Histopathology Flashcards
Which cells are associated with acute inflammation?
Neutrophils
Which cells are associated with chronic inflammation?
Lymphocytes and plasma cells
Which cells are associated with allergic reactions, parasitic infections and tumours?
Eosinophils
Which cells are associated with urticarial/allergic reactions?
Mast cells
Which cells are associated with late acute inflammation and chronic inflammation?
Macrophages
Which condition would you find a high neutrophil count?
Acute inflammation e.g. appendicitis
Which conditions would you find high lymphocytic or plasma cell count?
Ulcerative colitis
Lymphoma
Which conditions would you find high eosinophilic count?
Hodgkin’s disease
Eosinophilic Oesophagitis
Which cell would you find high quantities of in a granuloma?
Macrophages
Which stain would you use to see if there is a granuloma?
Ziehl-Neelson stain
What are the two functions of squamous epithelial tissue?
Intercellular bridges
Keratin production
What are the two functions of adenomatous tissue?
Mucin production
Glands
How would you be able to tell that there is a squamous cell carcinoma?
Huge parts of collagen in the middle of cell
Irregular nucleus
Which stain would you use for glandular tissue/adenocarcinomas?
Mucin stain
Which stain would you use to see if there is a melanoma present?
Fontana stain
Which histochemical stain would you use to test for haemochromatosis?
Prussian blue iron stain
Which stain would you use to test for amyloidosis?
Congo red stain
Apple green birefringence
What type of immunohistochemical test can you do to differentiate between types of tumour?
Immunoperoxidase
What is cytokeratin a marker of?
Epithelial marker
What is CD45 a marker of?
Lymphoid marker
What would you find after immunohistochemical tests in a large bowel cancer patient?
CD20+
CK7-
What type of endothelium do you find in the sinusoids in the liver?
Discontinued
What are the causes of high bilirubin?
Pre-hepatic - haemolysis
Hepatic disease
Post-hepatic - obstructive jaundice
What is the Van de Bergh test?
Direct reaction - measures conjugated bilirubin
Indirect reaction - measures unconjugated bilirubin
Why might paediatric jaundice be normal?
Only normal if unconjugated is raised since it may be due to liver immaturity coupled with fall in haemoglobin
What is the mode of inheritance of Gilberts syndrome?
Recessive - 50% carry genes
What is the percentage of people who have Gilberts disease?
5-6% of the population
1 in 20
What is the pathophysiology of Gilberts?
UDP glucuronyl transferase activity is reduced to 30% - unconjugated bilirubin tightly albumin bound and does not enter urine
What are the best tests for liver function?
- Albumin
- Clotting factors (PT, PTTK)
- Bilirubin
What are the normal values for ALP, AST, ALT and bilirubin?
Bilirubin - Normal results for a total bilirubin test are 1.2 milligrams per deciliter (mg/dL) for adults and usually 1 mg/dL for those under 18. Normal results for direct bilirubin are generally 0.3 mg/dL.
ALP<130
AST<50
ALT<50
What does raised AST and ALT suggest?
Hepatocyte damage
What does raised ALP suggest?
Obstructive jaundice
What are the different differential diagnoses for abnormal LFTs?
Pre-hepatic - Gilberts, haemolysis
Hepatic - viral, autoimmune, alcoholic, cirrhosis
Post-hepatic - gallstones, pancreatic cancer
What is the serology progression in someone with hepatitis A?
- Virus in faeces - 2-6 weeks
- IgM - 3.5-13 weeks
- IgG - 5 weeks
When would someone with hepatitis A get jaundice?
Weeks 4-7
What is the serology progression in someone with hepatitis B?
HBs Ag
HBe Ag
Anti-HBe
Anti-HBs - vaccinated
If both anti-HBe and anti-HBs = present infection
What are some of the histological features of alcoholic hepatitis?
Liver cell damage: ballooning degeneration, Mallory-Denk bodies
Inflammation
Fibrosis
How is alcoholic hepatitis treated?
- Supportive
- Stop alcohol
- Nutrition
- Vitamins
- Occasionally steroids
Which deficiency is caused by B1 deficiency?
Beri-Beri
What are these all signs of?
- Multiple spider naevi
- Dupuytren’s contracture
- Palmar erythema
- Gynaecomastia
Chronic stable liver disease
What are the clinical signs of portal hypertension?
Visible veins
Splenomegaly
Ascites
What is portal hypertension caused by?
Cirrhosis
What are some porto systemic anastomoses?
- Oesophageal varices
- Rectal varices
- Umbilical vein recanalising
- Spleno-renal shunt
What is Courvoisier’s law?
Courvoisier’s law; if gallbladder is palpable in a jaundiced patient, it is unlikely to be due to gallstones, because stones would have given rise to chronic inflammation and subsequently fibrosis of gallbladder therefore, rendering it incapable of dilatation.
How much does the liver weigh?
1500g
Which vessels compose the liver’s dual blood supply?
- Hepatic portal vein
2. Hepatic artery
Which cells is the liver made up of?
- Hepatocytes
- Bile ducts
- Blood vessels
- Endothelial cells
- Kupffer cells
- Stellate cells
What are differences between normal liver cells and damaged liver cells?
- Loss of microvilli
- Stellate cells are activated –> become myofibroblasts and make collagen –> invade endothelium
- Kupffer cells get activated
What are the defining features of cirrhosis?
- Whole liver involved
- Fibrosis
- Nodules of regenerating hepatocytes
- Distortion of liver vascular architecture:
intra- and extra- hepatic (e.g. gastro- oesophageal) shunting of blood
How is cirrhosis classified?
a) According to nodule size:
Micronodular or macronodular
b) According to aetiology:
1) Alcohol / insulin resistance
2) Viral hepatitis etc.
What are the complications of cirrhosis?
- Portal hypertension
- Hepatic encephalopathy
- Liver cell cancer
How is acute hepatitis recognised on histology?
Spotty necrosis
What are the causes of chronic hepatitis?
- Viral hepatitis
- Drugs
- Auto-immune
How is chronic hepatitis graded?
MUST be greater than 6 months
Severity of inflammation = Grade (portal tract inflammation, interface hepatitis, lobular inflammation)
Severity of fibrosis = Stage (collagen is blue in stain –> intrahepatic shunting of blood)
What happens to the blood if there is an intrahepatic or extra hepatic shunt?
Intrahepatic shunt: blood goes to liver, but is unfiltered and toxic blood when it returns to heart
Extrahepatic shunt: blood bypasses liver and goes straight to heart as unfiltered and toxic blood
What are the causes of acute hepatitis?
- Viruses (e.g. A and E)
2. Drugs
What are the 3 forms of alcoholic liver disease?
1) Fatty liver
2) Alcoholic hepatitis
3) Cirrhosis
Is fatty liver reversible?
Yes
Why is alcoholic hepatitis chronic?
- Ballooning ( +/- Mallory Denk Bodies)
- Apoptosis
- Pericellular fibrosis
- Mainly seen in Zone 3
What are the 3 zones of the liver
Three zones can be distinguished:
1) Periportal zone
2) Intermediary zone
3) Perivenous, pericentral, or centrilobular zone.
What is non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH)?
- 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
What is primary biliary cholangitis?
- Previously primary biliary cirrhosis
- F> M
- Bile duct loss associated with chronic inflammation (with granulomas)
- Diagnostic test is detection of anti-mitochondrial antibodies
What is primary sclerosing cholangitis?
- M>F
- Periductal bile duct fibrosis leading to loss
- Associated with ulcerative colitis
- Increased risk of cholangiocarcinoma
- Diagnostic test is bile duct imaging
What is haemochromatosis?
- Genetically determined increased gut iron absorption
- Gene on chromosome 6 (HFe)
- Parenchymal damage to organs secondary to iron deposition (bronzed diabetes)
What is meant by haemosiderosis?
The accumulation of iron in macrophages which may be due to multiple blood transfusions
What is Wilson’s disease?
- 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) including Kayser- Fleishcer rings
What stain would you use to see copper build up in Wilson’s disease?
Rhodanine stain for copper
What is autoimmune hepatitis?
- F>M
- Active chronic hepatitis with plasma cells
- Anti-smooth muscle actin antibodies in the serum
- Responds to steroids
What is alpha-one anti-trypsin deficiency?
- Failure to secrete alpha-one antitrypsin
- Intra-cytoplasmic inclusions due to misfolded protein
- Hepatitis and cirrhosis
What percentage of liver injury is drug-related?
10% of drug reactions involve the liver
May be dose-related or idiosyncratic
What are specific and general causes of hepatic granulomas?
Specific causes:
• PBC
• drugs
General causes
• TB
• Sarcoid etc
What are examples of benign liver tumours?
1) Liver cell adenoma
2) Bile duct adenoma
3) Haemangioma
What are 4 types of primary malignant liver tumours?
- hepatocellular carcinoma
- hepatoblastoma
- cholangiocarcinoma
- haemangiosarcoma
What is cholangiocarcinoma?
Associated with:
• PSC
• Worm infections
• Cirrhosis
Can arise from:
• intrahepatic ducts
• extrahepatic ducts (including gall bladder)
What are the skin layers composed of?
Epidermis
Dermis
Subcutaneous tissue (fat)
How does skin on the palms and soles of your hand differ from the rest of your body?
Thicker keratin layer
How does face skin differ to other skin in the body?
- More sebaceous glands
- More hair follicles
How does skin change with age?
- Epidermis thinner
- Quality of elastic fibres and collagen bundles is decreased
List 6 different inflammatory skin conditions
- Vesiculobullous
- Spongiotic
- Psoriasiform
- Lichenoid
- Vasculitic
- Granulomatous
What is bullous pemphigoid?
Forms tense bullae particularly in flexural surfaces particularly in the elderly.
Dermo-epidermal junction affected
What is the pathophysiology of bullous pemphigoid?
IgG and C3 attack the basement membrane
Detected by immunofluorescence
IgG anti-hemidesmosome
Eosinophils recruited to release elastase
Elastase damages the anchoring proteins
Fluid fills up gap between BM and epithelium
What is pemphigus vulgaris?
Flaccid blisters, rupture easily
Epiderma-epidermal junction affected (within epidermis)
What is the pathophysiology of pemphigoid vulgaris?
IgG attacks between the keratin layers (acantholysis)
I.E. Loss of intracellular connections (desmosomes)
Common for many conditions;
Nikolsky’s sign positive
Need immunofluorescence to confirm
What is pemphigus foliaceus mediated by?
Top layer is very thin so never blisters
IgG-mediated – outer layer of stratum corneum shears off
Diagnose with immunofluorescence
What is discoid eczema caused by?
A common type of eczema/dermatitis defined by scattered, well-defined, coin-shaped and coin-sized plaques of eczema. Causes involve elements of barrier dysfunction, alterations in cell mediated immune responses, IgE mediated hypersensitivity, and environmental factors.
Flexor surfaces
Very itchy; plaques form
What are the 7 most important layers of skin?
Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale Dermis Hypodermis
What is contact dermatitis?
Itchy; latex and nickel
Itchy –> hyperparakeratosis (thickening)
Epidermis gets thicker –> lichenification
What is the pathophysiology of contact dermatitis?
Epidermis gets thicker
Eczema is spongiotic because there is oedema in between the keratinocytes
T cell mediated and eosinophils are recruited
A differential for an eczematous reaction pattern is a drug reaction
What is plaque psoriasis?
Psoriasiform reaction pattern; extensor surfaces Silver plaques (similar to discoid eczema)
What is the pathophysiology of plaque psoriasis?
Normal keratinocyte turnover time = 56 days
Psoriasis keratinocyte turnover time = 7 days
Rapid turnover –> epidermis thicker
A layer of parakeratosis forms at the top
Stratum granulosum disappears as not enough time to form it; and dilated vessels form
Munro’s microabscesses form, made up from recruitment of neutrophils
What is lichen planus (lichenoid)?
T-cell mediated; itchy
Papules and plaques of purplish-red colour on the wrists and arms
In mouth it presents as white lines (Wickham striae)
What is the pathophysiology of lichen planus (lichenoid)?
T-lymphocytes have destroyed bottom keratinocytes
Creates band-like inflammation
Cannot see where dermis finished, and epidermis starts
What is pyoderma gangrenosum?
Vasculitis (not actually gangrenous)
Presents as non-healing ulcer
Often, first manifestation of a systemic disease
E.G. colitis, hepatitis, leukaemia
What is seborrhoeic keratosis?
“Cauliflower”, pigmented, gets caught on clothing (and taken off)
Stuck-on appearance, harmless and benign
Lots of growth and ordered proliferation
Ordered and benign growth
“Horn cysts” – epidermis entrapping keratin
What is a sebaceous cyst?
Transluminates, central punctum, circumscribed, hot
Squamous cell lining surrounding the cyst
What is basal cell carcinoma?
Rolled, pearly-edge, central ulcer, telangiectasia
“Rodent ulcer” as it burrows away
Benign but can disfigure
Occurs in sun-exposed areas
Dysplastic change
Cancer from keratinocytes at bottom of epidermis
Cannot break through the BM –> cannot metastasise
What is Bowen’s disease?
Squamous cell carcinoma in situ [i.e. pre-cancerous]
Keratinocytes become more pleiomorphic and larger with mitotic figures
Bowen’s disease name changes depending on location (i.e. anal vs. cervix)
Dysplasia can be 1, 2 or 3 (low, moderate or high grade)
What is squamous cell carcinoma?
Subdivided into level of differentiation:
Poorly to well differentiated
Poorly differentiated means you cannot determine origin cell lineage
Peri-neural invasion can occur (i.e. local invasion)
What are cafe-au-lait spots?
A form of melanocytic naevus
What are the 4 types of benign lesions and their descriptions?
1) Cafe-au-lait spots
2) Junctional nevus = melanocytes nest in the epidermis
Flat and coloured
Normally, melanocytes sit in the basal layer of the epidermis
Melanocytes can, however, physiologically exist in the dermis
As you age, melanocytes usually drop into the dermis
3) Compound nevus = nests in epidermis and dermis
Raised area
Surround by flat pigmented area
4) Intradermal naevus = nests in the dermis
Raised area
Skin-coloured or pigmented
What are the characteristics of malignant melanoma?
Irregular border
Variable pigmentation
Bleeding
Itchy
Growing
What is the pathophysiology of malignant melanoma?
The junctional melanocytes are not normally maturing and dropping out of the dermis – they are moving up through the dermis instead = “Pagetoid spread” this is NOT normal
Melanocytes also display mitotic figures (abnormal unless in pregnancy)
What is Breslow depth?
Melanoma is staged by “Breslow Thickness”
A melanoma with a thickness >4 mm, it has a very high mortality (> 50%)
Describe the staging system ‘Breslow Depth’ in detail
Stage I - through skin to epidermis - <1mm
Stage II - through skin, to epidermis and a bit of dermis - <1-2mm
Stage III - through skin, epidermis, more of dermis - <2-4mm
Stage IIII - through skin, epidermis, dermis and reaches SC fat - over 4mm
What is the A-G assessment of a skin lesion?
Asymmetry Border Colour Diameter Elevation Firm Growing
What are the functions of type I and II pneumocytes?
Type I:
Facilitate gas exchange
Maintain ion and fluid balance within the alveoli
Communicate with type II pneumocytes to secrete surfactant in response to stretch.
Type II:
Produce and secrete pulmonary surfactant - surfactant is a vital substance that reduces surface tension, preventing alveoli from collapsing.
Expression of immunomodulatory proteins that are necessary for host defense
Transepithelial movement of water
Regeneration of alveolar epithelium after injury
What is asthma?
A condition in which breathing periodically rendered difficult by widespread narrowing of the airways that changes in severity over short periods of time.
Severe attacks = status asthmaticus
What are the causes and associations of asthma?
Allergens and atopy Pollution Drugs - NSAIDs Occupational–inhaled gases/fumes Diet Physical exertion–“cold” Intrinsic Underlying genetic factors
Describe the immediate and late phase of asthma pathogenesis?
IMMEDIATE:
Mast cells degranulate on contact with antigen
Mediators released cause vascular permeability, eosinophil and mast cell recruitment, and bronchospasm
LATE:
Tissue damage
Increased mucus production
Muscle hypertrophy
What are some macroscopic features of asthma?
Mucus plug
Overinflated lung
Mucus plug in-situ
What would you see on histological analysis of asthmatic patients?
- Hyperaemia
- Hypertrophic constricted muscle
- Eosinophilic inflammation and goblet cell hyperplasia - mucus
What is COPD?
– Chronic cough productive of sputum
– Most days for at least 3 months over at least 2 consecutive years
What are the common causes of COPD?
- Smoking
- Air pollution
- Occupational exposures
What are the histological features of COPD?
Dilatation of airways
Goblet cell hyperplasia
Hypertrophy mucous glands
What are complications of chronic bronchitis/COPD?
- Repeated infections (most common cause of hospital admission and death)
- Chronic hypoxia and reduced exercise tolerance
- Chronic hypoxia results in pulmonary hypertension and right sided heart failure (cor pulmonale)
- Increased risk of lung cancer independent of smoking
What is bronchiectasis?
Permanent abnormal dilatation of bronchi
What are the common causes of bronchiectasis?
Congenital
Inflammatory
– Post-infectious (especially children or cystic fibrosis patients)
– Ciliary dyskinesia 1o [Kartagener’s] and 2o
– Obstruction (extrinsic/intrinsic/middle
lobe syn.)
– Post-inflammatory (aspiration)
– Secondary to bronchiolar disease (OB)
and interstitial fibrosis (CFA, sarcoidosis)
– Systemic disease (connective tissue
disorders)
– Asthma
What are complications of bronchiectasis?
- Recurrent infections
- Haemoptysis
- Pulmonary Hypertension and right sided heart failure
- Amyloidosis
What is the epidemiology of cystic fibrosis?
- Affects 1 in 2,500 live births
* Autosomal recessive (approx 1/20 of population are heterozygous carriers)
What is the pathophysiology of cystic fibrosis?
- Chr 7q3 = CFTR gene (Cystic Fibrosis Transmembrane Conductance Regulator) = ion transporter protein
- Abnormality leads to defective ion transport and therefore excessive resorption of water from secretions of exocrine glands
- Results in abnormally thick mucus secretion - affects all organ systems
What are the systemic manifestations of cystic fibrosis?
Lung –> airway obstruction, respiratory failure, recurrent infection
GI tract –> meconium ileus, malabsorption
Pancreas –> pancreatitis, secondary malabsorption
Liver –> cirrhosis
Male reproductive system –> infertility
List some common parenchymal diseases of the respiratory system
- Pulmonary oedema and diffuse alveolar damage (includes Acute respiratory distress syndrome and HMD)
- Infections
- COPD - Emphysema
- Granulomatous diseases
- Fibrosing interstitial lung disease and occupational lung disease
What is pulmonary oedema?
Accumulation of fluid in alveolar spaces as consequence of “leaky capillaries” or “back pressure” from failing left ventricle.
What are some common causes of pulmonary oedema?
– Left heart failure
– Alveolar injury
– Neurogenic
– High altitude
What is the pathogenesis of pulmonary oedema?
– Acute : heavy watery lungs, intra- alveolar fluid on histology
– Chronic: Iron laden macrophages, fibrosis
Poor gas exchange therefore hypoxia and respiratory failure
What is a histological feature of pulmonary oedema?
“Heart failure cells” – iron laden macrophages
What is diffuse alveolar damage and its pathogenesis?
Pattern of acute diffuse lung injury in which patients present with rapid onset of respiratory failure, requiring ventilation on ITU. CXR shows “white out” all lung fields
Pathogenesis : Acute damage to endothelium and/or alveolar epithelium leading to exudative inflammatory reaction.
What are examples of diffuse alveolar damage in adults and neonates?
Adults – Acute respiratory distress syndrome “shock lung”
• Numerous causes in adults:
– Infection (local or generalised sepsis), aspiration, trauma, inhaled irritant gases, shock, blood transfusion, DIC, drug overdose, pancreatitis, idiopathic.
– Common on ITU
Neonates - Hyaline membrane disease of newborn
• Insufficient surfactant production leading to stiff lungs and secondary alveolar epithelial
damage.
• Premature babies
What are some X-ray and histological features of diffuse alveolar damage?
X-ray: fluffy white infiltrates in all lung fields (“white out”)
Lungs are expanded and firm
Plum coloured, airless
Often weigh >1kg
Describe the progression of diffuse alveolar damage
1) Capillary congestion
2) Exudative phase
3) Hyaline membranes
4) Organising phase
What is the clinical outcome of diffuse alveolar damage?
- Death ~ 40% of cases
- Superimposed infection
- Resolution: lung returns to normal
- Residual fibrous scarring –> chronic impairment
What is the pattern of lung involvement in pneumonia dependent on?
Variety of patterns of lung involvement depending upon organism and other co-factors:
– Bronchopneumonia
– Lobar pneumonia
– Abscess formation
– Granulomatous inflammation
Which group is bronchopneumonia more prevalent in?
Compromised host defense - Elderly
Which organisms causes bronchopneumonia?
Often low virulence organisms - Staphylococcus, Haemophilius, Streptococcus, Pneumococcus,
Pathology - Patchy bronchial and peribronchial distribution, often lower lobes
What would you see on histology of someone with bronchopneumonia?
- Peribronchial distribution
* Acute inflammation surrounding airways and within alveoli
What is lobar pneumonia?
Acute bacterial infection of a large portion of a lobe or entire lobe.
- Infrequent with advent of antibiotics
- Widespread fibrinosuppurative consolidation
Which organism causes lobar pneumonia?
High virulence organism: 90-95% pneumococci (S. pneumoniae)
What are histological features of lobar pneumonia?
- Congestion – hyperaemia, intra-alveolar fluid
- Red hepatization - hyperaemia, intra-alveolar neutrophils
- Grey hepatization - intra-alveolar connective tissue
- Resolution - restoration normal architecture
What are the complications of infection?
- Abscess formation
- Pleuritis and pleural effusion
- Infected pleural effusion (EMPYEMA)
- Fibrous scarring
- Septicaemia
What is emphysema?
Emphysema is a permanent loss of the alveolar parenchyma distal to the terminal bronchiole
How does damage to alveolar epithelium occur in emphysema?
Damage to alveolar epithelium:
– SMOKING
– Alpha1 antitrypsin deficiency
– Rare – IVDU, connective tissue disease
What is the pathogenesis of emphysema?
Cigarette smoke –> neutrophil activation + macrophage activation –> proteases (elastase) –> tissue damage (emphysema)
Describe how alpha-1 antitrypsin deficiency cause emphysema
Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by low serum levels of alpha-1 antitrypsin (AAT). Loss of AAT disrupts the protease-antiprotease balance in the lungs, allowing proteases, specifically neutrophil elastase, to act uninhibited and destroy lung matrix and alveolar structures.
How do smoking and alpha-1 antitrypsin deficiency lead to different histological features?
Smoking - loss centred on bronchiole - CENTRILOBULAR
Alpha 1 antitrypsin deficiency - diffuse loss of alveolae - PANACINAR
What are the complications of emphysema?
- Large air spaces (bullae) – rupture - pneumothorax
- Respiratory failure: loss of area for gas exchange - compression of adjacent normal lung
- Pulmonary hypertension and cor pulmonale
What is a granuloma?
- Collection of histiocytes/macrophages +/- multinucleate giant cells
- Necrotising or non necrotising
What are examples of granulomatous lung disease?
– Infection – Sarcoidosis – Foreign body – aspiration or IVDU – Drugs – Occupational lung disease
What are the different types of fibrosis lung disease?
– Idiopathic pulmonary fibrosis (Cryptogenic fibrosing alveolitis)
– Extrinsic allergic alveolitis - “farmers lung”
– Industrial lung diseases – “pneumoconiosis”
What is pulmonary fibrosis?
- Also known as cryptogenic fibrosing alveolitis
- Chronic - SOB and cough
- Over 50 years, male predominance
What is the prognosis of idiopathic pulmonary fibrosis?
- Progressive disease
* Over 50% die in 2-3 years
What are the different types of idiopathic pulmonary fibrosis?
- Macro – Basal and peripheral fibrosis and cyst formation
* Micro - interstitial fibrosis at varying stages
How is idiopathic pulmonary fibrosis diagnosed?
Diagnosis by HRCT +/- biopsy
What are some causes of thrombos formation in pulmonary embolism?
Virchows triad:
– factors promoting blood stasis: obesity, immobility, cardiac failure, pregnancy, abdominal masses
– damage to endothelium: local trauma, cannulation
– increased coagulation: malignancy, haemoconcentration, polycythaemia, DIC, contraceptive pill, cannulation, anti-phospholipid syndrome
What is a small emboli?
- Small peripheral pulmonary arterial occlusion
- Haemorrhagic infarct
- Repeated emboli cause increasing occlusion of pulmonary vascular bed and pulmonary hypertension
- Patients present with pleuritic chest pain, acute SOB and/or chronic progressive shortness of breath
What do large emboli of the lungs result in?
- Large emboli can occlude the main pulmonary trunk (saddle embolus)
- Sudden death, acute right heart failure, or cardiovascular shock occurs in 5% of cases when >60% of pulmonary bed is occluded
- If patient survives, the embolus usually resolves
- 30% develop second or more emboli
What are examples of non-thrombotic emboli?
Bone marrow Amniotic fluid Trophoblast Tumour Foreign body Air
Define pulmonary hypertension
PHBP = mean pulmonary arterial pressure > 25mmHg at rest
What is the mean pulmonary hypertension?
Pulmonary circulation normally low pressure (mean PAP 12mmHg)
What are the pre-capillary, capillary and post-capillary causes of pulmonary hypertension?
Precapillary
Vasoconstrictive – Chronic hypoxia – Hyperkinetic congenital heart disease – Unknown (Primary pulmonary hypertension) – Chronic liver disease, HIV infection, Connective tissue disease Embolic – Thromboembolic – Parasitic (schistosomal) – Tumour emboli
Capillary
Widespread pulmonary fibrosis - mechanical vascular distortion and chronic hypoxia
Postcapillary
Veno-occlusive disease
Left-sided heart disease
What are the different cell types in lung tumours?
Arise from a variety of cell types: epithelial, mesenchymal (soft tissue), lymphoid
Where are the most common areas lung tumours can be found?
Arise at a variety of sites: airways, seromucinous glands, alveolar parenchyma, vessels, pleura
What is an example of a benign lung tumour? What problems can they cause?
Chondroma
Can cause local complications - airway obstruction
What is the commonest type of malignant lung tumour?
Commonest are epithelial tumours and of these main types (90-95%)
What are the two types of malignant lung carcinomas and the subtypes?
NON-small cell carcinoma
• Squamous cell carcinoma (30%)
• Adenocarcinoma (30%)
• Large cell carcinoma (20%)
SMALL cell carcinoma
• Small cell carcinoma (20%)
What are the majority of lung cancers caused by?
SMOKING
25% of lung ca in non-smokers attributed to passive smoking
Strongest association with squamous cell carcinoma and small cell carcinoma
What are the majority of lung cancers caused by?
SMOKING
25% of lung ca in non-smokers attributed to passive smoking
Strongest association with squamous cell carcinoma and small cell carcinoma
How can smoking cause lung cancer?
- Tumour initiators: Polycyclic aromatic hydrocarbons
- Tumour promotors: N Nitrosamines, Nicotine, Phenols
- Complete carcinogens: Nickel, Arsenic
What are some other causes of lung cancers?
10-20% in non-smokers
– Asbestos exposure (Asbestos + smoking = 50 fold increase risk)
– Radiation (Radon exposure, theraputic radiation, uranium miners)
– Air pollution
– Other: Heavy metals (Chromates, arsenic, nickel)\
Genetics - Familial lung cancers rare
Susceptibility genes
- Chemical modification of carcinogens
- Polymorphisms in genes for cytochrome p450 (CYP1A1) and glutathione S transferases which play a role in eliminating carcinogens
- Susceptibility to chromosome breaks and DNA damage
- Nicotine addiction
Describe the pathway of development of squamous cell carcinoma
Normal epithelium –> hyperplasia –> squamous metaplasia –> dysplasia –> carcinoma in situ –> invasive carcinoma
What is the site in which invasive squamous cell carcinoma is found?
Site
– Traditionally centrally located arising from bronchial epithelium, however increasing number of peripheral squamous cell carcinomas
Behaviour
– Local spread, metastasise late
How does adenocarcinoma develop?
Precursor lesion: Atypical adenomatous hyperplasia
Proliferation of atypical cells lining the alveolar walls. Increases in size and eventually can become invasive.
AAH –> Non-mucinous Adenocarcinoma-in-situ –> Mixed pattern invasive adenoCa (acquires invasive phenotype)
Which lung cancer is common in females and non-smokers?
Adenocarcinoma
What is the site, behaviour and histology of invasive adenocarcinoma?
Site
– Peripheral and more often multicentric
Behaviour
– Extrathoracic metastases common and early
Histology
– Histology shows evidence of glandular differentiation
– Variety patterns relate underlying molecular abnormalities and prognosis
Describe the histological findings in large cell carcinoma
Poorly differentiated tumours composed of large cells
No histological evidence of glandular or squamous differentiation
BUT on electron microscopy many show some evidence of glandular, squamous or neuroendocrine differentiation i.e are probably very poorly differentiated adeno/squamous cell carcinomas
Poorer prognosis
What are the site, behaviour and histological findings in small cell carcinoma?
Site
Often central near bronchi
Behaviour
80% present with advanced disease
Although very chemosensitive, have an abysmal prognosis
Paraneoplastic syndromes
Histology
Small poorly differentiated cells
p53 and RB1 mutations common
Compare small cell and non-small cell carcinomas
Small cell lung carcinoma
– Survival 2-4 months untreated
– 10-20 months with current therapy
Non-small cell lung carcinoma Early Stage 1: 60% 5yrs Late Stage 4: 5% 5yrs Less chemosensitive 20-30% have early stage tumours for surgical resection
Why is sub-typing non-small cell carcinoma essential?
Some adenocarcinomas show a variety molecular changes which can be targeted by specific therapies
EFGR
ALK
Ros1
In contrast some patients with squamous cell carcinoma develop fatal haemorrhage with some drugs (Bevacizumab)
What is needed to diagnose lung cancer?
X-ray
Cytology - bronchial washings/sputum, endoscopic fine needle aspiration of tumour/lymph nodes
Histology - biopsy, percutaneous CT, mediastinoscopy, open biopsy, resection specimen
What are examples of targeted molecular therapies in lung cancer?
TKI regulates several pathways including transcription, proliferation, migration and angiogenesis. TKI therapy (gefitinib) –> targets EGFR pathway in EGFR +ve lung cancers.
ALK translocation - responds to crizotinib
Ros1 translocation
What is an example of lung cancer immunotherapy?
High levels of PD1 or PDL1 protein expression (IHC) may inhibit Immune response. Blocking this will allow PDL1 immune damage to tumour.
What is currently tested for regarding molecular testing in lung cancer patients?
Adenocarcinoma/NSCLC • EGFR mutation • Responder mutation • Resistance mutation • Alk translocation • Ros1 translocation • PD-L1 expression
Squamous cell carcinoma
• PDL1 expression
How can breast cancer be diagnosed?
Pathology: cytopathology/biopsy
Lesion aspirated by a 16/18gauge needle
How are aspirates of breast lumps coded?
Aspirates of breast lumps are coded C1-5: C1 = inadequate C2 = benign C3 = atypia, probably benign C4 = suspicious of malignancy C5 = malignant
Describe how the histopathology of breast cancer is analysed
Intact tissue removed, fixed in formalin, embedded in paraffin wax, thinly sliced, stained with H&E
Core biopsies, surgical excisions
Takes 24 hours to process.
Architectural & cellular detail
What is duct ectasia?
Inflammation and dilation of large breast ducts
Aetiology unclear
Usually presents with nipple discharge
Sometimes causes breast pain, breast mass and nipple retraction
Cytology of nipple discharge shows proteinaceous material and inflammatory cells only
Benign condition with no increased risk of malignancy
What is acute mastitis?
Acute inflammation in the breast Often seen in lactating women due to cracked skin and stasis of milk May also complicate duct ectasia Staphylococci the usual organism Presents with a painful red breast Drainage & antibiotics usually curative
What is fat necrosis?
An inflammatory reaction to damaged adipose tissue
Caused by trauma, surgery, radiotherapy
Presents with a breast mass
Benign condition
What is fibrocystic disease?
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.
What is a fibroadenoma?
A benign fibroepithelial neoplasm of the breast.
Common.
Presents as a circumscribed mobile breast lump in young women aged 20-30.
Simple “shelling out” curative.
What is a fibroadenoma?
A benign fibroepithelial neoplasm of the breast.
Common.
Presents as a circumscribed mobile breast lump in young women aged 20-30.
Simple “shelling out” curative.
What are phyllodes tumours?
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.
What is an intraductal papilloma?
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).
What is the epidemiology and treatment of an intraductal papilloma?
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.
What is a radial scar in the context of breast tissue?
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”.
How is a radial scar on breast tissue treated?
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.
How is a radial scar on breast tissue treated?
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.
Define what is meant by proliferative breast diseases
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.
What is meant by flat epithelial atypic/atypical ductal carcinoma?
Emerging genetic data suggests FEA may represent the earliest morphological precursor to low grade ductal carcinoma in situ.
4 times relative risk of
developing cancer
