Histopathology UoB Flashcards
Intra tubular germ cell neoplasia
In situ stage
Proliferation of neoplasticism germ within seminiferous tubules
80% oh GCT show ITGCN in the adjacent tube
Sometimes seen in the biopsy for infertility and cryptorchidism
Classic seminoma
Commonest sub-type
Peak at the 4th decade
M/S sheets of rounded cells with clear cytoplasm and variable lymphocytic infiltrate in the stroma
Spermatocytic seminoma
3-5% of all seminomas
Older age group
M/S mixed population of small,intermediate and giant cells with increased mitosis rate
Excellent prognosis
Embryonal Carcinoma
20-30yrs More aggressive than seminoma M/S the cells are anaplastic and arranged in glandular, alveolar, solid, or papillary growth patterns. Associated with other germ cell tumours Pure form only 3%
Yolk sac tumour
Pure form in children
Most common GCT in infants and children up to 3yrs
In adults associated w/ embryonal carcinoma
Variable morphology
Schiller-Duval bodies by peri-vascular layer of tumour cells
AFP raised
Neoplasticism cells positive for AFP
Choriocarcinoma
0.3% pure, 1.5% in other NSGCT
Both cyto and syncitiotrophoblasts
Highly malignant
Raised HCG
Teratoma
Can differentiate into any of the three germ cell layers
They can have mature tissue TD or immature (foetal) tissue
Pure teratoma TD 2nd most common in children - good prognosis
In adults pure form rarely
Treated as malignant as it has metastatic potential
Testicular tumour staging
1 cancer contained in testes 2 nearby lymph nodes in pelvis abdomen 2A LN <2cm, 2B LN 2-5cm, 2C >5cm 3A distant LN or lungs, S0, S1 3B near LN and S2, or lungs/distant LN S2 3C as 3B but S3 or spread to brain/liver
Prostate cancer
Aetiology: hormones, 1q24-25, 1st degree relatives, far consumption, lycopene reduces risk
M/S adenocarcinoma, small glandular structures w/ single layer of cells
Grading - Gleason’s score
Staging: A; not palpable, B; palpable, confined, C;extra-capsular, D; metastatic
Minimal change disease/glomerulopathy
Commonest cause in nephrotic syndrome in childhood
No detectable immune deposit but immune basis
Strong association with respect. infection and immunisation
Diffuse effacement of foot processes (fused)
Focal segmental glomerulosclerosis
Primary or secondary
Some glomeruli (foci) show partial (segmental) hyalinisation
Unknown pathogenesis
Poor prognosis
Membranous glomerulonephritis
Deposition of anti-glomerular basal membrane antibodies
Thickened GBM and subepithelial deposits/spikes
Commonest cause of nephrotic syndrome in adults
85% idiopathic, 15% association with malignant tumours, SLE, drugs, chronic infection
Acute proliferative glomerulonephritis
Major cause of acute nephritis in childhood
Follows beta-haemolytic streptococcal infection
Endocapillary hypercellularity with numerous neutrophils and closure of glomerular vessels
Glomeruli increase in size and cellularity
Membranoproliferative glomerulonephritis
Crescenting or rapidly progressing Increase in mesangial substances Localised capillary wall thickening Increased cellularity Pronounced lobulation
Acute tubular necrosis
Focal necrosis
Desquamation of cells in tubular lumen
Causes: ischaemia, toxic injury, DIC, urinary obstruction
Acute pyelonephritis
Fever
Elevated creatinine
Acute inflammatory infiltrate in interstitium and tubular lumina
Chronic pyelonephritis
Kidney surface: irregular, depressed, scarred, bulging Can affect both kidneys at the same time Scarring is asymmetrical Dilated, blunted, deformed calyces Dilated colloid - filled tubules Thyroidisation of the kidney
Hypertensive kidney
Benign nephrosclerosis Some degree present with increased age HTN and DM can increase severity Fine, granular surface Fibrous intimal thickening NB: Malignant HTN & accelerated nephrosclerosis
ADPKD
1/500
Middle age
Haematuria, UTI, abdo mass, HTN, assoc. cerebral aneurysm
Rx: supportive, HTN, dialysis/transplant
ARPKD
1/20000 Large abdominal mass at birth Possible “potter” appearance Liver abnormalities Evolves into: death, renal failure, HTN, portal hypertension
Wim’s tumour
Benign
Papillary adenomas
Fibroma
Renal cell carcinoma
Risk factors: smoking, HTN, obesity, heavy metals, Von hippel lindau syndrome (naemangioblastoma of cerebellum, retina, renal cyst, bilateral RCC)
Haematuria
Backpain
Palpable mass
Paraneoplastic
Histotypes: clear cell, papillary and chromophobe
High power view: clear cytoplasm, sharply outlined cell membrane
Bladder carcinomas
Papillary (1%), benign Urothelial carcinoma RFs: Smoking Industrial exposure to arylamines Previous irradiation Long term use analgesia Cyclophosphamide Schistosoma (SCC)
Haemangioma
Benign vascular tumour
Most common benign tumour
Incidental pick up
Rarely rupture
Bile duct malformation
Common Incidental finding Often misinterpreted as metastasis Benign Along with bile duct adenoma
Liver cell adenoma
More common in women
Associated with OCP
Multiple subtypes
Some more likely to bebecome malignant
FNH
Tumour like malformation
Central scar
Can become very large
More common in women
Hepatocellular carcinoma
Most common primary malignant tumour
More common in men
5th most common malignancy in men
Huge regional variance
Causes of HCC
Cirrhosis Hep B/C ASH/NASH Autoimmune hepatitis Chronic biliary disease Much less common: haemochromatosi, A1AT- deficiency, wilson’s disease
Fibrolamellar HCC
Occurs in younger people
No background cirrhosis
Better prognosis
Hepatoblastoma
Occurs on children under 5 Most frequent liver tumour in children Most are male AFP often raised Lobulated appearence
Angiasarcoma
Rare but most common sarcoma of liver
Throrotrast, arsenic, anabolic steroids, vinyl chloride
More often in older men
Cholangiocarcinoma
Often aggressive with poor prognosis
Associated with chronic inflammation of bile ducts (PSC, parasites, pyogenic cholangitis)
Primary sclerosing cholangitis
Often in young/middle aged males Common in patients with ulcerative Progressive inflammation and fibrosis of large intra and extrahepatic bile ducts Can lead to secondary biliary cirrhosis Increased risk of CC AMA negative Can be p-ANCA +
Primary biliary cirrhosis
Middle aged females
AMA+, IgM+, Alk Phos raised
Affects small bile ducts
Can lead to cirrhosis
Wilson’s Disease
Autosomal recessive Ch 13
Aberrant storage of copper in many organs including the liver
Leads to liver failure
Often presents in childhood
Haemochromatosis
Autosomal recessive HFE gene on Ch 6
Leads to increased iron absorption and storage in the liver
Leads to cirrhosis
Increased risk of HCC
Alpha-1-antitrypsin deficiency
Mutation in the A1AT gene on Ch 14
Abnormal protein leeds to accumulation in the liver
Leads to fibrosis and cirrhosis
Increased risk of HCC
Fibroadenoma
Commonest benign breast tumour 20-35yrs Increased in size during pregnancy Decrease in size with age M/S composed of both proliferating ducts and connective tissue stroma
Phylloides tumour
4th-5th decade
M/S composed of epithelial and mesenchymal elements
Mesenchymal component is malignant and can produce metastasis through haematogenous route
Rx wide local excision
Recurrence is common
Carcinoma of the breast
Hormonal factors
Genetic factors: BRAC 1 (ch 17 ovaries and breast), BRAC2 (ch 13)
Environmental influence
Breast screening programme
All women aged between 50-69
Mammography
Every three years
Crohn’s
Involvement of both terminal ileum and caecum ~50% Confined to the colon ~20 Skip lesions Cobblestone appearance Mesentery thickened and oedematous Histopathology: Transmural inflammation Non-necrotising granulomas Crypt abscess Ulcers deep; abscess and fistulas Healing of ulcers > fibrosis and strictures
Crohn’s complications and Rx
Inflammatory adhesions Perforation Perirectal disease Malabsorption Small bowel carcinoma Rx: 5-aminosalycilic acid (mesalazine) Steroids Immunosupressive drugs Anti-TNFs infliximab Surgery
UC
Crypt abscesses with neutrophils in crypts, crypt wall and in lamina propria
Crypt architectural distortion, with gland branching, shortening and loss of normal parallel arrangement of glands
Complications: toxic megacolon, perforation, massive haemorrhage, colon cancer
Treatment: 5-ASA, steroids, immunosuppressive drugs, surgery
Inflammatory pseudopolyps
In UC and Crohn’s
Macroscopically can look like adenomas
Microscopically: inflammatory tissue, hyper-plastic mucosa
Hamartomatous polyps
Benign tumour-like lesion
Two or more differentiated tissue elements
Juvenile polyps: most common paeds GI polyp
Peutz-Jegher: GI polyps, pigmentation of oral polyps, lips, palsm, genitalia
Juvenile polyp
Cystic glands w/ normal or inflamed epithelium Germ line SMAD4 mutation (18q21-22) Children mean age 8 80% in rectum Clinical: bleeding, prolapse
Peutz-jeghers polyps
Autosomal dominant Occur throughout the GI tract Small>large Intussusception and partial or complete obstruction Carcinoma develops from dysplastic foci
Adenomas
All dysplastic Premalignant Tubular; tubular growth Tubo-villous adenoma; villi - elongated crypts, stalk Villous adenoma; more than 75% villous
Flat/depressed adenoma
High malignant potential
High incidence of severe dysplasia
Associated with HNPCC, or FAP
Colon cancer screening
Colonoscopy: UC, FAP/HNPCC, adenomatous polyps
Faecal occult blood (false positives)
Flexible sigmoidoscopy
Genetic testing
HNPCC
Dominant Carcinoma develops younger Right sided Multiple 5% of cases 4 mismatch repair Amsterdam criteria
FAP
Rare
No intervention > cancer
Multiple polyps (up to 1000s)
Polyps not present at birth
Role of virus in Lymphoma
EBV - Burkitt, Hodgkin, post transplant and AIDS related lymphoma
HTLV1 - T Cell NHL
Hepatitis C - low grade B cell NHL
HHV 8 kaposi plasma cell malignancy
Lymphoma diagnostic methods
Morphology, H + E (follicular lymphoma)
Immunochemistry
Flow cytometry
Molecular techniques - PCR, FISH (chromosomal abnormalities)
Reflux oesophagitis
Risk factors: hiatus hernia, peptic ulcer, smoking & alcohol, excessive vomiting, pregnancy, diabetes, GOJ surgery
Complications: stricture, barret’s, neoplasia
Achalasia
Aetiology unknown
Inflammatory destruction of myenteric ganglion cells
Long term complications: squamous cell carcinoma
Oesophageal infection
- Candida
- Herpes simplex virus
- Trypanosomiasis: transmitted in faeces of blood sucking reduviid bug - via it’s blood
Barret’s oesophagus
Metaplastic replacement of oesophageal lining by glandular mucosa
Aetiology: reflux
Normal squamous > Barret’s > dysplasia > adenocarcinoma 80% (20% SCC DXT +/- surgery)
Chemical/reactive gastritis
More frequently recognised Commonest form of chronic gastritis Bile reflux Drugs: aspirin, NSAIDs Alcohol
H. Pylori
Gastritis
Ulcer
MALT lymphoma: eradication of HP with PPI Abx and bismuth > regression
Carcinoma: superficial gastritis > atrophic gastritis > intestinal metaplasia > dysplasia > carcinoma
Adenocarcinoma of the stomach
M:F = 3:1
7th commonest cancer killer in the UK
Risk factors: diet (high salt, low dairy products), H. pylori
GIST
Rare
Stomach>SI>oesophagus and large bowel
Mutation in tyrosine kinase genes (KIT)
Rx: surgery +/- TKI inhibitors imatinib
Coeliac disease
Malabsorption (anaemia, low albumin)
Autoimmune (anti-tTG)
Abnormal immunological reaction to gluten
Improvement on gluten-free diet
Flat mucosa
Reduction of normal villous height to crypt depth ratio from 5:1 to <3:1
Crypt hyperplasia
Increased intra-epithelial lymphocytes
Infiltration of the lamina propria by plasma cells and lymphocytes
Coeliac complications
Refractory sprue - non responsive to gluten restriction
Ulcerative jejunitis
Neoplasia: enteropathy-associated T-cell lymphoma (EATL), small intestinal adenocarcinoma
Giardiasis
Giardia lamblia
Commonest SI protozoal infection worldwide
Contaminated water (orofeacal)
Immunocompromised more likely to get infected
SI mucosal may be normal or inflamed
SI neoplasia
Adenomas: duodenal (FAP) Adenocarcinoma - rare (coeliac, crohn’s, FAP) Lymphoma: Burkitt’s, EATL GIST Neuroendocrine tumours
Pr-eclamsia
Unknown cause
Maternal high BP + protein in urine
Autopsy: Asymmetrical IUGR
Placenta pathology
Common pathological findings in perinatal autopsy
Maceration; skin slippaged post mortem in stillborn
Intra ventricular haemorrhage
Anecephaly; absence of brain and skull vault
Spina bifida (neural tube defect)
Hydrops; generalised oedema of the foetus
Atresia of bowel
Single palmar crease (trisomy 21)
Findings in oligohydramnios (wrinkled glove like skin and potter facies)
Placenta pathology
Pre-eclampsia
Acute choriomanionitis: common after PROM, ascending infection
Hirschsprung’s disease
Developmental disorder with absence of ganglion cells in distal rectum
Aganglionic part of variable length
Due to failure of neuronal crest cells migration during development of enteric nervous system
Delayed meconium passage
Abdominal distentions
Bilious vomiting
Cystic fibrosis
Autosomal recessive mutation of CTFR
Lung involvement: mucus plugging of airways, severe suppurative lung disease, bronchiectasis
Bowel involvement: bowel lumen filled with inspissated meconium, interstitial atresia, rectal prolapse
Characteristic mucus extends deep into crypts
Coeliac disease
T-cell response in small intestine
Inflammatory reaction to gliadine
Seen in T1DM, trisomy 21
Breastfeeding protective
Young children: failure to thrive, malabsorption, abdo pain
Older children: abdo pain
Long term complications: osteoporosis, intestinal T-lymphoma
Anti-gliadine and anti-tissue transglutaminase Ab - AGA and TGA
Villous atrophy
Increased intraepithelial lymphocytes
Increased lamina inflammatory cells
Polycystic kidney disease
Autosomal recessive - PKHD1 (stillbirths and early neonatal death)
Autosomal dominant: 30-50
Effects of ischaemia on myocytes
Onset of ATP depletion - seconds Loss of contractility - <2min ATP reduced: to 50% - 10min, to 10% 40min Irreversible injury - 20-40min Microvascular injury - >1h
Gross changes of MI
None to occasional mottling ( up to 12 hours)
Dark mottling (12-24h)
Central yellow tan with hyperaemic border (3-7 days)
Grey white scar (2-8wks)
Microscopic changes of MI
Early coagulation necrosis and oedema; haemorrhage
Pyknosis of nucleic, hypereosinophilia, early neutrophilic infiltrate
Coagulation necrosis, interstitial infiltrate of neutrophils
Dense collagenous scar
Lab detection of MI
CK (MB isozyme)
Lactate dehydrogenase
Troponin - I and T
