treatment based on depth of invasion- Lamina propria, Muscularis propria

Answer 227

May be invisible or appear as a reddish area Flat urothelial lesion with unequivocal high grade features- High risk of progression

Answer 228

Lichen Sclerosus / Balanitis Xerotica Obliterans- Inflammatory condition that causes phimosis Zoon’s balanitis - Inflammatory condition that causes red areas Condylomas - HPV 6 and 11 --> warts Peyronie’s Disease - Scarring , inflammation, thickening of corpus cavernosa --> erectile issue (curvature) Penile carcinoma - Rare, elderly men Smoking, HPV, chronic Lichen Sclerosus are risk factors

Answer 229

Urethritis - N. gonorrhoeae, C. trachomatis Prostatic Urethral Polyp - Papillary lesion in prostatic urethra Urethral Caruncle - Common lesion at urethral meatus in women Urethral Carcinoma - Rare, more common in women, usually squamous cell carcinoma Malignant Melanoma - Rare

Answer 230

Epidermoid Cyst- Common Scrotal Calcinosis- Rare; may be related to old epidermoid cysts Angiokeratomas- Benign vascular lesions Fournier’s Gangrene -Necrotising fasciitis; mortality of 15-20% Scrotal squamous cell carcinoma - Very rare, Historical interest; chimney sweep

Answer 231

10% of intracranial tumours that come to clinical attention Discovered incidentally in up to 25% of autopsies Adults. Peak 4th - 6th decade Microadenomas if < 1cm

Answer 232

Calcitonin --> promotes absorption of calcium by the skeletal system

Answer 233

- Common if there is impaired synthesis of thyroid hormone - most often due to iodine deficiency - Endemic in areas where iodine in the soil and water is low (‘Derbyshire neck’) - May be seen at puberty particularly in females - May be due to ingestion of substances that interfere with thyroid hormone synthesis e.g. brassicas - May be due to hereditary enzyme defects

Answer 234

Struma ovarii (ovarian teratoma with ectopic thyroid) Factitious thyrotoxicosis (exogenous thyroid intake)

Answer 235

- Solitary nodules more often neoplastic than multiple nodules - Solid nodules more likely to be neoplastic than cystic nodules - Nodules in younger patients more likely to be neoplastic than in older patients - Nodules in males more likely to be neoplastic than those in females - Nodules that do not take up radioactive iodine (cold nodules) more commonly neoplastic than ‘hot’ nodules

Answer 236

- Sudden withdrawal of corticosteroid therapy - Haemorrhage (neonates) - Sepsis with DIC (Waterhouse-Friderichson syndrome)

Answer 237

Adenomas: most non-functional May be associated with Cushing’s syndrome or Conn’s syndrome Carcinomas: Rare Usually large More commonly associated with virilizing syndrome than adenoma

Answer 238

- 10% arise in association with a familial syndrome inc. MEN 2A and 2B, von Hippel-Lindau disease and Sturge-Weber syndrome - 10% are bilateral - 10% are malignant - In addition 10% of catecholamine-secreting tumours arise outside the adrenal (paragangliomas)

Answer 239

Macroscopically - ulceration of the oesophagus Coin-like nuclear inclusion (CMV inclusion) in epithelial cells. IHC for CMV stains brown.

Answer 240

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

Answer 241

Lymphoma may show fewer lymphocytes and the person is immunosuppressed and the nature of that is having fewer lymphocytes

Answer 242

Caeseating granulomas | Stain +ve for acid-fast bacilli

Answer 243

Non-caseating granulomas | Diagnosis of exclusion

Answer 244

- Inflammation dominated by IgG4 antibody producing plasma cells - Fibrosis, obliteration of veins Plasma cell rich, inflammatory infiltrate Immunohistochemistry for IgG4 - Salivary and lacrimal glands: Mikulicz syndrome - Thyroid: Riedel thyroiditis - Peritoneum: Retroperitoneal fibrosis - Liver: Biliary obstruction - Pancreas: Autoimmune pancreatitis - Mass lesions: Inflammatory pseudotumour

Answer 245

- Deposition of an abnormal proteinaceous substance in non branching fibrils, 7.5-10nm diameter - Always contains P component - Beta-pleated sheet structure - A variety of proteins can take on this conformation Resistant to enzymic degradation 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 Another classification: - Transthyretin e.g. mutation - Beta2-macroglobulin – peritoneal dialysis - Abeta2 protein - Alzheimer’s - Insulin, calcitonin – endocrine tumours

Answer 246

``` 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 247

65% inorganic salts - Ca and PO4 35% organic - 30-40% collagen (Type 1 mostly with some type V) 10-20% water and ~5% non-collagenous protein & carbohydrate. I know the percentages don't add up but just know the vibe lol

Answer 248

``` Long bones 80% of skeleton Appendicular (limbs) 80-90% calcified mainly mechanical and protective ```

Answer 249

``` Vertebrae & pelvis 20% of skeleton Axial 15-25% calcified mainly metabolic Large surface ```

Answer 250

Circumferential lamellae Concentric lamellae Interstitial lamellae Trabecular lamellae

Answer 251

1. Osteoblasts - build bone by laying down osteoid 2. Osteoclasts - multinucleate cells of macrophage family resorb or chew bone 3. Osteocytes - osteoblast like cells which sit in lacunae

Answer 252

Increased osteoclast activity - RANK/RANKL Decreased osteoclast activity - OPG binds RANKL Osteoclasts are derived from the same mononuclear cells that differentiate into macrophages. Osteoblast/stromal cell membrane-associated RANKL binds to its receptor RANK located on the cell surface of osteoclast precursors. This interaction in the background of macrophage colony-stimulating factor (M-CSF) causes the precursor cells to produce functional osteoclasts. Stromal cells also secrete osteoprotegerin (OPG), which acts as a “decoy” receptor for RANKL, preventing it from binding the RANK receptor on osteoclast precursors. Consequently, OPG prevents bone resorption by inhibiting osteoclast differentiation.

Answer 253

Histology requires bone biopsy from iliac crest, processed un-decalcified for histomorphometry ‘Static’ parameters include: - cortical thickness & porosity - trabecular bone volume - thickness, number & separation of trabeculae Bone mineralisation is studied using osteoid parameters --> orange= unmineralised osteoid, green = mineralised osteoid ‘Histodynamic parameters’ are obtained from fluorescent tetracycline labelling

Answer 254

Aetiology – 90% cases due to insufficient Ca intake and post-menopausal oestrogen deficiency: 1º - age, post-menopause 2º - drugs, systemic disease ‘High turnover’ OP results from ↑ bone resorption ‘Low turnover’ OP results from ↓ bone formation Fracture Pathogenesis – low initial bone mass or accelerated bone loss can reduce bone mass below the fracture threshold Incidence: 1/3 women; 1/12 men >50 £1.7bn / yr = Cost of Rx 310k fractures 50% fracture patients cannot live independently post fracture; 20% die

Answer 255

``` Advanced age Female sex Smoking Excess Alcohol Early menopause Long-term immobility Low body mass index Poor diet ↓vit D, ↓Ca2+ Malabsorption Thyroid disease Low testosterone Chronic renal disease Steroids ```

Answer 256

Osteoclasts: - Decreased osteoclastogenesis - Early transient increase in osteoclast survival, cancellous osteoclasts, bone resorption Osteocytes: - Increased apoptosis - Decreased canceller circulation - Decreased bone quality Osteoblasts: - Decreased osteoblastogenesis - Increased apoptosis - Early and continual decrease in cancellous osteoblasts, synthetic ability, bone formation

Answer 257

Patients commonly present with back pain and # wrist (Colles’), hip (NOF and intertrochanteric) & pelvis may be the first sign of disease > 60% vertebral # are asymptomatic Compression # usually in T11-L2 distribution

Answer 258

Lab: Serum calcium, phosphorous & alk phos (usually N) Urinary calcium Collagen breakdown products Imaging - XR fractures Bone Densitometry - T score between 1 & 2.5 SD below normal peak bone mass= osteopaenia - T score >2.5 SD below normal peak bone mass = osteoporosis

Answer 259

More orange than green i.e. more osteoid than mineralised bone Risk of horizontal fracture in Looser's zone

Answer 260

Comprises all the skeletal changes of chronic renal disease:- Increased bone resorption (osteitis fibrosa cystica) Osteomalacia Osteosclerosis Growth retardation Osteoporosis

Answer 261

- Lytic lesions | - hyperparathyroidism --> brown cell tumour

Answer 262

Comprises all the skeletal changes of chronic renal disease:- - Increased bone resorption (osteitis fibrosa cystica) - Osteomalacia - Osteosclerosis (abnormal hardening of bone and an elevation in bone density) - Growth retardation - Osteoporosis

Answer 263

1. Osteolytic 2. Osteolytic-osteosclerotic 3. Quiescent osteosclerotic

Answer 264

``` Onset > 40y M=F Rare in Asians and Africans Mono-ostotic 15% (one bone affected) Remainder polyostotic ``` Aetiology is unknown Familial cases show autosomal pattern of inheritance with incomplete penetrance (mutation 5q35-qter - sequestosome 1 gene) Parvomyxovirus type particles have been seen on EM in Pagetic bone

Answer 265

- pain - microfractures - nerve compression (incl. Spinal N and cord) - skull changes may put medulla at risk - +/- haemodynamic changes, cardiac failure - Development of sarcoma in area of involvement 1%

Answer 266

Only ALP raised Gross - Thickening of cortex and coarse/irregular/thickened trabeculae Histo- thickened bony trabeculae with characteristic mosaic pattern and osteoclastic and osteoblastic activity

Answer 267

Simple - a fracture of the bone only, without damage to the surrounding tissues or breaking of the skin Compound - extends through skin Greenstick - the cortex is broken, but only on one side, more common in children Comminuted- more than two parts (i.e. bone broken into multiple bits) Impacted- broken ends of the bone are jammed together by the force of the injury

Answer 268

1. Organisation of haematoma at # site (pro-callus) 2. Formation of fibrocartilaginous callus 3. Mineralisation of fibrocartilaginous callus 4. Remodelling of bone along weight-bearing lines

Answer 269

Disorganised mixture of bone and cartilage and vascular fibrous tissue. Could be mistaken for osteosarcoma by non specialist pathologists with insufficient clinical information.

Answer 270

- Type of fracture - Presence of infection - Pre-existing systemic condition :-Neoplasm, Metabolic disorder, Drugs, Vitamin deficiency

Answer 271

- Vertebrae - Jaw (2º to dental abscess) - Toe (2º to diabetic skin ulcer) (>3mm) - Long bones (usually metaphysis)

Answer 272

Clinical features - General - malaise, fever , chills , leucocytosis - Local - pain, swelling and redness 60% positive blood cultures X-ray - mixed picture; eventually lytic

Answer 273

Almost always bacterial, rarely fungal Routes of infection: a) haematogenous (blood borne) b) direct extension (from nearby soft tissue infection) c) traumatic (inc surgery) ``` Organisms - general: Staph Aureus(90%) E. Coli Klebsiella Salmonella (associated with sickle cell disease) Pseudomonas (IVDA) ``` Organisms - neonates: Haemophilus influenzae Group B Streptococcus Occasionally enterobacter

Answer 274

Usually appear 10 days or so post onset Mottled rarefaction and lifting of periosteum >1week - irregular sub-periosteal new bone formation called involucrum Later - irregular lytic destruction (takes 10-14days) Some areas of necrotic cortex may become detached called sequestra (takes 3-6 weeks)

Answer 275

3-5% cases of extra-pulmonary TB Affects immunocompromised patients More destructive and resistant to control Spinal disease (50% cases) may result in psoas abscess and severe skeletal deformity (Pott’s disease) Systemic amyloidosis may result in protracted cases Presence of Langhans-type Giant cells

Answer 276

Another rare cause of OM (Treponema pallidum) ``` May be congenital or acquired Congenital skeletal lesions:- - Osteochondritis - Osteoperiostitis - Diaphyseal osteomyelitis ``` Aquired – late skeletal lesions:- - Non-gummatous periostitis - gummatous inflammation of bone and joints - Neuropathic joints (Tabes Dorsalis) - Neuropathic shaft fractures

Answer 277

Definition:- - Inflammatory arthropathy as part of a complex multisystem illness resulting from tick bite. - It is the most prevalent vector bone disease in temperate Northern hemisphere Organism:- Borrelia burgdorferi Tick Species:- Ixodes dammini Associated tic bite - ‘erythema chronicum migrans’ (targetoid)

Answer 278

Early localised - Characterised by rash (90%) usually within 7-10 days and between 1 & 50cm diameter. - Often thigh, groin, axilla (earlobe in children) Early Disseminated - Affects many organs, musculoskeletal, heart, nervous system. Late, persistent - Dominated by arthritis.

Answer 279

``` Treatment is based on prevention. Vaccines are available. Antibiotics for proven disease. No effective prophylaxis. Diagnosis is clinical. No specific histological features. ```

Answer 280

Degenerative joint disease Primary- age related Secondary - any age, previously damaged or congenitally abnormal joint Aetiology: ?biomechanical factors, ?biochemical factors, ?aging, ?genetic Result in: - Cartilage degeneration - Fissuring - Abnormal matrix calcification - Osteophytes Sites: Main sites vertebrae hips and knees +/-DIPJ PIPJ of the hand +/- carpometacarpal and metatarsophalangeal joints

Answer 281

- Severe chronic relapsing synovitis - Unpredictable course - Incidence 1% world population - 3F:1M, Age 30-40y Aetiology: likely autoimmune, genetic predisposition (risk alleles TNFA1P3, STAT4) 80% pts rheumatoid factor +ve - mostly IgM, forms immunocomplexes with IgG (these may underlie extra-articular disease)

Answer 282

``` Clinical features: Mild anaemia Raised ESR RF+ve(80%) +/- rheumatoid nodules (25%) *can be multisystem disease ``` Sites: - Small joints, hands and feet, sparing DIPJ - Wrists elbows ankles and knees Characteristic Deformities: - Radial deviation of wrist - Ulnar deviation of fingers - ‘Swan neck’ & ‘Boutonniere’ deformity of fingers - ‘Z’ shaped thumb

Answer 283

Proliferative synovitis with 1. Thickening of synovial membranes ( villous) 2. Hyperplasia of surface synoviocytes 3. Intense inflammatory cell infiltrate 4. Fibrin deposition and necrosis Pannus (abnormal layer of fibrovascular tissue or granulation tissue) formation with exuberant inflamed synovium overlying the articular surface.

Answer 284

- Affects any joint but great toe in 90% - Usually limited to lower extremities - Precipitate of needle shaped crystals into joint - Tophus is the pathognomic lesion

Answer 285

Usual age > 50y Crystals of: - Calcium pyrophosphate - mainly knees or - Calcium phosphates (hydroxyapatite) - knees and shoulders ``` Subsets: Sporadic Metabolic Hereditary (autosomal dominant) Traumatic ```

Answer 286

Pseudo: positively birefringent rhomboid crystals Gout: negatively birefringent needle-like crystals

Answer 287

Thyroid, breast, lung, kidney, prostate

Answer 288

Neuroblastoma, Wilm's tumour, osteosarcoma, ewings, rhabdomyosarcoma

Answer 289

Osteosarcoma Chondrosarcoma Ewing's sarcoma/PNET (primitive peripheral neuroectodermal tumour)

Answer 290

Commonest primary bone sarcoma Age: peak in adolescence (75% patients are <20y) Site: 60% occur around the knee X-ray: usually metaphyseal, lytic, permeative, elevated periosteum (Codman’s Triangle) Histo: malignant mesenchymal cells +/- bone and cartilage formation Prognosis: poor- 60% 5 year survival. Treatment is usually chemo and limb salvage surgery

Answer 291

Malignant cartilage producing tumour Age: 40y and over Site: pelvis, axial skeleton, prox femur, prox tibia X-ray: lytic with fluffy calcification Histo: malignant chondrocytes +/- chondroid matrix may dedifferentiate to high grade sarcoma Prognosis: 70% 5y survival (depends on grade & size)

Answer 292

Highly malignant small round cell tumour Age: usually < 20y (80%) Site: diaphysis/metaphysis of long bones, pelvis X-ray: onion skinning of periosteum, lytic +/- sclerosis Histo: sheets of small round cells Prognosis : - 75% 5y survival 50% longterm Specific chromosome translocation 11:22 (EWS/Fli1)

Answer 293

epidermis (keratinocytes, squamous epithelial cells), dermis (collagen, elastic fibres, adenexal structures) subcutaneous fat

Answer 294

- Vesiculobullous inflammatory reaction pattern - Reasonably high morbidity rate --> need to be admitted - Tense bullae that tend to present in the flexural surfaces - Autoimmune – complement attacks the way in which the keratinocytes sit on the basement membrane. - Complement attracts eosinophils which then release elastase --> fluid build up. - Subepidermal - the whole epidermis lifts up - Immunofluorescence IgG and C3- dermoepidermal junction (along the basement membrane zone)

Answer 295

- Vesiculobullous inflammatory reaction pattern - Flaccid looking blisters - Antigens against proteins that keep the keratinocytes stuck together so you get splitting WITHIN the epidermis - Autoimmune – IgG related --> immunofluorescence

Answer 296

- Vesiculobullous inflammatory reaction pattern - but don't really see bullae as they are very thin and often come off after a period of time (leaving excoriated looking area) - Rare - Loss of top layer of epidermis - stratum corneum - IgG related --> immunofluorescence key for making diagnosis

Answer 297

- Spongiotic inflammatory reaction pattern - Atopic/contact dermatitis - Scaly while plaques on flexural surfaces - Itchy - Spongiosis --> oedema between the keratinocytes - Eosinophil recruitment - Thickening of the epidermis over time

Answer 298

- Psorisaform inflammatory reaction pattern - Extensor surfaces - Silvery white plaques - Rapid shedding of skin - Normal Stem cell to keratinocyte = 56 days. 7 days in this. Thickening of the epidermis as a result. - Lose some normal layers of epidermis. - Munro micro abscesses --> little accumulations of neutrophils.

Answer 299

- Lichenoid inflammatory reaction pattern - Itchy purple/red patches/plaques - Extensor surfaces - Wickham striae – white lines in mouth - Histologically can't see where the epidermis stops and the dermis starts --> T lymphocytes damage bottom layer of keratinocytes in the epithelium. They die and you get "band-like" inflammation

Answer 300

Ulcer | Manifestation of many underlying diseases

Answer 301

``` Cauliflower shape Pigmented Completely harmless Keratinocytes proliferating upwards in an orderly fashion Keratin horn cysts – gaps ```

Answer 302

Central punctum, smooth, round, well circumscribed | Epidermis invaginates the dermis  produce keratin  get caseous stuff coming out

Answer 303

Sun exposed areas in the elderly Ulcerated, pearly rim, ‘rodent ulcer’ Tumour cells infiltrate into the dermis (beyond BM) Don't metastasise but are locally invasive

Answer 304

Big keratin horn Pre-cancerous/Full thickness dysplasia - Keratinocytes, bigger, pleiomorphic, hyperpigmented but haven’t broken basement membrane

Answer 305

Can be poorly or well differentiated | Can wrap round nerve --> perineurial invasion. Risk of recurrence greater with this.

Answer 306

Melanocytes sit on basement layer of epidermis --> make naevi when they accumulate/proliferate Junctional - group of melanocytes creating nests in epidermis. Compound - nests within epidermis and nests within dermis Intradermal - within the dermis Melanocytes allowed to break through basement membrane without being cancer.

Answer 307

Irregular outline, variable pigmentation, bleeding, itchy, growing. Junctional melanocytes moving up through the epidermis- upward migration/pagetoid spread (usually will drop down to dermis). Cells are bigger than expected in epidermis. In dermis- melanocytes should get smaller as they mature and move downwards, here they are all the same size so aren’t maturing and also there is increased mitosis (shouldn't see mitotic figures in melanocytes in the dermis except in pregnancy). Graded by depth in mm

Answer 308

Presentation: Skin (malar rash, discoid rash, raynaud's "even gangrene"), Oral ulcers, Joints, Neurological, Serositis (pleuritic chest pain, abdo pain etc), Renal, Haemotogical (can have pancytopenia), Immunological ANA - anti-nuclear antibodies - immunoflurosence screening test Specific antigens: Anti-dsDNA (Crithidia luciliae protozoan with lots of dsDNA - yellow, ELISA) Anti-smith (against ribonucleoproteins) - most specific but not v sensitive Anti-histone (drug related e.g. hydralazine)

Answer 309

Lymphocyte infiltration in the upper dermis Vacuolization of the basal layer of epidermis RBCs extravasated into the upper dermis (which are the reasons for the rash) Immunofluorescence staining (antibody to IgG showing evidence for immune complexes at the dermal-epidermal junction)

Answer 310

Thickened pink glomerular capillary loops (‘wire loops’) due to immune complex deposition Deposits of IgG and complement in the basement membrane - Immunofluorescence Electron dense deposit within the glomerular basement membrane - electron microscopy

Answer 311

Non-infective endocarditis | Strands of fibrin, neutrophils, lymphocytes, histiocytes

Answer 312

Tight skin Fibrosis & excess collagen (localised form is called morphoea in the skin) Tight skin over trunk = diffuse form No tight skin over trunk = limited form ``` Diffuse form: Antibodies to DNA topoisomerase (Scl70) Limited form (CREST): Anticentromere antibody ``` ``` Calcinosis Raynauds Esophageal dysmotility Sclerodactyly Telagiectasia Nailfold capillary dilatation Microstomia ```

Answer 313

Nucleolar pattern immunofluorescence Increased dermal collagen resulting in reduced skin elasticity ‘Onion skin’ intimal thickening of small arteries

Answer 314

Proximal myopathy High CK Speckled pattern of ANA test Dermato- Gottron's papules: erythematous rash over knuckles & dorsal aspect of hand

Answer 315

Pres: Joints, Skin (nodules/papules, lupus pernio, erythema nodosum), Lungs, Lymphadenopathy, Heart, Eyes, Neuro, Liver Skin: Lupus pernio, erythema nodosum CNS: Meningitis, cranial nerve lesions Eyes: Uveitis, keratoconjunctivitis Parotids: Bilateral enlargement Lungs: BHL (bilateral hilar lymphadenopathy), fibrosis, lymphocytosis (CD4+ in BAL) Liver: Hepatitis, cholestasis & cirrhosis

Answer 316

Non-caseating granulomas- histiocytes (epithelioid cells), multinucleated giant cells of Langhans (peripheral nuclei) and lymphocytes. Hypergammaglobulinaemia Raised ACE Hypercalcaemia - Vit D hydroxylation by activated macrophages

Answer 317

``` Necrotising arteritis Polymorphs, lymphocytes, eosinophils Arteritis is focal and sharply demarcated Heals by fibrosis More often renal and mesenteric arteries ``` Nodular appearance on angiography (small aneurysms) Associated with hep B

Answer 318

Palpable purpuric rash

Answer 319

Steroids ESR Biopsy - Chronic lymphocytic inflammation in the media, giant cells, narrowing of the lumen

Answer 320

Small vessel vasculitis ENT Lung Kidneys C-ANCA (cytoplasmic ANCA) directed against proteinase 3

Answer 321

Small vessel vasculitis Asthma Eosinophilia Vasculitis P-ANCA (perinuclear ANCA) directed against myeloperoxidase

Answer 322

``` C1 = inadequate C2 = benign C3 = atypia, probably benign C4 = suspicious of malignancy C5 = malignant ```

Answer 323

“complex sclerosing lesions”

Answer 324

Not considered a direct precursor lesion to invasive breast carcinoma but is a marker for a slightly increased risk (relative risk of 1.5-2.0) for subsequent invasive carcinoma.

Answer 325

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 326

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 327

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

Answer 328

All invasive breast cancers are graded histologically by assessing 1) tubule formation 2) nuclear pleomorphism, and 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 329

All invasive breast carcinomas are assessed for oestrogen receptor (ER), progesterone receptor (PR) and 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 330

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 331

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. About 5% of women have an abnormal mammogram and are recalled to an assessment clinic for further investigation. 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 332

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 stroma is often cellular and oedematous. Benign, no risk of malignancy.

Answer 333

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 334

Non-productive/latent phase: 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 Productive Viral Infection Viral DNA replication occurs independently of host chromosomal DNA synthesis. Large numbers of viral DNA are produced and results in infectious virions. Characteristic cytological and histological features are seen.

Answer 335

Develop through the accumulation of mutations of at least 4 different genes: - PTEN (10q23; 37-61%) - PI3KCA (39%) (mainly codons 9 and 20) - K-ras (10-30%) - CTNNB1 (14%-44%) - FGFR2 (16%) - P53 (10%)

Answer 336

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 337

Stage 1 – confined to uterus Stage 2 – spread to cervix Stage 3 – spread to adnexae, vagina, local lymph nodes (pelvic or para-aortic) Stage 4 – other pelvic organs distant spread inc any other distant lymph node groups

Answer 338

- None of partial and only 2.5% of complete moles progress to malignancy - 10% of complete moles develop into invasive moles – locally destructive - Complete moles may persist or recur - Chromosomal abnormalities play an important role in development of moles.

Answer 339

``` 1 in 20,000 to 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 340

Epithelial tumours make up 65% of all ovarian tumours & 95% of malignant ovarian tumours Epithelial tumours: 50% found in 45-65 age group Germ cell tumours have bimodal distribution; one peak 15-21 year olds and one peak at 65-69. Sex cord tumours most common in post-menopausal women but some sub-types peak in 25-30 year age group

Answer 341

Low grade, relatively indolent, arise from well characterised precursors (BOT) and endometriosis Usually present as large stage I tumours Mutations in K-ras, BRAF, PI3KCA and HER2, PTEN and beta–catenin Usually have precursors Include low grade serous, low grade endometrioid, mucinous and tentatively CCC. (CCC is high grade, but molecular changes are more like type I and also having endometriosis as precursor lesion

Answer 342

High grade mostly of serous type Aggressive More than 75% have p53 mutations No precursor lesions

Answer 343

- Indicates presence of embryonic elements - Neural tissue particularly conspicuous - A malignant neoplasm that grows rapidly, penetrates the capsule and forms adhesions to the surrounding structures - Spreads in the peritoneal cavity by implantation - Mets to lymph nodes, lung, liver and other organs - Three grading system according to amount of primitive elements

Answer 344

Malignant transformation is rare occurring in 2% of cases, usually in post menopausal women Most frequently SCC Also carcinoid, thyroid ca, BCC, malignant melanoma, intestinal adenocarcinoma, leiomyosarcoma, chondrosarcoma and hemangiosarcoma

Answer 345

Up to 10% of epithelial ovarian cancer cases are familial 10% of women with ovarian carcinoma are carries of a breast/ovarian ca susceptibility gene 3 familial syndromes: All are transmitted in an autosomal dominant fashion familial breast-ovarian cancer syndrome site-specific ovarian cancer cancer family syndrome (Lynch type II) Familial breast-ovarian cancer and site-specific ovarian cancer syndromes both associated with mutations of the BRCA1 suppressor gene; account for 90% of familial ovarian cancers Hereditary ovarian cancer occurs at a younger age than sporadic Carriers have 15 fold increase risk of ovarian carcinoma to non-carriers Multiple cases of early onset breast cancer

Answer 346

``` Benign tumours: Papillary Hidradenoma Malignancy:3% of female genital tract tumours SCC: 85% HPV or lichen sclerosus VIN: vulval intraepithelial neoplasia Paget’s disease: (adenocarcinoma-in-situ) rarely associated with invasive adenocarcinoma Adenocarcinoma Malignant melanoma Basal cell carcinoma ```

Answer 347

Congenital anomalies: Absence or atresia Tumours: 1% of female genital tract tumours Carcinoma: squamous cell carcinoma Adenocarcinoma: Clear cell adenocarcinoma if mother was treated during pregnancy by Diethyl stilbosterol for threatened abortion Rhabdomyosarcoma

Answer 348

Heavy watery lungs, intra-alveolar fluid on histology. Iron laden macrophages - stain blue. Fluid in alveoli leads to reduced gas exchange.

Answer 349

Important cause of rapid onset respiratory failure Pathogenesis: acute damage to endothelium and/or alveolar epithelium leading to exudative inflammatory reaction. Get diffuse alveolar damage - lungs expanded and firm, plum coloured, airless, often weight >1kg. Exudative phase --> hyaline membranes --> Organising phase = fibrosis of the exudates Adults – Acute respiratory distress syndrome “shock lung” Neonates - Hyaline membrane disease of newborn (surfactant deficiency) Outcomes: death (40%), superimposed infection, resolution (lung returns to normal), residual fibrous scarring of lung (chronic resp impairment).

Answer 350

Widespread narrowing of the airways that changes in severity over short periods of time. Acute change: Bronchospasm, oedema, hyperaemia, inflammation ``` Chronic change: Muscular hypertrophy Airway narrowing Mucus plugging Overinflated lungs ``` Histology: Lots of eosiniophils. Lots of goblet cells producing mucus. Thickened airway and dilated blood vessels.

Answer 351

Dilated airways Mucus gland hyperplasia Goblet cell hyperplasia Mild inflammation

Answer 352

Permanent loss of the alveolar parenchyma distal to the terminal bronchiole Pathogenesis Inflammation --> neutrophil and macrophage activation This leads to an increase in proteases (e.g. elastase) --> tissue damage SMOKING: Loss centred on bronchiole - CENTRILOBULAR ALPHA 1 ANTITRYPSIN DEF - Diffuse loss of alveolae - PANACINAR

Answer 353

Permanent abnormal dilatation of bronchi with inflammation and fibrosis extending into adjacent parenchyma. Can be inflammatory or congenital. Most commonly associated with infection (especially in children with CF), also in ciliary dyskinesia (primary = kartagener's)

Answer 354

Community acquired: streptococcus pneumoniae, haemophilis influenzae, mycoplasma Hospital acquired: gram –ve (klebsiella, pseudomonas) Aspiration: Mixed aerobic and anaerobic Variety of patterns of lung involvement depending upon organism and other co-factors - Bronchopneumonia - Lobar pneumonia - Abscess formation - Granulomatous inflammation

Answer 355

Compromised host defense - Elderly Often low virulence organisms - Staphylococcus, Haemophilius, Streptococcus, Pneumococcus, Pathology - Patchy bronchial and peribronchial distribution, often lower lobes Histopathology- Peribronchial distribution. Acute inflammation surrounding airways and within alveoli.

Answer 356

Acute bacterial infection of a large portion of a lobe or entire lobe. Infrequent with advent of antibiotics 90-95% pneumococci (S. pneumoniae) Widespread fibrinosuppurative consolidation Histopath: 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. Scarring in some pts.

Answer 357

Mycoplasma, viruses (e.g. CMV, influenza), Coxiella, Chlamydia Interstitial inflammation (pneumonitis) without accumulation of intra-alveolar inflammatory cells Chronic inflammatory cells within alveolar septa with oedema +/- viral inclusions

Answer 358

Discrete epithelioid and giant cell granulomas, preferential distribution in upper zones with tendency to be perilymphatic, peribronchial Advanced disease may be fibrotic and cystic Diagnosis: - Biopsy (Bronchial/OLB) - Non-necrotising granulomas, either singly or coalescent. May undergo fibrosis. - Elevated serum Angiotensin Converting Enzyme (ACE)

Answer 359

Intravascular talc granulomas in an intravenous drug abuser | Aspirated material

Answer 360

Macro – Basal and peripheral fibrosis and cyst formation Micro - interstitial fibrosis at varying stages Diagnosis by HRCT +/- biopsy. Progressive disease Over 50% die in 2-3 years

Answer 361

Fine subpleural basal fibrosis with asbestos bodies in tissue. May also see pleural disease - fibrosis, pleural plaques. Increased risk of lung cancer in the presence of asbestosis.

Answer 362

PHBP = mean pulmonary arterial pressure > 25mmHg at rest ``` Precapillary: VASOCONSTRICTIVE - Chronic hypoxia - Hyperkinetic congenital heart disease - Unknown (primary pulmonary HTN) - Chronic liver disease, HIV, 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 363

Normal response of lung is to reduce blood supply to hypoxic areas of lung and divert it to aerated zones Chronic hypoxia results in chronic vasoconstriction pulmonary arterioles (COPD, Fibrosing lung disease) Morphological changes in vessels: - Eccentric intimal fibrosis - Thickening muscle wall

Answer 364

Common site formation in deep veins of leg (95%) Thrombus formation- Virchows triad: - factors promoting blood stasis - damage to endothelium - increased coagulation SMALL EMBOLI - 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 or chronic progressive shortness of breath LARGE EMBOLI - 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 ``` NON-THROMBOTIC EMBOLI Bone marrow Amniotic fluid Trophoblast Tumour Foreign body Air ```

Answer 365

Fibrotic occlusion of pulmonary veins Collagenous occlusion of vein (pink stains Collagen, black stains elastic lamina of vein).

Answer 366

Right sided heart failure - Venous congestion of visceral organs – “nutmeg liver” - Peripheral oedema - Pleural effusions and ascites - Poor lung perfusion and hypoxia

Answer 367

Uncommon Present as life threatening haemorrhage, chronic haemoptysis, mass lesion, interstitial lung disease Variety of patterns from granulomatous vasculitis involving small-medium sized vessels (GPA) through to a leukocytoclastic vasculitis involving capillaries (e.g with Rheumatoid arthritis)

Answer 368

Peripheral or central 10% of tumours 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 369

Small cell lung carcinoma: Survival 2-4 months untreated 10-20 months with current therapy chemoradiotherapy (surgery very rarely undertaken as most have spread at time of diagnosis) ``` Non-small cell lung carcinoma: Early Stage 1: 60% 5 yr survival Late Stage 4: 5% 5 yr survival 20-30% have early stage tumours suitable for surgical resection. Less chemosensitive ``` Adenocarcinoma vs squamous cell carcinoma: 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) Pathologists frequently need to sub-type small biopsy material/cytology material to guide diagnosis.

Answer 370

(Adenocarcinomas) EGFR- Cetuximab, Gefitinib, Erlotinib. Tyrosine kinase inhibitor therapy. ALK translocation and Ros1 translocation respond to crizotinib.

Answer 371

High levels of PD1 or PDL1 protein expression (IHC) may inhibit Immune response. Cytotoxic T cells express PD-1 Tumour cells express PD L1 – binds PD-1, inhibits t cells from killing tumour cells, escape immune response Other cells also express PD L1, dendritic cells, macrophages, fibroblasts which may also modulate cytotoxic t cell activity.

Histopath Flashcards

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