Histopathology Flashcards

(500 cards)

1
Q

Question

A

Answer

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2
Q

Neutrophil appearance + associated with

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Polymorphonuclear granulocyte, multi-lobular

Marker of acute inflammation

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3
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Hyper-segmented neutrophil

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> 5 lobes

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4
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Hallmark of acute inflammation

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Neutrophils

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5
Q

Lymphocyte appearance

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Large nucleus, little cytoplasm

Marker of chronic inflammation

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6
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Eosinophils appearance

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Bilobed nucleus, granules

Associated with allergic reactions, parasitic infections, tumours

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7
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Mast cells appearance + associated with

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Granules (histamine)

Associated with allergy and anaphylaxis

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8
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Macrophages appearance + associated with

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Associatted with late acute inflammation (neutrophils arrive first, then macrophages clear debris) AND chronic inflammation (granulomas)

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9
Q

Activated macrophages are called

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Epitheloid macropphages

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10
Q

Define carcinoma

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Malignancy tumour of epithelial cells

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11
Q

Define sarcoma

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Malignant tumour of connective tissue

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12
Q

Features of squamous cell carcinoma

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Intercellular bridges, Keratin production

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13
Q

Features of adenocarcinoma

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Mucin production, Glands

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14
Q

Ziehl-Neelsen stain

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Acid fast bacilli

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15
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Prussian blue stain

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Iron (e.g. haemachromatosis)

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16
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Congo Red stain

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Amyloid (apple green birefringence)

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17
Q

Fontana stain

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Melanin

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18
Q

+ve for Cytokeratin

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Epithelium

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19
Q

Types of stains

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Histochemical stains, Immunohistochemical stains (immunofluorescence, immunoperoxidase)

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20
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Immunofluorescence stain

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Antibody binds to antigen, another antibody with fluorescent tag binds to that antibody

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21
Q

Immunoperoxidase stain

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Antibody binds to antigen, antibody had a enzyme, if substrate added –> colour change

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22
Q

Composition of bone

A
Inorganic component (65%) = calcium hydroxyapatite (99% of Ca store in body)
Organic components (35%) = bone cells, bone matrix
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23
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Cortical bone vs Cancellous bone

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Corticol bone (80%) - appendicular, mechanical and protective function
Cancellous bone (20%) - axial, metabolic function
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24
Q

Define osteon

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= Haversian system = functional unit of compact Bone

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25
Define Haversian canal
= central blood supply for each osteon
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Bone cells + function
Osteoblasts build bone (small cell, single nucleus) Osteoclasts consume / resorb bone (large cell, multi-nucleated) Osteocytes (very small cell)
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Osteoclast differentiation
Monocytes --> osteocyte precursors --> + RANK ligand + M-CSF --> DDx into osteoclasts Osteoblasts have osteoprotegrin (OPG) surface protein to block RANK-RANKL interaction --> ↓ DDx to osteoclasts
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Ix for metabolic bone disease
Bone biopsy + histology (thickness, porosity, bone volume)
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Osteoporosis - pathogenesis, aetio, Sx, Ix
Osteoporosis = loss of bone mass, normal mineralisation Primary osteoporosis (age, post-menopause) and Secondary osteoporosis (drugs, systemic disease) ↑ risk of fractures (low-impact fractures) DEXA scan (T score 1-2.5 SD below normal = osteopaenia, T score 2.5 below normal = osteoporosis) Bloods NORMAL in osteoporosis
30
Osteomalacia - pathogenesis
= Vitamin D deficiency = ↓ bone mineralisation
31
X-ray findings in Rickets
Bowing of femur/tibia (Rickets)
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X-ray findings in Osteomalacia
Horizontal fractures in Looser's zone (pseudofractures)
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Types of renal stone seen in hypercalcaemia
Calcium oxalate renal stones
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Histological finding in Primary hyperparathyroidism
Brown cell tumour = multinucleate giant cells, due to ↑ osteoclast activity (primary hyperparathyroidism) Osteitis fibrosa cystica (= marrow fibrosis + cysts = Brown tumour)
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X-ray finding in Primary hyperparathyroidism
Brown's tumours Salt and Pepper skull Subperiosteal bone resorption in phalanges
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Paget's disease - pathogenesis
Paget's disease = disorder of bone turnover (1) Osteoclasts consume bone (2) Osteoclasts consume bone + Osteoblasts build bone (3) Quiescent phase --> Mosaic pattern
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Paget's disease - Sx
Bone pain Microfractures Nerve compression --> deafness
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Site predilection in Paget's disease
Lumbar spine, Skull
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Complication of Paget's disaese
1% risk of osteosarcoma
40
Bloods in Paget's disase
↑ ↑ ALP
41
X-ray finding in Paget's disease
Cotton wool appearance
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Histological finding in Paget's disease
``` Mosaic pattern (jigsaw puzzple like pattern of lamellar bone) Huge osteoclasts (>100 nuclei) ```
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Types of fractures
``` Simple = bone fracture only, no damage to surrounding tissue Compound = broken bone pierces skin Greenstick = bone bends and breaks (children) Comminuted = break in bone into more than 2 fragments Impacted = broken ends of bone forced together ```
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Stages of fracture repair
Haematoma --> fibrocartilaginous callus (replaced with hyaline cartiage) --> mineraliastion --> re-modelling (along weight-bearing lines)
45
Osteomyelitis organisms
Adults: S aureus (90%), E coli, Klebsiella, Salmonella Children: H influezena, Group B strep Rarer causes - TB (immunocompromised), syphilis (congenital/acquired) Route of infection: haematogenous, direct extention, traumatic
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Sx of osteomyelitis
Fever, Pain, Swelling, Redness, Heat, Loss of function
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X-ray findings in Osteomyelitis
(from 10 days post-onset) Mottled rarefaction Lifting of periosetum Lytic destruction of bone
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Histological finding in osteomyelitis
Fibrosis, Chronic inflammatory cells (lymphocytes, histiocytes)
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Histology of Pott's disease / TB ostemyelitis
Multi-nucleated Langhans giant cells (horseshoe nuclei, granulomas)
50
Organism causing Syphilis
Treponema pallidum
51
Organism causing Lyme disease
Borrelia burgdorferi (found in ticks)
52
Lyme disease - Sx, Tx
Erythema chronicum migrans Arthritis Tx with ABx
53
Osteoarthritis - pathogenesis
Degenerative joint disease
54
Sites of predilection for Osteoarthritis
Knee, Hip, Vertebrae
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Characteristic deformities of Osteoarthritis
Heberden's nodes (DIPJ) | Bouchards's nodes (PIPJ)
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X-ray findings in Osteoarthritis
``` LOSS Loss of joint space Osteophytes Subchondral sclerosis Subchondral cysts ```
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Histology in Osteoarthritis
Irregular arterticular surface Signs of inflammation Cartilage degeneration Abnormal matrix calcification
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Characteristic deformities of RhA
``` Symmetrical deformities Radial deviation of wrist Ulnar deviation of fingers Swan neck Boutonniere deformity Z shaped thumb ```
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Sites of predilection for RhA
Small joints of hands and feet, wrist, elbow, ankles, knees | Sparing DIPJ
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Ix in RhA
RhF +ve (80%), ↓ Hb, ↑ ESR | Anti-CCP antibodies
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What is rheumatoid factor
Anti-IgG IgM
62
Histology in RhA
Proliferative synovitis Pannus Grimley-Sokoloff cells (multi-nucleate giant cells, similar to Langhans, but no horseshoe nucleus)
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Gout vs Pseudogout
GOUT: monosodium urate crystals, needle-shaped, negative birefringence, perpendicular to axis of red compensator PSEUDOGOUT: calcium pyrophosphate crystals, rhomboid shaped, positive birefringence, parallel to axis of red compensator
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Sx of bone tumour
Pain, swelling, deformity, pathological fractures
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Ix for bone tumours
X-ray | Jamshidi needle core biospy under radiological guidance
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Benign bone tumours
``` Bone differentiation ------- Osteoid ostoma ------- Osteoma ------- Osteoblastoma Cartilaginous differentiation ------- Osteochondroma ------- Enchondroma ------- Chondroblastoma Other ------- Fibrous dysplasia ------- Simple bone cyst ```
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Fibrous dysplasia - pathogenesis
Bone replaced by fibrosis tissue
68
Fibrous dysplasia is associated with
McCune-Alright syndrome (polyostotic dysplias, café au lait spots, precocious puberty) is associated with Fibrous dysplasia
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X-ray finding in Fibrous dysplasia
Soap-bubble osteolysis | Shepherd's crook deformity
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Histological finding in Fibrous dysplasia
Chinese letters (mis-shappen bone trabeculae)
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Most common benign bone tumour
Osteochondroma
72
Osteochondroma - Pathogenesis, Sx
Cartilaginous surface overlying normal cortical/trabecular bone (cartilage capped bony outgrowth) Swelling at end of long bone (near tendon attachment sites)
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Histology of Osteochondroma
Cartilage capped bony outgowth
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X-ray findings for Osteochondroma
``` Bony protuberance from bone Mushroom appearance (cartilage capped bony spur on surface of bone mushroom on X-ray) ```
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Enchondroma - pathogenesis
Benign tumour of cartilage --> cartilaginous proliferation within bone Often affects hands and feet (ENDS)
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Enchondroma is associated with
Ollier's syndrome and Maffuci's syndrome
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X-ray findings of Enchondroma
Cotton wool calcification / Popcorn calcification Lytic lesions O ring sign
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Histology of Enchondroma
Proliferation of normal cartilage
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Osteoma - pathogenesis
Bony outgrowths attached to normal bone
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Osteoma is associated with
Associated with Gardner syndrome (GI polyps, osteomas, epidermoid cysts)
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Histology of Osteoma
Normal bone
82
Osteoid osteoma - Sx
``` Small benign bone-forming lesion Night pain (relieved by aspirin) Common in Adolescents ```
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Histology of Osteoid osteoma
Normal bone (arises from osteoblasts)
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X-ray of Osteoid osteoma
Bull's eye sign (radiolucent nidus with sclerotic rim) found in osteoid osteoma (Tip: bull's eye is surrounded by rings, ∴ osteoid osteoma)
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Osteoblastoma - Sx
Same as Osteoid osteoma - Small benign bone-forming lesion - Night pain (relieved by aspirin) - Common in Adolescents
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X-ray findings in Osteoblastoma
Speckled mineralisation (multiple bone cells diffusely ↑ mineralisation?)
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Simple bone cyst - Sx + X-ray
Fluid-filled unilocular cyst | Well defined lytic lesion
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Primary bone tumours (malignant)
Osteosarcoma Chondrosarcoma Ewing's sarcoma Gaint cell (borderline malignancy)
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Histology of Giant cell tumour
Well-dermacated, expansile lesions close to surface (can easily burst throug cortex into surroudings) Osteoclast giant cells (non-neoplastic) Background of spindle or ovoid cells - stromal cells (neoplastic)
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X-ray of Giant cells
Lytic lesions right up to articular surface
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Most common malignant bone tumour
Metastases (breast, prostate, lung, kidney, thyroid, neuroblastoma)
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Most common primary bone sarcoma
Osteosarcoma
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Site of predilection for Osteosarcoma
Knee
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X-ray of Osteosarcoma
Codman's triangle = elevated periosteum (periosteum usually runs along outer surface of bone, sclerotic/lytic lesions pushes periostem up) Sunburst appearance
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Histology of Osteosarcoma
Malignant mesenchymal cells +/- bone or cartilage formation | ALP +ve (Touch preparation)
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Staining for ALP
Touch preparation
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Chondrosarcoma - pathogenesis
Chondrosarcoma = malignant cartiagle producing tumour | > 40 years old
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Site of predilection for Chondrosarcoma
Pelvis
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X-ray of chondrosarcoma + epidemiology
Lytic lesion with Fluffy calcification
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Histology in Chondrosarcoma
Malignant chondrocytes | Atypical cartilage formation
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Ewing's sarcoma is also known as
Peripheral primitive neuroectodermal tumour (PPNET) = Ewing's sarcoma
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Sites of predilection for Ewing's sarcoma
Diaphysis of long bones | Pelvis
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X-ray appearance of Ewing's sarcoma
Onion skinning of periosteum
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Histology of Ewing's sarcoma
Sheets of small round cells | Lifting of periosteum
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Molecular diagnosis in Ewing's sarcoma
t(11;22) --> EWS/Fli1 fusion protein | Anti-CD99 antibody (against MIC2)
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Elevated periosteum if found in (3)
Found in osteomyelitis, osteosarcoma (if in Codman's triange) and Ewing's sarcoma
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Triple assessment
Examination + Imaging (mammography / USS / MRI) + Biopsy (FNA, Cytology)
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Cytopathology codes for breast lump biopsy
``` C1 = inadequate C2 = benign clusters of cells C3 = atypia C4 = suspicious of malignancy C5 = malignant ```
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Inflammatory breast conditions
Duct ectasia Acute mastitis Fat necrosis
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Duct ectasia - Sx, Ix
Inflammation of breast ducts Thick, white nipple secretions Breast pain, Breast mass, Nipple retraction Cytology: Pink proteinaceous material, ductal distention, inflammatory cells
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Acute mastitis
Milk stasis --> acute inflammation in lactating women +/- Bacterial infection (Staph - most common, Strep) Large, lumpy breast Painful, red breast Cytology: Neutrophils, Necrotic material
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Fat necrosis
Trauma --> Damage to adipose tissue Hard, firm lump Painless breast mass Cytology: large, empty spaces of fat + surrounded by gaint cells
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Benign proliferative breast conditions (3)
Fibrocystic disease Fibroadenoma Gynaecomastia
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Fibrocystic disease
Breast lump | Histology: Fibrosis + Cystic changes, Calcification, Thinner secretions (c.w. ductal ectasia)
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Fibroadenoma
Well-circumscribed, mobile, bresat lump (breast mouse) Histology: ↑ number of acini per lobule (adenosis) --> glands compressed into "slit-like" spaces - Overgrowth of stroma + glandular ducts "Shelling out" is curative
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Gynaecomastia
↑ oestrogen in males --> enlargement of male breast Histology: Epithelial hyperplasia, finger-like projections into ducts No risk of malignancy
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Benigh neoplastic conditions (5)
``` Intraductal papilloma Radial scar Usual epithelial hyperplasia Atypical ductal hyperplasia In situ lobular neoplasia ```
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Intraductal papilloma
Benign papillary tumour arising from the breast ducts (terminal ducts --> peripheral papilloma, larger ducts --> central papilloma) Central papilloma --> Bloody discharge, no lump Peripheral papilloma --> asymptoamtic Associated with malignancy
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Radial scar
Benign sclerosing lesion with central zone of scarring and radiating zone of proliferating glandular tissue Mammogram: Stellate masses (resembles carcioma on mamorgram) Histology: central stellate fibrous area with prolifeartion of ducts and anini
120
Usual epithelial hyperplasia (UEH)
Histology: Growth of glandular tissue --> form fronds, Irregular lumen, Bridges NOT a precursor lesion for invasive breast carcinoma
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Atypical ductal hyperplasia
Precursor to low-grade DCIS | Histology: multi-layered cells, punched out holes within proliferation)
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Lobular in situ neoplasia (LCIS)
ALWAYS incidental finding on biopsy (since no calcifications, no stromal reactions) Histology: solid proliferation WITHN acinar lobule Loss of e-Cadherin and single chain file cells Risk factor to subsequent invasive breast cancer
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Malignanct breast disease (4)
Ductal carcinoma in situ Invasive breast carcinoma Basal-like carcinoma Phyllodes tumour
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Ductal carcinoma in situ (DCIS)
DCIS is NOT invasive Microcalcification within lumen Lump, Nipple discharge, Paget's disease of nipple (eczematous change) If untreated, high risk of progression to invasive breast carcinoma
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Invasive breast cancer
DCIS or LCIS invades through basememnt membranes Associated with ↑ oestrogen exposure Associated with BRCA mutation (85% lifetime risk)
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Histological categories for invasive breast cancer
``` Ductal carcinoma (island of cells) - most common Lobular carcinoma (linear arragement = Indian File Pattern) Tubular carcinoma (tubules) Mucinous carcinoma (produce mucin) ```
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Basal-like carcinoma
Sheets of pleimorphic cells | Prominent lymphocytic infiltrate
128
Breast cancer screening
Age 47 - 73 (every 3 years) --> Mammogram (detect DCIS or early invasive breast cancinomas) - calcifications, lumps If abnormal --> biopsy
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Histological grading (Bloom-Richardson Grading)
Score out of 3 for each of Tubules, Nuclear pleomorphism, Mitotic activity 3-5 points = Well differentiatied (grade 1) 6-7 points = Moderately differentiated (grade 2) 8-9 points = Poorly differentiated (grade 3)
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Breast cancer - assess for receptor status
``` Oestrogen receptor (ER) - good prognosis (respond to Tamoxifen) Progesterone receptor (PR) - good prognosis (respond to Tamoxifen) HER2 status - bad prognosis ```
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Phyllodes tumour
Left-like, fibroepithelial neoplasm Enlarging mass Cytology: overlapping cells, all smudged Histology: Leaf like fronds / Artichoke-like appearance Majority behave like fibroadenomas (borderline phyllodes) Small proportion are aggressive (malignant phyllodes)
132
Plical fusion
Complication of salpingitis, resulting in fallopian tubes adhering to ovary
133
2nd most common cancer affecting women worldwide
Cervical cancer
134
Transformation zone
Area where columnar epithelium transforms into squamous cells (area is susceptible to malignant change)
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CIN1
Lower 1/3 of epithelium (next to BM)
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CIN2
Middle 1/3 of epithelium (i.e. 2/3)
137
CIN3
Full thickness
138
Cervical cancer
Through BM
139
FIGO Cervical cancer
``` 1 = Cervix 2 = Upper 2/3 of vagina 3 = Lower 1/3 of vagina + pelvic side wall 4 = Distant mets (bladder, rectum, distant mets) ```
140
Types of cervical cancer
Squamous cell carcinoma (from CIN) | Adenocarcinoma (from CGIN)
141
HPV proteins + action
E7 --> inactivates Retinoblastoma gene (TS) | E6 --> inactivates p53 (TS)
142
Characteristic cytological features in HPV infection
Koilocyte = large, irrecular, well-defined peri-nuclear halos = HPV vacuole
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Name of HPV vaccine
Gardasil (quadrivalent - HPV 6, 11, 16, 18)
144
Most common type of uterine tumour
Fibroid (leiomyoma), no risk of malignancy
145
Leiomyosarcoma
Malignant counterpart to fibroid (leiomyoma), but arises de novo, post-menopausal women
146
Causes of endometrial hyperplasia
``` Peri-menopausal Persiant anovulation PCOS Granulosa cell tumour Unpposed oestrogen therapy ```
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Type 1 Endometrial cancer
(85%) Younger patients, Associated with atypical endometrial hyperplasia
148
Type 2 Endometrial cancer
(15%) Older, post-menopausal women, arise from atrophic endometrium
149
FIGO staging endometrial cancer
``` 1 = Endometrium 2 = Cervix 3 = Adnexae 4 = Distant mets ```
150
Complete vs Partial mole
Complete mole = diploid DNA, empty egg + 2 sperm | Partial mole = triploid DNA, normal egg + 2 sperm
151
Which types of mole has a risk of malignancy
Complete moles --> invasive mole
152
Types 1 Ovarian tumour
Low grade, indolent tumour Precusor lesion = BOT and endometriosis Includes serous, endometrioid, mucinous, clear cell carcinoma
153
Type 2 Ovarian tumour
High grade + aggressive | No precursor lesions
154
FIGO staging ovarian cancer
``` 1 = limited to Ovary 2 = limited to Pelvis (uterus, tubes, other pelvic organs) 3 = limited to Abdomen 4 = Distant mets ```
155
Most common type of ovarian tumour
Serous tumour
156
Ovarian tumours associated with endometriosis
Endometrioid tumour, Clear cell carcinoma
157
Which ovarian tumours secrete hormones
Sex cord stromal tumours Granulosa --> oestrogen Thecoma --> oestrogen Sertoli-Leydig cell --> androgens
158
Signet ring cells in ovary
Krukenberg tumours = metastases to ovary, composed of mucin-producing signet rings cells
159
Paget's diisease of vulva
Adenocarcinoma in situ, low risk of progression to invasive adenocarcinoma
160
BRCA-associated tumours
Breast and Ovarian (serous)
161
HNPCC-associated tumours
Colorectal, Endometrial cancer, Ovarian cancer (mucinous, endometrioid)
162
Posterior pituary hormones
Supraoptic + Paraventricular nuclei release ADH/Vasopressin and Oxytocin
163
Most common type of pitutiary adenoma
Prolactinoma (20%), Non-functioning (20%)
164
Prolactinoma Sx
Amenorrhoea, Galactorrhoea, Loss of libido, Infertility
165
GH pituitary adenoma
Gigantism in pre-pubertal children Acromegaly in Adults DM, HTN, Muscle weakness
166
Corticotroph cell adenoma
Cushing's disease
167
Causes of Hypo-pit
Non-secretory pituitary adenoma Ischaemic necrosis (sheehan's) Surgery Irradiation
168
What do parafollicular C cells produce
Calcitonin
169
Most common cause of goitre worldwide
Iodine deficiency
170
Causes of hyperthyroidism
Primary - Graves', multi-nodular goitre, adenoma, thyroiditis Secondary - TSH-secreting pitutiary adenoma
171
Auto-antibody in Graves'
Anti-TSH receptor antibody
172
Auto-antibody in Hashimoto's thyroiditis
Anti-thyroglobulin Ab and Anti-TPO antibody
173
Histology in Hashimoto's thyroiditis
Infiltration with lymphoid cells Presence of germinal centre within the thyroid Hurtle cells = characteristic eosinophils
174
4 types of thyroid cancer
Papillary (most common), Follicular, Medullary, Anaplastic
175
Histology of Papillary carcinoma
``` Non-functional thyroid carcinoma Papillary architecture Psammoma bodies (foci of calcification within cells) ```
176
Histology of Follicular carcinoma
Follicular morphology, similar to normal thyroid | Minimal invasion
177
Histology of Medullary carcinoma + what hormone
Derived from parafollicular C-cells | Secretes Calcitonin
178
Stain for medullary carcinoma
``` Congo Red (stains for amyloid) Excess calcitonin broken down into amyloid ```
179
Histology + prognosis Anaplastic carcinoma
Aggressive, metastasises early, death within 1 year
180
Causes of adrenal insufficiency
(Primary) Acute - stopping long-term corticosteroid therapy, haemorrhage into adrenals, Sepsis with DIC (waterhouse-friderichson syndrome) (Primary) Chronic = Addion's disease (TB, autoimmune, mets, amyloid) Secondary - ↓ ACTH (non-functional pitutiary adenoma, pituitary infarction)
181
Features of SLE
SOAP BRAIN MD (4 out of 11 required) Serositis (recurrent pleutric chest pain, recurrent abdo pain) Oral ulcers Arthritis Photosensitivity Blood disorders (AIHA, ITP, leucopenia) - ∑ classical complement deficiency Renal involvement (proteinuria, haematuria) / Raynaud's ANA +ve Immune antibodies (anti-dsDNA, anti-Smith antibodies, anti-histone antibody - in drug-induced SLE) - Type III hypersensitivity Neuro symptoms Malar rash Discoid rash
182
Most common auto-antibody in SLE
ANA (95%), others include anti-dsDNA, anti-Smith
183
Skin immunofluorescence in SLE
Immune-complex deposition along the dermis-epidermis junction
184
Lupus erythematous cell (LE cells)
= denatured nuclei found in serum, engulfed by neutrophils | Old test, now superseded by ANA
185
Histology of lupus nephritis
Wire loop capillaries (thickening) - due deposition of immune complexes within GBM
186
Scleroderma = Systemic sclerosis - pathogenesis
Excess fibrosis + excess collagen --> tight skin
187
Auto-antibodies in Diffuse scleroderma
Anti-topoisomerase antibody (Anti-Scl70)
188
Auto-antibodies in Limited scleroderma
Anti-centromere antibody
189
Diffuse vs Limited SS
Diffuse scleroderma has truncal involvement, associated with pulmonary HTN Limited scleroderma has NO truncal involvement (limited to distal to elbows and knees) + CREST features, associated with pulmonary fibrosis
190
CREST features
Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasia Calcinosis = Calcium deposits Sclerodactyly = tightening of skin on fingers
191
Histology of Limited SS
Collagen deposits in epidermis Trichrome staining (2 acids + polyacid dye) --> red staining of muscle, blue staining of collage Onion skin thickening of arterioles
192
Histology of Diffuse SS
Inflammation within or around muscle fibres
193
Speckled pattern (of ANA)
Seen in Sjogren's syndrome and Mixed connective tissue disease
194
Dermatomyositis vs Polymyositis
Similar features - proximal muscle weakness, ↑ CK, abnormal EMG Dermatomyositis has skin features - Heliotrope rash, Gottron's papules
195
Auto-antibody in Polymyositis
Anti-Jo-1
196
Auto-antibody in Dermatomyositis
Anti-Jo-1
197
Hallmark of Sarcoidosis
``` Non-caseating granuloma Schaumann bodies (inclusions of protein) Asteroid bodies (inclusions of calcium) ```
198
Features of sarcoidosis
Bilateral hilar lymphadenopathy (DDx: sarcoidosis, TB, lymphoma, bronchial cancer) Erythema nodosum Lupus pernio Arthritis Lymphadenopathy Uveitis Hepatosplenomegaly Hypergamaglobulinaemia ↑ ACE (due to abnormalities in lung where ACE is made) Hypercalacemia (due to ectopic hydroxylation of Vitamin D)
199
Large vessel vasculitis (2)
Takayasu's arteritis | Temporal arteritis
200
Medium vessel vasculitis (3)
``` Polyarteritis nodosa (PAN) Kawasaki Thrombangitis obliterans (Buerger's disease) ```
201
Small vessel vasculitis (4)
Wegener's granulomatosis Churg-Strauss Microscopic polyangiitis Henoch-Schonlein purpura
202
Takayasu's arteritis
Absent pulses, Japanese women, Claudication
203
Temporal arteritis
Elderly, scalp tenderness, temporal headache, jaw claudication, ↑ ESR, Skip lesions, granulomatous transmural inflammation
204
Polyarteritis nodosa
Multiple beads of vessels (microaneurysms on angiography) Focal arteritis Renal involvement common
205
Kawasaki's disease
Fever, Conjunctivitis, Rash, Cervical adenopathy, Strawberry tongue, Hands and feet swollen, coronary artery aneurysm
206
Buerger's disease
Heavy smoker, Corkscrew appearance on angiogram (segmental occlusive lesions), arteritis of extremities (tibial, radial)
207
Wegener's granulomatosis =
Granulomatosis with polyangiitis
208
Wegener's granulomatosis auto-antibody
c-ANCA (against proteinase 3)
209
Wegener's granulomatosis TRIAD
Upper resp tract: saddle nose, sinusitis, nosebleeds Lower resp tract: pulmonary haemorrhage Renal: crescentic glomerulonephritis
210
Churg-Strauss =
Eosinophilic granulomatosis with polyangiitis
211
Churg-Strauss Sx
Asthma, Eosinophilia, Vasculitis
212
Churg-Strauss auto-antibody
p-ANCA (against myeloperoxidase)
213
Microscopic polyangiitis
Pulmonary-renal syndrome = pulmonary haemorrhage + glomerulonephritis also p-ANCA +ve
214
Henoch-Schonlein purpura
``` IgA mediated vasculitis Children < 10 years old Preceding URTI Palpable purpuric rash (lower limb extensors + buttocks) Colicky abdo pain Glomerulonephritis ```
215
Steps of atherosclerosis
Endothelial injury LDL enter sub-intimal space and oxidised Macrophages take up oxidised LDL --> Foam cells Apoptosis of foam cells --> cholesterol core ↑ adhesion molecules for more macrophages and T cells to enter plaque Vascular smooth muscle form fibrous cap
216
Earliest lesion of atherosclerosis
Fatty steak
217
Where do atherosclerotic plaques tend to occur
Points of disturbed flow, Branched points | Laminar flow is protective
218
Types of acute plaque changes
Rupture, Erosion, Haemorrhage
219
Point of critical stenosis
70% occlusion or <1mm diameter --> stable angina
220
Types of angina
Stable angina = pain with exertion, relieved with rest Unstable angina = pain at rest Prinzmetal angina = coronary artery spasm --> narrowing
221
Coronary arteries + % affected by occlusion
LAD (50%) - LV anterior wall, anterior septum, apex RCA (40%) - LV posterior wall, posterior septum, posterior RV LCx - LV lateral wall
222
Order of cell entry to MI
Neutrophils, Macrophages, Angioblasts, Fibroblasts
223
Histology of MI over time
< 6 hr: normal histology 6-24hr: loss of nuclei, necrotic cell death 1-4 days: neutrophils, then macrophages (clear up debris) 1-2 weeks: granulation tissue, myofibroblasts Weeks-months: decellularising scar tissue
224
Reperfusion injury
Area of necrosis suddenly starts receiving blood --> electrolyte imbalance --> arrhythmia
225
Dressler syndrome
Post-MI pericarditis (days-months)
226
Define sudden cardiac death
Unexpected death from cardiac cause in individual without cardiac symptoms or death within 1 hour of cardiac symptoms 90% have atherosclerosis Commonly due to arrhythmias (VF)
227
Common cause of cardiac death after MI
Arrhythmia (90% post-MI)
228
Congestive heart failure
R heart failure + L heart failure
229
Signs of L heart failure
SOB + pulmonary oedema
230
Signs of R heart failure
Peripheral oedema Ascites Nutmeg liver
231
Dilated cardiomyopathy
Loss of myocytes --> dilated heart (idiopathic)
232
HOCM
LV hypertrophy due to thickening of septum --> narrows LV outflow (50% familial)
233
Restrictive cardiomyopathy
Normal sized heart, too stiff, idiopathic or secondary to amyloidosis or sarcoidosis
234
Acute rheumatic fever - pathogenesis + Tx
2-4 weeks after Group A strep infection (molecular mimicry) | Tx: Benzylpenicillin
235
Acute rheumatic fever - Sx
``` CASES (Jones' major criteria) - 2 major criteria Carditis Arthritis Sydenham's chorea (St Vitus Dance) Erythema marginatum Subcutaneous nodules ```
236
Histology of Acute rheumatic fever
``` Beady fibrous vegetations (verrucae) Aschoff bodies (small giant cell granuloma) Anitschkov myocytes (regenerating myocytes) ```
237
Rheumatic heart disease - valve
Mitral stenosis (70%)
238
Cause of aortic stenosis
Calcification
239
Causes of aortic regurgitation
Rheumatic heart disease, Endocarditis (destorys it), Marfans
240
True aneurysm
All layers of wall involved
241
False aneurysm
Extravascular haematoma (due to hole in artery which enables exsanguination)
242
Types of endocarditis + characteristic vegetations
Rheumatic heart disease: warty vegetations (verrucae) Infective endocarditis: irregular masses on valve cusps Non-bacterial thrombotic endocarditis (DIC): small vetations attachment to lines of closure (thrombi) Libman-Sacks endocarditis (SLE, anti-phospholipid syndrome): small warty vegetations, sterile, platelet rich
243
Acute infective endocarditis
Staph aureus / Strep pyogenes, high virulence, large vegetation
244
Subacute infective endocarditis
Strep viridans, Staph epidermis, low virulence, small vegetation
245
Which valves affected in IVDU
R sided valves
246
Signs of IE
Fever, new heart murmur (MR/AR usually), Roth spots, Osler's nodes, haematuria, Janeway lesions, Splinter haemorrhages
247
Duke criteria for IE (major - 2 required)
+ve blood culture with typical IE organisms OR 2 +ve cultures > 12 hours apart Evidence of vegations on echo or new regurg murmur
248
ABx for subacute IE
Benzylpenicillin and Gentamicin
249
ABx of acute IE
Flucloxacillin for MSSA
250
Typical valves affected in IE
Aortic regurgitation, Mitral regurgitation
251
Function of Stellate cell
Stores Vitamin A
252
Limiting plate
Found between portal tract and hepatocytes
253
Portal triad
Hepatic artery, Hepatic vein, Biliary duct
254
Define cirrhosis
Whole liver affected Fibrosis Nodules of regenerating hepatocytes Intrahepatic shunting (within liver) or extraheptic shunting (portal HTN, oesaphgeal varices, splenomegaly)
255
Prognostic scoring system for cirrhosis
Child's Pugh Score
256
Types of porto-systemic shunts
Lower oesophagus, umbilicus, rectum
257
Causes of micronodular vs macrodular cirrhosis
Micronodular < 2mm (alcohol) and Macronodular > 2mm (viral hepatitis)
258
Causes of acute hepatitis
Hepatitis A, Hepatitis E, Drugs
259
Histology of acute hepatitis
Spotty necrosis
260
Histology of chronic hepatitis
Scarring Piecemeal necrosis (inflammation across limiting place --> difficult to discern boundary between portal tract and hepatocytes) Fibrosis
261
Stages of alcoholic hepatitis
Fatty liver Alcoholic hepatitis Cirrhosis
262
Histology of fatty liver
Fatty change (reversible) = Steatosis
263
Histology of alcoholic hepatitis
Mallory Denk bodies - mainly in Zone 3 | Ballooning (cell swelling)
264
Cirrhosis
Micronodular cirrhosis | Fibrosis
265
Histology of NASH
Same as Alcoholic liver disease | Difference arises clinical Hx
266
Histology of Primary biliary cholangitis
Granulomatous destruction of bile ducts - pathognomonic lesion of PBC
267
Auto-antibody in Primary biliary cholangitis
Anti-mitochondrial antibody
268
Histology of Primary sclerosing cholangitis
Onion-skinning fibrosis of bile duct
269
PSC is associated
Ulcerative colitis
270
Diagnosis of PSC
ERCP/MRCP --> beading of bile ducts (due to multifocal strictures)
271
PSC --> ↑ risk of
Cholangiocarcinoma
272
Haemochromatosis - Sx
``` Mutation --> ↑ iron absorption --> Iron deposition in parenchymal cells Cardiomyopathy Infertility Bronzed diabetes Chronic pancreatitis ```
273
Histology of Haemachromatosis
Chocolate brown organs
274
Tx for Haemachromatosis
Venesection, Desferrioxamine
275
Histology of haemsiderosis
Accumulation of iron in macrophages (differs from haemachromatosis in where the iron lies)
276
Stain for Iron (2)
Perl stain, Prussian blue stain
277
Wilson's disease - Sx, Ix
``` ↓ copper EXCRETION Kayser-Fleischer rings Deposition in basal gnalgia ↑ serum copper ↓ caeruloplasmin ↑ 24hr urinary copper ```
278
Wilson's disease - Tx
Lifelong penicillamine
279
Stain for copper
Rhodanine stain
280
Auto-antibody in autoimmune hepatitis
Anti-smooth muscle antibody (Anti-SMA Ab)
281
Histology of α1 antitrypsin deficiency
``` Intracytoplasmic inclusions (misfolded a1-antitrypsin) Emphysema ```
282
Histology of drug-induced liver damage
Worst damage in Zone 2 and Zone 3
283
Most common liver cancer
metastases
284
Primary liver tumours
Hepatocytes --> Liver cell adenoma --> Hepatocellular carcinoma (RF: Aflatoxin) Cholangiocytes --> Bile duct adenoma --> Cholangiocarcinoma Endothelial cells --> Haemangioma --> Haemangiosarcoma
285
Most common causes of acute pancreatitis
Gallstones, Alcohol
286
Most common causes of chronic pancreatitis
Alcohol
287
Acute pancreatitis - pathogenesis
Activated enzymes --> Acinar necrosis --> further enzyme release (+ve cycle) Fat necrosis --> Free fatty acids bind Ca2+ --> hypocalcaemia
288
Acute pancreatitis - complications
Pseudocyst +/- abscess, Hypoglycaemia, Hypocalcaemia
289
Cyst vs Pseudocyst
``` Cyst = collection of fluid with epithelial lining Pseudocyst = collection of fluid WITHOUT an epithelial lining (may be lined with fibrosis tissue) ```
290
histology of acute pancreatitis
``` Acinar necrosis (periductal or perilobular or panlobular) Fat necrosis Pseudocyst ```
291
Histology of chronic pancreatitis
Fibrosis - defines chronic process Loss of acinar cells Duct strictures
292
Chronic pancreatitis - Ix
Pancreatitis calcifications (diagnostic)
293
Chronic pancreatitis - complications
``` Malabsorption (loss of exocrine function) Diabetes mellitus (loss of endocrine function) ```
294
Anto-antibody in Autoimmune pancreatitis
IgG4 +ve plasma cells (specific monoclonal response)
295
Types of pancreatic cancer
Ductal carcinoma - most common pancreatic cancer Acinar carcinoma Cystic neoplasis (serous, mucinous) Pancreatic neuroendocrine tumour (e.g. insulinoma)
296
Precursor lesions for pancreatic cancer
Pancreatic intraductal neoplasm (PanIN) | Intraductal mucinous papillary neoplasm (IMP)
297
Most common mutation in pancreatic cancer
K-ras (95%)
298
Histology of Pancreatic cancer
Adenocarcinoma (mucing-secreting glands) Perineural invasion (wraps around nerves) Ca19-9 +ve
299
Types of pancreatic based on location
Head of pancreas associated with ductal carcinoma | Tail of pancreas associated with neuroendocrine tumour
300
Complications of pancreatic cancer
Bile duct obstruction --> obstructive jaundice Pancreatic duct obstruction --> chronic pancreatitis Migratory thrombophlebitis = Trosseau's sign of malignancy
301
Histology of pancreatic neuroendocrine tumours
Most are non-secretory Insulinoma is most common secretory type Chromogranin +ve Rosette formation of cells
302
Role of podocytes
Podocyte's foot processes (on oustide of BM) create a charge-dependent and size-dependent barrier Podocyte slit barrer = thin area between end feet
303
Define mesangium
Smooth muscle around arterioles (both afferent and efferent arterioles) - holds glomerular structure together
304
Main functions of the kdiney
``` Excretion of waste products Fluid balance, eletrolyte balace, acid/base balance Regulation of BP (RAAS) Regulation of Ca2+ Regulation of haematocrit ```
305
Glomerular disease results in
Failure of filter --> ↑ Cr, ↑ Ur | Failure to maintain barrier function --> proteinuria, haematuria
306
Pathogenesis of immune complex deposition in kidney
Immune complex deposition in glomerulus --> inflammation + complement activation May deposit at different rates (post-strep glomerulonephritis takes 2-3 weeks, HepB infection takes years) May deposit at different areas - Mesangial area --> mild proteinuria - Sub-epithelial area (below podocytes) --> disrupts podocyte/filtration barrier - Sub-endothelial area (between endothelium and BM) --> inflammatory activation (most severe)
307
Ix for immune complex deposition in kidney
Immunohistochemistry, Electron microscopy
308
PKD - Aetiology, Sx, Cx
Autosomal dominant mutation in PKD1/2 --> cysts in renal parenchyma Associated with berry aneurysms and liver cysts Presents with HTN, flank pain, haemturia
309
Acquired renal cystic disease - Aetiology, Cx
Associated with end-stage renal failure --> cysts develop --> replace kidney ↑ risk of papillary renal cell carcinoma
310
Acute tubular necrosis - causes
Ischaemic, toxins (contrast, Hb, myoglobin), drugs (NSAIDs) | Damage to tubular epithelial cells
311
Histology of acute tubular necrosis
``` Loss of brush border Loss of polarity Loss of integrins on basal surface --> cells drop off into lumen --> cell casts (muddy casts) Necrosis of tubules Tubules no longer back-to-black Tubules appear flattened ```
312
Acute tubulo-interstial nephritis - causes
Immune damage to tubules and interstitum - Acute pyelonephritis (bacterial infection, white cell cases in urine) - Chronic pyelonephritis (chronic obstruction, urine reflux) - Acute interstitial nephritis (hypersensitivity to drugs - ABx, NSAIDs, Diuretics) - Chronic interstial nephritis (elderly with long-term analgesic consumption)
313
Histology of acute-interstitial nephritis
Signs of tubular injury (as above) | + Inflammatory infiltrate (eosinophils, granulomas)
314
Define casts
Solid cellular elements seen on urine microscopy
315
Define glomerular cresents
Proliferation of cells within Bowman's space --> pushes glomerulus to one side Inflammation creates permanent holes in basement membrane (do not re-form)
316
Causes of acute crescentic GN
(1) Immune complex (2) Anti-GBM (3) Pauci-immune All characterised by presence of glomerular cresents All rapidly progressive (end-stage renal failure within weeks)
317
Immune complex crescentic GN - causes, pathogenesis
Subendothelial deposition of immune complexes (most severe type) --> inflammation Causes: SLE, IgA nephropathy, Post-strep glomerulonephritis (subendothelial humps on EM, ↑ ASOT titre)
318
Immunohistochemistry of immune complex mediated C GN
Granular (lumpy bump) deposition of IgG immune complex on GBM/mesangium
319
Anti-GBM disease =
Goodpasture's syndrome = anti-GBM IgG antibodies against Type 4 collagen (GN, pulmonary haemorrhage) --> haemturia + haemopytsis
320
Immunohistochemistry of anti-GBM disease
LINEAR deposition of IgG highlights glomerular basement membrane
321
Silver stain look sfor
Presence of glomerular cresents
322
Pauci-immune cresentic GN - pathogenesis
ANCA-associated (anti-neutrophil cytoplasma antibodies)-associated ------- c-ANCA = Wegener's granulomatosis ------- p-ANCA - microscopic polyangiitis Antibodies bind to neutrophils --> activation within glomeruli --> glomerular necrosis No glomerular Ig deposits Associated with vasculitis
323
Immunohistochemistry of Pauci-immune cresentic GN
Fluorescence of neutrophils | Lack of immune complex deposition
324
Thrombotic microangiopathy
Damage to endothelium MAHA = deposition of fibrin --> shears RBC --> schistocytes, release Hb (↓ haptoglobuin), release BR (jaundice) HUS = MAHA + Thrombocytopaenia + AKI TTP = HUS + Fever + CNS signs
325
Nephrotic syndrome triad
Proteinuria, Hypoalbuminaemia, Oedema Frothy urine Swelling (classically facial swelling in children and peripheral oedema in adults)
326
Causes of nephrotic syndrome
``` Glomerular disease ------ Minimal change disease ------ Focal segmental glomerulosclerosis Immune-complex mediated ------ Membranous glomerulonephritis Systemic disease ------ DM ------ SLE ------ Amyloidosis ```
327
Minimal change glomerulonephritis - light microscopy
Normal appearance
328
Minimal change glomerulonephritis - electron microscopy
Loss of podocyte foot processes
329
Minimal change glomerulonephritis - immunofluorescence
No immune deposits
330
Most common cause of nephrotic syndrome in children
Minimal change glomerulonephritis
331
Treatment of minimal change glomerulonephritis
Steroids (immunosupression)
332
Focal segment glomerulosclerosis - Light microscopy
Focal and segmental glomerular consolidation Scarring Hyalinopsis
333
Focal segment glomerulosclerosis - EM
Loss of podocyte foot processes (same as minimal change disease) + Scars within glomeruli
334
Focal segment glomerulosclerosis - immunofluorescence
Ig and complement deposition within scarred areas
335
Membranous glomerulonephritis - cause, pathogenesis
Caused by Anti-PLA2 receptor antibody (found on Podocytes) or secondary to epithelial malignancy, drugs, infection SLE Immune deposition on outside of glomerular BM (subepithelially) Subepithelial deposition ∴ no inflammation
336
Membranous glomerulonephritis - light microscopy
Diffuse GBM thickening
337
Membranous glomerulonephritis - electron microscopy
Loss of podocyte foot process | Subepitheliual 'spikey' deposits
338
Membranous glomerulonephritis - immunofluorescence
Ig and complement in granular deposits along entire GBM
339
Most common cause of glomerulonephritis in adults
Membranous glomerulonephritis
340
Stages of diabetic nephropathy
Stage 1 - thickening of BM Stage 2 - ↑ mesangial matrix Stage 3 - Kimmelstiel-Wilson nodules (mesangial matrix nodules) --> at this point, nephrotic syndrome Stage 4 - obliterated glomerulus (requires dialysis)
341
Define amyloidosis
Deposition of extracellular protein with a β-sheet structure which is insoluble
342
AA amyloidosis
Derived from serum amyloid-associated protein (SAA) | - SAA is an acute phase protein - ↑ in RhA, SLE
343
AL amyloidosis
Derived from Ig light chains | - Associated with multiple myeloma
344
Stain for amyloid
Congo red stain --> salmon pink | + Polarised light --> apple-green birefringence
345
Lupus nephritis
Class I - immune complexes but minimal change in structure Class 2 - mesangial pattern of injury Class 3 + 4 - endothelial pattern of injury Class 5 - epithelial pattern of injury -----> looks similar to membranous nephropathy Granular lumpy bumpy pattern on Immunohistochemistry
346
Causes of microscopic haematuria
Thin BM disease (autosomal dominant mutation in T4 collagen synthesis, associated with Alport's syndrome) IgA nephropathy - often presents 1-2 after URTI with frank haematuria
347
DDx asymptomatic haematuria
Thin basement membrane disease (benign familial haematuria) IgA nephropathy --> frank haematuria, more common in Asians Alport syndrome
348
Most common cause of glomerulonephritis worldwide
IgA nephropathy
349
Histopathology of hypertension nephropathy
``` Shruken kidneys Nephrosclerosis - Arteriolar hyalinosis - Arterial intimal thickening - Ischaemic glomerular changes - Segmental and global glomerulosclerosis ```
350
Nephritic syndrome
``` PHAROH Proteinuria Haematuria (coke-coloured urine) Azzotemia - ↑ Urea, ↑ Cr Red cell casts (in urine) Oliguria Hypertension ```
351
Alport's syndrome
X-linked mutation in Type IV collage (α5 chain) | Nephritic syndrome + Sensorineural deafness + Eye disorders (cataracts, lens dislocation)
352
Oesophagus epithelium
Stratified squamous epithelium
353
Z line
Squamo-columnar epithelium
354
Stomach fundus/body characteristics
Columnar epithelium, specialised glands secrete acid
355
Stomach pylorus characteristics
Columnar epithelium, non-specialised glands, neuroendocrine cells, affected by H. pylori infection
356
Goblet cells
Secrete mucin, define intestinal-type epithelium Goblet cells are NOT normally found in the stomach Goblet cells in stomach indicates intestinal type metaplasia
357
Cause + Histology of acute oesphagitis
Caused by oesophgeal reflux of acid Red, swollen Neutrophils (acute inflammation)
358
Cause + Histology of GORD
Caused by reflux of gastric acid into oesophagus Ulceration = loss of surface epithelium Surface epithelium replaced by fibrosis Fibrosis (defines chronic disease)
359
Complications of GORD
Haemorrhage, perforation, strictures | Barrett's oesophagus
360
Barrett's oesophagus = columnar lined oesophagus (CLO)
Metaplasia from squamous epithelium --> columnar epithelium + Goblet cells (intestinal type epithelium)
361
Metaplasia
Reverse change in cell type
362
Dysplasia
Cytological and histological features of malignancy BUT no invasion (e.g. high nuclear-cytoplasmic ratio, mitotic figures)
363
Types of oesophageal cancer
Adenocarcinoma of Oesophagus ------- invades basement membrane ------- Lower oesophagus (acid reflux) ------- Most common oesophageal cancer in UK Squamous cell carcinoma of Oesophagus ------- invades basement membrane + submucosa ------- Mid oesophagus ------- Associated with alcohol and smoking ------- Most common oesophageal cancer worldwide ------- Histology: produces keratin, intercellular bridges
364
Porto-systemic anatomoses
Oesophageal, Para-umbilical, Rectal, Retroperitoneal | Due to portal vein HTN
365
Causes + Histology of acute gastritis
Redness, Swelling, Neutrophils | Caused by H pylori, NSAIDs, Alcohol, Corrosives
366
Cause + Histology of chronic gastritis
Lymphocytes (chronic) +/- Neutrophils (acute on chronic) | Caused by anti-parietal antibodies (pernicious anaemia), H. pylori (MALToma), NSAIDs, Bile reflux
367
CAG +ve H pylori
CAG +ve is associated with more severe + chronic inflammation H pylori produces urease --> alters pH (less acidic, ∴ stomach --> ↑ H+ to kill H pylori) H pylori does NOT invade epithelium, it binds to epithelium cells
368
Complications of H pylori
CLO-IM-Dysplasia (columnar lined oesophagus - intestinal metaplasia - dysplasia) ↑ Gastric cancer ↑ Adenocarcinoma ↑ MALToma
369
Define ulcer
Ulcer = loss of tissue extends beyond muscularis mucosa
370
Define erosion
Erosion = loss of surface epithlium +/- lamina propria | Erosion may progress to Ulcer
371
2 pathways to GI cancer
Upper GI tract --> metaplasia-dysplasia pathway | Lower GI tract --> adenoma-carcinoma pathway
372
Precursor lesion for gastric cancer
Gastric epithelium dysplasia (no invasion)
373
Types of gastric cancer
Gastric adenocarcinoma - most common ------ Intestinal type (Well differentiated, large glands with mucin) ------ Diffuse type (poorly differentiated, no glands, signet ring cell carcinoma, linitis plastica / leather bottle stomach - diffuse spread of abnormal cells) Squamous cell carcinoma Gastric MALToma (B cell lymphoma, chronic antigen stimulation with H pylori) Gastrointestinal stromal tumour Neuroendocrine tumour
374
Duodenitis
↑ acid in stomach --> spills into duodenum --> duodenal metaplasia (intestinal type --> gastric type) Gastric epithelium can withstand acid
375
Giardia lamblia
Pear-shaped trophozoite
376
Histology of Coeliac disease
Villous atrophy Crypt hyperplasia ↑ intraepithelial lymphocytes (CD8 T cells)
377
DDx for flattened villi
Tropical spure (E ccoli)
378
Dx of coeliac disease
``` Anti-TTG antibodies Anti-endomysial antibodies Duodenal biopsy (villous atrophy) ```
379
Enteropathy associated T-cell lymphoma
EATL = T cell lymphoma | Associated with uncontrolled Coeliac disease
380
Nutmeg liver
R heart failure --> nutmeg lever (congestive hepatopathy)
381
Thickened pleura
Mesothelioma (associated with asbestos)
382
Lung infection confined to single lobe
Lobular pneumonia
383
Seed-like deposits in lung
Miliary TB
384
Outpouching of normal bowel lumen
Diverticular disease
385
Oesophageal varices
Liver cirrhosis
386
Infarcted spleen
Sickle cell disease
387
Bleeding, change in bowel habit
Colon cancer (adenocarcinoma)
388
Torrential bleeding, perforated stomach
Peptic ulcer (eroded through wall of stomach)
389
Multiple deposits in liver
Liver mets
390
Dilated renal pelvis
Renal stone
391
Renal parenchyma replaced with cysts
Polycystic kidnes
392
High impact trauma, LOC --> wakes up --> dies
Extradural haemorrhage (arterial bleed)
393
Thunderclap headache, PMHx of polycystic kidney disease
Berry aneurysm in circle of willis --> Subarachnoid haemorrhage
394
Death certificate 1a
Actual cause of death (e.g. PE) (e.g. Stroke)
395
Death certificate 1b
Causes 1b (e.g. DVT) (e.g. Embolism due to MI)
396
Death certificate 1c
Causes 1b, which causes 1a (e.g. Hip fracture)
397
Death certificate 2
Contributing factors (e.g. Diabetes)
398
Layers of skin
``` Epidermis - St. corneum - St Granulosum - St. spinosum - St. basale Dermis Subcutaneous fat ```
399
Bullous pemphigoiD - pathogenesis, Sx
Autoimmune disorder against basement membrane Damages achoring filaments linking basal keratinocytes to BM --> whole epidermis lifts up Tense bullae - found Deep
400
Histology of bullous pemphigoid
Epidermis lifts up | Bullae
401
Immunofluorescence of bullous pemphigoid
IgG and C3 highlights dermoepidermal junction (linear deposition)
402
PemphiguS valgaris - pathogenesis, Sx
Autoimmune IgG against desmosomes --> acantholysis Flaccid blisters with red surface underneath Bullae are Superficial
403
Histology of pemphigus valgaris
Acantholysis/Separation between layers of epidermis
404
Define acantholysis
Loss of intercellular connections (e.g. desmosomes) --> loss of cohesion between keratinocytes (between layers)
405
Pemphigus foliaceus - pathogenesis, Sx
Autoimmune IgG against desmosomes in upper epidermis --> acantholysis Very thin bullae, no intact bullae
406
Histology of pemphigus foliaceus
Acantholysis/Separation between upper layers of epidermis | Net like pattern of intercellular IgG deposits
407
Discoid eczema - Sx
Silvery plaques, Itchy, Flexure surfaces
408
Contact dermatitis - pathogenesis, Sx
Type IV hypersensitvitiy reaction to allergn (Nickel, Starch) = T cell mediated response
409
Histology of Contact dermatitis
Hyperkeratosis (epidermis thickens) | Spongiosis (oedema between keratinocytes)
410
Plaque psoriasis - Sx
White, silvery plaques on extensor surfaces
411
Histology of plaque psoriasis
Thickened epidermis (rapid turnover of keratinocytes) Loss of Granular cell layer (stratum granulosum) - due to rapid turnover Munro's micro-abscesses within the epidermis Test tubes in rack appearance (clubbing of rete ridges) Parakeratosis (nuclei in S corneum layer)
412
Psoriasis - signs
Auspitz sign = rubbing causes pin-point bleeding | Koebner phenomen - lesions form at sites of trauma
413
Lichen planus - Sx
``` Papules, Plaques Wickham striae (white lines) ```
414
Histology of lichen planus
Difficult to see epidermal-dermal boundary Band-like inflammatory infilrate under epidermis Saw toothing of rete ridges
415
Pyoderma gangrenosum
Vascultitis ulcer (well-defined edge), pus-like
416
Histology of pyoderma gangrenosum
Ulcer
417
Seborrhoeic keratosis
Cauliflower appearance Easily removed Stuck on appearance
418
Histology of seborrhoeic keratosis
horn cysts (trapped keratin)
419
Sebaceous cyst
Smooth surface, central puctum +/- infection
420
Histology of sebaceous cyst
Kertin within a cyst
421
Most common skin cancer in UK
Basal cell carcinoma
422
BCC - Sx
Rolled, pearly white border Rodent ulcer --> highly invasive Does NOT metastasise
423
Histology of BCC
BCC invades local tissue
424
Bowen's disease
Pre-cancerous (confined to epidermis) | Keratin horn
425
Histology of Bowen's disease
Dysplasia (pre-cancerous) | BM intact
426
Histology of SCC
Perineural invasion (wraps around nerves)
427
Benign junctional naevus - Sx
Benign Well circumscribed Uniform pigmentation
428
Histology of Benign junctional naevus
Melanocytes form nests at bottom of epidermis
429
Compound naevus - Sx
Two-toned | Symmetrical
430
Histology of compound naevus
Melanocytes within epidermis and dermis
431
Histology of malignant melanoma
In epidemis --> in situ melanoma (cannot metstasise, Pagetoid spread) --> buckshot appearance In dermis --> malignant melanoma
432
Pagetoid spread
Invasion of melanocytes into epidermis
433
Staging of malignant meloma
Breslow thickness
434
SJS and TENS
<10% body surface area affected in SJS >30% in TENs Nikolsky sign +ve
435
Pityriasis rosea
Salmon pink rash appears first (herald patch) | Christmas tree distribution
436
Types of renal stones
Calcium oxalate - hypercalciuria Magnesium Ammonium Phosphate - infection with urease-producing organisms (Proteus) --> Staghorn calculi Uric acid - gout, chemotherapy
437
Common sites of blockage
Pelvi-ureteric junction Pelvic brim Vesico-ureteric junction
438
Benign renal neoplasms
Papillary adenoma Renal oncocytoma Angiomyolipoma
439
Histology of papillary adenoma
<15mm Well circumscribed Disorganised papillae and tubules
440
Histology of renal oncocytoma
Mahogony-brown tumour | Nests of pink oncocytic cells
441
Histology of angiomyolipoma
3 components: blood vessels, smooth muscle, fat | Associated with tuberous sclerosis
442
Types of renal cell carcinoma
Clear cell RCC - most common Papillary RCC Chromophobe RCC
443
Histology of clear cell RCC
Nests of clear cells | Golden-yellow tumour
444
Histology of papillary RCC
Papillae/Tubules >15mm Type 1 - islands of cells (end-on papillae) Type 2 - multilayering
445
Histology of chromophobe RCC
Well circumscribed brown tumour | Plant-like cells (thick walls)
446
Nephroblastoma =
Wilm's tumour, 2nd most common tumour in children | Abdominal mass in children
447
Types of urothelial carcinoma (transitional cell carcinoma)
Non-invasive papillary UC Infiltrating UC (highly invasive) Flat UC in situ (flat lesion with high grade features)
448
Histology of non-invasive papillary UC
Frond-like lumps on bladder wall
449
Histology of BPH
Expanding nodule | Glandular and stromal components of prostate (hyperplasia)
450
Most common malignant tumour in men
Prostate cancer
451
Prognostic scoring for prostate cancer
Gleason score (x + y, based on how they resemble glands)
452
Types of testicular germ cell tumours
Seminoma = clear cells, lymphoid infiltrate Embryonal carcinoma: anaplastic tissue Teratoma: multiple tissue types Yolk sac tumour: lace-like growth pattern Choriocarcinoma
453
Types of testicular non-germ cell tumour
Lymphoma Leydig Cell tumour --> precocious puberty (due to hormone secretions) Sertoli cell
454
Paratesticular disease
``` Epididymal cyst (benign cyst) Epididymitis Varicocele (dilated venous plexus) Hydrocele (fluid between layers of tunica vaginalis) Adenomatoid tumour ```
455
Lichen sclerosus in males =
Balanitis xerotica obliterans (BXO) --> causes phimosis
456
Peyronie's disease
Curved penis (due to scarring)
457
Fournier's gangrene
Necrotising fasciitis (pain not in keeping with size of lesion)
458
Define fistula
connection between two hollow tissues
459
Pseudomembranous colitis - Aetiology, Ix
C difficile, ABx use | Ix: C diff toxin stool assay
460
Histology of pseudomembranous colitis
Signs of inflammation (colitis) Pseudomembrane formation (appear at wet cornflakes) Neutrophil-composed conflakes (volcano like)
461
Tx of pseudomembraneous colitis
Metronidazole and Vancomycin
462
Histology of ischaemic colitis
Watershed zones (most affected) - furthest from blood vessels
463
Histology of CD
``` ANY part of GI tract Skip lesions TRANSMURAL inflammation Non-caseating granuloma Cobblestoning Extra-GI features - pyoderma gangrenosum, erythema nodosums ```
464
Histology of UC
Spreads in contiguous fashion (only affects large bowel) Inflammation confined to mucosa and submocosa Backwash ilietis Extra-GI features - erythema nodosum, pyoderma gangrenosum, PSC Cx: toxic megacolon --> perforation
465
Complications of UC
↑ risk of adenocarcinoma (UC>CD)
466
Types of non-neoplastic polyps
``` Hyperplastic - due to scarring producing excess tissue Inflammatory pseudo-polyps - due to inflammation Hamartomatous polyps (Juvenile, Peutz-Jeghers) ```
467
Types of neoplastic polyps
Adenoma - Tubular adenoma (tube-like) - Tubulovillous adenoma - Villous adenoma (finger-like)
468
Familial polyp syndromes
``` Peutz-Jegher's Familial adenomatous polyposis - Gardner's syndrome - Turcot syndrome Hereditary non-polyposis colon cancer (HNPCC) = Lynch syndrome ```
469
FAP - aetiology
autosomal dominant mutation in APC (tumour suppressor gene)
470
Gardner's syndrome
FAP + extra-Gi manifestations (osteomas)
471
HNPCC - aetiology
autosomal dominant mutation in DNA mismatch repair gene
472
Staging for colorectal carcinoma
``` Dukes' staging (no longer used) ----- A = confined to bowel wall ----- B = through bowel wall ----- C = lymph node mets ----- D = distant mets TNM ```
473
Cervical screening ages
25 - 65 years old
474
Ectocervix vs Endocervix
Ectocervix (outer region) lined by squamous epithelilum | Endocervix (inner region) lined by glandular epithelium / columnar epithelium
475
Define dyskaryosis
pre-cancerous changes in outermost squamous cells of the cervix
476
CIN1 changes
Large nucleus Areas of dense chromatin Lower 1/3 affected
477
CIN2 changes
Metaplastic squamous cells Irregular nuclei Lower 2/3 affected (including middle 1/3)
478
CIN3 changes
Full thickness epithelium involved
479
Histology of HPV infection
Koilocyte = large, irrecular, well-defined peri-nuclear halos = HPV vacuole
480
High risk HPV subtypes
HPV 16 and 18 --> cervical cancer
481
Low risk HPV subtypes
HPV 6 and 11 --> genital warts
482
Common mutation in Lung cancer
EGFR
483
Common mutation in Melanoma
BRAF
484
Common mutation in Breast cancer
BRCA 1/2
485
Common mutation in Colon cancer
AFP, K-ras
486
Common mutation in Pancreatic cancer
K-ras (95%)
487
Most common brain cancer
Metastases
488
Most common primary brain cancer
Glial tumours
489
WHO grading determines
Survival Grade I - low grade, long term survival Grade II - low grade, death in 5+ years Grade III - high grade, death within 5 years Grave IV - high grade, death within 1 year
490
Change in WHO classification 2016
Genetic prolifing --> integrated diagnosis
491
IDH1/2 mutation
``` Good prognostic factor IDH mutant (+ve) = "I don't hurt" IDH wildtype (-ve) = bad prognosis ```
492
Gliomas
Astrocytoma Oligodendroglioma Pilocytic astrocytoma
493
Most common brain tumour in children
Pilocytic astrocytoma
494
2nd most common brain tumour in children
Medulloblastoma
495
Pilocytic astrocytoma is associated with
NF1
496
Histology of pilocytic astrocytoma
Piloid "hairy" cell Rosenthal fibres Granular bodies
497
MRI of pilocytic astrocytoma
Well circumscribed, cystic lesion
498
Diffuse astrocytoma may progress to
Glioblastoma
499
Glioblastoma location
Children --> Cerebellum | Adults --> Cerebral hemispheres
500
MRI of glioblastoma
Non-enhancing lesions | Poorly defined margins