Histopathology Flashcards
1
Q
Lymphocytes are seen in
A
- Chronic inflammation
- Sheets of lymphocytes - think lymphoma
2
Q
Eosinophils are seen in
A
- Allergy
- Parasitic infection
- Hodgkin Lymphoma
3
Q
Macrophages are seen in
A
- Late stages of acute inflammation
- Granulomas
4
Q
Non-caseating granuloma
A
Sarcoidosis
5
Q
Caseating granuloma
A
TB - stains positive on Ziehl-Neelsen staining
6
Q
Tumours from epithelial cells
A
CARCINOMAS
- These express cytokeratins
Squamous cell carcinoma
- intercellular bridges and keratin
Adenocarcinoma - from glandular epithelium
- goblet cells and glands
Transitional cell carcinoma
7
Q
Histological staining types
A
Histochemical - chemical reaction to specific tissue components
Immunohistochemical - antibodies which bind to specific antigens present in the cell
8
Q
Congo red stain
A
Amyloidosis
Congo red positive and shows apple-green birefringence under polarised light
9
Q
Prussian blue stain
A
Haematochromatosis (iron overload)
10
Q
Ziehl-Neelsen staining
A
- Acid-fast bacilli
- Goes bright red
11
Q
Imunohistochemical markers
A
- Cytokeratin - epithelial marker. NO CYTROKERATINS MEANS IT IS NOT A CARCINOMA!
- CD45 - lymphoid marker
12
Q
Fontana stain
A
Positive for melanin (turns brown-black)
13
Q
Differences between parts of stomach
A
The fundus and body have specialised glands which secrete acid and enzymes
the antrum and pylorus have non-specialised glands (gastric pits)
14
Q
Duodenum - crypts and villi
A
- The cells proliferate in the crypts and midrate up to the villi
- Villous:crypt ratio 2:!
15
Q
Barrett’s oesophagus
A
- Squamous epithelium of the oesophagus can become relines with metaplastic columnar epithelium (gastric-type epithelium)
16
Q
Eosophagus - progression to adenocarcinoma
A
- Barret’s oesophagus is gastric-type epithelium
- This can go one step further to intestinal-type metaplasia (contains goblet cells)
- Intestinal type metaplasia carries high risk of cancer BUT it is reversible with the treatment of GORD
- If there are cytological and histological features of malignancy, but DM not involved, it is dysplasia
- If there is invasion of the BM, it is adenocarcinoma
17
Q
Commonest types of oesophageal cancers
A
UK - adenocarcinoma (GORD)
Globally - SCC (smoking, alcohol)
18
Q
Causes of chronic gastritis
A
ABC
- Auto-immune (e.g. pernicious anaemia)
- Bacterial - H. pylori
- Chemicals - NSAIDs, bile reflux
19
Q
What feature on stomach biopsy would indicate H.pylori infection?
A
Lymphoid follicles - indicates patient has had H. pylori infection at SOME POINT
20
Q
Effect of H. pylori on stomach cells
A
Binds to epithelial cell surfaces
injects toxins into cells (such as urease)
These lower the pH in the stomach
21
Q
Different strains of H. pylori
A
Cag A +ve – needle-like appendage injects toxins into intercellular junctions, so organism can attach more easily
Cag A -ve – associated with severe chronic inflammation
22
Q
What is the risk of cancer with chronic H. pylori infection?
A
8x increased risk of gastric cancer
23
Q
Types of cancer that chronic H. pylori can cause
A
- adenocarcinoma
- lymphoma (MALT)
24
Q
Causes of gastritis is an immunosuppressed patient
A
- CMV
- Strongyloides
25
Definitions:
- Gastric ulcer
- Gastric erosion
- Chronic ulcer
Ulcer - loss of epithelial tissue extending deeper than muscularis mucosae
Erosion - loss of epithelial tissue extending up to the lamina propria
Chronic ulcers - have fibrosis
26
Classification of stomach adenocarcinomas
- Intestinal type - well differentiated, large mucin-containing glands
- Diffuse type - poorly differentiated cells, not producing glands
SIGNET CELL IS HALLMARK (diffuse type)
27
Causes of duodenitis
- H. pylori - leading cause (spills over from gastritis)
- Giardiasis
- CMV (in immunosuppressed)
- Cryptosporydiosis
- Whipple's disease - very rare
28
Histological features of coeliac disease
- villous atrophy (damage from T-cell response to gliadin)
- crypt hyperplasia (to try and replace villi)
- increased numbers of intraepithelial lymphocytes
29
Lymphocytic duodenitis
- lymphocytic infiltration of duodenum without architectural changes
- may cause mild coeliac disease
30
Duodenal MALToma
- associated with coeliac disease
- very aggressive lymphoma
- can manage by treating H. pylori infection and abiding to gluten-free diet
31
Hirschsprung disease - gene
RET proto-oncogene Cr10
32
Diagnosis of Hirschsprung disease
Full thickness biopsy shows hypertrophies nerve fibres with no ganglia
33
Volvulus sites by age
Small children - small bowel
Old people - sigmoid colon
34
Pseudomembranous colitis
- Acute colitis caused by enterotoxins of C. difficile
- Associated with antibiotic use
- There is pseudomembrane formation
- Histology shoes volcano-like epithelial surface, these are the necrotic pseudomembranous regions filled with pus and inflammatory cells
- Detection of C. diff on toxin stool assay
- Tx - metronidazole or vancomycin
35
Risk of adenocarcinoma with UC?
20-30x increased risk
36
Neoplastic polyps of the colon
3 types of neoplastic polyps:
- Tubular
- Tubovillous
- Villous adenoma
With villous adenoma you can get hypoproteinaemic hypokalaemia
37
Risk factors for polyp - cancer
- Size of polyp
- Proportion of villous component
- degree of dysplastic change within a polyp
38
Familial Adenomatous Polyps
- Autosomal dominant
- large numbers (min 100) of adenomatous polyps
- APC gene mutation
- 100% risk cancer in 10-15 years
Features
- Retinal pigment epithelium hypertrophy at birth
39
Gardner's Syndrome
- Same as FAP but with significant extra-intestinal manifestations
- Osteomas of skull and mandible
- Epidermoid cysts
- Desmoid tumours
- Dental caries, unerupted teeth
40
Hereditary Non-Polyposis Hereditary Cancer
- Autosomal Dominant
- Mutation in DNA repair gene, so there are DNA replication erroris
- High frequency of early onset carcinomas proximal to the splenic flexure
- There can be extra-colonic cancers
41
Dukes staging for Bowel Cancer
A - confined to bowel wall
B - through the bowel wall
C - lymph node metastases
D - distant metastases
42
Renal stones
75% calcium oxalate - associated with hypercalcURIA
10% triple stones (magnesium ammonium phosphate) - associated with Proteus infection and staghorn calculi
5% uric acid stones - associated with gout and high cell turnover e.g. chemotherapy
43
Benign renal tumours
1. Papillary adenoma
- Formed of papillary cells ± tubules
- <15mm by definition
2. Renal oncocytoma
- PINK oncocytic cells
- Naked eye - mahogany brown with central scar
3. Renal angiomyolipoma
- Made of blood vessels, smooth muscle and fat
- Can be seen in tuberous sclerosis
- Remove if >4cm
44
Malignant renal tumours
1. Clear cell renal carcinoma
- Most common type
- Clear cells = small round blue cells
- LEIBOVICH RISK MODEL (risk progression index)
2. Renal papillary carcinoma
- Papillary cells
- >15mm by definition
3. Chromophobe renal cell carcinoma
- Different coloured cells
4. Nephroblastoma
- Made of 3 layers of tissue: stromal, epithelial and blastoma
- Children
- Good prognosis
45
Bladder cancers
Transitional cell carcinomas
- Most common bladder cancer
- Associated with smoking and aromatic amines
- Painless haematuria
- 3 subtypes: Clear cell transitional carcinoma, Infiltrations transitional carcinoma and flat epithelial carcinoma in situ
SCC
- Associated with Schistosomiasis
Adenocarcinoma
- Rare
46
Prostate pathology
Benign Prostate Hyperplasia
- Increase in the numbers of cells in the prostate
- Very common, aetiology unknown
- Presents with LUTS
- Mx - alpha-blockers (tamsulosin), 5a=reductase inhibitors (finasteride), TURP
Prostate cancer
- Develops from prostate intraepithelial neoplasia
- Risk factors = smoking, FHx, red meat consumption
- Prognosis - GLEASON SCORE
47
Testicular pathology
Testicular tumours
- 95% are germ cell tumours and 5% are non-germ cell tumours
- Most germ cell tumours are seminomas (clear cells)
Other germ cell tumours;
- Teratoma - can occur at any age, but always pathological in post-pubertal males
- Embryonal carcinoma
- Yolk sac tumour
- Choriocarcinoma
Non-germ cell tumours
- Leydig cell tumour - precocious puberty
- Sertoli cell tumours
Epididymitis
- Associated with N gonorrhoea/C. trachomatis in men <35
- Men >35 - E. coli
48
Gold standard for diagnosing breast cancer?
Histopathology, because you can see cellular detail AND cellular architecture.
49
What's the terminal duct lobular unit?
Duct + acinar tissue
All breast cancers arise from here
50
What are the two layers of epithelium in breast tissue?
- Outer layer = myoepithelium
| - Inner layer = luminal cells
51
Inflammatory breast disease
DUCT ECTASIA
- Inflammation and dilation of breast duct
- Smoking = biggest risk factor
- Lump with thick white nipple secretions
- There can be slit-like nipple retraction
- Cytology of nipple discharge = proteinaceous material, inflammatory cells
ACUTE MASTITIS
- Inflammation of breast tissue
- Associated with lactation(Staphyloccal infection)
- If not lacating - keratinising squamous metaplasia
- Painful tender breast
- Neutrophils
- Incision & drainage + Abx
FAT NECROSIS
- Inflammatory reaction to adipose injury e.g. radiotherapy
- PAINLESS breast lump
- Giant multinucleate cells
52
Benign Breast Disease
Fibrocystic breast disease
- Fibrous and cystic changes to breast tissue
- Changes with cycle
- Calcification may be seen
Fibroadenoma
- Fibrosis of stroma and glandular tissue
- Mouse
- Generally self-resolving
Phyllodes tumour
- Leaf-like
- Malignant potential
- Pink = benign, purple = malignant
Duct papilloma
- NO LUMP!!!
- Central papillomas - arise from large lactiferous ducts
- Perpheral papillomas - arise from small terminal ductules
- Central papillomas can give bloody discharge
Radial scar
- Central scarring surrounded by proliferating glandular mesenchyme
- Excise, because there can be malignancy at the edges
53
Proliferative breast disease
Usual epithelial neoplasia
- Proliferation of the epithelial cells
- No direct increase risk in malignancy
- Serrated lumen
Atypical ductal hyperplasia
- Epithelial proliferation - multiple layers of cells
- Rounded lumen
Atypical lobular hyperplasia
- Proliferation into the acinar space
- May not be able to see lumen
54
Breast cancer - carcinoma in situ
30% of breast cancer
- Can be DUCTAL (DCIS) or LOBULAR (LCIS)
Lobular CIS
- Loss of E-adherin
Ductal CIS
- Areas of calcification
- Proliferation along the length of the duct
- Low-grade - cribriform appearance
- High-grade - only one central lumen, containing necrotic material
55
Invasive breast cancer
- Invasion through the BM and into the stromal tissue
- Associated with high lifetime oestrogen exposure and BRCA mutation
Types of invasive breast cancer
- Ductal
- Tubular - elongated tubules of cells
- Lobular - linear arrangement of cells in Indian file pattern
- Mucinous - lots of mucin production
56
Breast basal-like carcinoma
- Sheets of atypical cells with predominantly lymphocytic infiltration
- Associated with BRCA mutations
- Positive staining for CK5/6, CK14
- Usually triple-negative
57
Breast cancer screening
- All women aged 47-73, every 3 years
- Looks for masses and abnormal calcification
- If mammogram is abnormal, may need to be recalled for further investigation
- Triple assessment = examination + USS + FNA/core biopsy
58
Prognostic factors in breast cancer
ER or PR positive - good prognosis (tamoxifen responsive)
Her2 positive - poor prognosis
59
Hyperpituitarism
- Functional adenoma
- Most common is prolactinoma
- Others are GH adenoma (gigantism/acromegaly) or CRH adenoma (Cushing's syndrome)
60
Hypopituitarism
Causes:
- Non-secretory adenomas
- Ischaemic necrosis e.g. Sheehan's)
- DIC/shock etc
Clinical manifestations in adults:
1. Gonadotrophin deficiency - low libido, low fertility, amenorrhea
2. TSH and ACTH deficiency
3. Prolactin deficiency - rarely
61
Thyroid physiology
Usual thyroid stuff but also
PARAFOLLICULAR CELLS
- These produce CALCITONIN
- Promotes absorption of calcium to increase serum calcium
62
Hashimoto's thyroiditis - histology
- Painless enlargement of the thyroid
| - There is massive lymphocytic infiltration with HURTHLE CELLS
63
Thyroid cancer - histology
PAPILLARY CARCINOMA
- Optically clear nuclei
- Intranuclear inclusions
- Psammoma bodies
MEDULLARY CARCINOMA
- Arises from parafollicular C-cells
- Secretion of calcitonin and CEA
- AMYLOID DEPOSITION IN THE TUMOUR
64
3 layers of skin?
Top layer = Epidermis (keratinocytes)
Middle layer = dermis (connective tissue and macrophages, mast cells and fibroblasts - fibroblasts produce ECM)
Bottom layer - = subcutaneous fat
65
6 inflammatory reactions (rashes) of skin?
- Pemphigoid
- Spngiotic
- Psoriaform
- Lichenoid
- Vasculitis
66
Vesicobullous skin disease
Bullous Pemphigoid
- DEEP = tense bullae, don't rupture
- Complement-driven attack on the BM
- IgG binds to hemidesmosomes of the BM
- IgG and C3 along the dermal-epidermal junction
Pemphigus vulgaris
- SUPERFICIAL = these rupture
- IgG=mediated damage to keratinocytes with intact BM (acantholysis)
- Intercellular IgG deposits
Pemphigus foliaceous
- Thin blister which may not be visible if they have burst
- IgG-mediated damage to stratum corneum
67
Spongiotic skin disease
Eczema
- T-cell mediated recruitment of eosinophils
- Hyperkeratosis with oedema between keratinocytes
68
Psoriaform skin disease
Plaque psoriasis
| - Munroe's microabscesses on microscopy
69
Lichenoid skin disease
LICHEN PLANUS
- purple plaques on wrists and arms + white striae inside mouth
- T-cell mediated destruction of deepest later of keratinocytes
- Band-like lymphocytic infiltrate under the epidermis
- Sawtoothing of Rete ridges
70
Vasculitis skin disease
Pyoderma gangrenosum
| - ULCER WITH CLEAR EDGE
71
Seborrheic keratosis
- Cauliflower lesion on old people
| - Microscopy - horn cysts
72
Epidermoid cyst
- Non-mobile lump with central punctum
| - Keratin forms inside a cyst
73
Bowen's disease
- Keratin horns
- Confined to epidermis, not invading BM
- Affects sun-exposed areas
74
Pigmented skin lesions
BENIGN JUNCTIONAL NAEVUS
- Expansion of melanocytes at the bottom of the epidermis
COMPOUND NAEVUS
- Two-tone
- Melanocytes in dermis and epidermis
MALIGNANT MELANOMA
- Breslow system for grading
- Buckshot appearance
75
How do steroids cause osteoporosis?
Reduces osteoclastogenesis
Reduced osteoblasotogenesis
Increased osteocyte apoptosis
76
Hyperparathyroidism - histological association
- Brown cell tumour
| - Multinucleate giant cells (pink cells) in fibrous stroma with haemorrhage
77
Paget's disease - histology
Cement lines
- Seen in the osteolytic-osteosclerotic phase
Mosaic pattern
- Seen in the quiescent phase
Thickened cortex
Thickened trabeculae
78
Paget's disease - X-ray
Cotton wool appearance
| Bowed bone
79
Types of fractures
Transverse (simple) fracture - straight across
Compound fracture - bone pierces through skin
Greenstick fracture - one side of bone is broken and the other side is bent
Comminuted fracture - 3+ pieces with fragments
80
What happens in fracture repair?
Pro-callus - organisation of haematoma at the site of the fracture
Fibrocartilagenous fracture forms, and then mineralises
Remodelling of bone along weight-bearing lines
81
X-ray changes in osteomyelitis
- X-ray usually normal for first 7-10 days
WEEK 1 - INVOLUCURM
- irregular sub-periosteal new bone formation
WEEK 2 - irregular lytic destruction
82
TB histology
CASEATING GRANULOMAS
LANGERHANS GIANT CELLS
83
Osteoarthritis X-ray changes
- Loss of bone space
- Osteophytes
- Subchondral sclerosis
- Subchondral cysts
84
Rheumatoid arthritis - features
- Swan neck
- Z-thumb
- Boutonniere's deformity
- Pannus formation (abnormal layer of fibrovascular tissue)
- GRIMLEY-SOKOLOFF CELLS
85
Osteosarcoma
- Bone-producing tumour
- Peaks in adolescence
- Codman's triangle
- Histology - bone, cartilage and stroma
- ALP +ve
86
Chondrosarcoma
- Cartilage-producing tumours in axial skeleton
- Age >40
- X-ray shows LYTIC LESIONS with FLUFFY CALCIFICATION
- Ring and arc mineralisation
- Malignant chondrocytes - purple/blue - found in matrix
87
Ewing's sarcoma
- t(11;22)
- Age <20y
- Joints of long bones but not in knees
- Lytic lesions
-ONION SKINNING OF PERIOSTEUM
SHEETS OF SMALL ROUND BLUE CELLS
- CD99 +ve, MIC2 +ve, ALP -ve
88
What needle is used for bone biopsy?
Jamshidi needle, under USS guidance
89
Features of malignant bone tumours
- No normal marrow tissue
- Irregular trabecular bone
- Cartilagenous tissue infiltrates the marrow
90
Fibrous dysplasia
- Young people
- Femur involved
- X-ray: SOAP-BUBBLE OSTEOLYSIS
- Bone Bx: marrow replaced with FIBROUS STROMA
- SHEPHERD CROOK DEFORMITY if NOF involved
91
Benign bone tumours?
Osteochondroma
- Age 10-20, M>F
- Cartilagenous surface overlying the normal bone
- Affects knees and elbows
Endochondroma
- Cartilganeous proliferation within the bone
- Hands and feet
- X-ray - POPCORN CALCIFICATION
Giant cell tumour
- Borderline malignancy
- Malignant stromal cells
- Occurs in the epiphyses and can burst through the bone into surrounding tissue
- X-ray - lytic lesions
- Histology - osteoclasts, on a background of spindle cells
92
Name the malignant bone tumours
- Osteocarcoma :(
- Chondrosarcoma :)
- Ewing's sarcoma :/
93
What are the major manifestations of glomerular disease?
- Raised creatinine and urea, as kidneys aren't filtering these out
- Haematuria and proteinuria, due to failure of maintaining barrier function
94
What are the 3 layers of the kidney filtration barrier?
ENDOTHELIUM - inner layer, fenestrated
GLOMERULAR BASEMENT MEMBRANE - Type IV collagen
PODOCYTES - outer layer, cells have processed with interdigitate to completely cover the BM
95
Immune complex deposition in the kidneys - variation by site?
MESANGIUM - some proteinuria, seen on dipstick
SUBEPITHELIAL (between BM and podocytes) - heavy proteinuria ad nephrotic syndrome
SUBENDOTHELIAL (between BM and endothelium) - activates inflammatory cells in the blood -- irreversible glomerular damage and scarring
96
How can we detect immune complexes in the kidneys?
- Immunohistochemistry - using fluorescently-labelled IgG
| - Electron microscopy - always look at the glomerulus with EM!!!!
97
Polycystic kidney disease
- Autosomal dominant
- Cysts arise from all portions of the nephron and press on the surrounding parenchyma
- PKD1 and PKD2 mutations
- Associated with liver cysts and berry aneurysms
98
Acute tubular necrosis - pathophysiology
- Commonest cause of AKI
- Damage to tubular epithelial cells (myoglobin, toxins)
- Cells lose the brush border and cannot reabsorb
- Some cells are lost into the lumen
- Surviving cells can compensate at first, but not with repeat attacks
99
Why does GFR drop in ATN?
- Tubule lumens become blocked by casts
- Fluid leaks from tubules to interstitium
- Injured tubules send signals to JGA to drop the GFR
100
ATN - Histology
Oedema - fluid-filled spaces between the tubules
Flattened tubular morphology
Tubules contain granular material (sloughed-off cells)
101
Characteristic features of acute glomerulonephritis
Urine contains casts of RBCs and WBCs
Glomerular crescents - accumulation of cells in bowman's space, indicates severe and irreversible damage
102
Causes of acute crescenteric glomerulonephritis
IMMUNE COMPLEX DEPOSITION
- Especially subendothelial deposition
- Seen on immunohistochemistry and EM
- e.g. IgA nephropathy, SLE
ANTI-GBM DISEASE
- Antibodies can be detected in circulation
- Linear deposition of IgG on the Type IV collagen on basement membrane
PAUCI-IMMUNE
- Scanty deposits of immunoglobulin and complement in the glomeruli
- Associated with p-ANCA
- There is glomerular necrosis
- Associated with vasculitis in other organs e.g. rash
103
Goodpasture's syndrome
Antibodies bind to the Type IV Collagen of basement membrane in kidneys and alveoli
Lung haemorrhage + glomerulonephritis
104
Systemic causes of nephrotic syndrome
DIABETES MELLITUS
- Mesangial expansion followed by nodular sclerosis
AMYLOIDOSIS
- AA (acute phase protein)
- AL (immunoglobulin light chains, seen in myeloma patients)
SLE
- ANA and anti-dsDNA
105
Primary glomerular disease
MINIMAL CHANGE DISEASE
- LM looks normal
- EM shows loss of foot processes
- Generally steroid-responsive
FOCAL AND SEGMENTAL GLOMERULONEPHRITIS
- More common in adults
- Glomeruli develop segmental scars
MEMBRANOUS GLOMERULONEPHRITIS
- Immuno complexes deposit outside of the glomerular basement membrane
- Associated with autoimmune disease
- Screen for malignancy in elderly patients
106
Microscopic haematuria
THIN BASEMENT DISEASE
- Hereditary defect in Type IV collagen
IgA NEPHROPATHY
- IgA deposition in glomeruli
- 30% progress to end-stage renal failure
107
Autoantibodies in SLE
ANA = SCREENING TEST
- Anti-dsDNA
- Anti-ribonucleoproteins (most specific but not sensitive)
- Anti-histone antibodies - seen in drug-related SLE
108
Skin pathology in SLE
- Lymphocytic infiltration of the upper dermis
- Damage to basal epidermic
- Extravasation of RBCs
- Immune complex (IgG) deposition at the dermal-epidermal junction
109
Renal pathology in SLE
- Thickened pink glomerular capillary loops, these are clled wire loops
- Immunofluorescence shows deposition of immune complexes
- EM shows dark areas of immune complex deposits in the glomerular BM
110
Cardiac pathology in SLE
- Non-infective endocarditis = LIBMAN SACKS
| - Presents the same as bacterial endocarditis
111
Diffuse scleroderma
ANTI-SCL70
| - Truncal skin involved
112
Limited scleroderma
ANTICENTROMERE ANTIBODY
- no truncal involvement
- this is 'CREST' syndrome
113
Initial screening for Scleroderma?
ANA screen shows nucleolar pattern immunofluorescence
114
Scleroderma histology
- Increased collagen deposition in dermis
- Excess collagen in stomach and oesophagus (trichome staining)
- Onion-skin thickening of the arteries
115
Features of dermatomyositis
- Tender, inflamed muscles
| - Gottron's papules (red rash on knuckles)
116
Features of myositis
- Raised CK
| - Proximal muscle weakness and tenderness
117
Sarcoidosis
- Non-necrotising granuloma
- Langerhans cells (multinucleated giant cells)
- Histiocytes
- Lymphocytes
Investigations;
- Immunoglobulins (hypergammaglobulinaemia)
- Raised serum ACE
- Hypercalcaemia
118
Giant cell arteritis
"Temporal arteritis"
- Headaches and jaw claudication in patients aged 50+
- Temporal artery pulse not palpable
- ESR and biopsy for diagnosis
Histology
- Narrowed lumen
- Granulomas
- Lymphocytic infiltration of the tunica media
Tx
- High dose steroids
119
Polyarteritis nodosa
ASSOCIATED WITH HEP B
- Necrotising arteritis, most commonly affecting the renal and mesenteric vessels
- Renal impairment + gut ischaemia
Ix
- Angiogram - beading of vessels
120
Granulomatosis with Polyangiitis
3 hallmarks:
- ENT (nosebleeds, sinusitis and ear problems)
- LUNGS
- KIDNEYS
c-ANCA
121
Eosinophilic Granulomatosis with Polyangiitis
| "Churg-Strauss disease"
Triad:
- ASTHMA
- EOSINOPHILIA
- VASCULITIS
p-ANCA (binds to MPO)
122
2 main mechanisms of cerebral oedema
VASOGENIC - disruption of blood-brain barrier
CYTOTOXIC - secondary to cellular injury e.g. hypoxia
123
What water transporter is found in the brain?
aqp4 :)
124
Normal flow of CSF in the brain
1. CSF produced in the CHOROID PLEXUS
2. Flows to the LATERAL VENTRICLES --> 3RD VENTRICLE --> 4TH VENTRICLE
3. From here, some CSF goes down into the spinal cord but most of it flows into the SUBARACHNOID SPACE
125
Types of hydrocephalus
Communicating
- No obstruction but there is problem with resorption of CSF
- e.g. INFECTION
Non-communicating
- Obstruction to the flow of CSF
126
What are the three sites of brain herniation?
SUBFALCINE
- Cortex pushed under the FALX CEREBRI of the dura
- Usually due to SOL
TRANSTENTORIAL
- Medial temporal lobe is pushed through the tentorial notch
TONSILLAR
- Cerebellar tonsil is pushed through the foramen magnum :(
127
Non-traumatic intraparenchymal haemorrhage of the brain
- Haemorrhage into the brain parenchyma, due to rupture of a small vessel
- Most commonly in BASAL GANGLIA
- Often due to HTN
Charcot-Bouchard aneurysm = associated with chronic HTN
128
Cavernous angioma
Well-defined malformative lesions composed of closely packed vessels with no parenchyma in between
Bleeds can occur with low pressure
Recurrent small bleeds
T2 weighted MRI - TARGET SIGN
129
Sub-arachnoid haemorrhage
- Rupture of berry aneurysm
- Highest risk of rupture at 6-10mm diameter
Associated conditions:
- PKD
- EDS
- coarctation of the aorta
130
Brain infarct versus brain haemorrhage
Infarct:
- Tissue necrosis
- Rarely haemorrhagic
- Permanent damage - no recovery
Haemorrhage
- Bleeding
- Dissection of parenchyma
- Limited tissue damage
- Partial recovery
131
Contusion
Collision of brain with suface of skull, causing bruising of the surface
Rebound of the brain after direct impact can cause CONTRECOUP damage to the opposite side
132
Laceration
Rupture of the pia mater
133
Genetic predisposition to brain tumours
- Tuberous sclerosis
- Li-Fraumeni syndrome
- von Hippel Lindau syndrome
134
What is the most common type of primary CNS tumour?
Glial tumour
135
Glial tumours - classification
Circumscribed gliomas - Children
- Rarely undergo malignant transformation :)
- Most common type is PILOCYTIC ASTROCYTOMA
- Others are pleiomorphic xanthoastrocytoma and subependymal giant cell astrocytoma
Diffuse infiltration - Adults
- Can be astrocytomas or oligodendrocytomas
- IDH1/2 mutation
- Become more malignant over time
136
Pilocytic astrocytoma
- Most common primary CNS tumour in children
- Infratentorial
Genetics:
- Seen in NF1
- BRAF mutation
Histological features:
- Hallmark is piloid (hairy) cell
- Rosenthal fibres
- Granular bodies
137
Astrocytomas - location and age?
- Children - cerebellum
| - Adults - cerebral hemispheres
138
Natural history of astrocytomas
Astrocytomas eventually become glioblastomas
- de novo gliocytomas are the most frequent and most aggressive form
- IDH2 mutation
139
What are the main neuroglial cells of the brain?
ASTROCYTES
- maintain BBB
EPENDYMAL CELLS
- Cuboidal/columnar ciliated cells
- Line the ventricles
- Regular production and flow of CSF
140
What are the main neuroglial cells of the brain?
ASTROCYTES
- maintain BBB
EPENDYMAL CELLS
- Cuboidal/columnar ciliated cells
- Line the ventricles
- Regular production and flow of CSF
141
Histological feature of ependymoma
Perivascular Pseudorosette
142
What are the types of glial tumours?
- Astrocytoma
- Pilocytic astrocytomas
- Glioblastoma multiforme
- Oligodendrocytoma
143
Meningioma
- 2nd most common primary intracranial tumour after glioma
- Patients >40y
- Causes focal symptoms
Pathophysiology
- Come from arachnoid mater cells
- Multiple meningiomas seen in NF2
- Causes focal symptoms
Histology
- Psammoma bodies
Grading
- Depends on histology
- Mitotic activity is an important factor in grading
- Also brain invasion
144
What do oligodendrocytes do?
Produce myelin
145
Glioblastoma multiforme
- Highly malignant
- MRI - contrast enhancement
- Histology -. microvascular proliferation + necrosis
- Genetics - IDH mutation
146
Oligodendroglioma
- Young adults (aged 20-40)
- Presents with a long history of neuro signs e.g. seizures
- MRI shows no/little contract enhancement
- Histology - round cells with clear cytoplasm (fried eggs)
- Genetics - IDH 1/2 mutation or co-deletion 1p/19q
147
Medulloblastoma
- Common in children
- Embryonal tumour
- ALWAYS IN CEREBELLUM
Histology
- Small round blue cells
- Very little differentiation
- HOMER-WRIGHT ROSETTES
148
Neuropathology of Alzheimer's Disease
- Extracellular plaques (amyloid-beta)
- Neurofibrilliary tangles
- Central amyloid angiopathy - proteins deposit in vascular walls
- Neuronal loss
- Amyloid precursor protein - cleaved to form amyloid-beta, which is toxic
149
Parkinson's disease - neuropathology
- Death of dopaminergic cells in substantia nigra
- Abhorrent metabolism of alpha-synuclein
- Lewy bodies = collections of alpha-synuclein and beta-amyloid
- GOLD STANDARD = alpha-synuclein staining
Braak staging is also used for Parkinson's disease
150
Pick's Disease
- Fronto-temporal atrophy
- Disorders of frontal lobe function e.g.executive function
Histology
- Gliosis
- Neuronal loss
- Ballooned neurons
- Tau-positive Pick's bodies
Pick's disease is a 3-R tauopathy
151
Cardiomyopathy
DILATED CARDIOMYOPATHY
- Progressive loss of myocytes
HYPERTROPHIC CARDIOMYOPATHY
- LVH
- Familial in 50% cases
- Thickening of the septum causes left ventricular outflow obstruction
RESTRICTIVE CARDIOMYOPATHY
- Impaired ventricular compliance
- Can be idiopathic, or secondary to myocardial disease (e.g. amyloid)
- Normal size heart with big atria
152
Rheumatic valvular disease
- Previous rheumatic fever, with immune cross-reactivity with the cardiac valves
- Almost always mitral stenosis
- Button hole valves
153
Causes of aortic regurgitation
RIGIDITY
- Rheumatic disease
- Degenerative
DESTRUCTION
- Bacterial endocarditis
DISEASE OF AORTIC VALVE RING
- Dilatation
- Marfan's
- Syphilis
154
Aneurysms
TRUE ANEURYSM
- All layers of the wall dilate
FALSE ANEURYSM
- Extravascular haematoma
Causes of aneurysms:
- Congenital e.g. Marfan's syndrome
- Atherosclerosis
- Hypertension
155
Cardiac failure
LEFT-SIDED CARDIAC FAILURE
- Pulmonary oedema
- SOB
RIGHT-SIDED CARDIAC FAILURE
- Peripheral oedema
- Nutmeg liver
- Most common cause of right-sided heart failure is left-sided heart failure!
Histology
- Dilated heart
- Scarred, thin walls
- Fibrosis
156
Acute Coronary Syndrome
- Occurs when a stable plaque becomes unstable
| - There is often a superimposed thrombus
157
Angina pectoris - definition
Transient ischaemia which does not produce myocyte necrosis!
158
Angina pectoris - types
STABLE
- Comes on with exertion
- Relieved by rest
- No plaque disruption
UNSTABLE
- Pain comes on with less exertion or at rest
- Due to disruption of plaque, with superimposed thrombus
PRINZMETAL
- Uncommon
- Due to coronary artery spasm
159
Dressler's syndrome
Pericarditis following MI
160
Myocardial infarction - definition
Death of myocardial tissue following prolonged ischaemia
161
Myocardial infarction - histology
1-3 days:
- Coagulation necrosis
- Loss of nuclei and striations
- Neutrophil infiltration
10-14 days
- Granulation tissue
- Macrophages
162
Reperfusion injury after MI
- When blood flows back into an area of myocardial necrosis, there is oxidative damage, calcium overload and inflammation
- Causes further injury
163
Acute pancreatitis - causes
Most common causes = gallstones (50%) and alcohol (33%)
- These cause duct obstruction
All other causes - direct acinar injury
164
Patterns of injury in acute pancreatitis
- Periductal injury - most common, usually secondary to obstruction
- Perlobular injury - necrosis at edges of lobules
- Panlobular injury - develops from periductal or perilobular injury
165
Why does hypocalacaemia occur in acute pancreatitis?
- Release of lipases results in fat digestion and fat necrosis
- Calcium ions bind to free fatty acids, forming soaps
166
Causes of chronic pancreatitis
Metabolic/toxic causes
- Alcohol (80%)
- Haemochromatosis
Duct obstruction
- Gallstones
- Abnormal duct anatomy
- Cystic fibrosis
NB drugs do not play a role in chronic pancreatitis!
167
Pancreatic pseudocysts
- Occur in acute and chronic pancreatitis
- There is necrotic tissue, lined with fibrotic tissue
- no epithelial lining !
- Usually contain fluid that is rich with pancreatic enzymes
168
Autoimmune pancreatitis
IgG4-POSITIVE PLASMA CELLS
| Tx with steroids
169
Pancreatic neoplasms
CARCINOMA
- 85% of all pancreatic cancers are ductal carcinomas
- Acinar carcinoma
CYSTIC NEOPLASMS - usually benign
- Seroud cystadenoma
- Mucinous cystadenoma
170
Pancreatic ductal carcinoma
- Usually at head of pancreas
- K-RAS MUTATION!!
Ductal carcinoma arises from dysplastic ductal lesions in one of 2 pathways:
1. Pancreatic Intraductal Neoplasm (PanIN)
2. Intraductal Mucinous Papillary Neoplasm (IMP)
171
Pancreatic islet cell tumours
- Non-secretory
- MEN1
- commonest = insulinoma
- arises from B-cells and causes hypoglycaemia
172
Chronic cholecystitis
1. Thickened GB wall
2. Rokitansky Acschoff sinuses
- Diverticula in the gallbladder
- Seen in chronic cholecystitis
- Occur with gallstones
173
PID - Causative organisms
Sexually active women - Chlamydia, Gonorrhea
Post-abortion:
- Staph
- Strep
- Coliform
- Clostridium perfringens
174
Characteristic histological feature of HPV infection
Halo around the nucleus (koilocyte)
175
Most common location of fibroids?
Intramural
176
Classification of endometrical carcinoma
Type 1 (85%)
- Secretory, endometroid and mucinous
- Oestrogen dependent
- Occur with atypical endometrial hyperplasia
- Low-grade tumours
Type 2 (15%)
- Serous and clear cell carcinomas
- Older patients
- Less oestrogen-dependent - they arise in atrophic endometrium
- Serous is associated with p53 mutation
177
Types of ovarian cancer
Most common is epithelial tumour (95%)
Others:
- germ cell tumours
- sex cord tumours
178
Types of teratoma
MATURE TERATOMA
- Benign
- Mature adult-type tissues e.g. bone, hair, teeth
IMMATURE TERATOMA
- Malignant
- Contains embryonic elements (usually neural tissue)
- Spreads within peritoneal cavity and metastasises to distant organs
MATURE CYSTIC TERATOMA WITH MALIGNANY TRANSFORMATION
- Rare
- Most commonly a SCC
- Any type of tissue in the teratoma can become malignant, so it can become BCC, melanoma, thyroid cancer etc
179
Krukenberg tumour
- Secondary ovarian tumour
- Comes from gastric or breast cells
- Mucin-producing signet cells
180
Name the benign bone tumours
- Osteochondroma
- Endochondroma
- Giant cell tumour
181
Histological features of Crohn's disease
- Mouth to anus
- Transmural
SKIP LESIONS
COBBLESTONE MUCOSA
NON-CASEATING GRANULOMA
The first lesion is an APTHOUS ULCER (rosethorn)
Ulcers join to form SERPENTINE ULCER
182
Non-neoplastic polyps
HAMARTAMOUS POLYPS
- These can be JUVENILE POLYPS or PEUTZ-JEHGER SYNDROME
Juvenile polyps
- Children <5, rectum
- Malformation of mucosa and lamina propria
Peutz-Jehger syndrome
- AD
- mutated LBK1
- Multiple polyps and macules
HYPERPLASTIC POLYPS
- Cells build up due to shedding of endothelium
- Affects middle-aged people
183
Carcinoid Syndrome
- Group of tumours of the ENTEROCHROMAFFIN CELLS
- These produce 5-HT
Presentation
- Headache, flushing, diarrhoea, bronchoconstriction
Ix - 24h urinary 5HAA
Mx - Ocreotide
184
What are the different types of lung cancer?
- Squamous cell carcinoma
- Adenocarcinoma
- Small cell carcinoma
- Large cell carcinoma
- Mesothelioma
185
Squamous cell carcinoma - lung
- Associated with smoking
- Affects central bronchi
- c-myc/P53 mutations
- Local spread, late mets
- Cavitation
- Hypercalcaemia
HISTOLOGY:
- Keratinisation
- Desmosome = intracellular prickles
186
Small cell lung cancer
- Associated with smoking
- Arises from NEUROENDOCRINE CELLS
- usually central
- ECTOPIC ACTH SECRETION
EARLY METS :(
Histology - small poorly differentiated cells
187
Lung adenocarcinoma
NON-SMOKER'S CANCER :(
Occurs peripherally with early mets
EGFR MUTATION
GLANDULAR PROLIFERATION
MUCIN PRODUCTION
Cytology - mucin vacuoles
188
Large cell carcinoma
- Large cells
- Large nuclei
- Prominent nucleoli
- Poor prognosis
- No evidence of squamous or glandular differentation
189
Diffuse alveolar damage
- RDS/ARDS
- Rapid onset respiratory failure
Post-mortem histology:
- Heavy, plum-coloured lungs
- Airless
- Expanded
- Firm
190
Histological features of asthma
- Charcot-Leyden crystals
| - Curschmann spirals (shed epithelium)
191
Idiopathic pulmonary fibrosis
- Honeycomb fibrosis
| - CLUBBING
192
Lung pneumocytes?
- Type 1 = thing alveolar cells, for gas exchange
| - Type 2 = produce surfactant
