Histopathology Flashcards

Question

Aspartate aminotransferase (AST)

Answer 1

takes the amino acid off aspartate and converts into a glucose derivative

Answer 2

takes amino acid off alanine when liver is damaged, leaks into the blood

Answer 3

Prothrombin time (liver makes clotting factors) also albumin because made by liver and bilirubin because metabolised by liver liver enzymes (ALT, AST, ALP, GGT) don't actually tell you about liver function but leak out when liver is damaged NB: in paracetamol overdose, PT determines prognosis (if high, will need transplant)

Answer 4

virus in faeces incubation period become infective immune response begins: IgM start to get jaundiced and symptomatic IgG response begins at 5-weeks post-exposure immune for life vaccine available

Answer 5

2 forms: acute (like Hep A) and chronic acute: become unwell 2-months post exposure, increased HBs Ag and HBe Ag then start antibody response with anti-HBc, HBs and HBe (only when antigen titre reaches 0 for corresponding antigen) - end up with 3 antibodies and no antigen, probably won't get it again but may be a carrier vaccine is against surface antigen (anti-HBs, won't have HBe antibody)

Answer 6

surface antigen remains for years remains infectious to others only have anti-HBc and anti-HBe but not anti-HBs as remain antigenic cannot undergo surgery due to infectious risk

Answer 7

neutrophilic inflammation balloon cells with mallory's hyaline (pink cells) - damaged hepatocytes alcoholic fatty liver is reversible but alcoholic hepatitis may not be reversible may see fatty change left over from early stages positive blue collagen stain - high risk of end-stage liver disease (cirrhosis) megamitochondria (big and swollen - damage due to alcohol)

Answer 8

commonest cause of fatty liver disease today causes: overweight, malnourished same histological features as alcoholic hepatitis associated with high BMI and diabetes 10% of people with normal BMI also have it

Answer 9

supportive: stop alcohol nutrition: vitamins esp b1(IV pabrinex) occasionally steroids liver hepatocytes will regenerate (as long as alcohol stops) - not uniform distribution with hexagonal arrangement and portal triads so may develop cirrhotic nodules (regenerating hepatocytes) eventually leading to portal hypertension (continued cycle of drinking alcohol)

Answer 10

liver breaks down oestradiol, dysfunctional liver leads to build-up of oestradiol and decreased testosterone, causing gynaecomastia

Answer 11

spider naevi palmar erythema gynaecomastia dupuytren's contracture (alcohol)

Answer 12

1.visible veins on the abdominal wall 2. splenomegaly (portal vein includes splenic vein) 3. ascites NB: caput medusae from umbilicus (damage to portal triads causes high pressure in umbilical vein because blood can't leave liver through artery so blood travels back down through the portal vein and ductus venosus to the umbilicus)

Answer 13

normal - fat (doesn't move)

Answer 14

= ascites sign of portal hypertension

Answer 15

sign of liver failure possibly caused by ammonia but unsure (same flap as CO2 retention)

Answer 16

failed synthetic function failed clotting factor and albumin production failed clearance of bilirubin (jaundice) failed clearance of ammonia (encephalopathy) need to decrease protein intake and minimise risk of GI bleed but many die treatment: liver transplant

Answer 17

micro or macro cirrhotic nodules (caused by regenerating hepatocytes) surrounded by a fibrous fat cuff characteristic of alcohol pathology fatty changes are reversible scarring in hepatocytes between portal vein and hepatic vein therefore blood entering liver completely bypasses hepatocytes (intrahepatic shunting of blood) - blood isn't filtered and liver is not receiving blood NB: caput medusae and visible veins on abdomen = extrahepatic shunting of blood

Answer 18

Alcoholic hepatitis (reversible) Chronic stable liver disease (cycle) Portal hypertension Liver failure (end-stage)

Answer 19

oesophagus (portal hypertension causes varices - if they tear, bleed to death because no muscle in them) rectal varices umbilical vein recanalising spleno-renal shunt

Answer 20

obstruction of bile ducts only (not just jaundice) - causes by bile salts not bilirubin bile salts/acids emulsify fats and are reabsorbed in the entero-hepatic circulation but when there's an obstruction of the bile duct, bile salts/acids enter the systemic circulation and make you itch

Answer 21

if a gallbladder is palpable in a jaundiced patient the cause is likely pancreatic cancer and not gall stones (gall stones cause a small, shrunken, fibrotic gallbladder so won't be palpable)

Answer 22

Abdo USS: dilated bile ducts metastasis

Answer 23

fibrous white tumour tissue metastasis through lymphatics multiple tumour deposits in liver (likely to be secondary as there are multiple deposits) - rapid metastasis through portal vein usually adenocarcinoma (glandular)

Answer 24

Rule of 2s: 2 main structures: - Large ducts - TDLU (terminal ductus lobular unit) 2 types of epithelial cells: - luminal cells - myoepithelial cells 2 types of stroma: - interlobular stroma (found between ductules and acini) - intralobular stroma Lactiferous ducts divide into extra and intra-lobular terminal ducts which further divide into acini and ductules

Answer 25

= extralobular terminal duct with lobule = functional unit of the breast

Answer 26

glandular structure lined by outer myoepithelial cell layer and inner luminal cell layer

Answer 27

breast lump abnormal screening mammogram nipple discharge most problems are benign but breast cancer is second biggest cancer killes

Answer 28

triple assessment: physical exam imaging (sonography, mammography, MRI) pathology (cyto/histopathology)

Answer 29

indicated if palpable lump or nipple discharge

Answer 30

papilloma is most common breast lesion that presents with nipple discharge weak association with cancer but increased if discharge is bloody or associated with lump

Answer 31

safe, reliable, accurate, fast, cost-effective, almost complication-free good cellular detail and quick to prepare but cannot differentiate atypical ductal hyperplasia from low grade cancer or high grade in situ carcinoma from invasive cancer ancillary testing not always possible

Answer 32

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

Answer 33

intact tissue is removed, fixed in formalin, embedded in paraffin wax, thinly sliced and stained with H&E includes biopsies and surgical excisions takes 24 hours to process gives architectural and cellular detail

Answer 34

B1 - normal tissue / inadequate sample B2 - benign lesion B3 - uncertain malignant potential (need to follow-up with surgical excision eg.) B4 - suspicious of malignancy B5 - malignant

Answer 35

acute inflammation in the breast usually seen in context of lactation due to cracked skin and stasis of milk may complicate duct ectasis or abscess staph is usual organisms painful red breast (unilateral) drainage and antibiotics histology: lots of inflammatory cells (neutrophils) - may obscure view of normal breast tissue, gram positive

Answer 36

5th-6th decade, multiparous women inflammation and dilation of large breast ducts aetiology unclear usually presents with nipple discharge sometimes: breast pain, breast mass, nipple retraction benign with no increased risk of malignancy cytology (of nipple discharge): proteinaceous material and inflammatory cells only can give rise to giant cell reaction

Answer 37

An inflammatory reaction to damaged adipose tissue. Caused by trauma, surgery, radiotherapy. Presents with a breast mass, late stages may show focal calcification. Benign condition. histology: lipid vacuoles surrounded by inflammatory cells (macrophages and large cells)

Answer 38

Cystic dilation of a duct during lactation Usually multiple ducts Tender palpable nodules Secondary infection may convert these to acute mastitis or abscess

Answer 39

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

Answer 40

A group of alterations in the breast which reflect normal, albeit exaggerated, responses to hormonal influences. Very common. Presents with breast lumpiness. No increased risk for subsequent breast carcinoma. histology: fibrous tissue, large cystic glands, adenosis (increased number of glands), may also get apocrine metaplasias

Answer 41

A benign sclerosing lesion characterised by a central zone of scarring surrounded by a radiating zone of proliferating glandular tissue. Range in size from tiny microscopic lesions to large clinically apparent masses. Lesions >1 cm are sometimes called “complex sclerosing lesions”. Reasonably common lesions. Thought to represent an exuberant reparative phenomenon in response to areas of tissue damage in the breast. Usually present as stellate masses on screening mammograms which may closely a carcinoma. Excision is curative. Scar is a misnomer; not related to prior trauma or surgery Radiological presents as spiculated mass, architectural distortion, may be indistinguishable from invasive carcinoma – often biopsied Associated risk with invasive breast cancer debated

Answer 42

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 Proliferation of cells of luminal and myoepithelial lineages Cytologic features Mild variation in cellular and nuclear size and shape Architectural features Cohesive proliferation with haphazard, jumbled cell arrangement or streaming growth pattern, Irregular slit-like fenestrations are common, especially along periphery

Answer 43

Emerging genetic data suggests FEA may represent the earliest morphological precursor to low grade ductal carcinoma in situ. relative risk ~1.5 of developing cancer Frequent secretions and calcifications within cystically dilated glands One to several layers of low columnar or cuboidal cells with low grade cytologic atypia Prominent apical tufting (snouts) Nuclei are usually round with variably prominent nucleoli

Answer 44

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 8-10 times that expected in women without lobular neCurrent 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 8-10 times that expected in women without lobular neoplasia. More commonly diagnosed in the 50s Does NOT form a palpable mass Solid, (so no arcades, lumens or papillary projections) discohesive proliferation of cells that are monomorphic, small, have pale pink cytoplasm, uniform oval nuclei and indistinct nucleoli, distends >50% of the acini in the lobule

Answer 45

A benign neoplasm composed of fibrous and glandular tissue. Common. Presents as a circumscribed mobile breast lump in young women aged 20-30. Simple “shelling out” curative. cytology: stromal naked cells (no cytoplasm), luminal cells (honeycomb epithelial cells), Antlo-horn formations (reassuring its benign) histology: fibrous tissue around ducts or stromal overgrowth compressing ducts

Answer 46

A group of potentially aggressive fibroepithelial neoplasms of the breast. Uncommon tumours. Present as enlarging masses in women aged over 50. Some may arise within pre-existing fibroadenomas. Vast majority behave in a benign fashion, but a small proportion can behave more aggressively. cytology: only stromal cells (no glandular features) histology: increasing stromal proliferation --> leaf-like architecture

Answer 47

A benign papillary tumour arising within the duct system of the breast. Arise within small terminal ductules (peripheral papillomas) or larger lactiferous ducts (central papillomas). Common. Seen mostly in women aged 40-60. Central papillomas present with nipple discharge. Peripheral papillomas may remain clinically silent if small. Excision of involved duct is curative. cytology: Large stellate tissue fragments of benign ductal cells in a proteinaceous background histology: intraductal proliferation comprised of arborizing fibrovascular cores lined by outer layer of luminal cells and an inner layer of myoepithelial cells Myoepithelial cells also present at the periphery of the involved duct associated with usual type ductal hyperplasia and apocrine metaplasia, less frequently squamous, osseous or chondroid metaplasia may be seen May undergo ischemic or hemorrhagic changes, either spontaneously or secondary to biopsy / trauma May show prominent fibrosis / sclerosis which may contained entrapped glands (sclerosing papilloma)

Answer 48

Proliferation of malignant glandular epithelial cells (in situ carcinoma) in the nipple areolar epidermis. Uncommon clinical presentation of breast cancer, occurs in 1 - 4% of women and 1 - 2% of men Peak incidence between 6th and 7th decade. Pathogenesis: Epidermotropic theory (most widely accepted) - Paget cells are DCIS cells that migrate along the basement membrane of the nipple, supported by the presence of DCIS deeper in the breast identical to Paget cells in almost all cases; Transformation theory - Paget cells originate from malignant transformation of keratinocytes or Toker cells; it would explain rare cases (< 5%) in which cancer is not present in underlying breast - could also be due to biopsy not sampling cancer cells Underlying high grade DCIS or invasive carcinoma is present in > 95% of patients. Majority of Paget cells and associated underlying carcinoma are HER2+

Answer 49

Nipple areolar complex with red-pink crusting lesion, discoloration, thickening, ulceration, exudate, nipple retraction Paget cells have abundant pale, clear cytoplasm, which often contains mucin. The nuclei are large and show prominent nucleoli. Paget cells are typically present at the basal portion of the epidermis but can extend throughout the entire thickness and be present very superficially.

Answer 50

A neoplastic intraductal epithelial proliferation in the breast with an inherent, but not inevitable, risk of progression to invasive breast carcinoma (2 - 8.6 times). Common. Incidence has markedly increased since the introduction of breast screening programs. 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. Treatment is surgical excision. Complete excision with clear margins is curative. Recurrence is more likely with extensive disease and high grade DCIS.

Answer 51

Fenestrated proliferation with multiple, round, rigid extracellular lumens with punched out appearance Neoplastic cells are frequently evenly distributed equidistant and polarized with long axis of cell perpendicular to the central lumen Monotonous, round nuclei with smooth contours, small size nuclei

Answer 52

Lumen of ducts or lobules filled with sheets of cohesive cells Cells are evenly spaced especially in low or intermediate grade DCIS Prominent pleomorphism, large size nuclei Comedonecrosis (central necrosis with specks of calcification)

Answer 53

A group of malignant epithelial tumours which infiltrate within the breast and have the capacity to spread to distant sites. The most common cancer in women with a lifetime risk of 1 in 8. Incidence rates rise rapidly with increasing age, such that most cases occur in older women. Aetiology: Early menarche, late menopause, increased weight, high alcohol consumption, oral contraceptive use, and a positive family history are all associated with increased risk. About 5% show clear evidence of inheritance. BRCA mutations cause a lifetime risk of invasive breast carcinoma of up to 85%. Presentation: Most cases present symptomatically with a breast lump. An increasing proportion of asymptomatic cases are detected on screening mammography.

Answer 54

Most common type of invasive breast carcinoma (75 - 80%). Majority are sporadic; 5 - 10% of all breast cancers are associated with hereditary cancer susceptibility genes lacks the histologic features to classify morphologically as a special subtype of breast cancer Cytology - cellular pleomorphism, nuclear size, nucleoli, lack of naked nuclei, cellular dyscohesion and mitoses & necrosis

Answer 55

Comprises about 10% of invasive breast carcinomas Most common special subtype of invasive breast carcinoma Only comprises 1% of male breast carcinomas More frequently bilateral and multifocal (need MRI of other breast to identify if another lesion) histology: monotonous proliferation of cells distending the ducts --> break basement membrane and into adjacent stroma --> indian filing (nuclei on top of eachother)

Answer 56

A well differentiated variant with very favorable prognosis Histology: irregular angulated contours of glands ("teardrop-like"), open lumina with apocrine-like snouts and basophilic secretions

Answer 57

Clusters / nests of tumor cells with low or intermediate nuclear grade floating in pools of extracellular mucin, associated with favorable prognosis

Answer 58

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

Answer 59

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). Histologic grading is based on the Nottingham / modified Bloom & Richardson Score

Answer 60

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 61

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 62

The aim of screening is to pick up DCIS or early invasive carcinomas. Women aged 50-71 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. This may include more mammograms, or an ultrasound followed by sampling of the abnormal area, usually by core biopsy. - given b grade --> B4 and B5 need further investigation (B5a = DCIS, B5b = invasive carcinoma, B5c = certain it is malignant but cannot tell if DCIS or invasive)

Answer 63

Composed of ductal structures only within collagenized stroma, with no / rare acini (no/very rare diseases that affect acini) pathologies: gynaecomastia and male breast cancer

Answer 64

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

Answer 65

rare (0.2% of all cancers). Median age at diagnosis 65 years old. Most present with a palpable lump. Histologically the tumors show similar features to female breast cancers. (lobular cancers rare due to lack of lobules)

Answer 66

Oncotype DX assay is a genomic test that predicts adjuvant (radiotx for DCIS, Chemotx/radiotx for IDC) therapy benefit and the likelihood of 10-year breast cancer local recurrence risk in patients with DCIS treated with breast conserving surgery and low stage ER positive invasive breast cancers Novel biomarkers not used in routine clinical practice High Ki67 proliferation index has reported to correlate with increased recurrence risk tumor immune microenvironment is an important factor in identifying DCIS cases with the highest risk for recurrence

Answer 67

lined by stratified squamous epithelium transition into columnar epithelium of stomach: Z-line

Answer 68

oedema neutrophils (inflammatory cells) causes: alcohol, drugs, GORD appearance on endoscopy: red and inflamed

Answer 69

ulceration (goes through muscularis into submucosa wheras erosion is superficial) haemorrhage perforation stricture Barrett’s oesophagus

Answer 70

The same as columnar lined oesophagus (CLO) Replacement of squamous epithelium by metaplastic columnar epithelium: 2 types: - without goblet cells = gastric metaplasia - with goblet cells = intestinal type metaplasia Flat pathway: metaplasia -> LGD -> HGD -> adenocarcinoma (want to diagnose at metaplasia or dysplasia stage due to very poor prognosis)

Answer 71

The commonest oesophageal carcinoma in Developed Countries Associated with reflux (flat pathway) Lower oesophagus --> commonly at gastro-oesophageal junction

Answer 72

Commonest oesophageal cancer in Developing Countries Associated with alcohol and smoking Mid/lower oesophagus (higher up than adenocarcinoma) also association with HPV histology: production of keratin, intercellular bridges

Answer 73

= varicose veins in oesophagus associated with portal hypertension (caused by extrahepatic shunting of blood) important cause of mortality and morbidity

Answer 74

lined by gastric mucosa columnar epithelium (foveolar, mucin secreting) specialised glands in the lamina propria (secrete IF, acid, pepsinogen) muscularis mucosae

Answer 75

lined by gastric mucosa columnar epithelium (fovelolar, mucin secreting) Non-specialised glands in the lamina propria (gastric pits) mucularis mucosae

Answer 76

Chemical: aspirin/NSAIDs alcohol corrosives Infection: e.g. Helicobacter pylori

Answer 77

Autoimmune (antiparietal antibodies etc. body) Bacterial (H. pylori; antrum ) Chemical (NSAIDs, bile reflux; antrum)

Answer 78

Infection e.g. CMV (commonest opportunistic viral pathogen), strongyloides (worms) Inflammatory bowel disease Crohn’s Disease (gastric involvement more common in children)

Answer 79

Cause H. pylori Pattern chronic gastritis +/- activity Outcome Peptic ulcer (gastric and duodenal) - commonest cause Metaplasia +/- dysplasia, Adenocarcinoma Lymphoma (MALToma) - can be reversible if treat helicobacter

Answer 80

Bleeding Anaemia Shock (massive haemorrhage) Perforation Peritonitis Cancer (rare)

Answer 81

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. This strain is associated with more chronic inflammation. Treatment of the infection with antibiotics drastically reduces the risk of cancer.

Answer 82

chronic gastritis --> intestinal metaplasia --> dysplasia --> cancer

Answer 83

Presence of goblet and Paneth cells In response to chronic gastritis Increased cancer risk (if significantly widespread --> need careful follow-up)

Answer 84

Abnormal epithelial pattern of growth Some of the cytological and histological features of malignancy are present, but no invasive through the basement membrane

Answer 85

High incidence in Japan, Chile, Italy, China, Portugal, Russia More common in men (1.8:1 ♂:♀) >95% of all malignant tumors in stomach are adenocarcinomas (glandular - secrete mucin) These are split morphologically into: - Intestinal – form glands, well differentiated - Diffuse – poorly differentiated (Linitis plastica), includes signet ring cell carcinoma The remaining 5% is mainly made up of: - Lymphoma (MALToma) - Gastrointestinal stromal tumour (GIST) - Neuroendocrine tumours (mostly in terminal ileum)

Answer 86

Chronic inflammation - Chronic immune stimulation B cell (marginal zone) lymphocytes Treatment - If limited to the stomach and H.pylori is present: H.pylori eradication

Answer 87

Derived from the interstitial cells of Cajal. Spindle cell tumours Stain with CD117 (not smooth muscle actin) Anywhere in the GIT but stomach is the commonest site. Prognosis depends on site (stomach best), size (the smaller the better) and mitotic index (the lower the better)

Answer 88

Glandular epithelium with goblet cells (intestinal type epithelium) Villous architecture villous:crypt ratio of >2:1

Answer 89

Increased acid production in the stomach which spills over into duodenum Chronic inflammation and gastric metaplasia with helicobacter infection no significant risk of dysplasia and cancer

Answer 90

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

Answer 91

Histology - Villous atrophy - Crypt hyperplasia - Increased Intraepithelial lymphocytes (normal range less than 20 lymphocytes /100 enterocytes)

Answer 92

Diagnosis requires: endomysial antibodies and tissue transglutaminase antibodies Duodenal biopsies: - On gluten rich diet showing villous atrophy - Off gluten showing normal villi (can make it difficult to diagnose if pt has already stopped consuming gluten) There are other causes of malabsorption with similar histology e.g. tropical sprue (from developed countries go to developing countries and exposed to new mircobiome), drugs

Answer 93

Patients with coeliac disease have an increased risk of GIT cancers MALToma associated with Coeliac is in the duodenum T-cell origin (Enteropathy Associated T-cell Lymphoma) histology: big nuclei and lots of nucleoli

Answer 94

Exocrine: ducts and acini Endocrine: islets of langerhan cells, alpha and beta cells

Answer 95

Acute inflammation of the pancreas caused by aberrant release of pancreatic enzymes. (can lead to positive feedback loop) Relatively common, incidence increasing. Causes: Duct obstruction: - Gall stones (50%) - Trauma - Tumours Metabolic/toxic: - Alcohol (33%) - 5% of alcoholics develop acute pancreatitis - Drugs (e.g. thiazides) - Hypercalcaemia - Hyperlipidaemia Poor blood supply: - Shock - Hypothermia Infection/ inflammation: - Viruses (e.g. mumps) Autoimmune Idiopathic (15%)

Answer 96

2 major pathways: (1) Duct obstruction: - Gallstone stuck distal to where the common bile duct and pancreatic ducts join leads to: reflux of bile up the pancreatic duct followed by damage to acini and release of proenzymes which then become activated - Alcohol leads to spasm/oedema of Sphincter of Oddi and the formation of a protein rich pancreatic fluid which obstructs the pancreatic ducts (2) Direct acinar injury (eg. mumps) --> rest of causes

Answer 97

Periductal - necrosis of acinar cells near ducts (usually secondary to obstruction) Perilobular – necrosis at the edges of the lobules (usually due to poor blood supply) Panlobular – develops from both of the above Activated enzymes --> acinar necrosis --> enzyme release etc. Ranges from stromal oedema, to haemorrhagic necrosis e.g. Lipases --> fat necrosis: 1. Lipase splits triglycerides into glycerol and free fatty acids 2. calcium ions bind to the free fatty acids forming soaps which are seen as yellow-white foci (calcium levels will be normal as being used up to bind to fatty acids unless cause of pancreatitis was hypercalcaemia in which case the calcium may be normal)

Answer 98

Complications Pancreatic : pseudocyst (lacks an epithelial lining, fluid-filled, localised and looks like a cyst), abscess (very infected pseudocyst) Systemic: shock, hypoglycaemia (damage to islets), hypocalcaemia (calcium binds to free fatty acids forming fat necrosis) Prognosis Overall mortality up to 50% for haemorrhagic pancreatitis

Answer 99

Relapsing or persistent, associated with acute pancreatitis in half of cases Relatively uncommon Mortality 3% per year Causes: Metabolic/toxic: - Alcohol (80%) - Haemochromatosis (iron deposition in pancreas causing damage) Duct obstruction: - Gallstones - Abnormal pancreatic duct anatomy - Cystic fibrosis (“mucoviscoidosis”) - thick secretions causing obstruction Tumours Idiopathic Autoimmune

Answer 100

Pathogenesis = same as acute but with fibrosis and atrophy , loss of acini --> loss of secretory function Pattern of injury: Chronic inflammation with parenchymal fibrosis and loss of parenchyma Duct strictures with calcified stones with secondary dilatations

Answer 101

Malabsorption (loss of exocrine function) Diabetes mellitus (eventual loss of islets of langherhans) Pseudocyst Carcinoma of the pancreas (?) (multi-directional ie. can both cause eachother)

Answer 102

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

Answer 103

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

Answer 104

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

Answer 105

Smoking BMI and dietary factors Chronic pancreatitis Diabetes

Answer 106

5% of cancer deaths Increasingly common with age, 2M: 1F 5 year survival: 5% Arise from dysplastic ductal lesions: Pancreatic Intraductal Neoplasia (PanIN) Intraducal Mucinous Papillary Neoplasm (IMPN) K-Ras mutations in 95% of cases

Answer 107

Macroscopic Appearance - Gritty and grey - Invades adjacent structures - Tumours in the head present earlier (early obstruction and clinical presentation) Microscopic Appearance Adenocarcinomas: mucin secreting glands set in desmoplastic stroma (response to cancer growing in it) very aggressive: peri-neural invasion (common way of spread)

Answer 108

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

Answer 109

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

Answer 110

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

Answer 111

usually non-secretory (most common secretion = insulin --> present with hypogylcaemia) contain neuroendocrine markers e.g. chromogranin (granules) - can stain for it or measure blood levels (for diagnosis and follow-up) behaviour difficult to predict (usually associated with mitotic index) may be associated with the Multiple Endocrine Neoplasia (MEN) 1 syndrome

Answer 112

derived from beta cells = commonest type of secretory tumour

Answer 113

1. Gall stones 2. Inflammation 3. Cancer All associated with stones stones are very common: 20% of adults

Answer 114

Age and gender: increasing age, F>M Ethnic and geographic: e.g. Native Americans Hereditary: e.g. disorders of bile metabolism Drugs e.g. oral contraceptive (increased oestrogen) Acquired disorders e.g. rapid weight loss (causing more bile secretion and movement)

Answer 115

Cholesterol (more than 50% cholesterol) May be single, mostly radiolucent (not picked up on abdo x-ray) Pigment (contain calcium salts of unconjugated bilirubin) Multiple, mostly radio-opaque Mixed type

Answer 116

most cause no problems Bile duct obstruction Acute and chronic cholecystitis Gall bladder cancer Pancreatitis

Answer 117

Acute inflammation 90% associated with gall stones

Answer 118

Chronic inflammation Fibrosis (thick and hard GB wall) Diverticula (mucosa going through muscularis) – Rokitansky-Aschoff sinuses 90% contain gall stones

Answer 119

Adenocarcinomas 90% associated with gall stones most common in Chile and Andes, less common in UK

Answer 120

CNS: Brain and coverings Spinal cord and coverings Pituitary gland PNS: Small nerves in any organ – usually neurofibromas of soft tissue or skin Large nerves – cranial and spinal nerve schwannomas Most are benign tumours

Answer 121

Primary: tumours that originated within CNS Secondary: Metastases - 10x more frequent than primary tumours in adults (30% of patients with systemic cancer develop CNS metastases) NB: primary tumours most common CNS tumours in children

Answer 122

EXTRA-AXIAL (coverings) Tumours of bone, cranial soft tissue, meninges, nerves INTRA-AXIAL (parenchyma) Derived from normal cell populations of the CNS: glia, neurons and neuroendocrine cells Derived from other cell types: lymphomas, germ cell tumours WHO grade 1 tend to be more extra-axial WHO grade 2-4 tend to be more intra-axial Glioblastomas grade 4 and have worst prognosis

Answer 123

Largely unknown Only known environmental factor: Previous radiotherapy to head and neck associated with increased risk of meningiomas (and rarely gliomas) Genetic predisposition <5% of primary brain tumours Familial syndromes: Autosomal dominant inheritance with frequent de novo mutations Some examples: Neurofibromatosis 1 (17q11) neurofibroma, astrocytoma Neurofibromatosis 2 (22q12) schwannoma, meningioma Brain Tumour Polyposis syndrome 1 malignant gliomas Gorlin syndrome (PTCH1, 9q31) medulloblastoma Von Hippel Lindau (3p25) hemangioblastoma

Answer 124

Not specific but can be subtle in slow growing tumours whereas there may be a very short history for malignant tumours Intracranial hypertension: headache vomiting change in mental status Supratentorial: focal neurological deficit seizures personality changes Infratentorial (posterior fossa): cerebellar ataxia long tract signs cranial nerve palsy

Answer 125

Modalities: CT-scan MR-scan MR-spectroscopy (metabolism) Perfusion MRI Functional MRI PET-scan Uses: Assess tumour type Guide resection & biopsy Assess post-surgery Assess response to treatments Follow-up recurrence and progression

Answer 126

SURGERY: Maximal safe resection with minimal damage to adjacent normal tissue gives best outcome Resection: location, size, number of lesions RADIOTHERAPY: Low and high-grade gliomas, metastases, some benign tumours External fractionated RT, stereotactic radiosurgery CHEMOTHERAPY: Mainly for high-grade gliomas (temozolomide) and lymphomas Biological agents (EGFR inhibitors, PD-L1 inhibitors, etc.)

Answer 127

Craniotomy for debulking may be sub-total or complete resections remove as much tumour as possible Open biopsy inoperable but approachable tumours (about 1cm of tissue) usually representative Stereotactic biopsy if open biopsy not indicated (about 0.5cm of tissue) tissue may be insufficient

Answer 128

Tumour type: Putative cell of origin or lineage of differentiation Tumour grade: Tumour aggressiveness It is based on morphological criteria of malignancy (proliferative activity, cell differentiation, necrosis) and increasingly on genetic profile Molecular profile: Most tumour types have molecular markers A four-tier system: Grade 1 – benign – long-term survival (eg. meningiomas) Grade 2 – more than 5 yrs Grade 3 – less than 5 yrs Grade 4 – less than 1 yr (eg. glioblastomas) Some tumour types have only one possible grade, but others have more than one

Answer 129

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

Answer 130

Diffuse gliomas: Grades ≥ 2, adults, supratentorial, malignant progression Astrocytomas (grades 2-4) Oligodendrogliomas (grades 2-3) Circumscribed gliomas: Grades 1-2, children, often posterior fossa, rare malignant transformation Pilocytic astrocytoma (grade 1) Subependymal giant cell astrocytoma (grade1) Ependymomas (usually)

Answer 131

Usually 1st & 2nd decade (account for 20% CNS tumours below 14 yrs) Often cerebellar, optic-hypothalamus, brainstem Genetic profile: BRAF mutation in 70% of PA MRI – well circumscribed, cystic, enhancing lesion Histology: Piloid “hairy” cells Very often Rosenthal fibres Slowly growing, low mitotic activity

Answer 132

Patients usually 20-40 yrs Astrocytoma (IDH mutant) and Oligodendroglioma (IDH mutant) Pathogenic point mutation in the IDH1/2 gene IDH mutation is associated with longer survival and a better response to chemotherapy and radiotherapy

Answer 133

Patients usually 20-40 yrs, cerebral hemispheres Genetic profile: point mutation in IDH1/2 MRI – T1 hypointense, T2 hyperintense, non-enhancing lesion. Low choline/creatinine ratio in MR spectroscopy Histology: low to moderate cellularity Mitotic activity is low. No vascular proliferation or necrosis. IDH1 mutants can be detected Immunocytochemically Progression to higher grades over time

Answer 134

Most aggressive and most frequent glioma; incidence increase with age Most patients >50 yrs, cerebral hemispheres Median survival 8 months Genetic profile IDH1 wildtype Common mutations in: TERT, PTEN, EGFR MRI – heterogenous, enhancing post contrast Histology: High cellularity Neoangiogenesis Necrosis

Answer 135

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

Answer 136

Determines grade Mitosis per 10HPF (0.16mm2) <4 = grade 1 4-20 = grade 2 >20 = grade 3

Answer 137

Most frequent CNS tumour in adults (10 x intrinsic tumours) Increasing incidence due to longer survival Often multiple, located at grey/white matter junction and/or leptomeningeal disease May be the first presentation of the disease Origin can be challenging to determine: immunohistochemical markers Any cancer can give CNS metastasis, but most frequent tumours are: lung ca, breast ca, melanoma, renal cell ca Very poor prognosis

Answer 138

EMBRYONAL TUMOUR: originates from neuroepithelial cells/neuronal precursors of the cerebellum or dorsal brainstem Rare (2 per 1,000,000 year), but second most common brain malignancy in children; also in young adults Outcome considerably improved with radio-chemotherapy and subtype stratification Histology 4 histological subtypes: classic, nodular/desmoplastic, extensive nodularity, large cell anaplastic 3 molecular subtypes by transcriptome or methylome profiling: WNT-activated, SHH-activated, nonWNT/nonSHH

Answer 139

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

Answer 140

Oedema Hydrocephalus Raised intracranial pressure Stroke - Haemorrhage - Infarction Traumatic brain injury

Answer 141

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/ ischemia Result is raised intracranial pressure

Answer 142

Non-communicating involves obstruction of flow of CSF (most common site = at cerebral aqueduct) Communicating involves no obstruction but problems with reabsorption of CSF into venous sinuses (often a complication of meningitis)

Answer 143

ICP is normally 7–15 mm Hg for a supine adult Raised ICP due to space occupying lesions, oedema or both Unyielding bony wall of skull and inflexible dural folds Herniation of brain structures (subfalcine [supratentorial, cingulate cortex herniation through falx cerebri), transtentorial/uncal [at level of midbrain, medial temporal lobe into posterior fossa] and tonsillar [at level of cerebellum passing through foramen magnum])

Answer 144

Haemorrhage into the substance of the brain - rupture of a small intraparenchymal vessel Most common in basal ganglia Hypertension (chronic) account for more than 50% of bleeds Presentation with severe headache, vomiting, rapid loss of consciousness, focal neurological signs (more acute than tumours)

Answer 145

Close interweaving of arterial and venous vessels Occur anywhere in the CNS Present from birth 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

Answer 146

“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

Answer 147

Rupture of a berry aneurysm (present in 1% of general population) 80 % of berry aneurysms- 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 Mixed prognosis Treatment: endovascular platinum coil into aneurysm (radiologists through femoral artery)

Answer 148

Tissue death due to ischemia Commonest form of cerebrovascular disease 70-80% of strokes Cerebral atherosclerosis most common cause hypertension, diabetes, smoking are major risks factors Worst atherosclerosis in larger vessels (extracerebral arteries) – thrombosis Often near carotid bifurcation or in basilar artery Other cause - emboli (intracerebral arteries) Usually from heart or atherosclerotic plaques Embolic occlusion usually in middle cerebral artery branches a) Focal cerebral ischaemia: defined vascular territory b) Global cerebral ischaemia: systemic circulation fails

Answer 149

Infarct: Tissue necrosis Rarely haemorrhagic Permanent damage in the affected area No recovery Haemorrhage: Bleeding Dissection of parenchyma Fewer macrophages Limited tissue damage Partial recovery (really important: don't want to give thrombolytics to haemorrhagic patients)

Answer 150

Fissure fractures often extend into base of skull May pass through middle ear or anterior cranial fossa (resulting in CSF leakage) Otorrhea or rhinorrhea (may be mixed with blood and therefore less obvious) Battle sign: bruising behind ears due to skull base fracture Infection risk

Answer 151

Brain in collision with skull caused by impact Surface “bruising” If pia mater torn, then becomes laceration Lateral surfaces of hemispheres, inferior surfaces of frontal and temporal lobes Coup or contrecoup (rebound causing damage on both the front and back of skull)

Answer 152

Occurs at moment of injury Shear & tensile forces affecting axons causing white matter damage Commonest cause of coma (when no bleed) Midline structures particularly affected e.g. corpus callosum, rostral brainstem and septum pellucidum

Answer 153

multiple repetitive sub-clinical/sub-concussive impacts initiating a neurodegenerative process seen in american football players who presented after retirement with psychiatric/early dementia symptoms now also seen in rugby and football players in the UK

Answer 154

Extracellular plaques (beta amyloid protein, can be diffuse or classic [target-shaped]) Neurofibrillary tangles (Paired helical filaments (PHF), Tau = a microtubule associated protein (MAP), Stabilization of microtubules dependent on phosphorylation state. In AD, tau hyperphosphorylated) Cerebral amyloid angiopathy (CAA) (amyloid in blood vessel walls) Neuronal loss (cerebral atrophy; cortical and hippocampal)

Answer 155

Amyloid: Where are amyloid plaques found in brain? --> 5 phases given score of 0-3 Braak Staging: neurofibrillary tangles and spread --> 0-3 Counting: How many plaques? --> 0-3 score of 333 = high chance of clinical AD

Answer 156

Loss of dopaminergic neurones in substantia nigra in the midbrain (basal ganglia) causing movement disorders and difficulty to initiate movements Build-up of lewy bodies (hyaline inclusions within dopaminergic cells in substantia nigra) Polymeropoulos in 1997 found that mutations in the α-synuclein gene can result in PD Spillantini reported that Lewy bodies and Lewy neurites are immunoreactive for α-synuclein Now α-synuclein immunostaining is considered as the diagnostic gold standard neuro-melanin = by-product of dopaminergic cell metabolism, seen as black line in midbrain sample post-mortem, not seen in parkinson's brains

Answer 157

Braak staging depending on spread throughout brain (from cerebellum upwards to cortices)

Answer 158

Bradykinesia Rigidity Rest tremor Response to L-dopa

Answer 159

Idiopathic Parkinson’s disease Drug-induced parkinsonism Multiple system atrophy Progressive supranuclear palsy Corticobasal degeneration Vascular pseudo-parkinsonism Alzheimer’s changes Frontotemporal neurodegenerative disorders 20 other disorders

Answer 160

Term covering three disorders: Olivopontocerebellar atrophy (OPCA) Shy-Drager syndrome (autonomic presentation eg postural hypotension) Striatonigral degeneration (exactly like PD) Now characterised clinically as: MSA-P – predominant parkinsonism MSA-C – cerebellar features Pathology: Cortical atrophy (motor, premotor) Cerebellar atrophy Shrinkage of middle cerebellar peduncle, pons and inferior olivary nucleus Pallor of locus coeruleus and substantia nigra Mixed neuronal and glial pathology α-synuclein immunoreactive glial cytoplasmic inclusions (GCI) Neuronal cytoplasmic inclusions, neuronal nuclear inclusions, glial nuclear inclusions and neuropil threads

Answer 161

Progressive neurodegenerative disorder Rigidity, clumsiness, stiffness and jerking of arm, “alien limb” (feeling like someone else is controlling limb) Affects cerebral cortex (fronto-parietal atrophy), deep cerebellar nuclei and substantia nigra Glial and neuronal inclusions Neuropil threads particularly prominent Pathology: Balloon neurons Astrocytic plaques (Tau pathology not alpha-synuclein)

Answer 162

Most common form of atypical parkinsonism Often show no response to L-DOPA Supranuclear gaze palsy & postural instability Atrophy of basal ganglia, subthalamus & brainstem Neuronal loss & gliosis Neuronal & glial tau-positive inclusions Pathology: Tufted astrocytes Coiled bodies (in oligodendrocytes)

Answer 163

Fronto–temporal atrophy Marked gliosis and neuronal loss Balloon neurons Tau positive Pick bodies (small round inclusions within hippocampus) - 3R Tau pathology

Answer 164

Transmissible Spongiform Encephalopathies A series of diseases with common molecular pathology Transmissible factor No DNA or RNA involved Prion (proteinaceous infectious only) eg. CJD (Creutzfeldt-Jakob disease) Pathology: generalised atrophy spongiform change (holes in the tissue) prion protein deposits Conversion of prion from alpha helical formation into beta-pleated sheet, possibly driving pathology Rapid progression, death within a year very rare

Answer 165

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

Answer 166

Cause discomfort but no serious complications: Candida: Diabetes mellitus, oral contraceptives and pregnancy enhance development of infection Tichomonas vaginalis: protozoan Gardenerella: gram negative bacillus causes vaginitis Have serious complications: Chlamydia: major cause of infertility Gonorrhoea: major cause of infertility Mycoplasma: causes spontaneous abortion and chorioamnionitis HPV: implicated in cancer

Answer 167

Acute, Chronic or granulomatous Usually direct ascent from the vagina (except TB) Depending on severity and treatment may result in: Resolution Complications: - Plical fusion - Adhesions to ovary - Tubo-ovarian abscess - Peritonitis - Hydrosalpinx (fluid build-up) - Infertility - Ectopic pregnancy

Answer 168

2nd most common cancer affecting women worldwide Mean age 45-50 years Important malignancy to know about: 1. Role of viruses in aetiology of cancer 2. Premalignant phase – (Cervical intraepithelial neoplasia) 3. Role of screening 4. Intervention possible at preinvasive stage 5. Possibility of prevention by vaccination

Answer 169

Human Papilloma Virus -present in 95% (low and high risk groups) Many sexual partners Sexually active early Smoking Immunosuppressive disorders

Answer 170

Most common types: 6, 11 Other types: 40, 42, 43, 44, 54, 61, 72, 73, 81 Genital and oral warts Low grade cervical dysplasia

Answer 171

Most common types: 16, 18 Other types: 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68,82 Low & high grade cervical dysplasia Cervical cancer Vulval, vaginal, penile, and anal cancer

Answer 172

This is the term for dysplasia in this site Epithelial cells have undergone some phenotypic and genetic changes which are premalignant and preinvasive Basal membrane immediately deep to the surface epithelium is intact Squamous epithelium is involved more often (CIN) than glandular epithelium (CGIN)

Answer 173

Invasion through the basement membrane defines change from CIN to invasive carcinoma Two principal types of cervical carcinoma Squamous cell carcinoma (almost always HPV dependent) Adenocarcinoma (20% of all invasive cases) HPV dependent or independent Prognosis: Tumour stage: FIGO Stage I (90%) – IV (10%) 5 year survival

Answer 174

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

Answer 175

Viral DNA replication occurs independently of host chromosomal DNA synthesis. Large numbers of viral DNA are produced and result in infectious virions. Characteristic cytological and histological features are seen (koilocyte)

Answer 176

Two proteins E6 and E7 encoded by the virus have effects on genes. E6 and E7 bind to and inactivate two tumour suppressor genes: Retinoblastoma gene (Rb) (E7) P53 (E6) Both effects interfere with apoptosis and increase unscheduled cellular proliferation both of which contribute to oncogenesis.

Answer 177

Helps protect against cancers caused by HPV (e.g. cervical, anal, head & neck) Girls and boys aged 12 to 13 years are offered the HPV vaccine as part of the NHS vaccination programme. In England, they are offered 1st dose in school Year 8 2nd dose offered 6 to 24 months after the 1st dose. It's important to have both doses of the vaccine to be properly protected.

Answer 178

Endometrium: Infertility Uterine bleeding Thickened endometrium on imaging Uterus or related mass: Lesion identified on imaging As part of a wider resection

Answer 179

Congenital anomalies Inflammation: acute or chronic endometritis Adenomyosis Dysfunctional uterine bleeding: e.g. hormonal imbalance Endometrial atrophy and hyperplasia Endometrial polyp Uterine tumours

Answer 180

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 181

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

Answer 182

Endometrial cancer is the most common gynaecological malignancy in developed countries, causing 6% of new cancer cases in women. Risk factors: Nulliparity Obesity Diabetes mellitus Excessive oestrogen stimulation Histological subtypes: Endometrioid Serous Clear cell Undifferentiated Mixed cell Mesonephric / mesonephric like Squamous cell Mucinous Carcinosarcoma

Answer 183

Are oestrogen dependent Often associated with atypical endometrial hyperplasia Low grade and high grade tumours Develop through the accumulation of mutations of different genes

Answer 184

Older, postmenopausal Less oestrogen dependent Arise in atrophic endometrium High grade, deeper invasion, higher stage 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 185

Serous, clear cell, mixed, undifferentiated, dedifferentiated and carcinosarcoma are considered high grade. Endometrioid carcinoma: FIGO 3 tier system: grade 1, 2 and 3 depending on Architecture: % of gland formation Cytological atypia

Answer 186

Group 1: EEC with mutations in POLE (Polymerase E- ultramutated) - better prognosis Group 2: EEC with MSI (hypermutated) Group 3: EEC with low copy number alterations Group 4: (serous-like) tumours show TP53 mutations and high copy number alterations - grades 1,2,3 POLE and MSI sensitive to anti-PD1 checkpoint inhibitor (immunotherapy)

Answer 187

(mesenchymal tumours) Smooth muscle tumour of myometrium Commonest uterine tumour 20% of women >35yrs Lay term is fibroid Usually multiple May be intramural, submucosal or subserosal

Answer 188

Malignant counterpart of leiomyoma - rare Usually solitary Usually postmenopausal Local invasion and blood stream spread 5yr survival 20-30%

Answer 189

Presence of endometrial glands and stroma outside the uterus Common – 10% of premenopausal women Origin: Metaplasia of pelvic peritoneum Implantation of endometrium, retrograde menstruation Ectopic endometrial tissue is functional and bleeds at time of menstruation > pain, scarring and infertility Can develop hyperplasia and malignancy

Answer 190

(mainly) Non neoplastic cysts: Follicular and luteal cysts Polycystic ovarian disease: 3-6% of reproductive age women patients have persistent anovulation obesity and hirsutism / virilism Endometriotic cyst

Answer 191

Primary tumours: Epithelial tumours Sex cord-stromal tumours Germ cell tumours Miscellaneous tumours Secondary tumours

Answer 192

Epithelial tumours: make up 65% of all ovarian tumours & 95% of malignant ovarian 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 stromal tumours: most commonly seen in post-menopausal women but some sub-types peak in 25-30 year age group

Answer 193

Serous Cystadenomas Cystadenofibromas Mucinous cystadenomas Brenner tumour

Answer 194

(Serous, mucinous, endometrioid, clear cell, seromucinous & Brenner) Tumours whose biologic behaviour cannot be predicted on histologic grounds Tumours that have very low but definite metastatic potential Morphologically similar tumours may behave differently To date, there are no reliable histological or molecular predictive markers for the behaviour of these tumours

Answer 195

Worldwide is the 6th most common cancer in women 2nd commonest female cancer causing death in women Difficult to diagnosis at an early stage Develops resistance to therapeutic agents Risk factors: Nulliparity, infertility, early menarche, late menopause. Genetic predisposition: Family history of ovarian and breast cancers

Answer 196

Up to 10% of epithelial ovarian cancer cases are familial 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 Associated with mutations of the BRCA1 and BRCA2; 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 > 90% cancers are of serous: ovarian, peritoneal, fallopian tube.

Answer 197

HNPCC is responsible for 3% of ovarian carcinomas Ovarian cancers associated are mainly of the endometrioid and clear cell types

Answer 198

Most common type of malignant tumours (80%) Aggressive Alteration in P53, in virtually all BRCA1 or BRCA2 abnormalities (germline and somatic mutations; BRCA1 promoter methylation) These genes encode proteins that play important roles in DNA repair (homologous recombination).

Answer 199

Identification of hereditary cases. Current data suggests that BRCA2 mutations confer an overall survival advantage compared with either being BRCA-negative or having a BRCA1 mutation in high-grade serous ovarian cancer. BRCA mutation status has a major influence on response to chemotherapy. Patients can benefit from targeted therapy by PARP inhibitors.

Answer 200

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

Answer 201

Morphological features similar to mucinous tumours of the gastrointestinal tract. KRAS mutations.

Answer 202

Metastatic colorectal carcinoma: Ovaries, an anatomic site prone to involvement by metastatic colorectal adenocarcinoma. 4-10% of CRC go to ovary. Ovarian lesions are identified prior to the primary tumor in 14-32% of cases. Krukenberg tumours: Bilateral metastases composed of mucin producing signet ring cells. Most often of gastric origin or breast.

Answer 203

10-20% associated with endometriosis, but most others thought to be derived from surface epithelium Co-existence with endometrioid carcinoma in uterus common Molecular changes CTNNB1 (38%-50%) PTEN (15-20%) KRAS and BRAF (4%-36%) MSI (8-38%) PIK3Ca in (20%) P53 >60% and usually in high Endometriosis is a precursor

Answer 204

Strong association with endometriosis Molecular changes: MSI (6-21%) PTEN (6%) P53 (8.3%) BRAF (6.3%) PIK3Ca (20-25%) B-catenin (3%)

Answer 205

Pure stromal tumours: e.g. Fibroma, Thecoma, microcystic stromal tumour Pure sex cord cells: e.g. Adult type and juvenile granulosa cell tumour Mixed sex cord-stromal tumours: e.g. Sertoli Leydig cell tumour Fibroblasts: Fibromas: benign, no endocrine production Granulosa cells: Granulosa cell tumor variable behaviour, may produce estrogen Thecal cells: Thecoma: benign, may secrete oestrogen, or rarely androgens Sertoli-Leydig cells: Sertoli-Leydig cell tumor variable behaviour, may be androgenic

Answer 206

Adult type granulosa cell tumour (GCT): 97% of adult GCT show somatic mutation of the Forkhead transcription factor FOXL2, is a master transcription factor that regulates cell proliferation and apoptosis. FOXL2 mutation can be done in AGCT to confirm the diagnosis in cases where the diagnosis is in question. Mutation in CTNNB1

Answer 207

DICER1 Syndrome: Germline mutation in DICER1, a gene encoding an RNAse III endoribonuclease. Familial multinodular goitre with sertoli / leydig cell tumour, and tumour susceptibility includes pleuropulonry blastoma in childhood. Found in up to 60% of seroli-Leydig cell tumours. Peutz Jeghers syndrome: Germline mutations of STK11 Sex cord stromal tumour with annular tubules Cases occurring in PJS usually show indolent behaviour.

Answer 208

Benign Solid or cystic May show many lines of differentiation but all mature adult type tissues Teeth and hair very common type of germ cell tumour

Answer 209

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 Metastasis to lymph nodes, lung, liver and other organs Three tier grading system according to amount of primitive elements

Answer 210

Malignant transformation is rare occurring in 2% of cases, usually in post menopausal women Most frequently squamous cell carcinoma Also carcinoid, thyroid carcinoma, basal cell carcinoma, malignant melanoma, intestinal adenocarcinoma, leiomyosarcoma, chondrosarcoma and angiosarcoma

Answer 211

Absence of ganglion cells in the submucosal and myenteric plexuses Starts in the rectum which fails to dilate] 80% male Associated with Down’s syndrome (2%) RET proto-oncogene mutation Treatment: resection of affected (constricted) segment with frozen section to identify when the ganglion cells

Answer 212

excretion fluid and electrolyte balance regulation of blood pressure (renin) regulation of calcium (1,25 alpha hydroxylase) regulation of haematocrit (erythropoieitin)

Answer 213

high hydrostatic pressure (60mmHg) podocytes create charge-dependent (anionic) and size-dependent barrier normal rate: 125 mL/min

Answer 214

sodium actively resorbed hydrogen is exchanged to allow carbonate resorption co-transport of amino acids, phosphate and glucose potassium is also resorbed

Answer 215

descending/thin ascending limb are permeable to water but not ions or urea, ascending limb actively resorbs sodium and chloride countercurrent multiplier: aligned with vasa recta

Answer 216

(impermeable to water) regulates pH via active transport (proton/bicarb) regulates sodium, potassium via active transport (aldosterone) regulates calcium (PTH, 1,25 dihydroxycholecalciferol)

Answer 217

resorbs water (principal cell, ADH) regulates pH (intercalated cells, proton excretion)

Answer 218

latticework of antibody and antigen (antigen may be endogenous or exogenous) may deposit in glomerulus and cause: inflammatory response, complement activation, stimulation of inflammatory cells may deposit at different rates and sites

Answer 219

1:500 Adult dominant 10% of end-stage renal failure presents in adulthood with hypertension, flank pain and haematuria Genetic element: PKD1, PKD2 associated with berry aneurysms

Answer 220

cysts commonly develop in patients with end-stage renal disease who are on dialysis can be: multiple, bilateral, cortical and medullary increased risk of malignancy development (7% risk at 10 years, papillary renal cell carcinoma)

Answer 221

acute renal failure (AKI) nephrotic syndrome isolated urinary abnormalities chronic kidney disease

Answer 222

rapid deterioration in renal function (hours, days) common, often in setting of pre-existing disease causes: - pre-renal: failure of perfusion - renal: acute tubular injury, acute glomerulonephritis, thrombotic microangiopathy - post-renal: obstruction presentation and prognosis are variable

Answer 223

commonest cause of AKI tubular epithelial cells are damaged by ischaemia, toxins (contrast, Hb, myoglobin, ethylene glycol), drugs common in critical illness drugs that inhibit vasodilatory prostaglandins (NSAIDs) predispose

Answer 224

normal epithelium with brush border ischaema/toxins cause loss of polarity and brush border apoptosis and sloughing of viable and dead cells proliferation, differentiation, re-polarisation spreading and dedifferentiation of viable cells

Answer 225

blockage of tubules by casts leakage of tubules into interstitial space secondary haemodynamic changes

Answer 226

immune injury to tubules and interstitium can also be due to infection and drugs: NSAIDs, Abx, diuretics, allopurinol, PPIs heavy interstitial inflammatory infiltrate with tubular injury (can see eosinophils and granulomas)

Answer 227

acute inflammation of glomeruli presents with oliguria with urine casts, containing erythrocytes and leucocytes when sufficient to cause AKI, there are almost always crescents (proliferation of cells within Bowman's space)

Answer 228

immune complex anti-GBM disease Pauci-immune (anti-neutrophil cytoplasm antibodies) leads rapidly to irreversible renal failure correct diagnosis and treatment urgent

Answer 229

aetiologies include SLE, IgA nephropathy and post-infectious immune complexes can be identified and localised with IHC and electron microscopy

Answer 230

rare and severe caused by Abs directed against glomerular basement membrane c-terminal domain of type IV collagen may cross react with alveolar BM leading to pulmonary haemorrhage Abs may be detected with serology linear deposition of IgG demonstrable on GBM

Answer 231

only scanty glomerular Ig deposits usually ANCA-associated; trigger neutrophil activation and glomerular necrosis vasculitis everywhere

Answer 232

damage to endothelium in glomeruli, arterioles, arteries leading to thrombosis red cells may be damaged by fibrin: MAHA, HUS Diarrhoea associated: bacterial gut infections ie E.coli, toxins released that target renal endothelium Non-diarrhoea associated: defectes in complement regulation, ADAMTS13 def, drugs (calcineurin inhib), radiation, HTN, scleroderma, APL Ab syndrome

Answer 233

breakdown in selectivity of glomerular filtration barrier leading to protein leak Presentation: proteinuria, hypoalbuminaema, oedema, hyperlipidaemia

Answer 234

(non-immune complex mediated) glomeruli look normal by light microscopy effacement of foot processes on EM common cause of nephrotic syndrome in children generally responds to immunosuppression

Answer 235

(non-immune complex mediated) some glomeruli are partially scarred less likely to respond to immunosuppression must exclude possible other diseases that can produce similar appearance (tend to not be nephrotic)

Answer 236

(immune complex mediated) associated with immune deposits on outside of GBM (subepithelial) common cause of nephrotic syndrome in adults primary disease is autoimmune (Ab against PLA2R) need to exclude possibility of secondary disease (epithelial malignancy, drugs, infections, SLE)

Answer 237

(systemic nephrotic syndrome) high glucose levels directly injurious typically starts as microalbuminuria before progression to proteinuria and nephrotic syndrome Nodular glomerulosclerosis: - stage 1: thickening of BM on EM - stage 2: increase in mesangial matrix, without nodules - stage 3: nodular lesions / kimmelstiel-wilson - stage 4: advanced glomerulosclerosis commonest cause of renal replacement therapy

Answer 238

(systemic nephrotic syndrome) deposition of extracellular proteinaceous material exhibiting beta-sheet structure commonest forms in kidney are: - AA; derived from SAA protein, an acute phase protein; tends to have chronic inflammatory state - AL; derived from Ig light chains, 80% have multiple myeloma NB: congo red stain

Answer 239

Microscopic haematuria: - thin basement membranes - IgA nephropathy Asymptomatic proteinuria: - may be associated with broad range of glomerular structural abnormalities or immune complex deposition - diagnosis often requires renal biopsy for histology, IHC or EM

Answer 240

hereditary defect in type IV collagen synthesis basement membrane <250nm thickness haematuria is only consequence in most cases Alport's syndrome: - X-linked dominant mutations affecting alpha5 subunit - forms exist in which mutation affect alpha3 or 4 subunit - typically progressive, renal failure in middle age - often have deafness, ocular disease

Answer 241

commonest glomerulonephritis IgA predominant mesangial immune complex deposition aetiology not well understood in primary form - secondary forms observed in lover, bowel, skin - can be seen with henoch-schonlein purpura - 30% develop end stage renal failure Scoring: oxford classification

Answer 242

can be caused by a large number of diseases significant cause of morbidity and mortality associated with ischaemic heart disease (HTN, hyperlipidaemia, calcification of blood vessels) association with calcium and phosphate metabolic derangement (hyper PTH, osteomalacia, osteoporosis)

Answer 243

pathophysiology 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 histopath may show nephrosclerosis (arteriolar hyalinosis, arterial intimal thickening, ischaemic glomerular changes, segmental and global glomerulosclerosis)

Answer 244

= systemic autoimmune disease affects kidney, skin, joints, heart, serosal surfaces, CNS affects 1/2500 people 9:1 f:m deposition of immune complexes in kidney is common - Abs directed at a broad range of intracellular and extracellular antigens - anti-nuclear and anti-dsDNA Abs are typical

Answer 245

I - minimal mesangial disease, near normal on light microscopy II - mesangial proliferative disease; mesangial hypercellularity, at most isolated subepithelial or subendothelial depositis III - focal disease; active or inactive segmental

Answer 246

crystal aggregates that form in renal CDs - can eb deposited anywhere in urinary tracts

Answer 247

related to hypercalciuria

Answer 248

magnesium, ammonium, phosphate

Answer 249

hyperuricaemia: gout or rapid cell turnover most patients don't have hyperuricaemia

Answer 250

small stones that stay in kidney may be asymptomatic (otherwise detected during investigation of haematuria or recurrent UTIs)

Answer 251

benign epithelial kidney tumour composed of papillae or tubules

Answer 252

benign epithelial kidney tumour composed of oncocytic cells - well circumscribed -

Answer 253

benign mesenchymal kidney tumour composed of thick-walled blood vessels, smooth muscle and fat

Answer 254

malignant epithelial kidney tumour

Answer 255

(no longer divided into two types based on morphology)

Answer 256

(Wilm's tumour)

Answer 257

by definition; high grade

Answer 258

benign enlargement of prostate as a consequence of increase in cell number

Answer 259

most common malignant epithelial tumour in men

Answer 260

highly sensitive to platinum-based chemo excellent prognosis

Answer 261

seminoma embryonal carcinoma post-pubertal teratoma yolk sac tumour choriocarcinoma

Answer 262

much less common that germ cell tumours

Answer 263

Obstruction: Adhesions Herniation Extrinsic mass Volvulus Diverticular disease

Answer 264

Complete twisting of a loop of bowel at mesenteric base around vascular pedicle Intestinal obstruction +/- infarction Small bowel (infants) Sigmoid colon (elderly)

Answer 265

High incidence in West Low fibre diet High intraluminal pressure needed to push stool through ‘Weak points’ in wall of bowel where muscular coating is less present 90% occur in left colon

Answer 266

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

Answer 267

Acute colitis: Infection Drug/toxin (especially antibiotic) Chemotherapy Radiation Chronic colitis: Crohn’s Ulcerative colitis TB

Answer 268

Viral e.g. CMV (can colonise and exacerbate IBD) Bacterial e.g. Salmonella Protozoal e.g. Entamoeba hystolytica Fungal e.g. candida

Answer 269

Follows antibiotic theraapy Acute colitis with pseudomembrane formation Caused by protein exotoxins of Clostridium difficile Histology: Characteristic microscopic features on biopsy Laboratory: C. difficile toxin stool assay

Answer 270

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

Answer 271

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

Answer 272

?Genetic predisposition (familial aggregation, twin studies, HLA ) ?Infection (Mycobacteria, Measles etc) ?Abnormal host immunoreactivity ?Microbiome

Answer 273

Diarrhoea +/- blood Fever Abdominal pain Acute abdomen Anaemia Weight loss Extra-intestinal manifestations

Answer 274

Western populations Occurs at any age but peak onset in teens/twenties White 2-5x > non-white Higher incidence in Jewish population Smoking Whole of GI tract can be affected (mouth to anus) ‘Skip lesions’ Transmural inflammation Fissure/ sinus/fistula formation Non-caseating granulomas (organised collection of activated macrophages)

Answer 275

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

Answer 276

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

Answer 277

Severe haemorrhage Toxic megacolon Adenocarcinoma (20-30 x risk) (adenocarcinoma risk also in Crohn's but less significant)

Answer 278

Arthritis Myositis Uveitis/iritis Erythema nodosum, pyoderma gangrenosum Primary Sclerosing Cholangitis (5.5% in pancolitis) --> increased risk of cholangiocarcinoma UC and PSC screened for when the other is present

Answer 279

marker of active inflammation in Crohn's and Ulcerative colitis caused by accumulation of neutrophils in lumen

Answer 280

Non-neoplastic polyps Neoplastic epithelial lesions - Adenoma - Adenocarcinoma (arise from adenomas) - Neuro-endocrine Tumours Mesenchymal lesions - Lipoma - Leiomyoma etc Lymphoma Stromal tumours

Answer 281

Polyps - Non-neoplastic: Hyperplastic polyps and Sessile Serrated Lesions Inflammatory (“pseudo-polyps”) Hamartomatous (Juvenile, Peutz Jeghers) Polyps – Neoplastic (adenomas) : Tubular adenoma (completely flat) Tubulovillous adenoma Villous adenoma (have finger-like projections)

Answer 282

subset of hyperplastic polyps (excessive epithelial proliferation) Hyperplastic polyp with architectural abnormalities (horizontal crypts at the base rather than vertical) May show dysplasia as well

Answer 283

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

Answer 284

Size (bigger = worse) Proportion of villous component (more = worse) Degree of dysplasia (high grade worse than low grade)

Answer 285

Usually none Bleeding/anaemia

Answer 286

(Peutz Jeghers) - hamartomatous (usually no increased cancer risk) Familial adenomatous polyposis Gardner’s Hereditary non polyposis (<10 polyps) colon cancer

Answer 287

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

Answer 288

subset of FAP FAP plus extra-intestinal manifestations e.g: osteomas desmoid tumors

Answer 289

= lynch syndrome Autosomal dominant May have polyps 3-5% of all colorectal cancers At least 1 of 4 DNA mismatch repair genes involved Numerous DNA replication errors Onset of colorectal cancer at an early age High frequency of carcinomas proximal to splenic flexure Poorly differentiated and mucinous carcinoma more frequent Multiple synchronous cancers Presence of extracolonic cancers (endometrium, prostate, breast, stomach)

Answer 290

98% are adenocarcinoma Age: 60-79 years If < 50yrs consider familial syndrome Western population aetiology: Familial Diet (low fibre, high fat etc) Lack of exercise Obesity Predisposing conditions: - Chronic Inflammatory bowel disease - Adenomas

Answer 291

Change of bowel habit Bleeding Anaemia Weight loss Pain

Answer 292

Hepatocytes Bile ducts Blood vessels Endothelial cells Kupffer cells Stellate cells

Answer 293

stellate cells lie between the hepatic sinusoid endothelial cells and the hepatocytes they store vitamin A when they become activated they become myofibroblasts (leading to collagen secretion and cirrhosis in chronic liver disease and also leads to decreased blood supply to hepatocytes due to barrier created between them and sinusoid)

Answer 294

1. whole liver involved 2. fibrosis 3. nodules of regenerating hepatocytes 4. distortion of liver vascular architecture: intra- and extra- hepatic (e.g. gastro-oesophageal) shunting of blood

Answer 295

a) according to nodule size: micronodular or macronodular b) according to aetiology: 1) alcohol (tend to cause micronodular) / insulin resistance 2) viral hepatitis (usually macronodular) etc.

Answer 296

1. Portal hypertension 2. Hepatic encephalopathy (toxins into systemic circulation instead of being taken up and broken down by kupffer cells) 3. Liver cell cancer

Answer 297

Aetiology: viruses and drugs Histology: spotty necrosis (little foci of hepatocyte damage)

Answer 298

> 6 months Aetiology: viral (B,C,D), drugs, auto-immune inflammation severity = grade fibrosis severity = stage histology: portal inflammation, interface hepatitis (piecemeal necrosis), lobular inflammation (spotty necrosis), fibrosis (bridging between portal tracts and central vein = intrahepatic shunting)

Answer 299

1) fatty liver (reversible) 2) alcohol-related hepatitis 3) cirrhosis (potentially reversible) (somewhat sequential)

Answer 300

Ballooning ( +/- Mallory Denk Bodies = cytoskeleton clumps) Fat Pericellular fibrosis Mainly seen in Zone 3 (most metabolically active cells so where most alcohol is converted to acetaldehyde which is the toxic compound causing damage)

Answer 301

Now MAFLD (metabolic associated fatty liver disease) and MASH (metabolic associated steatohepatitis) Histologically looks like alcoholic liver disease Due to insulin resistance associated with raised BMI and diabetes Becoming recognised as one of the commonest causes of liver disease, world-wide

Answer 302

Previously primary biliary cirrhosis. Autoimmune F> M Bile duct loss associated with chronic inflammation (with granulomas) Diagnostic test is detection of anti-mitochondrial antibodies associated with raised levels of IgM in blood

Answer 303

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

Answer 304

Genetically determined increased gut iron absorption (2mg instead of 1mg) manifests earlier in men because iron balance is more borderline in women Gene on chromosome 6 (HFe) - common mutation in celtic population Parenchymal damage to organs secondary to iron deposition (bronzed diabetes) causes liver cirrhosis (accumulation or iron in hepatocytes), cardiomyopathy, pancreatitis etc.

Answer 305

accumulation of iron in macrophages (better at dealing with excess iron than hepatocytes) caused by blood transfusion

Answer 306

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

Answer 307

F>M Active chronic hepatitis with plasma cells Anti-smooth muscle actin or anti-liver kidney microsomal antibodies in the serum Responds to steroids

Answer 308

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

Answer 309

“any kind of liver disease can be caused by a drug” ie. hepatocellular and / or cholestatic 10% of drug reactions involve the liver May be dose-related or idiosyncratic Paracetamol toxicity: damage in zone 3 (most metabolically active cells)

Answer 310

Specific causes: PBC drugs General causes TB Sarcoid etc

Answer 311

1) liver cell adenoma 2) bile duct adenoma 3) haemangioma (sharply circumscribed)

Answer 312

1. secondary tumours (metastasis through portal circulation) 2. primary tumours: hepatocellular carcinoma hepatoblastoma cholangiocarcinoma haemangiosarcoma

Answer 313

Usually associated with cirrhosis especially in the West. Raised alpha-fetoprotein Poor prognosis

Answer 314

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

Answer 315

characterised by atheromatous deposits in and fibrosis of the inner layer of the arteries can cause occlusion and protrude through lumen

Answer 316

- age (progressive between 40->60 incidence x5) - sex (M>F, premenopausal women protected, postmenopausal risk increases, older age F>M) genetics (family history, familial hypercholesterolaemia, genetic polymorphisms) - hyperlipidaemia (modifiable) - hypertension (motifiable, alone increases risk of IHD by 60%) - smoking (prolonged doubles death rate from IHD, stopping reduces risk considerably) - diabetes mellitus (increases hyperchol and atherosclerosis) risk factors have multiplicative effect other RFs: inflammation, metabolic syndrome, lipoprotein, haemostasis (procoagulation), lack of exercise, stress, obesity

Answer 317

chronic inflammatory and healing response of arterial wall to endothelial injury Lesion progression occurs through interaction of modified lipoproteins, monocyte-derived macrophages, and T lymphocytes with endothelial cells and smooth muscle cells of the arterial wall. 1. endothelial injury and dysfunction 2. LDL accumulation 3. Monocyte adhesion to endothelium 4. Monocyte migration into intima --> macrophages and foam cells 5. platelet adhesion 6. factor release and smooth muscle cell recruitment 7. wall thickening

Answer 318

earliest lesions lipid-filled foamy macrophages no flow disturbance in virtually all children relationship to plaques uncertain same sites as plaques

Answer 319

patchy - cause local flow disturbances only involve portion of wall rarely circumferential appear eccentric composed of: cells, lipid, matrix

Answer 320

stenosis: critical when demand>supply, occurs at approx 70% occlusion, causes stable angina, can lead to chronic IHD, acute plaque rupture can occur acute plaque change: rupture, erosion, haemorrhage (rupture and erosion expose prothrombogenic components)

Answer 321

adrenalin increases blood pressure and causes vasoconstriction increases physical stress on plaque hence emotional stress increases risk of sudden death circadian periodicity to sudden death (6am-noon) (thin fibrous cap and large lipid core: more likely to rupture)

Answer 322

group of conditions resulting from MI imbalance of supply to demand for oxygenated blood less nutrients and less waste removal less well tolerated than pure hypoxia gradual progression before symptoms Presentation: - angina pectoris - MI - chronic IHD with heart failure - sudden cardiac death

Answer 323

insufficient coronary perfusion relative to myocardial demand due to chronic progressive atherosclerotic narrowing of epicardial coronary arteries and variable degrees of superimposed plaque change, thrombosis, vasospasm 75% stenosis or more needed to cause symptoms precipitated by exercise, vasodilation cannot compensate above this level of stenosis 90% stenosis can lead to pain at rest

Answer 324

stable plaque becomes unstable due to rupture, erosion, haemorrhage can lead to superimposed thrombus which increases occlusion

Answer 325

transient ischaemia not producing myocyte necrosis includes: stable, Prinzmetal, Unstable stable comes on with exertion, relieved by rest no plaque disruption Prinzmetal is uncommon and is due to artery spasm

Answer 326

more frequent longer onset with less exertion or at rest disruption of plaque superimposed thrombus possible embolisation or vasospasm warning of impending infarction

Answer 327

death of cardiac muscle due to prolonged ischaemia = necrosis incidence increases with age M>F IHD most common cause of death in postmenopausal women

Answer 328

(artery occlusion) 1. sudden change to plaque 2. platelet aggregation 3. vasospasm 4. coagulation 5. thrombus evolves myocardial response: blood supply compromised --> ichaemia --> loss of contractility within 60 seconds (heart failure can precede myocyte death) potentially reversible but irreversible after 20-30 minutes

Answer 329

clinical importance uncertain due to oxidative stress, calcium overload and inflammation mitochondrial swelling and apoptosis leukocyte aggregation and occlusion of microvasculature arrhythmias common biochem abnormalities last days-weeks thought to cause stunned myocardium - reversible cardiac failure lasting several days

Answer 330

contractile dysfunction arrhythmia (myocardial irritability and conduction disturbance) myocardial rupture (LV free wall most common, septum less common, papillary muscle least common, at mean 4-5 days) pericarditis (dressler syndrome) RV infarction Infarct extension (necrosis spread) Infarct expansion (necrotic muscle stretches) mural thrombus

Answer 331

progressive HF due to ishaemic myocardial damage may not be prior infarction can arise with severe obstructive CAD enlarged heavy heart, hypertrophied, dilated LV atherosclerosis maybe mural thrombi microscopic fibrosis

Answer 332

unexpected death from cardiac causes in individuals without symptomatic heart disease or early (1hr) after symptoms onset usually due to lethal arrhythmia (sustained AF or asystole) usually on background of IHD ischaemia induced electrical instability marked atherosclerosis

Answer 333

* Very rare * can be benign or malignant * malignant tumours 60x less common than lung cancer * primary malignant bone tumours most common in children and young adults * Site predilection - around knee most common * Different tumours have different site and age predilection * Clinical information and ‘team’ approach to diagnosis essential

Answer 334

Clinical presentation: * pain, swelling, deformity, fracture History: * age, site, duration, ?hx of trauma * ?multiple lesions, ?associated disease X ray: * Evaluate site, size, margin * ?solitary or multiple, ?soft tissue extension * ?associated disease or fracture * Optimal treatment is early referral to specialist centre Biopsy: * Needle biopsy preferred option * Performed by radiologist usually with Jamshidi needle * +/- US or CT guidance * Open biopsy for sclerotic or inaccessible lesions * Imprint (cytology) preparations are very useful

Answer 335

* Fibrous dysplasia * Metaphyseal fibrous cortical defect/non-ossifying fibroma * Reparative giant cell granuloma * Ossifying fibroma * Simple bone cyst

Answer 336

* F>M mono-ostotic > polyostotic * Age: 1st 3 decades * Site: any bone, ribs, prox femur commonest * Xray: ‘soap bubble’ osteolysis * polyostotic disease can be associated with endocrine problems and rough border café au lait spots on skin (McCune Albright syndrome) * <1% malignant transformation * Somatic mutation in guanine-nucleotide binding protein (G-protein). (GNAS mutation chr 20 q13) * histology: trabecular bone (chinese letters) * complications: shepherd's crook deformity

Answer 337

* Cartilaginous differentiation * Osteochondroma (age 10-20, M:F 2:1, common sites = at ends of long bones) * Enchondroma (age 10-40, M:F equal, common sites = hands and fingers, popcorn calcification on x-ray) * Chondroblastoma * Bone forming * Osteoid osteoma * Osteoblastoma * Osteoma

Answer 338

borderline malignancy Site: epiphysis with metaphyseal extension Age: 20-40 y F>M X-ray: Lytic Histo: osteoclasts on a background of spindle/ovoid cells Locally aggressive, may recur, can metastasise Mx: excision with narrow margins

Answer 339

= metastases (unusual below knee/elbow) Adults: * Breast * Prostate * Lung * Kidney * Thyroid Children: * Neuroblastoma * Wilm’s tumour * Osteosarcoma * Ewings * Rhabdomyosarcoma

Answer 340

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

Answer 341

Commonest primary bone sarcoma Age: peak in adolescence (75% patients are <20y) M:F 2:1 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 342

1. According to site within bone:- i.e. intramedullary, intracortical, surface 2.Degree of differentiation:- i.e. high, intermediate or low grade 3. Multicentricity:- i.e. synchronous or metachronous 4.Primary or secondary.

Answer 343

Malignant cartilage producing tumour Age: 40y and over M:F 5:4 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 344

1. According to site intramedullary, juxtacortical 2. Histologically conventional (myxoid or hyaline), clear cell, dedifferentiated, mesenchymal

Answer 345

Highly malignant small round cell tumour Age: usually < 20y (80%) M:F 4:3 Site: diaphysis/metaphysis of long bones, pelvis X-ray: onion skinning of periosteum, lytic +/- sclerosis Histo: sheets of small round cells, MIC2 stain positive Prognosis : - 75% 5y survival 50% longterm Specific chromosome translocation 11:22 (EWS/Fli1)

Answer 346

Defined as mesenchymal proliferations which occur in the extraskeletal, non-epithelial tissues of the body - excluding meninges and lymphoreticular system Site: Anywhere. Majority occur in large muscles of extremities, chest wall, mediastinum, retroperitoneum Age: Any age. Majority older patients 15% < 15yrs 50% > 55yrs Sex: M>F overall, but sex and age varies between histological types Race: No proven racial variation Ewing’s and clear cell sarcoma rare in Afrocaribbean population

Answer 347

- uncertain Factors Include: - Genetic Predisposition - Chemical carcinogens - Physical ( asbestos, foreign body ) - Viruses - Immunodeficiency

Answer 348

liposarcoma/myxoid tumours spindle cell tumours pleomorphic sarcoma synovial sarcoma

Answer 349

Immunohistochemistry EM Cytogenetics (conventional & interphase) FISH M-FISH SKY CGH PCR RT-PCR

Answer 350

GOOD BAD Size <5cm >5cm Depth superficial to deep deep fascia to deep fascia Histological grade low high Excision margin clear involved Vascular invasion absent present Ploidy diploid aneuploid/ hyperdiploid Proliferation Index low high Tu. Supressor gene present absent Tu. Promoter gene absent present

Answer 351

Stage 0 3 good prognostic signs 1 2 good 1 bad 2 1 good 2+ bad 3 3+ bad 4 metastases, regional or distant

Answer 352

anterior: epithelial cells (derived from oral cavity), with blood supply from pituitary portal system releases hormones under stimulation from hypothalamus posterior: neuroendocrine cells with blood supply from nerves from hypothalamus

Answer 353

Hyperpituitarism: excess secretion of trophic hormones (usually due to functional adenoma) - classified on basis of hormones produced (most common are prolactin) Hypopituitarism: deficiency of trophic hormones Local mass effects

Answer 354

Prolactinomas: - amenorrhoea, galactorrhoea, loss of libido, infertility - usually diagnosed earlier in females of reproductive age Growth hormone adenomas: - in prepubertal children: gigantism - in adults: acromegaly - diabetes mellitus, muscle weakness, hypertension, congestive cardiac failure Corticotroph cell adenomas: - Cushing's syndrome

Answer 355

most are caused by: non-secretory pituitary adenomas Ischaemic necrosis (most commonly post-partum) - can also be causes by DIC, sickle cell anaemia, elevated ICP, shock Ablation of pituitary by surgery or irradiation

Answer 356

Children: growth failure (pituitary dwarfism) Gonadotrophin deficiency: amenorrhea and infertility in women, decreased libido and impotence in mean TSH & ACTH deficiency: hypothyroidism and hypoadrenalism Prolactin deficiency: failure of lactation post-partum

Answer 357

(mainly involves ADH) Diabetes insipidus (too little ADH) SIADH (due to brain trauma usually, will present with profound hyponatraemia)

Answer 358

compression of optic chiasm leading to bitemporal hemianopia signs and smptoms of elevated ICP (headaches and papilloedema) Obstructive hydrocephalus (late stage, compression of brain stem and herniation through foramen magnum)

Answer 359

(2 lobes connected by isthmus) colloid-filled follicles with interstitial tissue between them follicles lined by epithelial cells scattered cells between follicles: parafollicular cells/C cells (synthesis calcitonin)

Answer 360

= enlargement of thyroid common if impaired synthesis of thyroid hormone (most often due to iodine deficiency) commonly seen in puberty in females may be caused by ingestion of substances that interfere with thyroid hormone synthesis (eg brassicas) or hereditary enzyme defects (thyroglobulin) may progress to multinodular goitre which can be large in mass and cause airway/oesophageal obstruction

Answer 361

may occur at any age may have papillary architecture diagnosis based on nuclear features: - optically clear nuclei - intranuclear inclusions May have psammoma bodies (little foci of calcification) nonfunctional --> present as painless mass in neck, may present with metastasis in cervical lymph nodes 10 year survival 90% with appropriate treatment

Answer 362

peak incidence in middle age follicular morphology (look similar to normal tissue) may be well demarcated with minimal invasion or clearly infiltrative usually metastasise via bloodstream to lungs, bone and liver

Answer 363

occur in elderly patients very aggressive metastases common most cause death within one year due to local invasion (may just be very aggressive follicular carcinomas)

Answer 364

derive from developing pharyngeal pouches usually 4 of them usually to upper and lower poles of thyroid but may be in thymus or anterior mediastinum activity controlled by level of free calcium in blood --> decreased calcium stimulates release of PTH

Answer 365

- activates osteoclasts - increases renal tubular reabsorption of calcium - increases conversion of vitamin D to its active form - increases urinary phosphate excretion - increases intestinal calcium absorption

Answer 366

most commonly due to solitary benign adenoma less commonly due to hyperplasia of all 4 glands (sporadic or MEN1) very rarely due to carcinoma increased level of serum ionised calcium (usually incidental finding)

Answer 367

Osteitis fibrosa cystica (bone resorption with cortex thinning and cyst formation) Renal stones and obstructive uropathy GI disturbances; constipation, pancreatitis, gallstones CNS alterations; depression, lethargy, fits neuromuscular abnormalities; weakness polyuria and polydipsia

Answer 368

caused by any condition associated with chronic depression of serum calcium renal failure is most common cause parathyroid glands are enlarged (may be asymmetrical) leads to bone changes as with primary disease

Answer 369

causes: - surgical ablation - congenital absence - autoimmune clinical manifestations: - neuromuscular irritability (tingling, muscle spasms, tetany) - cardiac arrhythmias - fits - cataracts

Answer 370

Cortex surrounds medulla cortex is made up of epithelial cells medulla made up of neural cells and secretes noradrenaline and adrenaline

Answer 371

outer: zona glomerulosa, secretes aldosterone middle: zona fasciculata, secretes glucocorticoids inner: zona reticularis, secretes androgens and glucocorticoids

Answer 372

Acute: - sudden withdrawal of steroids - haemorrhage (neonates) - sepsis with DIC Chronic: - autoimmune (Addison's) - TB - HIV - metastatic tumour (esp lung and breast) - rarely amyloid, fungal infections, haemochromatosis, sarcoidosis

Answer 373

Mechanical: support and site for muscle attachment Protective: vital organs and bone marrow Metabolic: calcium reserve

Answer 374

Inorganic (65%): - calcium hydroxyapatite - storehouse for 99% of Ca in body - 85% of phosphorous and 65% of Na and Mg Organic (35%): - bone cells and protein matrix

Answer 375

Outside to in: periosteum, cortex, medulla Diaphysis (longer) and Epiphysis separated by metaphysis

Answer 376

Cortical: - long bones - 80% of skeleton - appendicular - 80-90% calcified - mainly mechanical and protective Cancellous: - vertebrae & pelvis - 20% of skeleton - axial - 15-25% calcified - mainly metabolic - large surface

Answer 377

Haversian canals going up and down surround haversian canals: concentric lamallae in between those units: interstitial lamallae surrounding (outside): circumferential lamallae deeper inside: trabecular lamallae

Answer 378

trabecular lamallae and haematopoietic cells on H&E staining

Answer 379

Osteoblasts: build bone by laying down osteoid (smaller cells, single nucleus) Osteoclasts: multinucleate cells of macrophage family resorb or chew bone Osteocytes: osteoblast-like cells which sit in lacunae (small, single nucleus)

Answer 380

Blocks RANK-RANK ligand interaction to prevent osteoclast differentiation for precursor

Answer 381

= disordered bone turnover due to imbalance of chemicals in body overall effect: osteopenia --> fractures with little trauma

Answer 382

1. Non-endocrine (eg. age-related osteoporosis) 2. related to endocrine abnormality (Vit D, PTH) 3. Disuse osteopenia

Answer 383

bone biopsy from iliac crest; processed in un-decalcified form for histomorphometry 'static' parameters: - cortical thickness and porosity - trabecular bone volume - thickness, number & separation of trabeculae bone mineralisation is studied using osteoid parameters 'histodynamic parameters' are obtained from fluorescent tetracycline labelling

Answer 384

90% of cases due to insufficient Ca intake and post-menopausal oestrogen deficiency (primary - age & post-menopause, secondary - drugs, systemic disease) high turnover = increased bone resorption low turnover = decreased bone formation fracture pathogenesis: low initial bone mass or accelerated bone loss can reduced bone mass below fracture threshold

Answer 385

advanced age female sex smoking excess alcohol early menopause long-term immobility low BMI poor diet (low vit D and Ca) malabsorption thyroid disease low testosterone chronic renal disease steroids

Answer 386

back pain + wrist (Colles'), hip (NOF, intertrochanteric) or pelvis fracture (may be asymptomatic) compression fractures can also occur at T11-12 level

Answer 387

Lab: - serum calcium, phosphorous, alk phos - urinary calcium - collagen breakdown products Imaging Bone densitometry: - T score 1-2.5 = osteopenia - T score >2.5 = osteoporosis

Answer 388

4 organs affected which control Ca metabolism: Parathyroid glands bones kidneys proximal small intestine

Answer 389

= defective bone mineralisation 2 types: deficiency of Vit d or phosphorous sequelae: bone pain/tenderness fracture (horizontal in looser's zone) proximal weakness bone deformity (eg. bowing in rickets)

Answer 390

- increased Ca and PO4 excretion in urine - hypercalcaemia - hypophosphataemia - skeletal changes of osteitis fibrosa cystica

Answer 391

Primary: - parathyroid adenoma (85-90%) - chief cell hyperplasia Secondary: - chronic renal deficiency - vit d deficiency - malabsorption

Answer 392

stones (renal), bones (osteitis fibrosa cystica), abdominal groans (constipation, pancreatitis), psychic moans (psychosis, depression)

Answer 393

= all skeletal changes of chronic renal disease: - osteitis fibrosa cystica - osteomalacia - osteosclerosis - growth retardation - osteoporosis

Answer 394

= disorder of bone turnover 3 phases: 1. osteolytic 2. osteolytic-osteosclerotic 3. quiescent osteosclerotic onset>40y M=F

Answer 395

unknown autosomal pattern of inheritance with incomplete penetrance parvomyxovirus type particles sites affected: mainly pelvis and skull

Answer 396

pain microfractures nerve compression skull changes (may put medulla at risk) haemodynamic changes (cardiac failure) development of sarcoma in area of involvement (1%)

Answer 397

simple, compound, greenstick (children), comminuted (trauma), impacted

Answer 398

1. organisation of haematoma at fracture site (pro-callus) 2. formation of fibrocartilaginous callus 3. Mineralisation callus 4. Remodelling of bone along weight-bearing lines

Answer 399

type presence of infection pre-existing systemic condition (tumour, metabolic disorder, drugs, vitamin deficiency)

Answer 400

malaise, fever, chills, leucocytosis pain, swelling, redness 60% positive blood cultures XR: mixed picture, eventually lytic almost always bacterial routes: haematogenous, direct extension, traumatic (incl. surgery)

Answer 401

mainly staph aureus also: E. coli, klebsiella, salmonella, psuedomonas, haemphilus influenzae, group b strep

Answer 402

10 days post-onset mottled rarefaction and lifting of periosteum Involucrum: irreg sub-periosteal new bone formation (>1week) Irregular lytic destruction (10-14 days) sequestra: necrotic cortex areas become detached (3-6 weeks)

Answer 403

spinal disease may result in psoas abscess and severe skeletal deformity (Pott's disease) systemic amyloidosis

Answer 404

(rare) congenital skeletal lesions: - osteochondritis - osteoperiostitis - diaphyseal osteomyelitis acquired (late) skeletal lesions: - non-gummatous periostitis - gummatous inflammation of bone and joints - neuropathic joints - neuropathic shaft fractures

Answer 405

inflammatory arthropathy from tick bite organism: borrelia burgdorferi Tick species: Ixodes dammini skin rash: erythema chronicum migrans Musculoskeletal effects seen in early disseminated phase and late/persistent phase dominated by arthritis Mx: prevention & vaccination, Abx for proven disease, clinical diagnosis

Answer 406

Primary: age-related Secondary: any age, previously damaged or congenitally abnormal joint aetiology unknown but results in: cartilage degeneration, fissuring, abnormal matrix calcification, osteophytes main sites: vertebrae, hips, knees

Answer 407

loss of joint space subchondral sclerosis cystic lesions osteophytes

Answer 408

severe chronic relapsing synovitis unpredictable course F:M = 3:1 Age 30-40y aetiology: most likely autoimmune, some genetic predisposition, association with HLA DR4 & DR1 80% RF +ve (RF forms immunocomplexes with IgG)

Answer 409

mild anaemia raised ESR RF +ve +/- rheumatoid nodules multisystem disease sites: small joints, hands, feet, sparing of DIPJ wrists, elbows, ankles, knees

Answer 410

radial deviation of wrist ulnar deviation of fingers 'swan neck' and 'boutonniere' deformity of fingers 'Z' shaped thumb

Answer 411

soft tissue swelling joint space narrowing erosions subchondral cysts

Answer 412

Proliferative synovitis with: 1. thickening of synovial membranes 2. hyperplasia of surface synoviocytes 3. intense inflammatory cell infiltrate 4. fibrin deposition and necrosis Pannus formation with exuberant inflamed synovium overlying the articular surface

Histopathology Flashcards

(453 cards)