histopathology Flashcards
squamous cell carcinoma - histological features, site
histological features:
- keratin production
- intracellular bridges (appears as little prickles on edge of cells)
- do NOT form glands
site:
- skin
- head and enck
- oesophagus (upper and middle 1/3)
- anus
- cervix
- vagina
adenocarcinomas - histological features, site
histological features:
- from glandular epithelium
- forms glands that can secrete substances (e.g., mucin)
site:
- lung
- breast
- stomach
- colon
- pancreas
transitional cell carcinoma - sites
urinary tract
kidney
ureters
bladder
histochemical stains - fontana, congo red, prussian blue
fontanta: +ve for melanin
congo red: +ve for amyloid (apple green birefringence)
prussian blue: +ve for iron (haemochromatosis)
NB: go-to stain for most histological samples is Haemotoxylin and Eosin (H&E)
immunohistochemical stains
involves antibodies directed against a specific antigen. you can then use either immunofluorescence (fluorescently tagged antibody) or immunoperoxidase (visualisation due to chemical reaction) to detect resulting complexes
- CD45: lymphoid cell marker
- cytokeratin: epithelial marker
- chromogranin: neuroendocrine marker (e.g., insulinomas or phaeochromocytoma)
define atherosclerosis
chronic inflammation in tunica intima (innermost layer) of large arteries characterised by intimal thickening and lipid accumulation
steps of atherosclerosis
- endothelial injury causes accumulation of LDL
- LDL enters intima and is trapped in sub-intimal space
- LDL is converted into modified and oxidised LDL causing inflammation
- macrophages take up ox/modLDL via scavenger receptors and become foam cells
- apoptosis of foam cells causes inflammation and cholesterol core of plaque
- increase in adhesion molecules on endothelium due to inflammation results in more macrophages and T cells entering the plaque
- vascular smooth muscle cells form the fibrous cap, segregating thrombogenic core from lumen
3 principal components of atherosclerotic plaques
- cells - including SMC, macrophages and other leukocytes
- ECM including collagen
- intracellular and extracellular lipid
risk factors for atherosclerosis
modifiable: type 2 diabetes mellitus, hypertension, hypercholesterolaemia, smoking
non-modifiable: gender (M>F), increasing age, family history
what is ischaemic heart disease?
group of conditions that occur when oxygen supply < demands of the myocardium due to narrowed coronary vessels. includes stable/unstable angina, MI
- stable angina: 70% vessel occlusion, pain on exertion
- unstable angina: >90% vessel occlusion, pain at rest also. high likelihood of impending infarction
- prinzmetal angina: rare, due to coronary artery spasm rather than atherosclerosis
NB: no muscle death in angina
pathogenesis of MI
coronary atherosclerosis - plaque rupture - superimposed platelet activation - thrombosis and vasospasm - occlusive intracoronary thrombus overlying disrupted plaque.
this results in myocardial necrosis secondary to ischaemia.
severe ischaemia lasting >20-40 mins results in irreversible injury and myocyte death
complications of MI
mechanical
- contractile dysfunction loss of muscle, cardiogenic shock
- congestive cardiac failure; due to ventricular dysfunction
- LV infarct; papillary muscle dysfunction/necrosis/rupture -> MR
- cardiac rupture of ventricular wall, septum (left to right shunt, VSD), papillary muscle (MR)
- ventricular aneurysm; develops >4 weeks post-MI (persistent ST elevation)
arrhythmia
- VF; usually occurs in the first 24hrs, common cause of sudden death
- 90% of patients develop an arrhythmia followed by an MI
pericardial
- early/peri-infarct associated pericarditis (dusky haemorrhagic tissue)
- pericardial effusion (+/- tamponade)
- Dressler’s syndrome; chest pain, fevers and effusion weeks-months after MI
- fibrinous pericarditis - occurs if infarct extends to epicardium
thrombotic
- embolisation of thrombus
evolution of MI - histological findings
- under 6 hours - normal by histology (CK-MB also normal)
- 6-24 hrs - loss of nuclei, homogenous cytoplasm, necrotic cell death
- 1-4 days - infiltration of polymorphs then macrophages (clear up debris)
- 5-10 days - removal of debris
- 1-2 weeks - granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
- weeks-months - strengthening, decellularising scar tissue
what is preload and afterload
preload: initial stretch of cardiomyocytes before contraction due to ventricular filling. increase will increase stroke volume
afterload: pressure of vessels (aortic or pulmonary artery pressures) against which heart must contract to eject blood. increase in afterload will decrease stroke volume
common causes of heart failure
- ischaemic heart disease
- myocarditis
- hypertension
- cardiomyopathy (dilated)
- valve disease
- arrhythmias
complications of heart failure
- sudden death (largely arrhythmia)
- systemic emboli
- arrhythmias
dilated cardiomyopathy - mechanisms of HF, causes, indirect myocardial dysfunction (not cardiomyopathy-induced)
mechanism:
- systolic dysfunction
causes:
- idiopathic, alcohol, thyroid disease, haemochromatosis, viral myocarditis
indirect myocardial dysfunction (not cardiomyopathy-induced)
- IHD, valvular heart disease, hypertension, congenital HD
hypertrophic cardiomyopathy - mechanisms of HF, causes, indirect myocardial dysfunction (not cardiomyopathy-induced)
mechanism:
- diastolic dysfunction
causes:
- genetic, storage diseases
indirect myocardial dysfunction (not cardiomyopathy-induced):
- hypertension, AS
restrictive cardiomyopathy - mechanisms of HF, causes, indirect myocardial dysfunction (not cardiomyopathy-induced)
mechanism:
- diastolic dysfunction
causes:
- sarcoidosis, amyloidosis, radiation-induced fibrosis
indirect myocardial dysfunction (not cardiomyopathy-induced):
- pericardial constriction
acute rheumatic fever summary
occurs at a peak age of 5-15 years. it is a multisystem illness affecting:
- heart: pancarditis e.g., endocarditis, myocarditis, pericarditis
- joints: arthritis and synovitis
- skin: erythema marginatum, subcutaneous nodules
- CNS: encephalopathy, sydenham’s chorea
acute rheumatic fever clinical features
- develops 2-4 weeks after strep throat infection
- diagnosis: group A strep infection + 2 major criteria or 1 major + 2 minor criteria
Jones’ Major criteria:
Major criteria:
- carditis
- arthritis
- syndenham’s chorea
- erythema marginatum
- subcutaneous nodules
Minor criteria:
- fever
- raised CRP/ESR
- migratory arthralgia
- prolonged PR
- prev. rheumatic fever
- malaise
- tachycardia
Evidence of GAS infection:
- positive throat culture
- elevate AsO
- recent scarlet fever
main pathogen for acute rheumatic fever
Lancefield group A strep
acute rheumatic fever - histology
beady fibrous vegetations (verrucae), Aschoff bodies (small giant-cell granulomas) and Anitshkov myocytes (regenerating myocytes)
acute rheumatic fever treatment
benzylpenicillin
erythromycin if penicillin-allergic
conditions that might cause vegetative endocarditis
- rheumatic heart disease
- infective endocarditis
- non-bacterial thrombotic endocarditis (marantic)
- Libman-Sacks endocarditis
rheumatic heart disease - pathology, characteristics of vegetations
pathology:
- antigenic mimicry - cross reaction of anti-streptococcal antibodies with heart tissue
characteristics of vegetations:
- small, warty vegetations found along the lines of closure of valve leaflet - ‘verrucae’
infective endocarditis - pathology, characteristics of vegetations
pathology:
- colonisation or invasion of heart valves or mural endocardium by microbe
characteristics of vegetations:
- large, irregular masses on valve cusps, extending into the chordae
non-bacterial thrombotic endocarditis (marantic) - pathology, characteristics of vegetations
pathology:
- DIC/hypercoagulable states
characteristics of vegetations:
- small, bland vegetations attached to lines of closure. formed of thrombi.
Limban-Sacks endocarditis - pathology, characteristics of vegetations
pathology:
- pathogenesis unknown. associated with SLE and anti-phospholipid syndrome
characteristics of vegetations:
- small (up to 2mm), warty vegetations that are sterile and platelet rich
infective endocarditis: bacteraemia secondary to…
- poor dental hygiene (strep viridans)
- IVDU
- soft tissue infection
- dental treatments
- cannulas/lines
- cardiac and valvular surgery/pacemakers
- previously damaged valve e.g., post rheumatic fever
acute vs subacute infective endocarditis
causative organisms
- acute: staph aureus (35-40%), strep pyogenes
- subacute: strep viridans, staph epidermis, HACEK*, coxiella, mycoplasma, candida
virulence
- acute: high
- subacute: low
vegetation morphology
- acute: larger and more localised
- subacute: friable, soft thrombi. a few mm in size
spread
- acute: aorta
- subacute: chordae
*HACEK: a group of unusual bacterial causes of infective endocarditis. Haemophilus, Aggregatibacter, Cardiobacterum, Eikenella, Kingella
clinical features of endocarditis
constitutional:
- fever
- malaise
- rigors
- anaemia
cardiac:
- new murmur (MR/AR usually)
immune phenomena:
- roth spots
- osler’s nodes
- haematuria due to glomerulonephritis
thromboembolic phenomena:
- janeway lesions
- septic abscesses in lungs/brain/spleen/kidney
- micro emboli
- splinter haemorrhages
- splenomegaly
stereotypical patient: non-specific systemic symptoms such as fevers, weight loss, night sweats and malaise ongoing for several months. haematuria (either macroscopic or likely microscopic - very common). often treated as bacterial infections and may improve with antibiotics only to worsen again when stopped
NB: usually mitral/aortic valve unless IVDU when right-sided valves invovled
Duke Criteria - infective endocarditis
major:
- positive blood culture growing typical IE organisms or 2 positive cultures > 12 hrs apart
- evidence of vegetation/abscess on echo or new regurgitant murmur
minor:
- risk factor (e.g., prosthetic valve, IVDU, congenital valve abnormalities)
- T > 38
- thromboembolic phenomena
- immune phenomena
- positive blood cultures not meeting major criteria
diagnosis:
- 2 major
- 1 major + 3 minor
- 5 minor
infective endocarditis treatment
start with broad spectrum Abx once cultures taken. then treat according to sensitivities.
subacute:
- benzylpenicillin + gentamicin; or vancomycin for 4 weeks
acute:
- flucloxacillin for MSSA, rifampicin + vancomycin + gentamycin for MRSA (S. aureus IE is very nasty so make sure there is cover for this)
aortic stenosis - pathophysiology, causes, murmur
pathophysiology:
- narrowed aortic valve high velocity, high pressure flow
causes:
- calcification (old age)
- congenital bicuspid valve
murmur:
- crescendo-decrescendo
- radiates to carotids
aortic regurgitation - pathophysiology, causes, murmur
pathophysiology:
- incompetent aortic valve blood flows back into LV after systole
causes:
- infective endocarditis, dissecting aortic aneurysm, LV dilation, connective tissue disease e.g., Marfans, ank spon
murmur:
- early diastolic, with collapsing pulse
mitral stenosis - pathophysiology, causes, murmur
pathophysiology:
- narrowed mitral valve high velocity, high pressure flow. back pressure in left atrium dilatation
causes:
- rheumatic fever
murmur:
- mid diastolic, opening click
mitral regurgitation - pathophysiology, causes, murmur
pathophysiology:
- incompetent mitral valve blood flows back into left atrium during systole
causes:
- infective endocarditis, connective tissue disease, post-MI, rheumatic fever, LV dilation (functional MR)
murmur:
- pansystolic
- radiates to axilla
which valves does chronic rheumatic valve disease most commonly affect
left-sided, mostly mitral
mitral > aortic > tricuspid > pulmonary
there is thickening of valve leaflet, especially along lines of closure and fusion of commissures.
there is also thickening, shortening and fusion of chordae tendinae
how does mitral valve prolapse usually present?
- clinically appears in middle-aged woman
- short of breath with chest pains
- clinical signs often described as mid systolic click + late systolic murmur
- often secondary to annular dilatation due to dilated cardiomyopathy
causes of pericarditis
- viral and idiopathic most common (90%)
- fibrinous (MI, uraemia)
- purulent (staphylococcus)
- granulomatous (TB)
- haemorrhagic tumour (tumour, TB, uraemia)
- fibrous (a.k.a., constrictive) (arises from any of above)
pericardial effusion
serous fluid in pericardial sac
usual cause:
- chronic heart failure
exudative fluids occur secondary to inflammatory, infectious, malignant or autoimmune processes within the pericardium.
can lead to cardiac tamponade which presents with Beck’s triad (muffled heart sounds, raised JVP, hypotension)
haemopericardium
= blood in the pericardial sac
can arise due to myocardial rupture from myocardial infarction or trauma
chronic bronchitis - site, pathology, aetiology, clinical features, histological features, complications
site:
- bronchus
pathology:
- dilatation of the airways and excess mucous production
aetiology:
- tobacco smoke, air pollution
clinical features:
- cough & sputum on most days for 3 months over 2 years
histological features:
- dilatation of the airways, goblet cell hyperplasia and hypertrophy of mucous glands
complications:
- recurrent infections, chronic hypoxia. pulmonary HTN
bronchiectasis - site, pathology, aetiology, clinical features, histological features, complications
site:
- bronchus
pathology:
- airway dilatation and scarring
aetiology:
- recurrent infections (CF major risk factor)
clinical features:
- cough, purulent sputum, fever
histological features:
- permanent fibrotic dilatation of the bronchi
complications:
- recurrent infections, haemoptysis, pulm HTN, amyloidosis
asthma - site, pathology, aetiology, clinical features, histological features, complications
site:
- bronchus
pathology:
- airway constriction due to mast cell degranulation
aetiology:
- immunologic: allergens, drugs, cold air, exercise
clinical features:
- episodic cough, reversible wheezing, acute dyspnoea
histological features:
- SM cell hyperplasia, excess mucus (goblet cell hypertrophy), inflammation
- whorls of shed epithelium (Curschmann spirals), eosinophils, Charcot-Leyden crystals
complications:
- chronic asthma, death
emphysema - site, pathology, aetiology, clinical features, histological features, complications
site:
- acinus
pathology:
- airspace enlargement, wall destruction
aetiology:
- tobacco smoke, alpha1-AT deficiency
clinical features:
- dyspnoea, cough
histological features:
- loss of the alveolar parenchyma distal to the terminal bronchiole
complications:
- pneumothorax, resp failure, pulm HTN
pathophysiology of bronchiectasis
- recurrent infection/inflammation
- bronchial wall oedema and excess mucous production
- lymphocyte recruitment and protease release
- bronchial wall damage
- more prone to infection and inflammation
- cycle repeats
causes of bronchiectasis
inflammatory:
- post-infectious (e.g., pertussis) - most common cause 18% of all adult patients
- abnormal host defence; primary (hypogammaglobulinaemia) and secondary (chemotherapy, NG)
- obstruction (extrinsic/intrinsic/middle lobe syndrome), secondary to COPD
- post-inflammatory (aspiration)
- secondary to bronchiolar disease (OB) and interstitial fibrosis (CFA, sarcoidosis)
- systemic disease (connective tissue disorders)
- asthma
congenital:
- cystic fibrosis
- primary ciliary dyskinesia
- hypogammaglobulinaemia
- young’s syndrome = rhinosinusitis, azoospermia and bronchiectasis
what is interstitial lung disease
group of >200 diseases characterised by inflammation and fibrosis of the pulmonary connective tissue, accounting for 15% of respiratory distress burden
shows features of RESTRICTIVE lung disease on spirometry (reduced FEV1 and FVR but normal FEV1/FVC ratio i.e., >70%):
- decreased CO diffusion capacity
- decreased lung volume
- decreased compliance
interstitial lung disease - typical presentation
- chronic shortness of breath
- fine end-inspiratory crackles
- cyanosis, pulmonary HTN and cor pulmonale
in advanced disease, interstitial lung disease will have a ground glass/honeycomb appearance on CT CAP
interstitial lung disease - categorisation
- fibrosing
- cryptogenic fibrosing alveolitis / idiopathic pulmonary fibrosis
- pneumoconiosis
- cryptogenic organising pneumonia
- associated with connective tissue disease
- drug-induced
- radiation pneumonitis - granulomatous
- sarcoid
- extrinsic allergic alveolitis
- associated with vasculitides e.g., Wegener’s, Churg-Strauss, microscopic polyangiitis - eosinophilic
- smoking related
cryptogenic fibrosing alveolitis / idiopathic pulmonary fibrosis
- M > F
- causative agents unknown: risk factors include smoking and GORD
histological pattern of fibrosis = usually interstitial pneumonia, required for diagnosis (also seen in connective tissue disease, asbestosis and EAA)
- progressive patchy interstitial fibrosis with loss of normal lung architecture and honeycomb change, beginning at periphery of the lobule, usually sub-pleural
- hyperplasia of type II pneumocytes causing cyst formation - honeycomb fibrosis
can have inflammatory causes e.g., RA, SLE, systemic sclerosis
clinical presentation:
- increasing exertional dyspnoea and non-productive cough
- 40-70y at presentation with hypoxaemia -> cyanosis and pulmonary HTN +/- cor pulmonale, and clubbing. diagnosed by high-resolution CT
management:
- steroids, cyclophosphamide, azathioprine, pirfenidone (not especially effective)
- poor prognosis (2-5 yrs)
pneumoconiosis
- occupational lung disease caused by inhalation of mineral dusts or inorganic particles
- classically seen in coal miners
- predilection for upper lobes
NB: asbestosis can cause benign pleural lesions (plaques, fibrosis) but can also cause malignant lesions (adenocarcinoma, mesothelioma). asbestosis (fibrosis resulting from asbestos exposure) tends to affect the lower lobe.
granulomatous lung diseases
granuloma = collection of histiocytes, macrophages +/- multi-nucleate giant cells
granulomatous infections:
- TB, fungal (histoplasma, Cryptococcus, coccidioides, aspergillus, mucor) and others (pneumocystis, parasites)
non-infectious granulomatous conditions:
- sarcoid, foreign body (aspiration or IVDU), drugs or occupational lung disease
extrinsic allergic alveolitis / hypersensitivity pneumonitis / cryptogenic organising pneumonia / bronchiolitis obliterans organising pneumonia (BOOP)
group of immune-mediated lung disorders caused by intense/prolonged exposure to inhaled ORGANIC antigens -> widespread ALVEOLAR inflammation (NB asthma = airway inflammation)
histologically:
- presence of polypod plugs of loose connective tissue within alveoli/bronchioles - granuloma formation and organising pneumonia
acute presentation:
- inhalation of antigenic dust in SENSITISED individual -> systemic symptoms (fever, chills, chest pain, SoB, cough) within hours of exposure, usually settle by following day. progresses to chronic EAA
chronic presentation:
- progressive persistent productive cough and SoB, finger clubbing and severe weight loss
squamous cell carcinoma of the lung
- risk factors; M>F, strongest correlation with smoking
- highest rate of p53/c-myc mutations
- usually proximal bronchi, local spread with late metastasis. less responsive to chemo
- histology: keratinisation, intercellular prickles (desmosomes)
- cytology: squamous cells
- there are a variety of subtypes e.g., papillary, basaloid. it is associated with cavitation and hypercalcaemia due to paraneoplastic syndrome (PTHrp secretion)
- progression: epithelium -> hyperplasia -> squamous metaplasia -> angiosquamous dysplasia -> carcinoma in situ -> invasive carcinoma
adenocarcinoma of the lung
- most common in women and non-smokers
- malignant epithelial tumour with glandular differentiation or mucin production
- tumour occurs peripherally and metastasises early
- histology: glandular differentiation (gland formation and mucin production)
- cytology - cells containing mucin vacuoles. molecular - EGFR mutations
- progression; atypical adenomatous hyperplasia -> non-mucinous BAC -> mixed pattern adenocarcinoma
small cell carcinoma of the lung
- usually occurs centrally, proximal bronchi
- arising from neuroendocrine cells. associated with ectopic ACTH secretion, Lambert-Eaton, SIADH
- histology: small, poorly differentiated “oat cells”
- highly malignant, metastasise early, usually by diagnosis commonly to bone, adrenal, liver, and brain
- poor prognosis due to rapid metastases and late presentation - despite being chemo sensitive
- it has a strong relationship to smoking. p53 and RB1 mutations are common
large cell carcinoma of the lung
- poorly differentiated malignant epithelial tumour - large cells, large nuclei, prominent nucleoli
- histology: no evidence of glandular or squamous differentiation
- poor prognosis
paraneoplastic syndromes
- ADH -> SIADH (small cell)
- ACTH -> cushing’s (small cell)
- PTH/PTHrP -> primary hyperparathyroidism, hypercalcaemia and bone pain (squamous cell)
- calcitonin -> hypocalcaemia
- serotonin -> carcinoid syndrome (flushing + diarrhoea + bronchoconstriction)
- bradykinin -> cough
what is mesothelioma
arise from either parietal or visceral pleura.
it spreads within the pleural space and usually associated with extensive pleural effusion, chest pain and dyspnoea.
there is a long latent period of 25-45 years for development of asbestos-related mesothelioma
what is pulmonary hypertension?
mean pulmonary arterial pressure > 25mmHg at rest
pulmonary hypertension classes
classified according to aetiology
class 1:
- pulmonary arterial hypertension (idiopathic, hereditary, drugs/toxins, associated with congenital heart disease) - primary PAH most common in women aged 20-40 yrs
class 2:
- pulmonary hypertension due to left heart disease (systolic/diastolic dysfunction, valve disease)
class 3:
- pulmonary hypertension due to lung disease (e.g., ILD)
class 4:
- chronic thromboembolic pulmonary hypertension i.e., due to many clots over time which cause fibrosis
class 5:
- pulmonary hypertension with unclear multifactorial mechanisms (metabolic disorders, systemic disorders, haematological disorders)
complications of pulmonary hypertension
RHF - venous congestion of organs (nutmeg liver), peripheral oedema
pulmonary oedema - main aetiology, histology, CXR findings
intra alveolar fluid accumulation leads to poor gas exchange
main aetiology:
- left heart failure
histology:
- acute - intra-alveolar fluid
- chronic - iron laden macrophages (“heart failure cells”)
CXR findings:
- alveolar opacification (batwing appearance), Kerley B-lines (cardiomegaly suggesting a cardiac cause), fluid in horizontal fissure
diffuse alveolar damage
= acute damage to alveoli leading to exudative inflammatory reaction, rapid onset of respiratory failure and often requiring ventilation in ITU:
- ARDS in adults (e.g., infection, drowning, burns, aspiration, trauma etc)
- HMD (hyaline membrane disease) in neonates (e.g., insufficient surfactant production in prems)
- histology: lung expanded, firm, plum-coloured, airless
- CXR: white out of all lung fields
reflux oesophagitis/GORD
commonest cause of oesophagitis
complications: ulceration, haemorrhage -> haematemesis/melaena, Barrett’s oesophagus, stricture, perforation
Los Angeles Classification of severity
Management: lifestyle changes (stop smoking, weight loss), PPI/H2 receptor antagonists
Barrett’s oesophagus
intestinal metaplasia of squamous mucosa -> columnar epithelium (have goblet cells) following chronic GORD -> upwards migration of the SCJ (squamo-columnar junction/z-line)
seen in 10% of those with symptomatic GORD
can lead to adenocarcinoma: metaplasia -> dysplasia -> Ca
NB: presence of goblet cells is intestinal metaplasia - confers even higher risk of development into Ca
oesophageal adenocarcinoma
associated with Barrett’s oesophagus so usually seen in distal 1/3
other risk factors including: smoking, obesity, prior radiation therapy
most common in Caucasians, M»F
squamous cell oesophageal carcinoma
associated with EtOH and smoking
other risk factors including: achalasia of cardia, Plummer-Vinson syndrome, nutritional deficiencies, nitrosamines, HPV (in high prevalence areas), 6x more common in Afro-Caribbeans, M>F
usually found in middle 1/3 (50%), upper 1/3 (20%), lower 1/3 (30%)
presentation:
- progressive dysphagia (solids then fluids), odynophagia (pain), anorexia, severe weight loss
rapid growth and early spread (to LNs, liver and directly to proximal structures) -> palliative care
oesophageal varices
engorged dilated veins, usually due to portal HTN (back pressure)
Pt vomits large volumes of blood
emergency endoscopy -> sclerotherapy/banding
lining of stomach
gastric mucosa (no goblet cells), columnar epithelium (mucin secreting) and glands
gastritis
acute (neutrophils): insult e.g., aspirin, NSAIDs, corrosives (bleach), acute H. pylori, severe stress (burns)
chronic (lymphocytes and plasma cells):
- insult e.g., H. pylori tends to be antral, AI e.g., pernicious anaemia, EtOH, smoking
complications:
- if chronic, gastric ulcer formation
- chronic due to H. pylori may induce lymphoid tissue in the stomach and increase future risk of Mucosa Associated Lymphoid Tissue (MALT) lymphoma
it may also however result in intestinal metaplasia -> dysplasia -> cancer
gastric ulcer
breach through muscularis mucosa into submucosa (otherwise an erosion, not an ulcer)
epigastric pain +/- weight loss
worse with food (contrast with duodenal ulcer), relieved by antacids
RFs: H. pylori, smoking, NSAIDs, stress, delayed gastric emptying. occurs mainly in elderly
Ix: biopsy for H. pylori histology status. pucnhed out lesion with rolled margins
complications: anaemia (IDA) and perforation (erect CXR), malignancy
gastric cancer
higher incidence in Japan, China where more fermented/pickled food eaten.
>95% of tumours in stomach will be adenocarcinomas.
can be intestinal (well differentiated, goblet cells present following intestinal metaplasia)
diffuse (poorly differentiated, no gland formation - includes signet ring cell carcinoma)
gastric (MALT) lymphoma
caused by H. pylori - chronic antigen stimulation
management: remove cause (H. pylori using triple therapy - PPI, clarithromycin+amoxicillin)
dudoenal ulcer
4 times more common than gastric ulcer
- epigastric pain, worse at night
- relieved by food and milk
- occurs in younger adults
RFs: H. pylori, drugs, aspirin, NSAIDs, steroids, smoking, drugs, acid secretion
complications: anaemia (IDA) and perforation (erect CXR)
coeliac disease
T cell mediated autoimmune disease (DQ2, DQ8 HLA status)
presentation:
- young children (paeds) and irish women (EMQs)
symptoms (of malabsorption):
- steatorrhoea, abdo pain, bloating, N&V, failure to thrive, rash (dermatitis herpetiformis)
- also associated w hyposplenism so may need extra vaccines
Ddx:
- tropical sprue
serological tests:
- anti-endomysial Ab (best sen and spec), anti-tissue transglutaminase (IgA), anti-gliadin (poor marker of disease control)
gold standard Ix:
- upper GI endoscopy and duodenal biopsy (villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes) while eating gluten
NB normal villous:crypt ratio is 2:1
management:
- gluten free diet
NB: around 10% progress to duodenal T-cell lymphoma (EATL) if not treated adequately
Hirschsprung’s disease
absence of ganglion cells in myenteric plexus (80% males)
- presents with symptoms and signs of obstruction in young babies, mostly males
- failure to pass meconium within first 48 hrs
- associated with Down’s syndrome (2%)
- genetics - RET proto-oncogene Cr10+
- gold standard Ix: full thickness biopsy; hypertrophied nerve fibres, no ganglia
- treatment: resection of affected (constricted) segment and pull-through of normal functioning bowel
extra-GI manifestations of IBD
- malabsorption & Fe def. anaemia -> angular stomatitis
- eyes: anterior uveitis (iris & ciliary body), conjuctivitis
- skin: erythema nodosum (tender bruise-like swellings on shins), pyoderma gangrenosum, erythema multiforme, digital clubbing
- joints: migratory asymmetrical polyarthropathy of large joints (15%), sacroilitis, myositis, ankylosing spondylitis
- liver: pericholangitis, primary sclerosing cholangitis (UC>CD), steatosis
Crohn’s - management
mild attack:
- prednisolone
severe attacks:
- IV hydrocortisone, metronidazole
additional therapies:
- azathioprine, methotrexate, infliximab
ulcerative colitis - management
mild:
- prednisolone + mesalazine (5 ASA)
moderate:
- prednisolone + 5 ASA + steroid enema bd
severe:
- admit, NBM IV fluids and IV hydrocortisone, rectal steroids
for remission:
- all 5-ASA (1st line), azathioprine (2nd line)
clostridium difficile - result of which antibiotics? investigations? management?
4Cs: ciprofloxacin, cephalosporins, co-amoxiclav, clindamycin
Ix: stool culture/toxin assay
Mx: vancomycin PO
- also put into side room, can use metronidazole
diverticular disease
- low fibre diet
- high intraluminal pressure results in outpouchings at ‘weak points’ in wall of bowel (seen on barium enema CT or endoscopy)
- 90% occur in L colon
- presence of diverticula = diverticulosis
- often asymptomatic, sometimes PR bleed
- complications: diverticulitis, fever & peritonism, gross perforation, fistula, obstruction (due to fibrosis)
carcinoid syndrome
- diverse group of tumours of enterochromaffin cell origin, produce 5-HT (serotonin)
- commonly found in the bowel (but also lung, ovaries, testes)
- usually slow growing
carcinoid syndrome:
- bronchoconstriction
- flushing
- diarrhoea
carcinoid crisis:
- life threatening vasodilation, hypotension, tachycardia, bronchoconstriction, hyperglycaemia
Ix: 24hr urine 5-HIAA (main metabolite of serotonin)
Mx: ocreotide (somatostatin analogue)
adenomas (neoplastic polyps) in colon and rectum
- benign dysplastic lesions that are the precursor lesion to most adenocarcinomas (although most remain benign)
- found in 50% >50yrs in Western world (very common)
- mostly asymptomatic so need regular surveillance if over 3.4cm 45% malignant change
- classified based on architecture as tubular, tubovillous or villous
- villous adenoma (rare) -> hypoproteinaemic hypokalaemia because they leak large amounts of protein and K
- large size is most important risk factor for malignancy, in addition to degree of dysplasia and increased villous component
- adenoma -> carcinoma progression ‘classical chromosomal instability sequence:
a. normal colon -> at risk mucosa after “first hit” mutation in 1st copy of APC gene
b. at risk -> adenoma after “second hit” mutation to remaining APC gene
c. progression to carcinoma follows activation of KRAS, LOF mutations of p53
hamartomatous polyp (non-neoplastic)
- found sporadically in some genetic/acquired syndromes
- juvenile polyps are focal malformations of mucosa and lamina propria, vast majority in those <5yrs old, mostly in rectum -> bleeding
- usually solitary, but up to 100 found in juvenile polyposis (AD) that may require colectomy to stop haemorrhage
- also seen in Peutz-Jeghers syndrome (AD-LKB1) = multiple polyps, mucocutaneous hyperpigmentation, freckles around mouth, palms and soles
- have increased risk of intussusception and of malignancy -> regular surveillance of GI tract, pelvis and gonads
Duke’s staging for colorectal cancer
A: confined to mucosa
- 5yr survival > 95%
B1: extending into muscularis propria
- 5yr survival 67%
B2: transmural invasion, no LN involved
- 5yr survival 54%
C1: extending to muscularis propria, with LN metastases
- 5yr survival 43%
C2: transmural invasion, with LN metastases
- 5yr survival 23%
D: distant metastases
- 5yr survival <10%
management of colorectal cancer
surgery
rectal cancer/low sigmoid cancer:
- <1-2cm above anal sphincter (lower third of rectum) -> abdomino-perineal resection
- >1-2cm above anal sphincter -> anterior resection
sigmoid cancer -> sigmoid colectomy
descending colon and distal transverse -> left hemicolectomy
caecum, ascending colon and proximal transverse -> right hemicolectomy
transverse colon -> extended right hemicolectomy
radiotherapy: post-op to decrease local recurrence
chemotherapy in palliation: 5-FU (fluorouracil)
familial adenomatous polyposis (FAP)
- 70% AD mutation in APC tumour suppressor gene (C5q1), 30% AR mutation in DNA mismatch repair genes
- present 10-15yrs -> 100 adenomatous polyps required for diagnosis, usually 100-1000s seen. ALL will -> adenocarcinoma if left untreated by 30yrs therefore most have prophylactic colectomy
- increased risk of neoplasia elsewhere e.g.: ampulla of Vater and stomach
what is Gardners syndrome?
subtype of FAP with extraintestinal features e.g., osteoma of the skull, dental caries
hereditary non-polyposis colorectal cancer/Lynch syndrome (HNPCC)
- AD mutations in DNA mismatch repair genes
- carcinomas usually in right colon, few polyps but fast progression to malignancy therefore present usually <50yrs
- associated with extra-colonic cancers also: endometrial, ovarian, small bowel, transitional cell and stomach carcinoma
these patients will need regular monitoring and likely a total colectomy eventually
metabolic syndrome
collection of conditions that increase risk of IHD
- fasting hyperglycaemia > 6mmol/l
- BP > 140/90
- central obesity (>94cm in M, >80cm F)
- dyslipidaemia: decreased HDL cholesterol <1mmol/l & increased TGs>2mmol/l
- microalbuminaemia
thesholds to diagnose DM
fasting plasma glucose > 7mmol/L or random plasma glucose > 11.1 mmol/L or HbA1c > 48 mmol/L
complications of diabetes
macrovascular
- cardiac - IHD
- PVD - claudication, change in colour/temp, poor healing ulcers
- cerebral - CVA
microvascular
- glomerulonephritis - renal
- ulcers - peripheral neuropathy
- ocular - diabetic retinopathy
causes of acute pancreatitis
‘I GET SMASHED’
- I - idiopathic
- G - gallstones
- E - ethanol
- T - trauma
- S - steroids
- M - mumps
- A - autoimmune
- S - scorpion venom
- H - hyperlipidaemia
- E - ERCP
- D - drugs e.g., thiazides
acute pancreatitis presentation
severe epigastric (or central) pain radiating to back, relieved by sitting forward, vomiting prominent
NB: amylase only transiently increased. serum lipase is more sensitive
can result in formation of pseudocyst (a pathological collection of fluid), associated with alcoholic pancreatitis or abscess
histology - coagulative necrosis
patterns of damage:
- periductal: necrosis of acinar cells near ducts, obstructive causes
- perilobular - necroses of edges of lobules, ischaemic causes
- panlobular - combination o f both
other complications can include shock, hypoglycaemia and hypocalcaemia as digestive enzymes react with visceral fat causing precipitation of calcium soaps (fat necrosis)
chronic pancreatitis - causes, presentation, histology
causes:
- alcoholism (most common), cystic fibrosis, hereditary, pancreatic duct obstruction e.g., stones/tumour, autoimmune (IgG4 produced by plasma cells)
presentation:
- epigastric pain radiating to back, malabsorption (weight loss and steatorrhoea) and secondary DM (malabsorption due to lack of enzymes to digest food)
histology:
- very similar to Ca pancreas
- fibrosis and loss of exocrine tissue parenchyma, duct dilatation with thick secretions, calcification
complications:
- pseudocysts, diabetes, pancreatic cancer
risk factors for gallstones
- increasing age
- F>M
- OCP
- disorders of bile metabolism
most common pancreatic malignancy
ductal adenocarcinoma of the pancreas
ductal adenocarcinoma of the pancreas - site, RFs, clinical features, Ix, Mx
site:
- head of pancreas
RFs:
- smoking, diet, genetics e.g., FAP, HNPCC
clinical features:
- weight loss (cachexia) and anorexia
- upper abdo and back pain (chronic, persistent and severe)
- jaundice (painless), pruritis, steatorrhoea
- DM
- trousseau’s syndrome (25%) - recurrent superficial thrombophlebitis
- ascites
- abdominal mass
- Virchow’s node
- Courvoisier’s sign
Ix:
- bloods: low Hb, raised BR, raised Ca
- CT/MRI/ERCP
- CA19.9 > 70Iu/mL
Mx:
- palliative chemo (5-FU)
- surgery (15% of cases): Whipple’s procedure - surgical resection
- prognosis v poor: 5yr survival rate < 5%
multiple endocrine neoplasia (MEN)
a group of genetic syndromes where there are functioning hormone-producing tumours in multiple organs e.g.,
- MEN 1= ‘PPP’, parathyroid hyperplasia/adenoma, Pancreatic endocrine tumour (often phaeochromocytoma), pituitary adenoma
- MEN 2A = parathyroid, thyroid, phaeochromocytoma
- MEN 2B = medullary thyroid, phaeochromocytoma, acoustic neuroma, marfanoid phenotype
pancreas - acinar cell carcinoma
rare, older adults
presentation:
- non-specific symptoms, abdo pain, weight loss, nausea & diarrhoea
- about 10% get multifocal fat necrosis and polyarthralgia due to lipase secretion
histopathology:
- neoplastic epithelial cells with eosinophilic granular cytoplasm
- positive immunoreactivity for lipase, trypsin and chymotrypsin
prognosis:
- median survival is 18 months from diagnosis
- 5yr survival <10%
pancreatic malformations
ectopic pancreas - esp. stomach, small intestine
pancreas divisum - failure of fusion of dorsal and ventral buds, increased risk of pancreatitis
annular pancreas - can present with duodenal obstruction approx. 1yo
3 zones of liver cells
zone 1 (closest to the portal triad)
- periportal hepatocytes receive more oxygen and affected first in viral hepatitis
zone 2
- mid zone
zone 3 (close to terminal hepatic vein)
- perivenular hepatocytes are the most mature and metabolically active. zone 3 has most liver enzymes and so most sensitive to metabolic toxins and ischaemia
functions of the liver
- metabolism
- involved in glycolysis, glycogen storage, glucose synthesis, amino acid synthesis, fatty acid synthesis and lipoprotein metabolism
- drug metabolism - protein synthesis
- makes all circulating proteins (except gamma globulins) including albumin, fibrinogen and coagulation factors - storage
- glycogen, vitamins A, D and B12 in large amounts, small amounts of vitamin K, folate, iron and copper - hormone metabolism
- activates vitamin D
- conjugation and excretion of steroid hormones (oestrogen/glucocorticoids)
- peptide hormone metabolism (insulin, GH, PTH) - bile synthesis
- 600-1000ml daily - immune function
- antigens from gut reach liver via portal circulation
- phagocytosis by Kupffer cells
histopathology of acute hepatitis
spotty necrosis (small foci of inflammation and infiltrates)
histopathology of chronic hepatitis
- portal inflammation
- interface hepatitis (piecemeal necrosis) - cannot see the border between the portal tract and parenchyma
- lobular inflammation
- bridge formed from the portal vein to central vein (critical stage in the evolution of hepatitis to cirrhosis). this causes blood to bypass hepatocytes and reduced function of liver (intrahepatic shunting) - loss of liver detoxification and development of hepatic encephalopathy
histopathology of a cirrhotic liver
- hepatocyte necrosis
- fibrosis
- nodules of regenerating hepatocytes
- disturbance of vascular architecture
consequences of fibrosis in the liver (cirrhosis)
loss of functional tissue
- reduced detoxification: encephalopathy
- decreased synthesis: bleeding, hypogonadism, osteodystrophy, ascites
increased resistance:
- portal hypertension: oesophageal varices, caput medusae, anorectal varices
major causes of cirrhosis
- alcoholic liver disease
- non-alcoholic fatty liver disease
- chronic viral hepatitis (hep B/C/D)
- autoimmune hepatitis
- biliary causes: primary biliary cirrhosis & primary sclerosing cholangitis
- genetic causes:
a. haemochromatosis - HFE gene Chr 6
b. Wilson’s disease - ATP7B Chr 13
c. alpha 1 antitrypsin deficiency (A1AT)
d. galactosaemia
e. glycogen storage disease - drugs e.g., methotrexate
micronodular vs macronodular liver cirrhosis
micronodular (nodules < 3mm) - uniform liver involvement
- caused by: alcoholic hepatitis, biliary tract disease
macronodular (nodules > 3mm) - variable nodule size:
- caused by: viral hepatitis, Wilson’s disease, alpha1 antitrypsin deficiency
modified Child’s Pugh Score (ABCDE)
indicates prognosis in liver cirrhosis and takes into account albumin, bilirubin, prothrombin times, presence of ascites and encephalopathy
- total score <7 = Child’s Pugh A (45% 5yr survival)
- total score 7-9 = Child’s Pugh B (20% 5yr survival)
- total score 10+ = Child Pugh C (<20% 5yr survival)
hepatic steatosis (fatty liver) - macroscopic, microscopic characteristics
macroscopic:
- larger, pale, yellow and greasy liver
microscopic:
- accumulation of fat droplets in hepatocytes (=steatosis)
- chronic exposure -> fibrosis (late stage)
- fully reversible if alcohol avoided
alcoholic hepatitis - macroscopic, microscopic features
macroscopic:
- large, fibrotic liver
microscopic:
- hepatocyte ballooning (they get bigger like balloons) and necrosis due to accumulation of fat, water and proteins
- Mallory Denk Bodies (clumped cytoskeleton)
- fibrosis
- seen acutely after night of heavy drinking. ranges from asymptomatic to fulminant liver failure. each episode has 10-20% mortality
alcoholic cirrhosis - macroscopic, microscopic features
macroscopic:
- yellow-tan, fatty, enlarged
- transforms into shrunken, non-fatty, brown organ
microscopic:
- micronodular cirrhosis. i.e.g, small nodules + bands of fibrous tissue
non-alcoholic fatty liver disease (NAFLD)
- = hepatic steatosis in non-alcoholics. histologically looks very similar to alcoholic hepatitis
- most common cause of chronic liver disease in West
- mainly in obese individuals with hyperlipidaemia/metabolic syndrome. diabetes is also a risk factor
- NAFLD includes:
a. simple steatosis: fatty infiltration, relatively benign
b. non-alcoholic steatohepatitis (NASH): - steatosis + hepatitis (fatty infiltration + inflammation)
- can progress to cirrhosis
autoimmune hepatitis
- common with other autoimmune diseases e.g, coeliac, SLE, RA, thyroiditis, Sjogren’s, IC
- 78% female - young and postmenopausal
- associated with HLA-DR3
- cells present in histology are plasma cells
- type 1: ANA (antinuclear Ig), anti-Sm (anti-smooth muscle Ig), anti-actin Ig, anti-soluble liver antigen Ig
- type 2: anti-LKM Ig (anti liver-kidney-microsomal Ig)
- treatment: immune suppression with steroids until transplant, BUT disease returns it up to 40%
primary biliary cholangitis (PBC)
- autoimmune inflammatory destruction of small/medium sized intrahepatic bile ducts -> cholestasis -> SLOW development of cirrhosis over many years
- F>M 10:1
- peak incidence at 40-50 yrs
- increased serum ALP, increased cholesterol, increased IgM, hyperbilirubinaemia (late)
- anti-mitochondrial antibodies in >90% (high yield)
- US scan shows no bile duct dilatation
- histology: bile duct loss with granulomas (high yield)
- presents with fatigue, pruritus and abdominal discomfort
- secondary symptoms inc. skin pigmentation, xanthelasma, steatorrhoea, vit D malabsorption, inflammatory arthropathy
- can treat with ursodeoxycholic acid in early phase -> remission in 25%
primary sclerosing cholangitis (PSC)
- inflammation and obliterative fibrosis of extrahepatic and intrahepatic bile ducts -> multi-focal stricture formation with dilation of preserved segments
- M>F
- peak incidence at 40-50 yrs
- associated with IBD (esp UC)
- increased serum ALP, several associated auto-Ig, particularly p-ANCA
- US scan: bile duct dilatation
- ERCP: shows beading of bile ducts
- strictures along the bile duct look like necklace beads on ERCP
- histology: onion skinning fibrosis - concentric fibrosis (high yield)
- increased incidence of cholangiocarcinoma
name 3 genetic causes of cirrhosis
- haemochromatosis
- wilson’s
- alpha 1 antitrypsin deficiency
haemochromatosis - age, pathophysiology, histology, signs/symptoms, investigations, treatment
age:
- 40-50 yrs
pathophysiology:
- autosomal recessive
- mutated HFE gene at 6p21.3 -> increased Fe gut absorption which deposits in liver, heart, pancreas, adrenals, pituitary, joints, skin -> fibrosis
histology:
- Fe deposits in liver - stains with Prussian blue stain
signs/symptoms:
- skin bronzing (melanin deposition)
- diabetes
- hepatomegaly with micronodular cirrhosis
- cardiomyopathy
- hypogonadism
- pseudogout
investigations:
- increased Fe & ferritin
- transferrin saturation > 45%
- low TIBC
treatment:
- venesection
- desferrioxamine
- 30% with cirrhosis -> HCC
wilson’s disease - age, pathophysiology, histology, signs/symptoms, investigations, treatment
age:
- 11-14 yrs
pathophysiology:
- autosomal recessive
- mutated gene ATP7B: encodes copper transporting ATPase expressed on canalicular membrane therefore -> reduced biliary Cu excretion and depositions in liver, CNS, iris
histology:
- copper stains with rhodanine stain
- mallory bodies and fibrosis on microscopy
signs/symptoms:
- liver disease: acute hepatitis, fulminant liver failure or cirrhosis
- neuro disease: parkinsonism, psychosis, dementia (basal ganglia involvement)
- Kayser Fleisher rings: copper deposits in Descemet’s membrane in cornea
investigations:
- low serum caeruloplasmin
- low serum copper
- increased urinary copper
treatment:
- lifelong penicillamine
- good prognosis with early treatment but any neuro damage is permanent and may require liver transplant
alpha 1 antitrypsin deficiency
pathophysiology:
- autosomal dominant
- failure to secrete A1AT in blood -> A1AT accumulates in hepatocytes -> intracytoplasmic inclusions -> hepatitis
- lack of A1AT in lungs -> emphysema
histology:
- intracytoplasmic globules of A1AT which stain with Periodic acid Schiff
signs/symptoms:
- Kids: neonatal jaundice
- Adults: emphysema and chronic liver disease
investigations:
- low serum A1AT
- absent alpha-globulin band on electrophoresis
benign liver tumours
hepatic adenoma
- associated with OCP
- present with abdo pain/intraperitoneal bleeding
- resection if symptomatic, >5cm or if no shrinkage when stopping OCP
haemangioma:
- most common benign lesion
- no Rx
malignant liver tumours
- hepatocellular carcinoma
- cholangiocarcinoma
- haemangiosarcoma
- hepatoblastoma
- secondary tumours
liver: hepatocellular carcinoma
causes: most commonly occurs in patients with chronic liver disease - closely linked with viral hepatitis, alcoholic cirrhosis, haemochromatosis, NAFLD, alfatoxin-B1, androgenic steroids
screening in cirrhotic patients with 6 monthly USS
inv: alpha fetoprotein, USS
liver: cholangiocarcinoma
- adenocarcinomas arising from bile ducts
- 10% of liver tumours
- can be intra or extrahepatic
- poor prognosis
- 90% associated with gallstones
causes: primary sclerosing cholangitis, parasitic liver disease, chronic liver disease, congenital liver abnormalities, Lynch syndrome type II
haemangiosarcoma - liver
= cancer of the vascular epithelium
highly invasive
hepatoblastoma
occurs in children/infants - presents with abdominal mass
originates from immature liver precursor cells
secondary tumours - liver
- most common malignant liver lesion
- usually from GI tract, breast or bronchus
- usually multiple
main types of renal stones
calcium oxalate (75%)
- too much calcium absorption from the gut
- intrinsic renal problems - impaired calcium absorption from proximal tubule
magnesium ammonium phosphate (15%)
- triple stones
- commonly due to urease producing organisms which alkanise urine promoting precipitation of magnesium ammonium phosphate salts
- often form ‘staghorn calculi’ - very large and painful
uric acid (5%)
- in patients with hyperuricaemia (gout/rapid cell turnover)
management of renal stones
- small stones may pass spontaneously
- large stones may be removed by endoscopic or percutaneous methods or using lithotripsy
benign prostatic hyperplasia (BPH)
- dihydrotestosterone-mediated hyperplasia of prostatic stromal and epithelial cells, resulting in formation of large nodules
- nodule formation compresses prostatic urethra leading to outflow tract obstruction
- symptoms: difficulty urinating, retention, frequency, nocturia, overflow dribbling
- histology: nodule formation, prostatic epithelial ducts with duct spaces
- management: TURP, 5alpha-reductase inhibitors, alpha blocker (tamsulosin, aware of BP effects)
prostate cancer
- adenocarcinoma is the commonest form in men over 50y
- arises from precursor lesion PIN (prostatic intraepithelial neoplasia)
- risk factors: age, race, family history, and hormonal and environmental influences
- classically arises in peripheral zone of gland and neoplastic tissue is firm
- local spread to the bladder and haematogenous spread to bone (pathological fractures)
- grading: gleason system, based on degree of differentiation and glandular patterns
- diagnosis: history, examination, PSA (over 4ng/ml is indicative)
prostate cancer - Gleason scoring
- 1-5 based on differentiation (5 is worst - least differentiated and most aggressive)
- take a biopsy and classify the most common pattern seen and the worst pattern seen
- add these 2 numbers together to get a result out of 10
- expressed as X+Y=Z
testicular tumours
most arise from a precursor lesion - intratubular germ cell neoplasia
- seminoma - most common type of germinal tumour. peak age: 30s. radiosensitive
- teratoma - occur at any age from infancy to adult life. regarded as malignant when occurs in the post-pubertal male. chemo sensitive. biologic markers for germ cell tumours: AFP, HCG and LDH
- embryonal carcinoma - resembles embryonic tissue
- yolk sac tumour
- choriocarcinoma
germ cell testicular tumour types
- seminoma
- spermatocytic seminoma
- embryonal carcinoma
- yolk sac tumour
- choriocarcinoma
- teratoma
non germ cell testicular tumour
- leydig cell tumour (derived from stroma)
- sertoli cell tumour (derived from sex cord)
testicular tumours management
- orchidectomy +/- lymph node dissection
- for grade I (locally invasive) and above - Bleomycin, Eoposide and cisPlatin (BEP)
- good prognosis even with metastatic disease (90% 5-year survival)
benign renal tumours
papillary adenoma
- renal epithelial tumour with a papillary architecture
- often incidental
- <15mm
- histology: bland epithelial cells growing in a papillary or tubopapilliary pattern
- well circumscribed cortical nodules
oncocytoma
- oncocytic renal epithelial neoplasm
- often incidental
- macroscopic - mahogany brown
- microscopic - sheets of oncolytic cells, pink cytoplasm, form nests of cells
angiomyolipoma
- mesenchymal tumour composed of fat, bloods, vessels and muscle
- histology: fat spaces, thick blood vessels and spindle cell components
malignant renal tumours
- renal cell carcinoma
- nephroblastoma/wilm’s tumour
- transitional cell carcinoma
renal cell carcinoma
most common - epithelial tumour
RFs - smoking, HTN, obesity, long-term dialysis, genetics (Von Hippel Lindau syndrome)
presents with painless haematuria
clear cell (70%)
- macroscopic - golden yellow with haemorrhagic areas
- microscopic - nests of epithelium with clear cytoplasm
papillary (15%)
- macroscopic - fragile, friable brown tumour
- microscopic - papillary/tubopapillary growth pattern >15mm
chromophobe (5%)
- macroscopic - well circumscribed, solid brown tumour
- microscopic - sheets of large cells, distinct cell borders
nephroblastoma / wilm’s tumour
childhood renal neoplasm, presenting as abdominal mass
2nd most common childhood malignancy
microscopic:
1. small round blue cells (very undifferentiated)
2. epithelial component - cells trying to differentiate and form primitive renal tubules
transitional cell carcinoma (renal tumour)
epithelial neoplasm arising from the urothelial tract (anywhere from renal pelvis, ureter, bladder, urethra)
most commonly in the bladder and associated with smoking.
most present with painless haematuria.
- non-invasive papillary urothelial carcinoma
- frond like growths projecting from bladder wall, often multifocal
- microscopic - papillary fronds lined by urothelium
- can either be low grade or high grade (higher risk of progression to invasive)
- invasive urothelial carcinoma. tumour with invasive behaviour. usually grow as solid masses, fixed to tissue
bladder tumours
transitional cell (urothelial) tumours
- 90% of all bladder tumours
- male:female = 3:1
- 80% occur between 50-80 yrs
squamous cell carcinoma
- more frequent in countries with endemic urinary schistosomiasis
adenocarcinoma
- rare, arising from extensive intestinal metaplasia or from urachal remnant
diseases affecting the glomerulus of the kidney
nephrotic syndrome:
primary
- minimal change disease
- membranous glomerular disease
- focal segmental glomerulosclerosis
secondary
- e.g., diabetes, amyloidosis, SLE
nephritic syndrome:
- acute post-infectious (aka Post-streptococcal)
- IgA nephropathy (aka Berger disease)
- rapidly progressive glomerulonephritis
- Alport’s syndrome (aka hereditary nephritis)
- thin basement membrane disease (aka Benign familial haeematuria)
