Histopath Flashcards
betaHMC mutation
Hypertrophic Cardiomyopathy
Erythema marginatum
Subcutaenous nodules
Acute Rheumatic Fever
Acute Rheumatic Fever
Strep throat infection
Heart: pancarditis (endocarditis, myocarditis, pericarditis) + vasculitis
Joint: arthritis and synovitis
Skin: Erythema marginatum, subcutaneous nodules
CNS: encephalitis, Sydenham’s chorea
Jones Criteria
Diagnosis of Rheumatic Fever = group A strep infection + 2 major OR 1 major + 2 minor
Major (CASES) Carditis Arthritis Sydenham's chorea Erythema marginatum Subcutaneous nodules
Minor criteria Fever Raised ESR or CRP Migratory arthralgia Prolonged PR interval Previous rheumatic fever Malaise Tachycardia
Beady fibrous vegetations
verrucae
Rheumatic fever
Aschoff bodies
Small giant-cell granulomas
Rheumatic fever
Anitschkov myocytes
regenerating myocytes
Rheumatic fever
Libman-Sacks
Associated with SLE and anti-phospholipid syndrome
small (<2mm) “warty” vegetations
Sterile
Platelet rich
Acute infective endocarditis
Staph aureus
Strep pyogenes
Subacute infective endocarditis
Strep viridans
Staph. epidemris
Culture negative infective endocarditis
Coxiella Mycoplasma Candida Brucella Chlamydia Mycoplasma Bartonella
HACEK
Haemophilus, Aggregatibacter (previously Actinobacillus), Cardiobacterium, Eikenella, Kingella
Tricuspid infective endocarditis
IVDU
Staph aureus
Duke Criteria
Diagnosis of Infetcive Endocarditis
2 major
1 major = 3 minor
5 minor
Major:
Positive blood culture growing typical IE organism OR 2 positive culture >12 hours apart
Evidence of vegetation/abscess on echo OR new regurgitant murmur
Minor:
Risk factor (prosthetic valve, IVDU, congenital valve abnormalities)
Fever >38
Thromboembolic phenomena
Immune phenomena
Positive blood culture not meeting major criteria
Treatment of infective endocarditis
Acute:
Flucloxacillin for MSSA
Rifampicin AND Vancomycin AND Gentamicin for MRSA
Subacute:
Benzylpenicillin AND Gentammicin OR Vancomycin for 4 weeks
Mid-diastolic click and late systolic murmur
Mitral valve prolapse
Pericarditis
Types
Fibrinous: MI, Uraemia
Purulent: Staphylococcus aureus
Grenulomatous: TB
Haemorrhagic: Tumour, Tb, Uraemia
Fibrous = constrictive (arises from the above)
Pericardial effusion
Chronic heart failure
Pericardial effusion
Usual cause: Chronic heart failure
Cardiomyopathy
Dilated = systolic dysfunction
Hypertrophic = dialstoilic dysfunction
Restrictive = diastolic dysfunction
Charcot-Leyden crystals
Asthma
Curschmann spirals
Asthma
Goblet cell hyperplasia, hypertrophy of mucous glands
Chronic bronchitis
Yellow nail syndrome
Yellow dystrophic nails
Pleural effusions
Lymphoedema
Bronchiectasis
Young’s syndrome
Rhinosinusitis
Azoospermia
Bronchiectasis
Keratinisation
Intercellular prickles
Squamous cell carcinoma
M>F
Most common
Smoking
p53, c-myc mutations
EGFR mutation
mucin vacuoles
Adenocarcinoma
F>M
NON-Smokers
glandular differentiation with mucin production
EGFR –> give TKI (tyrosine kinase inhibitor)
RB1 mutation
Ectoptic ACTH
Lambert-Eaton
Small cell carcinoma
Arise from neuroendocrine cells
Smoking
P53 and RB1 mutations
Poor prognosis: mets early to bone, adrenal, liver brain
Ectopic ACTH
Cerebellar degeneration
Lambert Eaton: rare autoimmune disorder that is characterized by muscle weakness of the limbs. It is the result of an autoimmune reaction in which antibodies are formed against presynaptic voltage-gated calcium channels
Poorly differentiated malignant epithelium tumour of the lung
Large cell carcinoma
Poor prognosis
Large cells
Large nuclei
No evidence of glandular or squamous differentiation
Carcinoid syndrome
Flushing
Diarrhoea
Bronchoconstriction
Ectopic serotonin
Tx: Octreotide
ERCC1
Poor response to cisplatin
Linitis plastica and signet ring cell
Gastric adenocarcinoma
5-ASA
Ulcerative colitis
Watershed areas of gut
Splenic flexure (SMA transition to IMA)
Rectosigmoid (IMA transition to internal iliac)
Carcinoid crisis
Life-threatening vasodilation Hypotenion Tachycardia Bronchoconstriction Hyperglycaemia
Enterochromaffin cell origin
Serotonin producing
Lung, bowel, ovaries, testes
Carcinoid syndrome
Urinary 5-HIAA
Enterochromaffin cell cancer
Carcinoid syndrome
Hypoproteinaemic Hypokalaemic
Villous adenoma
Risk factor for adenoma –> adenocarcinoma
1) Size (main factor)
2) dysplasia
3) villous component
Juvenile polyposis
Autosomal dominant
In children
Haemartomatous polyp
100s
May require colectomy to stop haemorrhage
Peutz–Jeghers syndrome
Autosomal dominant -LKB1
Hamartomatous polyps
Hyperpigmented macules on the lips and oral mucosa (melanosis)
Increased risk of intussusception and malignancy
Hyperplastic polyp
Shedding of epithelium, cell build up
50-60 yrs
Pseudo polyp
IBD (UC)
Microsatellite instability
Hereditary non-polyposis colorectal cancer
HNPCC
Colorectal cancer
95% adenocarcinoma
Right-sided bowel tumours
Iron deficiency anaemia
Weight loss
Left-sided bowel tumours
Change in bowel habit
Crampy LLQ pain
CEA
colorectal cancer
Accumulation of fat droplets in hepatocytes
Hepatic steatosis (fatty liver)
Ballooning hepaotcytes
Necrosis
Mallory-denk bodies
Fibrosis
Pericellular fibrosis
Alcoholic hepatitis
Micronodular cirrhosis
Bands of fibrous tissue
Intra- and extra- hepatic shunting
Alcoholic cirrhosis
Neutrophil polymorphs
Mallory-denk
Alcoholic hepatitis
Megamitochondria
Alcoholic hepatitis
NAFLD
Steatosis in non-alcoholics
NASH
NAFLD + inflammation
Steatosis + inflammation in non-alcoholics
Interface hepatitis with plasma cells
Autoimmune hepatitis
Anti-LKM
Type II autoimmune hepatitis
Anti-SMA
Type I autoimmune hepatitis
Primary Biliary Cholangitis
Autoimmune inflammatory destruction of medium sized INTRAhepatic bile ducts
Slow development of cirrhosis over many years (hence renamed form cirrhosis to cholangitis as can diagnose prior to cirrhosis)
F> M 10:1
Increased serum ALP
Increase cholesterol
Increase IgM (late feature)
Anti-mitochondrial antibodies
NO BILE DUCT DILATATION
Bile duct loss with granulomas
Present with fatigue, pruritis, abdo discomfort
Tx: ursodeoxycholic acid
Primary Scleroisng Cholangitis
Inflammation and obliterative fibrosis of EXTRAhepatic and INTRAhepatic bile ducts
Multi-focal stricture formation with dilitation of preserved segments
Onion-skinning fibrosis
M > F
Associated with IBD (Ulcerative colitis)
Increase ALP
p-ANCA
Bile duct dilatation
ERCP: beading of bile duct (multifocal strictures)
Increase in cholangiocarcinoma
Absent aslpha globulin band on electrophoresis
A1AT deficiency
Haemorrhagic cystitis
Cyclophoshphamide use
Urinary schistosomiasis
Squamous cell carcinoma of bladder
Most common bladder tumour
Transitional cell (Urothelial) tumour
90% of bladder tumours
Smoker
Aromatic amines
Gleason system
Grading of Prostate cancer
Acute bacterial prostatitis
E.Coli
Most common germinal tumour
Seminoma
95% of testicular tumours are germ cell origin
AFP, HCG and LDH
tumour markers for teratoma
- male peeing on pregnancy test story
Nephrotic syndrome
Triad:
>3g/24 hr protein
Hypoalbuminaemia
Oedoema
(+hyperlipidaemia)
Diffuse glomerular basement membrane thickening
Membranous glomerular disease
= primary cause of nephrotic syndrome
Primary causes of nephrotic syndrome
Minimal change disease
Membranous glomerular disease
Focal segmental glomerulosclerosis
Focal and segmental glomerular consolidation and scarring
Focal segmental glomerulosclerosis
Membranous glomerular disease
Causes nephrotic syndrome
Common in adults
Diffuse glomerular basement membrane thickening
Loss of podocyte foot processes
Subepithelial spikey depsotis
Can be primary or secondary to SLE, drug, malignancy
Ig and complement in granular deposits along entire GBM
40% ESRF 2-20 yrs
Focal segmental glomerulosclerosis
Causes nephrotic syndrome
Common in adults
Focal and segmental glomerular consolidation and scarring
Hyalinosis
Loss of podocyte foot processes
Ig and complement deposited in scarred areas
50% respond to steroids
50% ESFR in 10 years
Primary
Can be due to HIV nephropathy and Obesity
Mesangial matrix nodule = Kimmelstiel Wilson Nodules
= Diabetes nephropathy
causes nephrotic syndrome
Apple green birefringence with Congo red stain
Amyloidosis
Can cause nephrotic syndrome
Chronic inflammation
TB
RA
Multiple myeloma - AL protein deposition
Nephritic syndrome
Manifestation of glomerular inflammation (glomerulonephritis)
Characterised:
Haematuria (coca-cola urine)
Dysmorphic RBCs and red cell casts in urine
May also have: Oliguria Increased urea and creatinine Hypertension Proteinuria (but sub nephrotic levels)
Causes of Nephritic Syndrome (5)
Acute post-infectious glomerulonephritis
IgA nephropathy (Berger Disease)
Rapidly progressive (Cresenteric) Glomerulonephritis (3 types)
Hereditary nephritis (Alport’s syndrome)
Thin basement membrane disease (benign familial haematuria)
HLA-DRB1
Goodpasture’s
Acute post-infectious (post-streptococcal) glomerulonephritis
Causes Nephritic syndrome
1-3 weeks after Group A alpha-haemolytic strep throat infection
Streptococcus pyogenes
Immune complex deposition
Haematuria, red cell casts, hypertension, proteinuria, oedema,
ASOT titre increased
Decreased C3
LM: increased cellularity
FM: grnaular depsoits of IgG and C3 in GBM
EM: subendothelial humps
IgA Nephropathy (Berger Disease)
Commonest cause of glomerulonephritis worldwide (causes nephritic syndrome)
Deposition of IgA complexes in glomeruli
1-2 days after URTI –> Frank haematuria
Persistent or recurring frank haematuria
Can be asymptomatic microscopic haematuria
Can progress to ESRF
FM: Granular deposition of IgA and complement in mesangium
Rapidly progressive (Crescentic) Glomerulonephritis
Most aggressive glomerulonephritis - can cause ESRF in weeks
Nephritic syndrome + oliguria and renal failure
All have crescents on LM
3 Types
Type 1: Anti-GBM antibody (Goodpasture’s –> Type IV collagen alpha 3)
Linear deposition of igG in GBM
+pulmonary haemorrhage
Type 2: immune complexes
SLE, IgA, Post-strep
granular/lumps deposition of IgG in GBM/mesangium
Type 3: pauci-immune (Not anti-GBM or immune complexes)
c-ANCA: Wegner’s
p-ANCA: microscopic polyangiitis
Scanty/lack of immune complex deposition
+Vasculitis
Hereditary Nephritis (Alport’s syndrome)
Causes Nephritic syndrome
Can be asymptomatic haematuria
x-linked recessive mutation in collagen IV alpha 4 chain
Nephritic syndrome + sensorineural deafness + eye problems (cataracts and lens dislocation)
Presents at 5-20 years and prepossesses to ESRF
Thin Basement Membrane Disease (Benign Familial Haematuria)
Asymptomatic haematuria (v.rarely nephritic syndrome)
No decline in renal function
Autosomal dominant mutation in collagen IV alpha 4 chain
Aysmptomatic haematuria
Think basement membrane disease
Alport’s
IgA nephropathy
Nephritic syndrome + scanty immune deposition
Pauci-immune
Wegners
Microscopic polyangiitis
Nephritic syndrome + sensorineural deafness + lens dislocation
Alport’s syndrome
Frank haematuria 2 days post URTI
IgA nephropathy
Increased ASOT titre, Low C3 and URTI 3 weeks ago
Post-streptococcal GN
Causes of Acute Tubular Injury
Commonest cause of acute renal failure
Ischaemia –> prolonged pre-renal AKI
Nephrotoxins (CHARM chain)
Cisplatin Heavy metals Aminoglycosides (Gentamicin) Radiocontrast medium Myoglobin
Chain: light chains in multiple myeloma
Histology: necrosis of short segments of tubules
Tubulointerstitial Nephritis
A group of renal inflammatory disorders that involve the tubules and interstitium
Acute pyelonephritis = leukocytic casts
Chronic pyelonephritis
Reccurent infections –> scarring of parenchyma
Acute interstitial nephritis
Hypersensitivity reactions to drugs
Fever, skin rash, haematuria, proteinuria, eosinophilia
Chronic interstitial nephritis
Elderly with long-term analgesic consumption (NSAIDs/paracetamol)
Hypertension, anaemia, proteinuria, haematuria
Thrombotic microangipathies
Thrombosis
+MAHA
+Thrombocytopenia
+renal failure (mostly in HUS)
Causes
TTP - diffuse, esp in CNS
HUS - confined to kidneys
TTP = headache, altered consciousness HUS= renal failure
Pre-renal causes of AKI
Hypovolaemia Sepsis Burns Acute pancreatitis Renal artery stenosis
Pre-renal = most common cause of AKI
Complications of AKI
Metabolic acidosis Hyperkalaemia Fluid overload HTN Hypocalcaemia Uraemia
Renal causes of AKI
Acute glomerulonephritis
Acute tubular necrosis (most common renal cause)
Thrombotic MAHA
Post-renal causes of AKI
Stones
Tumours (Primary or Secondary)
Prostatic hypertrophy
Retroperitoneal fibrosis
Chronic renal failure stages
GFR >90 = stage 1 60-89 = stage 2 30-59 = stage 3 15-29 = stage 4 <15 = stage 5
Start with 15, double, double again, add 30
PKD1
Autosomal Dominant
Adult Polycystic Kidney Disease
Chromosome 16 (polycystin 1)
Also PKD2 chromosome 4 (polycystin-2)
Lupus Nephritis
Can progress to chronic renal failure
Stage from I - VI
Renal cell carcinoma
Clear cell carcinoma - well differentiated
Papillary carcinoma - commonest in dialysis-associated kidney disease
Chromophobe renal carcinoma - pale, eosiophilic cells
Presents: palpable mass, haematuria, costovertebral pain
Paraneoplastic syndrome: polycythaemia, hypercalcaemia, HTN, Cushing’s syndrome, Amyloidosis
RUQ and peri-hepatitis
Fits High Curtis Syndrome
Also: violin string peri-hepatic adhesions
“Powder burns”
Endometriosis
red-blue to brown nodules
Endometriosis
Bundles of smooth muscle
Fibroids
Endometrial Cancer
Subdivided:
Endometrioid (80%)
Oestrogen excess
Non-endometrioid (205) Papillary Serous Clear cell Unrelated to oestrogen --> more aggressive
VIN
Graded from I - III
Associated with HPV-16
Usual type: 35-55 years, warty/basaloid SCC
Differentiated type: older women, keratinising SCC (higher rate of malignant transformation)
Vulval Carcinoma
Mainly squamous cell carcinoma (arise from VIN)
Or from other skin abnormalities (Paget’s disease of the vulva - adenocarcinoma in situ)
Ovarian Tumour Types
Epitheloid cell types
Serous cystadenoma
Mucinous cystadenoma
Endometrioid
Clear cell
Germ cell types
Dysgerminoma
Teratoma
Choriocarcinoma
Sex cord/stroma cell types
Fibroma
Granuloa-theca cell tumour
Sertoli-Leydig cell tumour
Ovarian tumour producing androgens
Sertoli-Leydig cell tumour
Ovarian tumour producing b-hCG
Choriocarcinoma
Ovarian tumour producing E2
Granulosa-theca cell tumour
Hobnail appearance
Clear cell ovarian tumour
Psammoma bodies
Serous cystadenoma
Clear cytoplasma
Clear cell tumour
No Psammoma bodies
Mucinous cystadenoma
Oestrogen secreting tumour
Mucinous cystadenoma
Causes pseudomyxoma peritonei
Mucinous cystadenoma
Keratinising squamous epithelium + breast pain
Periductal mastitis
Smokers
Not associated with lactation
Fat necrosis
Inflammatory response to damaged adipose tissue
PAINLESS breast mass / skin thickening / mammographic lesion
Fibrocytic Disease
Fibrocystic disease (finbroadenosis)
Cystic changes: small cysts form by dilation of lobules
Contain fluid
Often calcified
Fibrosis: inflammation and fibrosis secondary to cyst rupture
Adenosis: increased number of acini per lobule (normally seen in pregnancy)
Finger-like projections into ducts
Gynaecomastia
Duct papilloma
Benign papillary tumour arising within duct system of breast
Peripheral: within small terminal ducts
Central: within larger lactiferous ducts
Causes bloody discharge
No LUMP
Not seen on mammogram
Ix: galactogram
Stellate pattern of glandular tissue
Radial scar
Benign sclerosing lesion
Central scarring surrounded by proliferating glandular tissue in a stellate pattern
Resembles carcinoma on mammogram
BRCA1/2
Increase risk of:
Breast cacrinoma
Ovarian caner
Prostate cancer
Pancreatic cancer
Carcinoma in situ (breast)
Proliferation limited ti ducts/lobules by basement membrane
Lobullar (LCIS): no calcification, ALWAYS incidental finding on biopsy
Ductal (DCIS): Microcalcifcation on mammogram, much increased risk of breast carcinoma
Invasive breast carcinoma
Categorised into ductal, lobular or tubular
Ductal: carcinoma that cannot be subclassified into another group - MOST COMMON
Lobular: cells aloigned in single file chains/ strands
Tubular: Well-formed tubules with low grade nuclei (rarely palpable as <1cm)
Can also be mucinous –> secretes mucin
Triple assessment
Examination
Mammorgaphy, USS or MRI
FNA & Cytology
Breast carcinoma prognosis
ER/PR receptor positive –> GOOD
HER 2 positive –> BAD
Basal-like carcinoma breast
Sheets of atypical cells with lymphocyte infiltration
Stain: CK5/6/14
Phyllodes tumour
Interlobular stroma
Typically large, fast-growing masses
Mostly low grade, but can be aggressive
Palpable mass >50 yrs
Low glucose, high protein and high lymphocyte on Lumbar Puncture
TB
Neurofibromatosis type II (NF2)
Meningioma
Ventricular tumour, hydrocephalus
Ependymoma
Indolent, chilhood brain tumour
Pilocytic astrocytoma
Soft, gelatinous calcified brain tumour
Oligodendroma
Commonest brain tumour (primary)
Astrocytomas
Metastatic is more common tumour in CNS (lung, breast, malignant melanoma)
Tau protein Dementias
Corticobasal degeneration
Frontotemporal dementia (linked to chromosome 17)
Pick’s disease
Alzheimers (Tau and beta-amyloid)
Alpha-synuclein, ubiquitin
Dementia awith Lewy Bodies
Alzheimers
Senile plaques of beta-amyloid
Neurofibrillary tangles of Tau
Alpha-synuclein
Present in both
Lewy Body Dementia
Parkinson’s disease
Multiple Sclerosis Proteins
Myelin basic protein
Proteo-lipid protein
MS plaques show sharp margins of myelin loss
Multisystem Atrophy
Shy Drager: Autonomic dysfunction
Striatonigral: difficulty with movement
Olivopontocerebellar: Difficulty with balance and coordination
Can appear very similar to Parkinson’s BUT show poor response to parkinson medications
Loss of cancellous bone
Osteoporosis
Looser’s zones
Pseudo fractures
= osteomalacia
Brown’s tumour
Primary Hyperparathyroidism
Bone lesion that arises in settings of excess osteoclast activity, such as hyperparathyroidism.
Brown tumours consist of fibrous tissue, woven bone and supporting vasculature, but no matrix.
Excess of unmineralised bone
Osteomalacia
Osteitis fibrosa cystica
Osteomalacia
Marrow fibrosis + cysts
Mixed lytic and sclerotic bone
Paget’s
Salt and pepper skull
Primary hyperparathyroidism
Subperiostal bone resorption in phalanges
Primary hyperparathyroidism
Mosaic pattern of lamellar bone
Paget’s
Huge osteoclasts
Paget’s
> 100 nuclei
Rachitic rosary
Prominent knobs of bone at the costochondral joints
= Ricket’s
Decrease bone mineralisation
Osteomalacia
X-ray feature of Paget’s
Skull
Osteoporosis circumscripta
Cotton wool
Vertebrae
Picture frame
Ivory vertebrae
Pelvis
Sclerosis and lucency
Colchicine
Acute treatment of gout
Pseudo-gout crystals
Calcium pyrophosphate crystals
Rhomboid shaped