Histopathology Flashcards

Question

Describe immunofluorscence stains.

Answer 1

Fluorescent tag to bridge antibody to make it visible Examined under a fluorescent microscope

Answer 2

Detector system is an enzyme which is tagged to antibody Bridging system to antibody to make it visible Add substrate which makes colour change

Answer 3

Lymphatics

Answer 4

Each corner of the hepatic lobule Bile ducts, portal venule, hepatic arteriole

Answer 5

Towards central vein via sinusoids

Answer 6

Produced by hepatocytes towards the bile ductule via canaliculi (away from the central vein)

Answer 7

Richest oxygen supply Highest levels of ALP

Answer 8

Lowest oxygen supply Most metabolically active cells - suscept to hypoxic or drug damage

Answer 9

Viruses - hepatitis viruses, other in immunosuprressed Drugs Alcohol

Answer 10

Viruses Drugs AI PBC PSC Wilson’s Haemachromatosis

Answer 11

Conjugated by the liver Excreted via bile and kidneys - Normal to have urinary urobilinogen (bilirubin converted by gut bacteria and reabsorbed via the enterohepatic circulation to be excreted via the kidneys)

Answer 12

- Lack of urinary urobilinogen - Itching - bile salts/acid deposition - Pale stool - lack of stercobilinogen Dark urine - conjugated bilirubin leaking out into urine

Answer 13

Protein content \<30g/L

Answer 14

Protein content \>30g/L

Answer 15

Cardiac failure Renal failure Cirrhosis Hypoalbuminaemia

Answer 16

Malignancy Pancreatitis Intra-abdominal TB

Answer 17

Fat deposition Neutrophil Polymorphs - IS REVERSIBLE

Answer 18

Neutrophils infiltrating the liver Balloon cells containing Mallory-Denk bodies (or mallory hyaline) Accumulation of bile as hepatocytes swell with the balloon cells & block the flow of bile (reversible/irreversible)

Answer 19

Use collagen blue stain → collagen deposition around hepatocytes indicating scarring

Answer 20

Regenerative nodules of hepatocytes Cuff of fibrous tissue (micronodular cirrhosis) Fibrous connective tissue that bridges between portal tracts Distortion of vascular architecture - regeneration is disorganised so blood trying to get around the nodules leads to the portal hypertension - IS IRREVERSIBLE

Answer 21

Palmar erythema Gynaecomastia Dupytren’s contracture Spider naevi

Answer 22

Caput medusae Splenomegaly Ascites

Answer 23

Alcoholic Fatty Liver Disease (AFLD)

Answer 24

Alcoholic hepatitis

Answer 25

Liver cirrhosis

Answer 26

Liver fibrosis

Answer 27

Similar features to AFLD but with alcohol history - Fat deposition - Neutrophil polymorphs Most NASH patients have diabetes

Answer 28

Inflammation Necrosis + Fibrosis → Cirrhosis & Liver failure

Answer 29

Anti-smooth muscle Abs +/- ANA Occurs from 10 years of age → elderly

Answer 30

Type 1 responds well to steriods whereas type 2 doesn't Type 1 has an overall better prognosis

Answer 31

Anti-liver kidney microsomal-1 Abs Tends to present in children Association with IgA deficiency

Answer 32

Anti-soluble liver antigen Abs

Answer 33

Chronic granulomatous inflammation of the bile duct

Answer 34

Itching Fatigue Abdominal pain

Answer 35

Anti-mitochondrial Abs F\>M Most common in middle-age Often have raised IgM levels Often associated with other AI disorders e.g. scleroderma, RA

Answer 36

Raised serum cholesterol High ALP High bilirubin

Answer 37

Beading of the bile ducts on ERCP - due to strictures Fibrosis of the bile ducts throughout the biliary tree with associated stricture formation Onion skinning fibrosis

Answer 38

Fibrosis symptoms M\>F p-ANCA +ve 60% associated with UC Bile duct dilatation on US Increased risk of cholangiocarcinoma

Answer 39

Metastases

Answer 40

Haemangioma

Answer 41

Dependent upon inflammation - Portal inflammation = inflammation confined within limiting plate - Interface hepatitis = between the portal tract and the parenchyma - Lobular inflammation = across the whole lobe

Answer 42

F0: no fibrosis F1: portal fibrosis without septa F2: portal fibrosis with few septa F3: numerous septa without cirrhosis F4: cirrhosis

Answer 43

Low ceruloplasmin AR inheritance of a mutated copper transport gene → inability of liver to secrete the copper-ceruloplasmin complex into the plasma

Answer 44

Parkinsonian features Liver disease Kayser-Fleisher rings around cornea Psychiatric history

Answer 45

Rhodanine stain

Answer 46

Penicillamine

Answer 47

Excess iron AR inheritance causing excess iron absorption in the gut and therefore excess iron deposition - haemosiderin deposition in organs

Answer 48

Rusty brown appearance

Answer 49

* Brown/bronze discolouration of the skin * Diabetes - previously known as golden diabetes * Slate-grey discolouration * Steatorrhoea

Answer 50

Therapeutic phlebotomy

Answer 51

AR benign condition resulting in reduced conjugation of bilirubin - due to reduced activity of UDP Glucuronyl transferase

Answer 52

LFTs will be normal - Isolated rises in unconjugated bilirubin

Answer 53

Alcohol Dehydration Infection Stress Exercise Fasting Menstration

Answer 54

Hepatic vein thrombosis causing outflow tract obstruction - Associated with polycythaemia rubra vera

Answer 55

Hepatomegaly Ascites - Sometimes symptoms of polycythaemia - often no symptoms but can be headaches, blurred vision, fatigue, weakness, itchy skin, dizziness, hight sweats

Answer 56

* Mesothelioma * Associated with asbestos exposure * Can be visceral or parietal pleura

Answer 57

* 20 years * Pleural fibrosis * Pleural plaques

Answer 58

* Plueral effusions

Answer 59

* The patient has suffered multiple chest infections * Suggests a likely Cystic fibrosis

Answer 60

Death Arrhythmia Rupture Tamponade Heart Failure Valve Disease Aneurysms Dressler's Syndrome Embolism Re-infacrtion

Answer 61

Systemic Hypertension

Answer 62

Right Coronary Artery - Inferior MI

Answer 63

A previous MI

Answer 64

Left Anterior Descending

Answer 65

Circumflex artery - Lateral

Answer 66

Right cornary artery - Inferior

Answer 67

Left anterior descending - Anterior

Answer 68

Nutmeg Liver

Answer 69

* Right heart failure - Most common * Obstruction of blood flow in hepatic vein * Obstruction of blood flow in the inferior venacava * Pathogensis: 1. Increased pressure in the hepatic veins cause stasis of blood causes deoxygenation of hepatocytes 2. Necrosis occurs which is surrounded by paler zone which contains damaged hepatocytes with fatty change 3. Adjacent to this zone normal unaffected hepatocytes are present which are adjacent to hepatic arteriole and are better oxygenated

Answer 70

Chronic stable liver disease

Answer 71

An autoimmune skin disease that causes tense bullae on flexor surfaces * Dermo-epithelial junction affected * 10-20% mortality - risk factor for serious skin infections/sepsis

Answer 72

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

Answer 73

Autoimmune skin condition resulting in the formation of flaccid blisters which are prone to rupture - Affects the epiderma-epidermal junction

Answer 74

* IgG attacks between the keratin layers (acantholysis) * i.e. loss of intracellular connections * Need immunofluorescence to confirm

Answer 75

IgG-mediated autoimmune condition in which the outer layer of stratum corneum shears off

Answer 76

Coin-shaped rashes on the flexor surfaces

Answer 77

A localized rash or irritation of the skin caused by direct contact the inducing substance to which the skin reacts - Itchy thickened skin

Answer 78

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

Answer 79

Bullous pemphigoid

Answer 80

Pemphigus vulgaris

Answer 81

Pemphigus foliaceus

Answer 82

Discoid eczema

Answer 83

Contact dermatitis

Answer 84

A skin disease that causes silver plaques on extensor surfaces

Answer 85

* Rapid keratinocyte turnover leads to a thicker epidermis * A layer of parakeratosis forms at the top * Stratum granulosum disappears as not enough time to form it; and dilated vessels form * Munro's microabscesses form, made up from recruitment of neutrophils

Answer 86

T-cell mediated autoimmune condition resulting in purplish-red papules and plaques on wrists and arms

Answer 87

Plaque psoriasis

Answer 88

White lines found in the mouth of patients with Lichen planus

Answer 89

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

Answer 90

Lichen planus

Answer 91

Vasculitis that presents as non-healing ulcer * Often, first manifestation of a systemic disease * Colitis, hepatitis, leukaemia

Answer 92

Pyoderma gangrenosum

Answer 93

Benign, pigmented lesion that has a stuck on appearance (often gets caught on clothing)

Answer 94

Seborrhoeic keratosis

Answer 95

A swelling in the skin arising in a sebaceous gland, typically filled with yellowish sebum - The cyst transluminates, has a central punctum and is circumscribed and hot

Answer 96

* Rolled, pearly-edge * Central ulcer * Telangiectasia * *“Rodent ulcer” as it burrows away*

Answer 97

Cancer cannot break through the basement membrane

Answer 98

Sun-exposed areas of skin

Answer 99

Gorlin's syndrome

Answer 100

Basal cell carcinoma

Answer 101

* Squamous cell carcinoma *in situ* [i.e. pre-cancerous] * Keratinocytes become more pleiomorphic and larger with mitotic figures

Answer 102

Rough, scaly surface and flat reddish patches

Answer 103

* Very very very rarely * More commonly Peri-neural invasion - Local invasion

Answer 104

Pink due to lots of keratin

Answer 105

Squamous cell carcinoma

Answer 106

* A common birthmark, presenting as a hyperpigmented skin patch with a sharp border and diameter of \> 0.5 cm * A form of melanocytic naevus

Answer 107

Café-au-lait spots

Answer 108

* Melanocytes nest in the epidermis * Flat and coloured * Normally, melanocytes sit in the basal layer of the epidermis * As you age, melanocytes usually drop into the dermis

Answer 109

Nests in epidermis and dermis * Raised area * Surround by flat pigmented area

Answer 110

* Nests in the dermis * Raised area * Skin-coloured or pigmented

Answer 111

* Irregular border * Variable pigmentation * Bleeding * Itchy * Growing

Answer 112

* B-raf 600 * Found in 60% * Is a target for treatment - B-raf inhibitors

Answer 113

Widespread reversible narrowing of the airways that changes in severity over short periods of time.

Answer 114

* Allergens/atopy * Pollution * Drugs (NSAIDs) * Occupational (gases/fumes) * Diet * Physical exertion * Intrinsic * Underlying Genetics

Answer 115

* Sensitisation to allergen; followed by: * Immediate phase = *mast cell degranulation causing* *mediator release whihc* *increases vascular permeability, eosinophil and mast cell recruitment and bronchospasm* * Late phase = *tissue damage, increased mucous production, muscle hypertrophy*

Answer 116

* Hyperaemia *(Top left)* * Eosinophils and goblet cell hyperplasia *(Top right)* * Hypertrophic constricted muscle *(Bottom left)* * Mucus plugging and inflammation *(Bottom Right)*

Answer 117

Chronic inflammatory lung disease that causes obstructed airflow from the lungs

Answer 118

* Smoking * Air Pollution * Occupational exposure * A1AT deficiency * Rare (IVDU, connective tissue disease)

Answer 119

* Dilatation of airways * Hypertrophy of mucous glands * Goblet cell hyperplasia

Answer 120

* Repeat infections * Chronic hypoxia/Reduced exercise tolerance * Pulmonary Hypertension/RHF * Lung cancer risk

Answer 121

Permanent abnormal dilatation of the terminal bronchi.

Answer 122

* Congenital * CF * Ciliary dyskinesia - *i.e. Kartagener’s syndrome* * Inflammatory * Post-infectious * Obstruction * 2^nd to bronchiolar disease and interstitial fibrosis * Asthma

Answer 123

* Recurrent infections * Haemoptysis * Cor pulmonale * Amyloidosis

Answer 124

A hereditary disorder affecting the exocrine glands It causes the production of abnormally thick mucus, leading to the blockage of the pancreatic ducts, intestines, and bronchi and often resulting in respiratory infection.

Answer 125

* CFTR gene on Chr 7 * Abnormal CFTR causess defective Cl^- ion transfer so less water transfer to secretions * Leads to thick secretions which are hard to clear

Answer 126

* Lung * Cough * Purulent Secretions that is foul smelling * Obstruction * Respiratory failure * Recurrent infection * Bronchiectasis (90%) * GI tract * Meconium ileus * Malabsorption * Pancreas * Pancreatitis * 2^nd malabsorption * Liver * Cirrhosis * Male infertility

Answer 127

* Physio * Trikafta - *elexacaftor, tezacaftor, and ivacaftor* * Antibiotics - Broad spectrum or Aminoglycosides * Lung transplant

Answer 128

* P. aeruginosa - most common * S. aureus - most common in very young * H. influenzae * B. cepacia

Answer 129

* LHF * Alveolar injury * Neurogenic * High altitude

Answer 130

Acute damage to endothelium ± alveolar epithelium leading to an exudative inflammatory reaction

Answer 131

* Infection * Aspiration * Trauma * Inhaled irritant * Shock * Blood transfusion * DIC * Drug overdose * Pancreatitis

Answer 132

Insufficient surfactant - most commonly due to premature briths

Answer 133

* Basic pathology = Diffuse alveolar damage * Gross pathology: * Fluffy white infiltrates in all lung fields * Lungs expanded/firm * Plum-coloured lungs, airless * \>1kg mass * Micro-pathology: * 1. Capillary congestion * 2. Exudative phase * 3. Hyaline membranes * 4. Organising phase

Answer 134

* Bronchopneumonia * Lobar pneumonia * Abscess formation * Granulomatous inflammation

Answer 135

Patchy bronchial and peribronchial distribution, lower lobes, inflammation surrounding the airways themselves and is within the alveoli

Answer 136

* Low virulence organisms * Staph * H. influenzae * Strep * Pneumococcus

Answer 137

Infection of an entire lobe - Infrequent due to Abx

Answer 138

Pneumococci - Strep

Answer 139

1. Congestion - *Hyperaemia, Intra-alveolar fluid* 2. Red hepatization - *Hyperaemia, Intra-alveolar neutrophils* 3. Grey hepatization - *Intra-alveolar connective tissue* 4. Resolution - *Restoration normal architecture*

Answer 140

* Abscess * Pleuritis * Effusion * Empyema (infected effusion) * Fibrosis * Sepsis

Answer 141

* Mycoplasma * Viruses (CMV, influenza) * Coxiella * Chlamydia * Legionella

Answer 142

Permanent loss of alveolar parenchyma distal to terminal bronchiole

Answer 143

* Bullae formation - Pneumothoraces * Respiratory failure * Cor pulmonale

Answer 144

* Irreversible enlargement of airspaces distal to terminal bronchioles * No scarring/fibrosis * Impaired gaseous exchange * Dyspnoea * Pneumothorax if vullae rupture * Pulmonary hypertension - Cor pulmonale/RHF

Answer 145

Collection of histiocytes, macrophages ± giant multinucleate cells

Answer 146

* Infection * TB must first be excluded before looking for other causes * Fungal = histoplasma, cryptococcus, coccidioides, aspergillus, Mucor * Other = pneumocystis, parasites * Sarcoidosis * Foreign body aspiration * IVDU * Drugs * Occupational

Answer 147

Abnormal host immunological response to variety of commonly encountered antigens, probably environmental in origin, resulting in granuloma formation

Answer 148

* Lungs * Skin * Lymph nodes * Eyes

Answer 149

* Discrete epithelioid and giant cell granulomas, preferential distribution in upper zones with a tendency to peri-lymphatic and peri-bronchial * In advanced disease becomes fibrocystic

Answer 150

* X-ray/CT = Non-caseating granuloma * Bloods: * Elevated serum ACE * Hypercalcaemia (1a-hydroxylase)

Answer 151

* Macro = basal and peripheral fibrosis and cyst formation * Micro = interstitial fibrosis (varying stages)

Answer 152

* IPF = Progressively gets worse regardsless - 50+% die within first 3 years * EAA = Gets beter when away from causative allergen * Farmer's lung - patient gets better over the weekend when they are away from work

Answer 153

* Asbestos - Asbestosis * Silicon - Silicosis * Coal - Coal-miner's lung

Answer 154

* Fine sub-pleural basal fibrosis with asbestos bodies in tissue * ± pleural disease - fibrosis, pleural plaques * Increased risk of lung cancer

Answer 155

* Bone marrow * Amniotic fluid * Trophoblast * Tumour * Foreign body * Air * Fat

Answer 156

* Small emboli: * Pleuritic chest pain or chronic progressive SoB due to pulmonary HTN * Repeated emboli will cause increasing occlusion of pulmonary vascular bed and pulmonary HTN * Large emboli: * Occlude main pulmonary tract (saddle embolus is possible) - sudden death/RHF/shock * 30% will develop a second embolus

Answer 157

* Life threatening haemorrhage * Chronic haemoptysis * Mass lesion * Interstitial lung disease

Answer 158

* Squamous cell carcinoma (30%) * Adenocarcinoma (30%) * Large cell carcinoma (20%) * Small Cell Lung Carcinoma (20%)

Answer 159

* Smoke = strongest association with **SCC** and **SCLC** * Other Risk Factors (25% of lung cancers are in non-smokers): * Asbestos * Radiation (radon exposure) * Air pollution * Heavy metals * Genetics (familial lung cancers are rare) * Susceptibility genes: * Chemical modification of carcinogens * Susceptibility to chromosomal damage * Nicotine addiction

Answer 160

* Tumour initiators - Polycyclic aromatic hydrocarbons * Tumour promoters - Nicotine * Complete carcinogens - Nickel, Arsenic

Answer 161

Adenocarcinoma

Answer 162

* Metaplasia - Dysplasia - Carcinoma in situ - Invasive carcinoma * Due to an accumulation of gene mutations

Answer 163

* It does NOT have cilia 1. Build-up of mucus as no cilia are present to sweep it away 2. Within this mucus, you will get loads of carcinogens 3. More carcinogens accumulate, hence the increased risk of cancer formation

Answer 164

Atypical adenomatous hyperplasia - Adenocarcinoma in-situ - Invasive adenocarinoma

Answer 165

* Smokers = **_K-ras_**, issues with _DNA methylation_ and _p53_ * Non-smokers = **_EGFR mutations_** * **__**Are drug targets

Answer 166

* Peripheral/Terminal airways with multi-centric pattern * Incidence is increasing * More common in Females, Far East and Smokers (is the most common in non-smokers)

Answer 167

* Glandular differentiation * Gland formation * Papillae formation * Mucin

Answer 168

* Poorly differentiated tumours composed of large cells * There is no histological evidence of glandular or squamous differentiation * Poor prognosis

Answer 169

* Very close association with smoking * Often CENTRAL and near the bronchi * 80% will present with advanced disease * Very chemosensitive but very poor prognosis - worst of any lung cancer * May cause paraneoplastic syndromes (i.e. SIADH)

Answer 170

* Small poorly differentiated cells * Common mutations: p53, RB1

Answer 171

* Small cells * Ciliated normal respiratory cell

Answer 172

* Small Cell Lung Cancer * Survival 2-4 months if untreated; 10-20 months on treatment * Chemoradiotherapy mainstay * Non-Small Cell Lung Cancer: * Early/Stage 1 tumours have 60% 5-year survival; Late/Stage 4 at 5% 5-year survival * Less chemosensitive

Answer 173

* Cytology – looking at cells: * Sputum * Bronchial washings and brushings * Pleural fluid * Endoscopic fine needle aspiration of tumour/enlarged lymph nodes * Histology – looking at tissue: * Biopsy at bronchoscopy – central tumours * Percutaneous CT guided biopsy – peripheral tumours * Mediastinoscopy and lymph node biopsy – for staging * Open biopsy at time of surgery if lesion not accessible otherwise - frozen section * Resection specimen - confirm excision and staging

Answer 174

* Malignant tumour of the pleura * Essentially fatal (poor prognosis) * There is a long lag/tumours develop decades after asbestos exposure * \<1% of cancer deaths but increasing incidence with a peak predicted in around 2010-2020 * More common in males: female (3: 1) * 50-70 years

Answer 175

* Endocrine: * SIADH * Causes hyponatremia * Especially common with SCC * Cushing’s syndrome * Especially SCC * Hypercalcaemia due Parathyroid hormone-related peptide * Especially SCC * Calcitonin - Hypocalcaemia * Gonadotropins - Gynecomastia * Carcinoid syndrome * Secretions of serotonin * Especially common in carcinoid tumours * Non-endocrine: * Haematologic/coagulation defects * Skin * Muscular * Miscellaneous disorders

Answer 176

* **Clinical examination** * **Imaging** (sonography, mammography, MRI) * MRI tends to only be used for very small lesions * **Pathology** (cytopathology and/or histopathology) – either FNA or core biopsy

Answer 177

* C1 = inadequate * C2 = benign * C3 = atypia, probably benign * C4 = atypia, probably malignant * C5 = malignant

Answer 178

Benign inflammation and dilatation of large breast ducts * Usually presents with nipple discharge * May cause breast pain, breast mass and nipple retraction

Answer 179

* Cytology * Proteinaceous material and neutrophils * Histology * Duct distension with proteinaceous material in it * Foamy macrophages

Answer 180

Acute inflammation in the breast * Painful/tender * Red/erythematous breast * Often seen in lactating women due to cracked skin and stasis of milk * May complicate duct ectasia * *Usual organism: staphylococci*

Answer 181

Neutrophils

Answer 182

Drainage and Antibiotics

Answer 183

Benign inflammatory reaction to damaged adipose tissue * Breast mass * Causes = trauma, surgery, radiotherapy

Answer 184

Fat cells surrounded by macrophages

Answer 185

Benign group of alterations which reflect normal, albeit exaggerated, responses to hormonal influences * Breast lump - presentation * Very common * No increased risk for subsequent breast carcinoma

Answer 186

Ducts dilated and calcified

Answer 187

Benign fibroepithelial neoplasm of breast * Presentation * Well circumscribed mobile breast lump * Young women - 20-30yo * Common

Answer 188

Glandular and stromal cells

Answer 189

A group of potentially aggressive fibroepithelial neoplasms of the breast * Presentation * Enlarging mass in women \>50 years * Some may arise within pre-existing fibroadenomas * Uncommon * Vast MAJORITY are BENIGN (but a small proportion can behave aggressively (malignant phyllodes))

Answer 190

* Overlapping cell layers, cellularity * Level of malignancy determined on cellularity of the stroma * High cellularity + stromal overgrowth = malignant

Answer 191

Benign papillary tumour arising within the duct system of the breast * Arises within the: * Small terminal ductules = peripheral papilloma * Can often remain clinically silent * Large lactiferous ductules = central papilloma * Present with bloody nipple discharge * Common - mainly in 40-60 years

Answer 192

* Cytology * Clusters of cells * Potential increased risk with multiple papillomas of carcinoma * Histology * Dilated ducts * Polypoid mass in the middle * Fibrovascular core * Blood vessels within the stroma

Answer 193

Excision of duct

Answer 194

Benign sclerosing lesion characterised by a central zone of scarring surrounded by a radiating zone of proliferating glandular tissue * Presentation * Stellate masses on screening mammograms - may closely resemble carcinoma * Range in size from microscopic to large * Lesions \>1 cm = complex sclerosing lesions

Answer 195

* Central stellate area * Peripheral proliferation of ducts and acini

Answer 196

Diverse group of microscopic intraductal proliferative lesions of the breast associated with an increased risk of subsequent development of invasive breast carcinoma but produce no symptoms * Usual epithelial hyperplasia * Marker of slightly increased risk of breast cancer * Flat epithelial atypia/atypical ductal carcinoma * FEA may represent the earliest morphological precursor to low grade ductal carcinoma in situ * 4 x increased risk of developing cancer * In situ lobular neoplasia * Associated with a 7-8x increased risk of invasive breast carcinoma

Answer 197

Neoplastic intraductal epithelial proliferation with risk of progression to breast cancer.

Answer 198

* Common * 85% are detected on mammography - *microcalcification* * 10% will produce clinical features - *lump, Paget's disease* * 5% diagnosed incidentally

Answer 199

* Low → “cribriform / punched-out DCIS” * Lumens compact/regular * Calcification * Overlapping cells * High * Central lumen necrotic material * Large cells * Pleiomorphic cells occlude the duct * Few lumens

Answer 200

Surgical excision - *chemo is very rarely given*

Answer 201

* Recurrence - more likely with high grade or extensive disease

Answer 202

A group of malignant epithelial tumours which infiltrate within the breast and have the capacity to spread to distant sites.

Answer 203

Invasive breast carcinoma → 1 in 8 women

Answer 204

* Early menarche/Late menopause * Age * Obesity * Alcohol * OCP * FHx (5% inheritance) * Genetics → BRCA mutations (up to 85% increased lifetime risk)

Answer 205

* Low Grade = arise from low grade DCIS or in situ lobular neoplasia and show 16q loss * High Grade = arise from high grade DCIS and show complex karyotypes with many unbalanced chromosomal aberrations

Answer 206

Breast lump

Answer 207

* Pleiomorphic cells with large nuclei * E-cadherin +ve

Answer 208

* Linear (‘Indian File’ pattern) * Monomorphic (look similar)

Answer 209

Elongated tubules invading the stroma

Answer 210

Empty spaces contain lots of mucin

Answer 211

Carcinoma type discovered following genetic analysis of breast carcinomas

Answer 212

* Histology * Sheets of markedly atypical cells * Prominent lymphocytic infiltrate * Central necrosis * Immunohistochemistry * +ve for “basal” cytokeratins CK5/6 and CK14 * Associated with BRCA mutations * Propensity for vascular invasion and metastasis

Answer 213

* Grading is dependent on * Tubule formation → 1, 2, 3 * Nuclear pleomorphism → 1, 2, 3 * Mitotic activity → 1, 2, 3 * Graded up to score from 3 to 9 * 3-5 = grade 1 = well differentiated * 6-7 = grade 2 = moderately differentiated * 8-9 = grade 3 = poorly differentiated

Answer 214

* All invasive breast cancers are assessed for * Oestrogen receptor (ER) * Progesterone receptor (PR) * Her2 receptor * Phenotype: * Low grade = ER/PR positive and Her2 negative * High grade = ER/PR negative and Her2 positive * Basal-like Carcinomas = ER/PR/Her2 negative - triple negative

Answer 215

* **The status of the axillary lymph nodes** * Other factors * Size * Histological type * Histological grade

Answer 216

* Women aged 47-73 years are screened every 3 years * The screening test is a mammogram * 5% will have an abnormal mammogram → recalled for further investigation * Further investigation may include FNA/biopsy or further scans

Answer 217

Enlargement of the male breast - benign

Answer 218

* Affects pubertal boys and men \>50 years * Idiopathic or associated with drugs - *therapeutic and recreational* * Histology * Epithelial hyperplasia of ducts with finger-like projections extending to duct lumen * Periductal stroma often cellular and oedematous

Answer 219

* Rare * Median age = 65 years * Presentation = palpable lump * Histologically similar to female breast cancers

Answer 220

* Atresia * Duplication * Imperforate anus - *closed anus*

Answer 221

Congenital absence of ganglion cells in myenteric plexus → distal colon fails to dilate

Answer 222

* Constipation * Abdominal distension * Vomiting * Overflow Diarrhoea * Male - 80%

Answer 223

* Down's syndrome (2%) * RET proto-oncogene Cr10+ and others

Answer 224

* Clinical impression - *child/baby not going to the toilet normally* * Biopsy - *hypertrophied nerve fibres but no ganglia*

Answer 225

Resection of affected segment - frozen section used to ensure full removal

Answer 226

* Obstruction * Adhesions * Herniation * Extrinsic mass * Volvulus * Diverticular disease

Answer 227

* Infants = Small bowel * Sigmoid = Elderly

Answer 228

Diverticular disease

Answer 229

Diverticular disease

Answer 230

Diverticular disease

Answer 231

* Pain * Diverticulitis * Gross perforation * Fistula - *bowel, bladder, vagina* * Obstruction

Answer 232

* Acute * Infection * Drug/toxin * Chemo * Radiation * Chronic * Crohn's * UC * TB

Answer 233

* Antibiotic associated → C. diff * Caused by protein exotoxins of C. diff

Answer 234

Pseudomembranous colitis → think of wet cornflakes in the bowel - pseudomembrane

Answer 235

* Stop causing antibiotic * Vancomycin or Metronidazole * Supportive measures

Answer 236

Pseudomembranous colitis → volcanic eruption of pus

Answer 237

* Watershed segments - inbetween/end of blood supply * Splenic flexure - *SMA and IMA* * Rectosigmoid - *IMA and interal iliac artery*

Answer 238

* Arterial occlusion * Venous obstruction * Small vessel disease - DM, cholesterol, vasculitis * Low flow state - CCF, haemorrhage, shock * Obstruction - hernia, intussusception, volvulus, adhesions

Answer 239

Ischaemic bowel

Answer 240

Ischaemic bowel

Answer 241

* Diarrhoea - can have blood in it * Fever * Abdominal pain * Acute abdomen * Anaemia * Weight loss * Extra-intestinal manifestations

Answer 242

* Western population - White 2-5 times higher than non-white * Higher incidence in Jewish population * Peak onset in teens to twenties * Smoking * UC is slightly more common than Crohn's

Answer 243

* Whole GI tract affected * Skip lesions * Cobblestone mucosa * Transmural inflammation * Non-caseating granulomas * Sinus/fistula/fissure/abscess formation * Fat wrapping * Thick ‘rubber hose’ like wall * Narrow lumen

Answer 244

* Starts at rectum and move contiguously * Only affects rectum and large bowel * Can get backwash damage to ileum and appendix * Inflammation confined to nucosa * Normal bowel wall thickness * Shallow ulcers

Answer 245

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

Answer 246

Crohn's - Look at granuloma

Answer 247

* Severe haemorrhage * Toxic megacolon * Adenocarcinoma - 20-30x risk

Answer 248

* Arthritis * Muositis * Uveitis/iritis * Erythema nodusum * Puoderma gangrenosum * PSC

Answer 249

* Non-neoplastic polyps * Neoplastic epithelial lesions * Adenoma * Adenomacarcinoma * Carcinoid tumour * Mesenchymal lesions * Stromal tumours * Lipoma * Sarcoma * Lymphoma

Answer 250

* Non-neoplastic * Hyperplastic * Inflammatory - pseudo-polyps * Haramtomatous * Neoplastic * Tubular adenoma * Tubulovillous adenoma * Villous adenoma

Answer 251

Hyperplastic polyp

Answer 252

(Tubular) adenoma

Answer 253

Tubular adenoma

Answer 254

Villous adenoma

Answer 255

(Villous) adenoma

Answer 256

* Size - \>4cm = 45% have invasive malignancy * Proportion of villous component * Degree of dysplastic change within polyp

Answer 257

* Familial adenomatous polyposis (FAP) * Gardner's * Turcot * HNPCC * Peutz Jeghers

Answer 258

* Autosomal dominant - average onset = 25 * Adenomatous polyps * Average 1,000 polyps - minimu is 100 * Chromosome 5q21 (APC tumour suppressor gene) * 100% will develop cancer within 10-15 years

Answer 259

* Autosomal dominant * 3-5% of all colorectal cancers * Multiple cancer presenting together → endometrial, prostate, breast, stomach * Often poorly differentiated * 1 of 4 DNA mismatch repair genes mutated * Numerous DNA replication errors

Answer 260

* Low fibre, high fat diet * Lack of exercise * Obesity * Smoking * Familial disease * FHx * IBD

Answer 261

Colorectal carcinoma - *some small polyps to the right*

Answer 262

Ulcerating cancer of the anus

Answer 263

* Bleeding * Change in bowel habit * Anaemia * Weight loss * Pain * Fistula

Answer 264

* Duke's * A = confined to wall of bowel * B = through wall of bowel * C = lymph node mets * D = distant mets * TNM is most commonly used in all carcinoma

Answer 265

* Pneumocystis jiroveci → *PCP pneumonia* * CMV → especially *retina and GIT* * Stains brown in immunohistochemistry * Candida * Tuberculosis and atypical mycobacteria * Cryptococcus → *meningitis* * Toxoplasma gondii → *encephalitis and mass lesions* * JC papovavirus → *progressive multifocal leukoencephalopathy* * Herpes simplex * Cryptosporidium, Isospora belli, microsporidia → *GIT*

Answer 266

* Kaposi’s sarcoma - HHV-8 * Dermis expanded by a solid tumour * Made of spindle-shaped cells – infiltrated by HHV-8 * HHV-8 identified in nuclei of tumour cells * Lymphoma * Systemic * B-cell lymphoma * EBV * SSC * Anus & cervix * HPV

Answer 267

* Progressive encephalopathy = **AIDS dementia complex** * **Opportunistic infections and tumours** * **CNS lymphoma**

Answer 268

* Lung * Lymph nodes * Bone * Heart * GIT * CNS

Answer 269

* Non-caseating granulomas = collection of macrophages with a cuff of lymphocytes around * Diagnosed as a diagnosis of exclusion

Answer 270

* Lung * Lymph nodes * Spleen * Liver * Heart * Joints * Basement membranes * Skin * Eyes * CNS * Salivary glands

Answer 271

* Inflammation dominated by **IgG4-AB producing plasma cells** * **Fibrosis** and obliteration of veins * Plasma cell rich inflammatory infiltrate * Immunohistochemistry for IgG4

Answer 272

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

Answer 273

* Liver * Fatty change/Steatosis * Steatohepatitis * Cirrhosis * Hepatocellular carcinoma * GI Tract * Acute gastritis * Oesophageal varices * Oral cavity and oesophagus cancers * Nervous system * Peripheral neuropathy * Wernicke-Korsakoff syndrome * Cardiovascular system * Dilated cardiomyopathy * Hypertension * Atheroma * Pancreas * Acute pancreatitis * Chronic pancreatitis * Cancer * Pharynx * Breast * Foetal alcohol syndrome

Answer 274

* 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

Answer 275

* First classification: * **AA** – derived from serum amyloid A * Chronic inflammatory diseases - RhA, Crohn’s Disease * **AL** – derived from light chains * Multiple myeloma, B cell lymphoma * Second classification: * Transthyretin - e.g. mutation * Beta2-macroglobulin – peritoneal dialysis * Abeta2 protein – Alzheimer’s * Insulin, calcitonin – endocrine tumours

Answer 276

* Stains with **Congo Red Dye** * Shows **apple-green birefringence** under polarised light

Answer 277

* 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 278

* Z-line = the point at which epithelium transitions from being squamous to columnar * Submucosal glands are an important feature of the oesophagus

Answer 279

Layers = **Mucosa** *(epithelium → lamina propria → muscularis mucosa)* → **submucosa → muscularis propria**

Answer 280

Lots of neutrophils

Answer 281

* Ulceration * Fibrosis * Haemorrhage * Perforation * Stricture * BARRETT'S OESOPHAGUS

Answer 282

* Necrotic slough * Inflammatory exudate * Granulation tissue

Answer 283

* Ulcer = past muscularis mucosa into submucosa * Erosion = before muscularis mucosa - not into submucosa

Answer 284

Classic metaplastic process = squamous epithelium of lower oesophagus replaced by columnar epithelium * Two main types: * CLO - metaplasia **without** goblet cells = gastric metaplasia * CLO with IM - metaplasia **with** goblet cells (intestinal metaplasia) → higher cancer risk

Answer 285

* Upper 2/3rd * Associations = smoking and alcohol

Answer 286

* Invades submucosa * Cells form keratin = defining feature * Cells have intercellular bridges

Answer 287

* Most common oesophageal cancer * Bottom 1/3rd * Associations = GORD, Barrett's oesophagus

Answer 288

* Glandular epithelium * Mucin

Answer 289

* Chemical * Aspirin/NSAIDs * Alcohol * Corrosives * Infective * H. pylori * CMV * Strongyloides

Answer 290

* Autoimmune * Bacterial * H. pylori * (CMV * Strongyloides * Chemical * NSAIDs * Bile reflux * D = IBD

Answer 291

* Acute = Neutrophils * Chronic = Lymphocytes * Can have co-existing neutrophils and lymphocytes if acute on chronic

Answer 292

Chronic gastritis associated with H. pylori infection induces lymphoid tissue in the stomach. * Increased risk of lymphoma

Answer 293

Erosion where depth of the loss of tissue goes beyond the muscularis mucosa (into the submucosa).

Answer 294

* Fibrosis * Acute = -ve * Chronic = +ve * If no fibrosis ulcer can heal

Answer 295

Biopsy → exclude malignancy

Answer 296

* **Bleeding** → anaemia, shock *(massive haemorrhage)* * **Perforation** → peritonitis

Answer 297

Presence of goblet cells in the mucosa of the stomach - occurs in response to long term damage.

Answer 298

Abnormal epithelial pattern of growth with some cytological / histological features of malignancy but no invasion through the basement membrane. * Cancer = invasion through the BM

Answer 299

* Male * Race - more common in Japan, Chile, Italy, China, Portugal and Russia - probably diet related * Host genetic factors * Bacterial virulence factors (i.e. Cag-A) * Environmental factors * Gastric cancer phenotypes

Answer 300

* **Intestinal** = well-differentiated * Mucin-containing big glands * **Diffuse** = poorly differentiated * Composed of single cells with no attempt at gland formation * *Types = Linitis plastica, Signet ring cell carcinoma (spreads all over stomach)*

Answer 301

* Adenocarcinoma - 95% * Intestinal or Diffuse * Squamous cell carcinoma * Lymphoma = MALToma - B-cell NHL * Gastrointestinal stromal tumour * Neuroendocrine tumours

Answer 302

* *H. pylori* as well as lymphoma * Will see crypts that are full of neutrophils * Good because if you treat H. pylori, the lymphoma could be reversed → CAP (Clarithromycin, Amoxicillin, PPI)

Answer 303

* H. pylori * CMV * Cryptosporidium * Giardia lamblia * Whipple's disease → *Tropheryma whippelii (parasites)*

Answer 304

* Increased acid in the antral-predominant strain that spills into duodenum + less duodenal HCO₃^- * Chronic inflammation leads to gastric metaplasia with H. pylori * Chronic inflammation can also lead to duodenal ulceration * H. pylori → many gastric ulcers * H. pylori → 100% of duodenal ulcers

Answer 305

* Loos of villi * Crypt hyperplasia * Inflammatory changes → increased intraepithelial lymphocytes

Answer 306

Inflammatory changes (increased intraepithelial lymphocytes) without architectural changes * Many people with this either have Coeliac’s or are going to develop Coeliac’s

Answer 307

* Antibodies: * Endomysial Antibodies- *anti-EMAs* * Tissue Transglutaminase Antibodies - *anti-TTG* * Duodenal Biopsy * On gluten rich diet = villous atrophy * Off gluten rich diet = normal villi

Answer 308

Tropical sprue

Answer 309

* MALTomas associated with coeliac disease * Found in the duodenum * Are T cell lymphomas / EATL * Lymphomas in the stomach due to H. pylori are B cell lymphomas

Answer 310

Excess accumulation of fluid in the brain parenchyma * Shows on CT as a loss of gyri

Answer 311

* **Vasogenic** – disruption of the blood brain barrier * **Cytotoxic** – secondary to cellular injury e.g. hypoxia/ischaemia * *Usually due to damage at the astrocyte end-foot processes* * *AQA4 is found in the brain (and is used to transport water)*

Answer 312

1. CSF produced in **choroid plexus** (mainly in the lateral ventricles) 2. Flows from the **lateral ventricle → intraventricular foramina → 3^rd ventricle** 3. Down the **cerebral aqueduct → 4^th ventricle** *(floor is the pons and the roof is the cerebellum)* 4. Into the **medulla → central canal of the spinal cord** (relatively little CSF goes down the spinal cord because most of it exits via a number of foramina in the 4^th ventricle into the subarachnoid space) 5. Circulate through the **subarachnoid space and via the arachnoid granulations (superior sagittal sinus) → systemic circulation**

Answer 313

* **Non-Communicating** = obstruction to the flow of CSF (usually involving the cerebral aqueduct) * **Communicating** = associated with problems in reabsorption of CSF into venous sinuses * Can be caused by infection (e.g. meningitis) * Inflammation of the meninges impinge and interfere with the normal flow of CSF to be reabsorbed

Answer 314

Herniation of brain structures * Subfalcine → cortex forced under rigid falx cerebri * Uncal → medial temporal lobe through tentorial notch * Tonsillar → tonsil of cerebellum pushed through foramen magnum

Answer 315

Clinical syndrome characterised by rapidly developing clinical symptoms and/or signs of focal, and at times global loss of cerebral function, with symptoms lasting more than 24 hours or leading to death due to vascular pathology. * Infarct → cerebral infarction * Haemorrhage → SUB-ARACHNOID, primary intracerebral or intraventricular * Excludes * Subdural haemorrhage * Epidural haemorrhage * Infarction / Haemorrhage caused by infection or tumour etc

Answer 316

* Temporary brain clot that lasts **\<24hrs** * 1/3^rd people with TIA get a significant infarct within 5 years → predictor of a future infarct * Most TIAs last \< 5 mins * There is usually NO permanent injury to the brain

Answer 317

Haemorrhage into the substance of the brain (parenchyma) due to rupture of a small intraparenchymal vessel * Most common in the basal ganglia * Hypertension plays a role in \>50% of bleeds * Presentation: * Severe headache * Vomiting * Rapid loss of consciousness * Focal neurological signs

Answer 318

* Can occur anywhere in the CNS * Symptomatic from 2^nd and 5^th decade → mean = 31 years * High pressure = massive bleed * Morbidity 50-80% * Mortality at 15% * Can be visualised on angiography

Answer 319

* Presentation: * Haemorrhage * Seizures * Headache * Focal neurological deficits * Treatment: * Surgery * Embolisation * Radiosurgery

Answer 320

* Well-defined malformative lesion composed of closely-packed vessels with no parenchyma interposed between vascular spaces * Similar to an AVM but no brain substance wrapped up amongst the vessels * Can be found anywhere in the CNS * Usually symptomatic over the age of 50 years * Pathogenesis is unknown * Strokes / bleeds can occur under lower pressure

Answer 321

* Presentation * Headache * Seizures * Focal deficits * Haemorrhage * Investigation = MRI * Target Sign – black ring around lesion (AVM has no ring) – no brain parenchyma * Treatment: * May not be necessary * Surgery

Answer 322

**Rupture of a berry aneurysm** * 1% of the general population; congenital * Highest risk of rupture when 6-10mm * 80% occur at the internal carotid bifurcation * 20% occur within the vertebrobasilar circulation * 30% of patients will have multiple berry aneurysms

Answer 323

* Presentation * Sudden-onset severe headache (Thunderclap) * Vomiting * Loss of consciousness * Treatment * Endovascular coiling

Answer 324

* Tissue necrosis (stains) * Rarely haemorrhagic * Permanent damage in the affected area * No recovery

Answer 325

* Bleeding * Dissection of parenchyma * Fewer macrophages * Limited tissue damage (periphery) * Partial recovery

Answer 326

TBI * Accounts for 25% of all trauma deaths * High morbidity * 19% in a vegetative or severely disabled state * 31% good recovery

Answer 327

* **Otorrhoea** and **Rhinorrhoea** → i.e. loss of CSF through the ear or nose) * Increases risk of infection - ruptured the containment of the CSF → acts as a route of infection into the cranial cavity

Answer 328

* Battle sign → basilar skull fracture * Bruise over mastoid process * Takes 1 day to appear * Racoon eyes → basal skull fracture * Takes 1 day to appear

Answer 329

Brain collides with the internal surface of the skull.

Answer 330

Brain colliding with the internal surface of the skull leading to rupture of the pia mater.

Answer 331

* Due to direct contact with the skull * **Lateral surfaces of the hemispheres** * **Inferior surfaces of frontal and temporal lobes** * *Rebound of the brain after a direct impact can cause contrecoup damage to the opposite side of the brain*

Answer 332

Shearing and tensile forces cause damage to the axons. * Occurs at the moment of injury * Most common cause of non-haemorrhagic coma * In some people who survive head injuries, they suffer cognitive and degenerative problems further down the line * Potentially due to persistent inflammation * Midline structures are particularly affected * Corpus callosum * Rostral brainstem * Septum pellucidum

Answer 333

**Series of diseases with common molecular pathology.** * There is a transmissible factor * There is no DNA or RNA involved * Prion protein is transmitted and changes the host protein into the pathological form → can't be metabolised and accumulates

Answer 334

* Creutzfeldt-Jakob disease (CJD) * Gerstmann-Straussler-Sheinker syndrome * Kuru – *endemic to Papua New Guinea* * Fatal familial insomnia

Answer 335

1. The normal PrP^Sc protein can unfold and refold into a beta-pleated sheet form which is much more susceptible to aggregation 2. Once a little bit of this forms, it can propagate 3. This leads to a lot of insoluble protein accumulating in the parenchyma of the brain

Answer 336

A prion disease which is **linked to BSE (Mad cow disease)** that has been diagnosed at autopsy since 1990 * Patients were \<45 years old * Clinical features: * Cerebellar ataxia * Dementia * Longer duration than CJD

Answer 337

* Extracellular / **Amyloid-beta plaques** - *right image* * Neurofibrillary tangles (**Tau**) * Disrupts cytoskeleton of neurones * Cerebral amyloid angiopathy - *left image* * Deposits of proteins in the blood vessel walls → impairs vascular function * Neuronal loss / Cerebral atrophy * Shrinkage of brain * Hippocampus → loss of short-term memory

Answer 338

Normal physiological function of AB protein is still unknown * Ab is formed by cleavage of APP at a transmembrane site * APP can be processed in TWO ways * Amyloidogenic * Amino terminus of Ab cleaved → amyloidogenic → too much Ab → Ab thrown out of cell → accumulates → Ab forms monomers → dimers → protofibrils → fibrils (polymers) * Non-amyloidogenic * Ab sequence directly cleaved in two * Toxicity of Ab is more likely to be intracellular * Extra-cellular plaques probably don’t cause direct problems

Answer 339

_Normal_ 1. APP cleaved by a-secretase 2. sAPPa released and the **C83** fragment remains 3. C83 is then digested by g-secretase 4. Products are then removed _Pathophysiology_ 1. APP cleaved by b-secretase 2. sAPPb released and the C99 fragment remains 3. C99 is digested by g-secretase releasing b-amyloid (Ab) protein 4. Ab protein forms the toxic aggregates

Answer 340

_Normal_ * Tau protein is a soluble protein present in axons * Tau important for assembly and stability of microtubules _Pathophysiology_ 1. Hyperphosphorylated tau is insoluble → self-aggregates 2. Self-aggregates form neurofibrillary tangles (neurotoxic) 3. The tangles result ultimately in microtubule instability and neurotoxic damage to neurones

Answer 341

_Normal_ * Microglial cells are specialist CNS macrophages _Pathophysiology_ 1. Increased inflammatory mediators and cytotoxic proteins 2. Increased phagocytosis 3. Decreased levels of neuroprotective proteins

Answer 342

* **Microtubule-associated protein** - used for maintaining stability of the cytoskeleton * When it becomes hyperphosphorylated it starts causing problems * Accumulates inside the cell and eventually it will cause cell death * Presence and spread of tau throughout the brain is quite stereotypical and matches up quite closely with the clinical symptoms seen in the patient → Braak staging

Answer 343

Braak staging → symptoms appear at stage 3 or 4: * Stage I = trans-entorhinal region * Stage II = entorhinal region (interfaces neocortex and hippocampus) * Stage III = temporo-occipital gyrus (see the immunostaining by eye) * Stage IV = temporal cortex * Stage V = peri-striatal cortex (cortex around the primary visual cortex) * Stage VI = striatal cortex (occipital lobe)

Answer 344

**Chronic Traumatic Encephalopathy = A tauopathy in people with a history of multiple repetitive TBI** * This has been seen in boxers, American footballers, rugby players and footballers

Answer 345

Parkinson's disease = death of dopaminergic cells of substantia nigra (projects to basal ganglia) → basal ganglia are very important in the initiation of movement * Characterised by the presence of Lewy bodies = cells with a-synuclein * Dopaminergic cells produce neuromelanin → colours the substantia nigra → decoloration of substantia nigra

Answer 346

* Bradykinesia * Rigidity * Pill-rolling tremor

Answer 347

* Lewy bodies are intracellular accumulations of a-synuclein * Proteinopathy developed from abhorrent metabolism of a-synuclein → mutations in a-synuclein gene à PD * a-synuclein immunostaining = diagnostic gold standard

Answer 348

Braak PD stages: * Based on the distribution of a-synuclein pathology throughout the brain 1. Bottom-up spread - originates in the brainstem 2. Goes from the medulla, up the pons and the midbrain 3. Moves into the basal forebrain and the cortices

Answer 349

* Retrograde from gut to medulla via vagus nerve * Through the nose

Answer 350

* Idiopathic Parkinson's disease * Drug-induced Parkinsonism * Multiple system atrophy - *a-synuclein in glial cells* * Progressive supranuclear palsy - *tau pathology* * Corticobasal degeneration - *tau pathology* * Vascular pseudoparkinsonism * Alzheimer's changes * Fronto-temporal neurodegenerative disorders

Answer 351

* **a-synucleinopathy** → however targets glial cells apposed to dopaminergic cells * Tends to affect the cerebellum * Patients are more likely to present with falls

Answer 352

* Progressive Supranuclear Palsy * Corticobasal Degeneration * Frontotemporal dementia (Pick's disease)

Answer 353

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

Answer 354

* Single gene on 17q21 with 16 exons * Alternative splicing leads to 6 isoforms * There are either 3R or 4R forms of tau that exist in the brain - two further subsets with unknown functions * The longest form is 4R/2N * The smallest form is 3R/0N

Answer 355

FTLD-U (ubiquitinated) * Fronto-temporal dementia associated with progranulin mutations → tendency for the atrophy to be unilateral * Problems with TDP-43 (trafficking protein) thought to be the basis for some types of FTLD (associated with MND) * TDP-43 = TAR DNA Binding Protein 43 * Other associations: * FUS pathology * C9ORF72 mutations

Answer 356

* **Extra-axial** * Tumours of bone, cranial soft tissue, meninges, nerves and metastatic deposits * **Intra-axial** * Derived from normal cell populations of the CNS (glia, neurons, vessels, connective tissue) * Derived from other cell types (metastases, lymphomas, germ cell tumours)

Answer 357

* Extra-axial * Meningothelial cells – meningioma * Schwann cells – schwannoma * Intra-axial * Astrocytes – astrocytoma * Oligodendrocytes – oligodendroglioma * Ependyma – ependymoma * Neurons – neurocytoma * Embryonal cells – medulloblastoma

Answer 358

* Largely unknown * Radiation to head and neck: meningiomas, rarely gliomas * Neurocarcinogens * Genetic predisposition (\<5% of primary brain tumours) * Neurofibromatosis is most common form * Autosomal dominant inheritance

Answer 359

* Increased ICP * Headache * Vomiting * Changed mental state * Supratentorial * Focal neurological deficits * Seizures * Personality change * Subtentorial * Cerebellar ataxia * Long tract signs * Cranial nerve palsies

Answer 360

* **Surgery** → maximal safe resection aims to obtain and extensive excision with minimal damage to the patient * Craniotomy → debulking (subtotal and complete resections) * Open biopsies → inoperable but approachable tumours * Stereotactic biopsy → open biopsy not indicated * **Radiotherapy** * Low and high-grade gliomas * Metastases * **Chemotherapy** *- biological agents → EGFR inhibitors, PD-1 inhibitors etc* * High-grade gliomas (temozolomide)

Answer 361

**Outcomes** * Some tumours only have a few possible types and not all 4 → i.e. only 1 possible grade * Grading does not tell us therapy response, disease spread or cell of origin (type) * Grade I = benign, long-term survival * Grade II = cause death in \>5 years * Grade III = cause death \<5 years * Grade IV = cause death \<1-year

Answer 362

* Circumscribed * **Pilocytic astrocytoma** (grade I) - most common * Pleomorphic xanthoastrocytoma (grade II) * Subependymal giant cell astrocytoma (grade I) * Diffuse * **Diffuse astrocytoma** (grades II-IV) * Oligodendroglioma (grades II-III)

Answer 363

* **Grades I-II** * **Occurs in children** * Rare malignant transformation * BRAF mutation present in 50% of cases (MAPK pathway mutation)

Answer 364

* **Grade I** * **Most common child brain tumour** → 20% CNS tumours \<14yo * Common in **neurofibromatosis I** (NF1) * MRI → cerebellar; well circumscribed, cystic, enhancing * Histopathology * **Piloid (hairy) cell** * **Rosenthal fibres** and granular bodies * Slow growing with **low mitotic activity** * **BRAF mutation** present in 70% of cases

Answer 365

* **Grades ≥II** * **Occurs in adults** * Malignant progression * IDH1/2 mutation present in 30% of cases - also a +ve prognostic factor

Answer 366

* **Grade II-IV** * **Patients 20-40yo** * Locations * **Adults = Cerebral hemispheres** * **Children = Cerebellum** * **Progresses to a glioblastoma** (Grade IV) → takes several years * MRI → T1 hypointense, T2 hyperintense, non-enhancing lesion * Low choline: creatinine ratio at MR-spectroscopy * Cytology * Low to moderate cellularity * **Mitotic activity negligible**/absent * **Vascular proliferation and necrosis absent** * **IDH1/2 mutation** present in \>80% of cases

Answer 367

* **Grade IV** * **Most common primary brain cancer** * **Most patients \>50yo** * MRI → heterogenous, enhancing post-contrast * Cytology * **High cellularity** * **High mitotic activity** * **Neoangiogenesis** * **Necrosis** * Histological criteria * **Pathological blood vessels** * **Blood vessel structural abnormalities** * **Cellularity on inspection** * Genetics: * 90% of cases = **wildtype IDH** * 10% of cases = **astrocytoma progression** (have the IDH mutation) * IDH mutant = +ve prognostic factor

Answer 368

* **Grade II-III** * 5% of all primary brain tumours * Patients **20-40yo with a long history of neurological signs** * MRI → no/patchy contrast enhancement * Cytology * **Round cells with clear cytoplasm = “fried eggs”** * **IDH1/2 mutation and co-deletion of 1p/19q** present in ~100% of cases = diagnostic

Answer 369

* Rare in patients \<40yo * Any site of craniospinal axis - can have multiple sites (i.e. NF2) * MRI → extra-axial, isodense, contrast-enhancing * Histology * Attaches to meninges but does not typically invade, just displaces brain matter * If they invade = often a micro-invasion (picture) * Globules found on histopathology

Answer 370

* **Grade I (80%) = Benign** * Recurrence \<25% * \<4 mitotic activity per 10 HPF * **Grade II (19%) = Atypical** * Recurrence 25-50% * 4-20 mitotic activity per 10 HPF * **Grade III (1%) = Malignant** * Recurrence 50-90% * \>20 mitotic activity per 10 HPF

Answer 371

**CNS Metastasis -** 10x more than intrinsic tumours * Increasing incidence due to longer survival * Often multiple * Very poor prognosis

Answer 372

* Any tumour can potentially give CNS metastases → can be the first presentation of the disease * Origin can be challenging to determine * **Most frequent tumours** * **Lung** * **Breast** * **Melanoma**

Answer 373

**Grey-white junction** * As structure of cerebral blood vessels changes at this point → become smaller as they enter the white matter → neoplastic emboli tend to get stuck at this level and then start growing

Answer 374

* Grade IV * Embryonal tumour = originates from neuroepithelial precursors of the cerebellum/dorsal brainstem * Located in the Cerebellum * Rare → but 2nd most common brain tumour in children * Histology: * “Small blue round cell” tumour = Wilm’s tumour * Expression of neuronal markers – i.e. synaptophysin * Homer-Wright rosettes

Answer 375

Metastatic carcinoma

Answer 376

Pilocystic astrocytoma

Answer 377

Glioblastoma

Answer 378

* In the western world = ½ of all deaths and more morbidity and mortality than any other disorder * USA mortality rate from IHD is 5x than in Japan * IHD is increasing in Japan (increasing western diet): now second leading cause of death there

Answer 379

Characterised by atheromatous deposits in and fibrosis of the inner layer of the arterioles.

Answer 380

* Non-modifiable: * Age * Sex (premenopausal women protected à post-menopausal women = \>risk than men) * Genetics (FHx, familial hypercholesterolaemia, polymorphisms) * Modifiable: * Hyperlipidaemia (LDL bad / HDL good, diet, statins inhibit HMG-CoA reductase) * Hypertension (increased IHD risk by 60%) * Smoking * Diabetes mellitus (induces hypercholesterolaemia and atherosclerosis) * Other risk factors: inflammation, hyperhomocyteinaemia, metabolic syndrome, lipoprotein a, haemostasis (pro-coagulation), lack of exercise, stress, obesity * Risk factors have a multiplicative effect – 2 risk factors increase the risk 4x (3 RFs = 7x increase risk) * 20% of CVD events occur in absence of RFs and 75% events in healthy women occur in LDL below the risk level

Answer 381

1. Endothelial injury à LDL accumulation 2. Monocyte adhesion to endothelium 3. Monocyte migration into intima → macrophages & foam cells 4. Platelet adhesion → factor release → smooth muscle cell recruitment 5. Lipid accumulation à extracellular and intracellular macrophages and smooth muscle cells

Answer 382

* Earliest lesion - tiny streaks in the vessel wall * Lipid filled foamy macrophages * No flow disturbance * In virtually all children \<10y/o * Relationship to plaques is uncertain but often found in the same sites as plaques

Answer 383

* Later stages * Patchy with local flow disturbance → only involve portion of the wall - rarely circumferential * Appear eccentric and composed of cells, lipid and matrix * Can rupture or obstruct * Occur in points of disturbed flow * Bifurcations * Curvatures

Answer 384

* **Stenosis** * Critical stenosis is when demand \> supply → occurs at 70% occlusion **=** “stable” angina * Acute plaque rupture can occur * **Acute plaque change** * **Rupture**: exposes prothrombogenic plaque contents * **Erosion**: exposes prothrombogenic subendothelial basement membrane * **Haemorrhage** into plaque (increases size) * *Majority of plaques which show acute change only show mild to moderate luminal stenosis prior to acute change: therefore, there are numerous asymptomatic potential victims*

Answer 385

* Lots of foam cells and extracellular lipid * Thin fibrous cap * Few smooth-muscle cells * Clusters of inflammatory cells

Answer 386

Stable = 70% Unstable = 90%

Answer 387

* First parts of LAD or LCx * Entire length of RCA

Answer 388

Transient ischaemia not producing myocyte necrosis * Stable = comes on with exertion, relieved by rest, no plaque disruption * Prinzmetal (uncommon) = artery spasm * Unstable = more frequent, longer, onset with less exertion or at rest * Disruption of plaque * Superimposed thrombus * Possible embolisation or vasospasm * Warning of impending infarction

Answer 389

* Artery occlusion due to: * Sudden change of plaque / Thrombus evolution * Coagulation / Platelet aggregation * Vasospasm * Myocardial response * Loss of contractility within 60 seconds → potentially reversible but irreversible after 20-30 minutes * *LAD: 50%, anterior wall left ventricle, anterior septum, apex* * *RCA: 40%, posterior wall left ventricle, posterior septum, posterior right ventricle* * *LCx: 20%, lateral left ventricle, not apex*

Answer 390

* \<6 hours = normal by histology (CK-MB also normal) * 6–24 hours = coagulative necrosis, loss of nuclei and striations * 1-4 days = infiltration of neutrophils * 5-10 days = removal of debris by macrophages * 10-14 days = granulation, angiogenesis, collagen synthesis * Weeks to months = strengthening, decellularising scar

Answer 391

**Reperfusion injury** * Due to oxidative stress, Ca²⁺ overload and inflammation * Arrhythmias common * Biochemical abnormalities last days to weeks * Thought to cause “stunned myocardium” → reversible cardiac failure lasting several days

Answer 392

* Chronic sublethal ischaemia causing lowered metabolism in myocytes is reversed with revascularisation

Answer 393

* Death (30% in 1 year but 3-4% after due to complications) * Arrhythmia * Rupture (papillary muscle) * Tamponade * Heart failure * Valvular disease * Aneurysm of ventricle * Dressler’s syndrome (pericarditis; 2nd or 3rd day) * Embolism (i.e. bowel ischaemia) * Recurrence

Answer 394

* Progressive heart failure due to ischaemic myocardial damage - may not be prior infarction * Can arise with: * Severe obstructive coronary artery disease * Enlarged heavy heart * Hypertrophied and dilated LV * Atherosclerosis * Fibrosis (microscopic)

Answer 395

Unexpected death from cardiac causes in individuals without symptomatic heart disease or within 1 hour after onset of symptom → usually due to lethal arrhythmia triggered by ischaemia-induced electrical instability * Usually on background of IHD (90%) * Drugs such a cocaine may be the cause * Acute myocardial ischaemia is usual trigger of arrhythmia * Can be heritable * Marked atherosclerosis (\>75% stenosis) in one or more vessels usually \>90% * 10% non-atherosclerotic cause (long QT) * Half have plaque rupture * 25% have MI changes but conflicting data on role of MI

Answer 396

* Types: * Left = SOB, pulmonary oedema (CXR = ABCDE) * Right = peripheral oedema (_nutmeg liver_) * Congestive heart failure * Causes: * IHD * Valve disease * Hypertension * Myocarditis * Cardiomyopathy * Left sided heart failure → right sided failure * Pathology * Dilated heart * Scarring * Thinning of the walls * Microscopy = fibrosis and replacement of the ventricular myocardium * Complications * Sudden death * Arrhythmias * Systemic emboli * Pulmonary oedema with superimposed infection

Answer 397

* Progressive loss of myocytes → dilated heart * Causes: * Idiopathic * Infective: viral myocarditis * Toxic: alcohol, chemotherapy (adriamycin, daunorubicin) * Cobalt, iron * Hormonal: hyper/hypothyroid, diabetes, peri-partum * Genetic: haemochromatosis, Fabry’s, McArdle’s * Immunological: myocarditis; inc. viral

Answer 398

* Left ventricular hypertrophy → narrows outflow * Familial in 50% (autosomal dominant, variable penetrance) * Beta-myosin heavy chain

Answer 399

* Impaired ventricular compliance * Idiopathic or secondary to myocardial disease (amyloid, sarcoidosis) * Normal heart size but big atria

Answer 400

* Sequelae of earlier rheumatic fever * Predominantly left-sided → almost always **_mitral stenosis_** * Mitral \> Aortic \> Tricuspid \> Pulmonic * Mitral alone 48%; mitral and aortic 42% * Thickening of valve leaflet → especially along lines of closure * Fusion of commissures * Thickening, shortening and fusion of chordae tendineae

Answer 401

* Commonest cause of aortic stenosis (esp. in elderly; 70-80s) * Calcium deposits in outflow side cusp which impair opening or orifice is compromised * Outflow tract obstruction

Answer 402

* **Rigidity**: RHD * **Destruction**: infective endocarditis * Left-sided normally - often the more ‘damaged valve’ * Right-sided in IVDU - first valve bacterium come across * **Disease of aortic valve ring**: dilatation means that valve is insufficient to cover increased area * Marfan's Syndrome * Dissecting aneurysm * Syphilitic aortitis * Ankylosing spondylitis

Answer 403

* True = all layers of the wall * False = extravascular haematoma → Aortic dissections * Causes = weak wall of large arteries * Marfan’s * Atherosclerosis * Hypertension

Answer 404

* Duplication (i.e. uterus didelphys) * Agenesis – missing part of the genital tract (e.g. a fallopian tube)

Answer 405

* Infections that cause discomfort with NO serious complications * **Candida**: more common in diabetes, OCP, pregnancy * **Trichomonas vaginalis**: protozoan * **Gardenerella**: Gram-negative bacillus causes vaginitis * Infections that cause SERIOUS complications * **Chlamydia**: major cause of infertility * **Gonorrhoea**: major cause of infertility * **Mycoplasma**: causes spontaneous abortion and chorioamnionitis * **HPV**: implicated in cancer

Answer 406

* **Chlamydia** \> gonococci, enteric bacteria * Usually starts at the lower genital tract and spreads upwards via the mucosal surface * *Other causes = staph/strep, coliform, clostridium perfringens* * *These tend to occur secondary to abortion* * *Usually starts in the uterus and spreads upwards via lymphatics and blood vessels* * *Involves the deep tissue layers*

Answer 407

* Peritonitis * Intestinal obstructions due to adhesions * Bacteraemia * Infertility

Answer 408

* Plical fusion * Adhesions to ovary * Tubo-ovarian abscess * Peritonitis * Hydrosalpinx (fallopian filled with fluid) * Infertility * Ectopic pregnancy

Answer 409

* **2^nd most common cancer affecting women worldwide** * Mean age: 45-50 years

Answer 410

* **HPV (95%)** * Many sexual partners * Sexually active early * Smoking * Immunosuppression (i.e. HIV)

Answer 411

* High-risk = CIN / Cancer * **16 and 18** * *Others = 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 82)* * Low-risk = genital / oral warts * **6 and 11** * *Other types: 40, 42, 43, 44, 54, 61, 72, 73, 81)*

Answer 412

* Most people = Nothing = Immune system eliminates HPV → undetectable within 2 years in 90% of cases * HPV 16 / 18 = encode proteins E6 and E7 which bind to and inactivate TSGs * **E6 → p53** * **E7 → retinoblastoma** * Interferes with apoptosis and increased cellular proliferation which contributes to oncogenesis

Answer 413

* Infection is either **latent** or **productive**: * Latent = HPV resides in cell and _only replicates when the cell divides_ * Complete viral particles not produced * Cellular changes of HPV **not seen** * Productive = HPV replicates _independently_ of cell cycle * Cellular changes of HPV are **seen** * Halo around the nucleus (koilocyte)

Answer 414

* CIN (endocervical) = dysplastic changes → invasive SCC * *80% - most common* * CGIN (glandular) = dysplastic changes → invasive adenocarcinoma * *20%*

Answer 415

* First invitation: 25 years * 25-49 = 3-yearly * 50-62 = 5-yearly * 65+ = only screen those not screened since they were 50 or have recent abnormal tests

Answer 416

* 2 vaccines available * Bivalent (16 + 18) * Quadrivalent (6, 11, 16, 18) * National vaccination programme for girls aged 12 and boys aged 13 (second dose 6-24 months later) * *Does not protect you from all high-risk types*

Answer 417

* Congenital anomalies * Inflammation: acute or chronic * Adenomyosis * Dysfunctional uterine bleeding: e.g. hormonal imbalance * Endometrial atrophy and hyperplasia * Endometrial polyp * Uterine tumours * *Endometrial epithelial tumours and precursors* * *Tumour like lesions; e.g. endometrial polyp* * *Mesenchymal tumours specific to the uterus* * *Mixed epithelial and mesenchymal tumours* * *Miscellaneous tumours*

Answer 418

* Smooth muscle tumour of the myometrium * Most common uterine tumour - found in 20% of \>35yo * Usually multiple * May be * Intramural * Submucosal * Subserosal

Answer 419

Leiomyosarcoma * Rare * Usually solitary * Post-menopausal women * Local invasion and spread via the blood stream * 5-year survival of 20-30%

Answer 420

Increase in stroma and glands (usually driven by oestrogen) * Causes = OESTROGEN * Peri-menopausal * Persistent anovulation (because of persistently raised oestrogen levels) * PCOS can also cause persistently elevated levels of oestrogen giving rise to endometrial hyperplasia * Granuloma cell tumours of the ovary * Oestrogen therapy * Can be associated with atypia / pre-cancerous changes

Answer 421

* Oestrogen * Nulliparity * COCP * Early menarche * Tamoxifen * HRT * Late menopause * Obesity * DM

Answer 422

* 85% of endometrial cancer * Subtypes: * Endometrioid * Mucinous * Secretory adenocarcinoma * Younger patients * Oestrogen-dependent * Associated with atypical Endometrial hyperplasia * Often present as low-grade tumours → superficially invasive * *Genetic Mutations – need accumulation ≥4 different mutations* * *PTEN* * *PI3KCA* * *K-Ras* * *CTNNB1* * *FGFR2* * *p53*

Answer 423

* 15% of endometrial cancer * Subtypes * Serous * Clear cell tumours * Older patients * Less oestrogen-dependent * Arise in atrophic endometrium * Present later → high grade, deeper invasion and higher stage * *Genetic Mutations* * *Serous Carcinoma* * *p53 (90%)* * *PI3KCA (15%)* * *Her 2 amplification* * *Clear Cell Carcinoma* * *PTEN* * *CTNNB1* * *Her-2 amplification*

Answer 424

* I = limited to uterus * II = spread to cervix * III = spread adjacent * IV = distant spread

Answer 425

* Complete * Partial mole * Invasive mole * Choriocarcinoma

Answer 426

* Presentation: * Spontaneous miscarriage * USS – snowstorm, cluster of grapes * Very high hCG * Complete moles may persist or recur * Prevalence = 1 in 1000 pregnancies * Complete = empty egg fertilised by 2 sperm (or 1 which duplicates DNA) → 46 XY or 46 XX (paternal origin only) * Partial = normal egg fertilised by 2 sperm (or 1 which duplicates DNA) → 69 XXX or 69 XXY (1x maternal and 2x paternal origin)

Answer 427

* **Incidence**: 1 in 20,000-30,000 pregnancies * Rapidly invasive, widely metastasising (lung, vagina, brain, liver, kidney) * Responds well to chemotherapy * 50% arise in moles * 25% arise in previous abortion * 22% arise in normal pregnancy

Answer 428

Presence of endometrial tissue outside the uterus - metaplasia of pelvic peritoneum → implantation of endometrial tissue * Ectopic endometrial tissue is functional and bleeds at the time of menstruation → pain, scarring and infertility * Associations: * Strongly → clear cell (mesonephroid/epithelial) ovarian cancer * Less strongly → endometroid (epithelial) ovarian cancer * 10% of premenopausal women

Answer 429

* Non-neoplastic functional Cysts * Follicular and luteal cysts * Endometriotic cyst * Polycystic Ovarian Syndrome (PCOS) * 3-6% of women of reproductive age * Patients have persistent anovulation * Other features include obesity and hirsutism/virilism

Answer 430

* Oestrogen - not COCP * Nulliparity * Early menarche * Late menopause * HRT * Genetic predisposition (1%) = Lynch II * FHx of ovarian or breast cancer * Endometriosis * Inflammation (PID)

Answer 431

* Pregnancy * COCP

Answer 432

**Epithelial** * Type 1 * Low-grade serous * Mucinous * Endometroid * Clear cell * Transitional * Mixed types * Type 2 * High-grade serous * 65% of all ovarian tumours * 95% of all malignant tumours **Germ cell tumours** * Bimodal peaks - 15-21 and 65-69 **Sex cord tumours** * Most common in post-menopausal women - some subtypes in 25-30-year olds

Answer 433

* Familial breast-ovarian cancer syndrome = BRCA1 association * Site-specific ovarian cancer = BRCA1 association * Lynch type II

Answer 434

* Type 1 ovarian carcinoma = low-grade * Low-grade serous * Endometroid * Mucinous * Clear cell * Arise from benign ovarian tumours and endometriosis * Present as large, stage 1 tumours * Mutations = K-Ras, BRAF, PI3KCA, Her2, PTEN, beta-catenin * Type 2 ovarian carcinoma = high grade and aggressive * High-grade serous carcinomas * NO precursor lesions * Mutations = p53 (75% of cases), K-Ras, BRAF, BRCA * *BRCA = better response to chemo plus can use PARP inhibitors*

Answer 435

* Krukenberg Tumour = bilateral metastases composed of mucin-producing signet ring cells * Most often from gastric or breast cancer * Metastatic Colorectal Carcinoma * Ovaries are prone to metastatic spread of colorectal cancer

Answer 436

* Epithelial - 10-24% of ovarian tumours * Associated with * Endometriosis (10-20% associated with endometriosis) * Endometrioid carcinoma co-existence in uterus * Better prognosis than mucinous and serous

Answer 437

* Epithelial – most common (usually cystic, 30-50% are bilateral) * Benign tumours – lined by bland epithelium * Borderline tumours – more complex, atypical epithelial lining with papillae (NO invasion through basement membrane) * Malignant tumours – invasive with poor prognosis (15% 5-year survival)

Answer 438

* Epithelial – 10-20% of ovarian tumours * Secrete mucin (epithelium resemble gastrointestinal or endocervical epithelium) * 4-10% of colorectal cancer metastases to ovary – 14-32% identified in ovary first

Answer 439

* Epithelial * Strong association with endometriosis * Called 'clear cell' because their cytoplasm is clear due to the presence of a lot of glycogen * Glycogen dissolves when the sample is processed for microscopy leaving an empty space)

Answer 440

* **Fibromas** (arising from fibroblasts): * Benign * No endocrine production * **Granulosa cell** (arising from granulosa cells): * Variable behaviour * May produce oestrogen * **Thecoma** (arising from thecal cells): * Benign * May secrete oestrogen (rarely secretes androgens) * **Sertoli-Leydig Cell** (arising from Sertoli-Leydig cells) * Variable behaviour * May be androgenic

Answer 441

* Dysgerminoma (no differentiation) * Embryonic Group * Teratoma (embryonic tissues) * Choriocarcinoma (trophoblastic cells from placenta) * Endodermal sinus tumour (extraemryonic tissue from amniotic sac) * Embryonal carcinoma

Answer 442

* **Mature Teratoma** - *most common type of germ cell tumour* * Benign - solid or cystic * Tissues all mature to adult-type tissues (teeth and hair are very common) * **Immature Teratoma** * Indicates presence of embryonic elements (most commonly neural tissue) * Malignant - grows rapidly, penetrates the capsule and forms adhesions * Spreads within the peritoneal cavity * Metastasises to the lymph nodes, lungs, liver and other organs * **Mature Cystic Teratoma with Malignant Transformation** * Rare * Any type of the mature tissue within the teratoma can become malignant → can give rise to carcinoid, thyroid cancer, BCC, melanoma etc * Most frequently SCC

Answer 443

* **Lichen sclerosus** = thinning epithelium with a layer of hyalinisation underneath * Sometimes associated with epithelial dysplasia and development of malignancy * **Papillary Hidradenoma** = benign tumour * **Malignant Tumours** * Squamous cell carcinoma (85%) * HPV or lichen sclerosus * VIN (vulval intraepithelial neoplasia) * Invasive adenocarcinoma or adenocarcinoma in situ (Paget’s disease) * Malignant melanoma * BCC

Answer 444

* Congenital anomalies (e.g. absence or atresia) * Carcinoma (squamous cell carcinoma) * Adenocarcinoma * Children of women with threatened abortion treated with diethyl stilbosterol = risk of clear cell carcinoma * Rhabdomyosarcoma

Answer 445

* Congenital * Hormonal * Inflammatory * Neoplastic * Genetic * Immunological

Answer 446

I GET SMASHED: * **Idiopathic** (15%) * **Gallstones** (50%) * **Ethanol** (33%) * Trauma * Steroids * Mumps * Autoimmune * Scorpion * Hyper-calcaemia/-lipidaemia * *Pancreatitis causes hypocalcaemia → if hypercalcaemia is the cause, calcium drops to a normal level* * ERCP * Drugs - thiazides

Answer 447

* Duct Obstruction * **Gallstone** distal to where the common bile duct and pancreatic ducts join → reflux of bile up the pancreatic duct → damage to acini and release of proenzymes which become activated → inflammation / damage * **Alcohol** leads to spasm/oedema of the sphincter of Oddi → formation of protein-rich pancreatic fluid → obstructs pancreatic ducts * Direct Acinar Injury = all other causes

Answer 448

* **Periductal** = necrosis of acinar cells near the ducts (usually secondary to obstruction) * **Perilobular** = necrosis at the edges of the lobules (usually due to poor blood supply) * **Panlobular** = worsening of periductal or perilobular inflammation

Answer 449

* Pancreatic * Pseudocyst formation = collection of fluid without epithelial lining * Abscess - *pseudocysts can become infected leading to abscess formation* * Systemic * Shock * Hypoglycaemia * Hypocalcaemia

Answer 450

* Dependent on severity * Haemorrhagic pancreatitis = 50% mortality

Answer 451

* Relapsing or persistent * Relatively uncommon - 50% associated with acute pancreatitis * Mortality of 3% per year

Answer 452

I GET SMASHED + Chronic disease * Idiopathic * Gallstones * **Ethanol** (80%) * Trauma * Steroids * Mumps * Autoimmune * Scorpion * Hyper-calcaemia/-lipidaemia * ERCP * Drugs - thiazides * Chronic disease * Haemochromatosis * Cystic fibrosis

Answer 453

* **Chronic inflammation with parenchymal fibrosis** and loss of parenchyma *(ascini become atrophic)* * **Duct strictures** with calcified stones with secondary dilatations * *Pancreatic calcifications are diagnostic of chronic pancreatitis*

Answer 454

* Early = **Malabsorption** * Late = **Diabetes mellitus** (endocrine parts survive much longer than exocrine components) * **Pseudocysts** - *also complication of acute* * **Carcinoma of the pancreas**

Answer 455

* Lined by fibrous tissue (no epithelial lining) * Contains fluid (rich in pancreatic enzymes or necrotic material) * Connects with pancreatic ducts

Answer 456

* Resolve * Perforate * Compress adjacent structures * Infected

Answer 457

* Characterised by large numbers of IgG4 positive plasma cells * May involve the pancreas, bile ducts and almost any other part of the body * Histology = duct is surrounded by loads of IgG4 expressing plasma cells * Patients respond very well to steroids

Answer 458

* **Carcinomas** * Ductal (85% of all neoplasms) * Increasingly common with age; M\>F (2: 1) * 5-year survival = 5% = 5% of all cancer deaths * Pre-malignant bridges; 95% k-ras mutation * Acinar * Acinar-ductal metaplasia * Associated with increased serum lipase * **Cystic Neoplasms** * Serous cystadenoma * Mucinous cystic neoplasm (usually benign) * **Pancreatic Neuroendocrine Tumours** (Islet cell tumours)

Answer 459

* Smoking * BMI * Dietary factors * Chronic pancreatitis * Diabetes mellitus

Answer 460

* 2 types of dysplastic ductal lesions * Pancreatic Intraductal Neoplasia (PanIN) * Intraductal Mucinous Papillary neoplasm - *doesn't invade through the BM* * K-Ras mutations are present in 95% of cases

Answer 461

* Macroscopic * Gritty and grey * Invades adjacent structures * Tumours in the head present earlier * Microscopic * Adenocarcinomas * Secrete mucin (stain for mucin) * Form glands * Set in desmoplastic stroma (i.e. tumour induces fibrous tissue growth around it)

Answer 462

Ductal Carcinoma = Head \> Body \> Tail Neuroendocrine = Tail \> Body \> Head

Answer 463

* Metastases * Chronic pancreatitis * Venous thrombosis * Circulating pancreatic cancer cells releasing mucous which activates the clotting cascade

Answer 464

* Serous cystadenoma + Mucinous cystic neoplasm * Contain serous or mucin secreting epithelium (like ovarian tumours) * Usually benign

Answer 465

* Usually non-secretory * Stained by neuroendocrine markers (chromogranin stain) * Behaviour is difficult to predict

Answer 466

* Insulinomas = most common type of functional tumour * Derived from beta cells * Whipple’s triad * Glucose \<50mg/dL * S/S hypo * Relief on glucose administration * MEN1 * Pituitary adenoma * Parathyroid hyperplasia * Pancreatic tumours

Answer 467

* Crohn's disease * Diabetes mellitus * High triglyceride + low fibre diet * Female * Ethnicity (e.g. Native Americans) * \>40 * Medication: * Somatostatin analogue (octreotide) * Glucagon-like peptide-1 analogues * Ceftriaxone * COCP / HRT * Non-alcoholic fatty liver disease * Obesity * Weight loss – particularly if fast * Hereditary factors (e.g. disorders of bile metabolism)

Answer 468

* Cholesterol * \>50% cholesterol * May be single * Mostly radiolucent - NOT seen on a plain abdominal X-ray → must USS * Pigment (contain calcium salts of unconjugated bilirubin) * Often multiple * Mostly radio-opaque (because they contain calcium)

Answer 469

**MOST PEOPLE** do not have any problems * Bile duct obstruction * Acute and chronic cholecystitis * Pancreatitis * Gallbladder cancer

Answer 470

* Acute cholecystitis * Acute inflammation = neutrophils, oedema * 90% are associated with gallstones * Chronic cholecystitis * 90% contain gallstones * Fibrosis, small, neoangiogenesis * Diverticula (Rokitansky-Aschoff sinuses) * Contracts against obstruction → diverticula

Answer 471

* Adenocarcinoma → technically a type of cholangiocarcinoma * 90% associated with gallstones * Uncommon

Histopathology Flashcards

(525 cards)