2 - Surgical Pathology Flashcards
What is a neoplasm?
An abnormal mass of tissue, the growth of which:
- is uncoordinated
- exceeds that of normal tissues
- persists in the same excessive manner after cessation of the stimulus which evoked change
How may neoplasms be classified?
- Benign or malignant (primary or secondary)
- 1 cell type of origin (epithelial, mesenchymal, lymphoma)
- > 1 cell type from 1 germ layer (pleomorphic adenoma, fibroadenoma breast)
- > 1 cell type from >1 germ layer (teratomas)
What is hyperplasia? Give examples
An increase in size of an organ or tissue through an increase in cell numbers
- physiological: breast, thyroid in pregnancy
- pathological: adrenal’s in Cushings, Grave’s disease
What is hypertrophy? Give examples
An increase in the size of an organ or tissue through an increase in the size of cells
- physiological: skeletal muscle with exercise, uterus in pregnancy
- pathological: HOCM cardiomyopathy
What is a harmatoma? Give examples
A tumour-like malformation composed of a haphazard arrangement of the different amount of tissues normally found at the site
- Peutz-Jadher’s polyps of bowel, haemangiomas
What is metaplasia? Give examples
A reversible replacement of one fully differentiated cell type with another differentiated cell type - an adaptive change in response to injury, irritation, altered cell function. Has greater susceptibility to malignant transformation
- Barret’s oesophagus (stratified squamous to glandular, columnar type epithelium)
- Bronchus (pseudo stratified ciliated columnar to stratified squamous epithelium)
What is dysplasia?
Disordered cellular development characterised by increased mitosis and pleomorphism BUT without the ability to invade throughout the basement membrane and metastasise to distant sites.
Severe dysplasia = carcinoma in situ
What is carcinoma?
A malignant tumour of epithelial cells
What is sarcoma?
A malignant tumour of connective tissue
How to carcinomas and sarcomas typically spread?
Carcinomas via the lymphatics
Sarcomas via the haematogenous route
There are exceptions e.g. follicular thyroid carcinoma - haematogenous
What makes a tumour malignant?
- invasion through the basement membrane
- ability to metastasise to distant sites
What is a metastasis?
The survival and growth of cells that have migrated or have otherwise been transferred from a malignant tumour to a site or sites distant from the primary
What are the routes by which tumours spread?
- local invasion
- lymphatics
- blood
- transcoelomic (carcinoma stomach, ovary, colon, pancreas)
- CSF
- peri-neural (adenoid cystic parotid)
- iatrogenic (implantation / seeding during surgery)
Which tumours typically spread to bone?
Carcinoma of - breast - bronchus - thyroid - kidney - prostate Myeloma
What are the cytological features of malignancy?
- hyperchromatism
- pleomorphism
- cellular atypia
- increased nuclear-cytoplasmic ratio
- large and prominent nucleoli
- increased mitotic index and abnormal mitoses
- loss of differentiation and/or failure of cellular maturation
What are the histological features of malignancy?
- loss of normal tissue architecture
- invasion beyond basement membrane
- necrosis
- haemorrhage
- infiltrate borders
- cell shedding
- lymphovascular invasion
What is the difference between staging and grading?
Staging = extent of growth (size and spread) Grading = how well differentiated a tumour is
What is Dukes’ staging?
A - in the wall: 95-100% 5 yr survival
B - through the wall: 65-75%
C - lymph node mets: 30-40%
D - distant mets: 5-10%
How is TNM applied to breast cancer?
Tx - tumour cannot be assessed
T0 - no evidence of primary tumour
Tis - carcinoma in situ
T1 - <2cm
T2 - >2cm but <5cm
T3 - >5cm
T4 - any size with direct extension to chest wall and/or skin
N0 - no regional lymph mets
N1 - mets to ipsilateral, mobile axillary lymph nodes
N2 - mets to ipsilateral, fixed axillary or internal mammary nodes
N3 - mets to infra/supraclavicular nodes or both axillary and internal mammary nodes
M0 - no clinical or radiological evidence of mets
M1 - distant detectable mets
Which viruses cause cancer?
DNA - EBV (nasopharyngeal carcinoma, Burkitt's and Hodgkin's lymphoma) - Hep B (Hepatocellular carcinoma) - HPV 16/18/31 (cervical cancer, anal carcinoma) - HHV-8 (Kaposi's sarcoma) RNA - HTLV-1 (leukaemia/lymphoma) - Hep C - Hepatocellular carcinoma)
How do viruses cause cancer?
- inappropriate activation of cellular oncogenes
- expression of viral oncogene
- production of viral proteins promoting growth / inhibiting cell death
- chronic inflammation
What types of thyroid neoplasms are there?
- Papillary
- Folicular
- Medullary
- Anaplastic
- Lymphoma
What are the risk factors for thyroid cancer?
Radiation exposure
Family history
What is multiple endocrine neoplasia?
A group of related conditions, inherited as AD traits, characterised by hyperplasias and/or neoplasms of several endocrine organs.
What does MEN 1 consist of?
- Pituitary adenomas (prolactinomas most commonly)
- Pancreatic islet cell tumours (gastronomes most commonly)
- Parathyroids (four-gland hyperplasia most commonly)
What does MEN 2a consist of?
- Medullary thyroid carcinoma
- Pheochromocytoma
- Parathyroid hyperplasia (four-gland hyperplasia most commonly)
What does MEN 2b consist of?
- Medullary thyroid carcinoma
- Pheochromocytoma
- Marfanoid-type body habitus
- Mucosal neuromastosis
What is acute inflammation?
Stereotypical response to tissue injury characterised by calor, dolor, rubor and tumour (heat, pain, redness, swelling)
What are the stages of acute inflammation?
- vasodilation
- increased vascular permeability
- diapedesis / extravasation
- phagocytosis
- resolution or progression to chronic inflammation
Name some chemical mediators that participate in acute inflammation
- vasoactive amines (histamine, 5-HT / serotonin)
- kinin system (bradykinin)
- complement cascade (C3a, C5a)
- coagulation cascade and fibrinolytic system
- arachidonic acid metabolites (leukotrienes, prostaglandins, thromboxane A2)
- cytokines (interleukins, TNF-alpha, TGF-beta)
What are the possible outcomes of acute inflammation?
- resolution
- progression to chronic inflammation
- organisation and repair culmination in scar formation
- death (e.g. meningitis)
- abscess formation
How does chronic inflammation differ from acute inflammation?
Chronic inflammation is defined by the cell types present
- macrophages
- lymphocytes
Typically, longer time course
What are the causes of chronic inflammation?
- persistant infections that evade host defence mechanisms (TB, syphilis, leprosy, H.pylori)
- endogenous injurious agent (acid in stomach in PUD)
- persistant / non-degradable toxins (silica dust, asbestos, lipid in arterial walls)
- autoimmune diseases
- immunodeficiency
- unknown/idiopathic (sarcoidosis, IBD)
What are the pathological consequences of chronic inflammation?
- tissue destruction and scaring
- malignant transformation
- amyloidosis (e.g. in RA, UC)
What is amyloidosis and how is it classified?
A condition that results from the aggregation of beta-pleated, insoluble amyloid protein that gets deposited in organs and tissues thereby disrupting their normal function.
Can be localised or systemic
Can be primary or secondary (RA, IBD)
Subtypes: AL (light chains), AA (inflammatory), A-beta (Alzheimer’s), ATTR (familial)
What special histological properties does amyloidosis exhibit?
Amyloid may be stained with Congo red and exhibits
‘apple-green birefringence’ under plane-polarised light
What is wound healing?
The process by which tissue restoration of structure and function occurs, with restitution of tissue integrity and tensile strength.
How does a wound heal?
- Primary, secondary (granulation) or delayed primary (tertiary) intention
- Resolution (no scar) or organisation and repair (scar)
Stages - haemostats / coagulation
- acute inflammation
- formation of granulation tissue (endothelial cells, fibroblasts, macrophages)
- angiogenesis
- epithelialisation, fibroplasia, wound contraction (myofibroblasts)
- maturation and remodelling
What factors affect wound healing?
Local factors
- poor blood supply, haematoma, infection, FBs, surgical technique (wound tension, suture material), radiotherapy
Systemic factors
- DM, steroids, immunodeficiency, heart/renal/liver failure, hypoxia, malnutrition, chemotherapy, malignancy
What is the key difference between hypertrophic and keloid scarring?
Hypertrophic
- confined to wound margins
- often across flexor surfaces and skin creases
Keloid
- scar extends beyond wound margins.
- more common in Black and Hispanic ethnic groups
- Earlobe, chin, neck, shoulder, chest, deltoid regions
What is an abscess?
A localised collection of pus surrounded by granulation tissue / fibrous tissue
What is pus?
A collection of neutrophils, together with dead and dying microorganisms
What is a sinus?
A blind ending tract lined by granulation tissue
What is a fistula?
An abnormal communication between two epithelial or endothelial (AV) surfaces.
Commonest - ear piercing
What is a stoma? How can they be classified?
A surgical opening into a hollow viscus.
- Anatomical site or output (colostomy, ileostomy, urostomy, tracheostomy, gastrostomy etc)
- Indication (temporary vs permanent)
- No. openings (end vs loop)
How may fistulae be classified?
- congenital vs acquired
- aetiology (infections, inflammation, malignancy, radiotherapy etc)
- internal vs external
- simple vs complex
- anatomical - by-site (entero-enteric, entero-cutaneous, colo-vaginal, vesicle-colic etc)
- physiological - high vs low output
What factors prevent an intestinal fistula from healing spontaneously?
- distal obstruction
- malignancy
- FB
- associated undrained infection
- radiation injury to tissues
- underlying inflammatory condition (e.g. Crohn’s)
- mucocutaneous continuity
- high output
- malnutrition
How are fistulae managed?
SNAP
- sepsis control
- nutritional suport
- anatomical assessment, adequate fluid and electrolyte replacement
- plan, protect skin to prevent excoriation
60% close spontaneously within 1 month when sepsis is controlled and distal obstruction is relieved
What are the macroscopic and microscopic differences between Crohn’s and UC?
Macro
- Crohn’s: any part of GI tract, ‘skip’ lesions, rectal sparing, full thickness, fistulae & sinuses, strictures
- UC: confined to colon (+/- backwash ileitis) starting at rectum, contiguous, mucosal, pseudopolyps
Micro
- Crohn’s: non-caseating granulomas, ‘cobblestone’ mucosa
- UC: no granulomas, Crypt abscesses (UC>CD), dysplasia
What are the extra-intestinal manifestations of IBD?
- Integument: clubbing, erythema nodosum, pyoderma gangrenosum, aphthous ulcers
- Eyes: conjunctivitis, episcleritis, scleritis, anterior, uveitis
- Liver: Fatty liver, chronic active hepatitis, cirrhosis, gallstones, PSC, cholangiocarcinoma
- Renal: calculi
- Joints: peripheral arthropathy, sacroilitis, ankylosing spondylitis
- Amyloidosis
What is a granuloma? Give examples
A focal area of chronic inflammation consisting of a microscopic aggregation of activation macrophages that are transformed into epithelium-like cells surrounded by a collar of mononuclear leukocytes.
- Infections: TB, leprosy, syphilis, actinomycosis
- Inflammation: sarcoidosis, Crohn’s, PBC, Wegener’s
- Foreign bodies: Beryllium, silicosis, talc, sutures
- Malignancy: e.g Hodgkin’s lymphoma
What is an aneurysm? How are they classified?
An abnormal, permanent, locatlised dilation of a blood vessel to 1.5-2x its normal diameter
- Aetiology: atherosclerotic, inflammatory etc
- Congenital vs acquired
- True vs False
- Site: thoracic, abdominal, intracranial
- Size: giant, berry
- Shape: fusiform, saccular, dissecting etc
What are the complications of aneurysms?
- rupture
- thrombosis
- embolism
- local compressive effects
- infection (mycotic)
- fistula (e.g. aorta-enteric fistula)
What is a polyp? How are they classified?
A pedunculated mass of tissue arising from an epithelial surface
- Non-neoplastic: hyperplastic, hamartomatous, inflammatory pesudopolyps, lymphoid hyperplasia
- Neoplastic: tubular, tubulo-villous, villous
What complications might polyps undergo?
- malignant transformation
- ulceration
- bleeding
- infection
- intussusception
- protein and potassium loss
What is a diverticulum? How are they classified?
An abnormal out pouching go a hollow viscus into the surrounding tissues
- congenital vs acquired
- pulsion vs traction (rare)
- anatomical site
- mesenteric (small intestine) vs anti-mesenteric
- true (Meckel’s) vs false (sigmoid, pharyngeal)
What complications might diverticula undergo?
- perforation
- inflammation +/- infection
- bleeding
- fistulae
- strictures
- malignancy (e.g. bladder diverticulula)
What is the difference between a clot, thrombus and embolus?
- Thrombus: ‘solid material formed from the constituents of blood in FLOWING blood’
- Clot: ‘solid material formed from the constituents of blood in STATIONARY blood
- Embolus: an abnormal mass of undissolved material that is carried in the bloodstream from one place to another
What causes a thrombus?
Vichow’s triad
- damage to vessel wall / endothelial injury
- abnormal blood flow
- alteration in constituents of blood / hypercoagulable state
What are the different types of emboli?
Can be solid, liquid or gas
- thrombus
- fat
- air
- atheromatous material
- amniotic fluid
- tumour cells
- foreign material e.g. broken cannula
What are the complications of atherosclerosis?
- distal ischaemia
- vessel occulation
- plaque ulceration & rupture
- thrombosis
- haemorrage into plaque
- embolism - lipid or thrombus
- calcification
- aneurysm formation
What is necrosis? What are the different types?
Abnormal tissue death during life, always pathological and accompanied by inflammation.
- coagulative / structured: from interruption of blood supply, tissue architecture preserved
- liquefactive / colliquative: in lipid-rich tissues lysosomal enzymes denature fat, characteristically occurs in brain
- caseous / unstructured: tissue architecture destroyed, TB
- fat necrosis: post trauma (breast) or enzymatic lipolysis (pancreatitis)
- fibrinoid: in arterial walls subjected to high pressures in malignant hypertension
- gangrenous: characterised by putrefaction. Wet, dry or gaseous.
What is the difference between apoptosis and necrosis?
- Apoptosis: energy dependent, internally programmed, affects single cells, no inflammation, physiological or pathological, intact plasma membrane, formation of apoptotic bodies
- Necrosis: energy independent, response to external injury, affects groups of cells, inflammation, pathological, loss of plasma membrane, cell swelling and lysis
What is a hypersensitivity reaction? How are they classified?
A condition in which undesirable tissue damage follows the development of humeral or cell mediated immunity. An exaggerated host immune response to a stimulus.
- Type I: mast cell degranulation (anaphylaxis, atopic allergies)
- Type II: antibodies (transfusion reactions, autoimmune haemolytic anaemia, Goodpasture’s syndrome)
- Type III: antibody-antigen complexes (serum sickness, systemic lupus erythematousus)
- Type IV: cell-mediated, granulomatous conditions
- Type V: stimulatory autoantibodies in autoimmune conditions (Grave’s disease, Myasthenia gravis)
What is an ulcer? What are the types / causes?
A break in an epithelia surface
- venous (70%)
- arterial
- neuropathic
- infection (TB, leprosy, syphilis)
- malignancy (SCC, BCC, melanoma, Marjolin’s, Karposi’s)
- haematological conditions (sickle cell, polycythaemia ruby vera, thalassaemia)
- vasculitides (RA, polyarteritis nodosa)
- metabolic (pyoderma gangrenosum)
- trauma (lacerations, burns, radiation, self-inflicted)
- iatrogenic (over-tight bandaging, ill-fitting cast)
- idiopathic
What is a tumour marker? Give examples
A substance reliable found in the circulation of a patient with neoplasia which is directly related to the presence of the neoplasm, disappears when the neoplasm is treated and reappears when the neoplasm returns.
- Hormones (beta HCG, calcitonin)
- Enzymes (PSA, placental ALP, LDH)
- Oncofetal antigens (alpha-fetoprotein, CEA, CA-125, CA19-9)
- Serum and tissue proteins (thyroglobulin)
What are the possible uses of tumour markers?
- diagnostic purposes
- prognostic information (tumour load)
- monitoring response to treatment
- surveillance to detect recurrence
- screening
What is colitis? How can it be classified?
Inflammation of the colon.
- Inflammatory: UC, CD, indeterminate colitis
- Infective
- Ischaemic
- Radiation
- Collagenous
- Microscopic (and lymphocytic/eosinophilic colitis)
What is malignant melanoma? What are the different types?
A malignant neoplasm of melanocytes
- superficial spreading (70%)
- nodular
- lentigo malignant melanoma (Hutchinon’s freckle)
- aural lentiginous
- amelanotic
What macroscopic features in naevi are suggestive of melanoma?
- Asymmetry
- Border irregularity
- Colour variation
- Diameter >6mm
- Elevation
- Tingling, itching, crusting, discharge, satellite lesions
- Only 10-20% form in pre-exisiting naevi, remainder de novo.
What are the risk factors for developing melanoma?
Congenital - xeroderma pigmentosum - dysplastic nevus sundrome - BRAF gene mutations - Giant congenital pigmented nevus Acquired - UV exposure, sunburn - Past history of melanomas - Red hair - Freckles - Pre-exisiting skin lesions (lentigo maligna) - >20 naevi - immunocompromise (HIV, Hodgkin's, Cycclosporin A therapy)
How is malignant melanoma staged?
Breslow's thickness - tumour invasion depth from top of granular layer of epidermis to deepest point of tumour I <0.75 mm II 0.76-1.5 mm III 1.51 - 2.25 mm IV 2.26 - 3.00 mm V > 3.00 mm
What is the difference between cytology and histology?
Cytology - study of individual cells and cell morphology obtained from FNA or brushings
Histology - study of cells within the context of tissues and their architecture, obtained by biopsy
What are the advantages and disadvantages of cytology?
Advantages - simple to perform, rapid - minimally invasive - cheap, requires minimal equipment Disadvantages - no info r.e. tissue architechture - large, poorly defined field sampled leading to sampling error or insufficient material for diagnosis - need experiences cytologist - operator dependent - potential for spread of malignant cells - less amenable to further studies
What are the advantages and disadvantages of histology?
Advantages
- defined lesion sampled
- provides info on tissue architecture and definitive diagnosis of invasion - staging of cancers
Disadvantages
- technically more difficult
- required fixation and processing (time)
- invasive
- painful
- expensive
- potential for spread of malignant cells
- may alter morphology of lesion for subsequent imaging
When would you refer a death to the coroner?
- cause of death unknown
- Dr not attended deceased within 14 days of death or in terminal illness
- all sudden deaths
- violent,, unnatural, or suspicious death
- if may be due to an accident
- if may be due to see-neglect or neglect by others
- if may be due to industrial disease or related to employment
- if may be due to abortion
- if occurred during an operation or before recovery from the effects of anaesthesia
- if may be due to suicide
- if death during or shortly after detention in police or prison custody
