Histopathology Flashcards
neutrophils vs lymphocytes and inflammation
neutrophils = acute inflammation lymphocytes = chronic inflammation
what does an eosinophil look like on microscope?
bilobed nucleus, red granules
what are macrophages like in their current state vs chronic inflammatory conditions?
- natural state: phagocytic
- chronic inflammatory conditions: secretory
cause of a caseating granuloma
TB
characteristics of an SCC
keratin production
intracellular bridges
characteristics of adenocarcinoma
mucin production
glands
what is the stain for melanin?
fontana stain
stain for iron overload?
prussian blue
what antibody shows it is an epithelial origin?
cytokeratin Ab
out to in structures of bone?
periosteum
cortex
medulla
diaphysis and epiphysis
diaphysis: main part of bone
epiphysis: head
what are the bone tumour-like conditions?
- fibrous dysplasia
- metaphyseal fibrous corticol defect/ non-ossifying fibroma
- reporative giant cell granuloma
- ossifying fibroma
- simple bone cyst
what happens in fibrous dysplasia?
marrow replaced by fibrous stroma with rounded trabecular bone
X-ray features of fibrous dysplasia
soap bubble appearance
femoral head = Shepherd’s Crook
chinese letters
features of McCune Albright Syndrome
- polyostotic fibrous dysplasia
- endocrine problems
- cafe au lait spots
cartilaginous benign bone tumours
- osteochondroma
- enchondroma
- chondroblastoma
bone forming benign bone tumours
osteoid osteoma
osteoblastoma
osteoma
features of osteochondroma
- end of long bones
- young males
- cartilaginous surface overlying normal trabecular bone
features of endochondroma
- cartilaginous proliferation within bone
- most in hands
- popcorn calcification
what is a borderline bone malignancy? where is it formed?
giant cell tumour
end of long bones, mostly around knee
X-ray and histology of giant cell tumour
X-ray: lytic appearance
Histology: osteoclasts on background of spindle/ovoid cells
what are the tumours that metastasize to bone?
breast prostate lung kidney thyroid
what are the types of malignant bone tumours?
- osteosarcoma: forms bone
- chondrosarcoma: forms cartilage
- Ewing’s: undifferentiated mesenchymal tumour
X-ray chondrosarcoma findings
lytic with fluffy calcification
what is Ewings? X-ray finding
small round cell tumour
X-ray: onion skinning of periosteum, lytic +/- sclerosis
what are soft tissues tumours?
mesenchymal proliferation
occur in extra-skeletal non-epithelial tissues of body (exc meninges + LR system)
types of soft tissue tumours
- liposarcoma: myxoid appearance
- spindle cell sarcoma
- pleomorphic sarcoma
bad prognostic sign in bone tumours
aneuploid/ hyperdiploid
>5cm
down side of cytopathology
does not show tissue architecture
different cytopathology grades
C1: inadequate C2: benign C3: atypia, probably benign C4: suspicious of malignancy C5: malignancy
what stain do you use for breast pathology?
H+E
features of breast histology under H+E stain
- purple = glandular tissue
- pink = stroma around gland
- duct with acini around
- myoepithelial cells (help pump milk)
histology of duct ectasia
duct distended, proteinaceous material
foamy macrophages
what is fibrocystic disease? histology?
exaggerated response to hormonal influence
ducts dilated, may get calcified
what is a fibroadenoma
benign fibroepithelial neoplasm of breast
what is an intraductal papilloma?
benign papillary tumour, arising duct system
peripheral vs central papilloma
- peripheral papilloma: small terminal ductules (clinically silent)
- central papilloma: large lactiferous ductules (nipple discharge)
histology of intraductal papilloma
- large dilated duct, polypoid mass in middle
- fibrovascular core
what is radial scar?
benign sclerosing scar
central zone of scarring surrounded by radiating zone of proliferating glandular tissue
histology of radial scar
central stellate area
process of proliferative breast disease
- usual epithelial hyperplasia
- epithelial atypia/ atypical ductal carcinoma
- in situ lobular neoplasia (within acinar unit)
DCIS on mammography
areas of calcification
histology of DCIS
- cribriform (punched out appearance)
- cells large, not many lumens left
- central lumen, full of necrotic material
2 distinct pathways to invasive breast cancer
- Low grade: from low grade DCIS, 16q loss
2. High grade: high grade DCIS, complex karotypes
cell type of invasive DUCTAL carcinoma
large pleomorphic nucleated cells
cell type of invasive LOBULAR carcinoma
linear, monomorphic
Indian file pattern
cell type of invasive TUBULAR carcinoma
elongated tubules
invade stroma
cell type of invasive MUCINOUS carcinoma
empty spaces, filled with mucin
what is breast cancer grading based on?
tubule formation
nuclear pleomorphism
mitotic activity
what receptor status are basal like carcinomas?
triple -ve
what is the most important prognostic factor in breast cancer?
axillary LNs
what does mammogram screening go on?
47-73
different mammogram gradings
B1 = normal breast tissue B2 = benign abnormality B3 = lesion of uncertain malignant potential B4 = suspicious of malignancy B5 = malignant a/ DCIS b/ invasive
cells of anterior and posterior pituitary
anterior = epithelial cells posterior = nerve cells
what is a non-toxic goitre and when is it common?
enlargement without overproduction of thyroid hormones
common if impaired synthesis of thyroid hormones
how does a multinodular goitre form?
with time simple enlargement develops into multinodular pattern
hyperfunctioning nodule may develop
what is struma ovarii?
ovarian teratoma
ectopic thyroid
Hashimotos histology
- lots of lymphoid cells within germinal centres
- epithelial cells become large, lots of eosinophillic cytoplasm
= Hurthle cell
histology of papillary carcinoma
optically clear nuclei
intranuclear inclusion
psommoma bodies
what can medullary carcinoma produce?
parafollicular C cells
calcitonin produced
deposited as amyloid
what is the problem in Cushing’s disease?
PITUITARY
hormone levels in CAH
dec cortisol production
inc ACTH
adrenal stimulation and inc androgen synthesis
acute causes of primary adrenal insufficiency
- sudden withdrawal of corticosteroid therapy
- haemorrhage (neonates)
- sepsis with DIC (waterhouse-fridenston syndrome)
chronic causes of primary adrenal insufficiency
AI
TB
HIV
Metastastic
SLE SOAPBRAINMD
Serositis Oral ulcers Arthritis Photosensitivity Blood (all counts low) Renal (proteinuria) ANA Immunologic (anti-dsDNA) Neurologic (psych, seizures) Malar Rash Discoid Rash
auto-Abs in SLE
- anti-dsDNA
- anti-smith
- anti-histone
what drug can cause SLE?
hydralazine
anti-histone
skin histology in SLE
- lymphocytic infiltration of dermis
- vascuolisation
- extravasation of RBCs = rash
- immune complexes at epidermal-dermal junciton
renal histology in SLE
wire loop capillaries (thickened = immune complex deposition)
what is Libman Sacks Endocarditis
- non-infective
- SLE associated
- vegetation: lymphocytes/neutrophils/fibrin stranfs
diffuse vs limited scleroderma
diffuse: involves trunk, anti-topoisomerase (Scl 70)
limited: does not involve trunk, anti-centromere
pattern of immunofluoresence in scleroderma
nucleolar
vascular histology seen in scleroderma
intimal proliferation = onion skin appearance
pattern of ANA and what is signifies
ANA = speckled pattern
suggests mixed connective tissue disease
main feature of sarcoidosis
non-caseating granuloma
investigation results in sarcoidosis
hypergammaglobuloinaemia
raised ACE
hypercalacaemia
what are the 2 medium vessel vasculitis?
polyarteritis nodosa
Kawasaki
features of polyarteritis nodosa
rosary bead appearance on angio
associated with Hep B
temporal arteritis biopsy findings
lymphocytic infiltration of tunica media of temporal artery
triad seen in granulomatosis with polyangiitis (Wegner’s)
- ENT (nosebleeds, sinusitis, saddle nose)
- Lungs (haemoptysis, SOB)
- Kidneys (haematuria)
cANCA
cANCA directed against
proteinase 3
triad in Churg Strauss (eosinophillic granulo w/ polyangiitis)
- asthma
- eosinophillia
- vasculitis
pANCA
pANCA directed against
myeloperoxidase
what is hydrosalpinx?
enlarged fallopian tube filled with fluid
what proteins are encoded by HPV and what do they bind to?
E6 and E7 = transforming genes
bind to and inactivate 2 tumour suppressors (retinoblastoma, p53)
what does productive HPV look like on histology?
halo around nucleus (koilocyte)
CIN 1/2/3
1; lower 1/3
- lower 2/3
- entire epithelium
cervical smear programme
at 25y
25-49: 3 years
50-62: 5 years
histology of endometrial hyperplasia
increase in stroma and glands
driven by oestrogen
type 1 endometrial carcinoma
85%
endometrioid
mucinous
secretory
type 2 endometrial carcinoma
serous
clear cell
arise in atrophic endometrium
what carriers a better prognosis in Endometrial Carcinoma?
diploidy
FIGO staging in EC
- confined to uterus
- spread to cervix
- spread to adnexae, vagina, local lymph nodes
- distant spread
complete mole and possible complications
fertilisation of empty egg
can convert to invasive mole or malignancy
partial mole
normal ovum fertilised by 2 sperms
none progress to malignancy
issue with choriocarcinoma
rapidly invasive
wide mets
theory of endometriosis
metaplasia of pelvic peritoneum
what do ovaries consist of
surface epithelium
ovarian stroma
germ cells
types of ovarian epithelial tumours
type 1: low grade (low grade serous, endometrioid, mucinous, clear cell)
type 2: high grade (mostly serous, p53 mutation)
what are the benign ovarian tumours
- serous cystadenoma
- cystadenofibroma
- mucinous cystadenoma
- brenner tumour
tumours associated with endometriosis
- endometrioid (better prognosis than mucinous and serous)
- clear cell (clear cytoplasm due to lots of glycogen)
types of germ cell tumours
dysgerminoma
teratoma
choriocarcinoma
endodermal sinus tumour (develop from extra embryonic tissue)
what are the steps of atherogenesis
- endothelial injury
- LDL enters intima, trapped in subintimal space
- LDL converted oxidized LDL = inflammation
- macrophages take up oxidized LDL via scavenger receptors
- form foam cells
- apoptosis of foam cells =inflammatio and cholesterol core of plaque
- increase adhesion molecules on endothelium
- more macrophages and T cells entering plaque
- VSMC form fibrous cap
what is the earliest change in atherosclerosis?
fatty streak
what are the different acute plaque changes?
- rupture: exposes prothrombogenic plaque contents
- erosion: exposes prothrombogenic subendothelial BM
- haemorrhage into plaque: increase size
what is dilated cardiomyopathy?
progressive loss of myocytes
= dilated hearts
causes of dilated cardiomyopathy
infective
toxic (alcohol)
hormonal (peripartum, thyroid)
genetic (haemochromatosis)
histology following an MI: under 6 hours
normal histology
CK-MB normal
histology following an MI: 6-24 hours
loss of nuclei
homogenous cytoplasm
necrotic cell death
histology following an MI: 1-4 days
infiltration of polymorphs
then macrophages to clear up debris
histology following an MI: 5-10 days
removal of debris
histology following an MI: 1-2 weeks
granulation tissue
new blood vessels
collagen synthesis
histology following an MI: weeks to months
strengthening
decellularising scar
MI complications
contractile dysfunction (cardiogenic shock)
arrhythmia
myocardial rupture (free wall most common)
pericarditis
RV infarction
infarct extension (new necrosis adjacent to old)
infarct expansion (necrotic muscle stretches)
what is the cause of chronic ischaemic heart disease?
progressive HF due to ischaemic myocardial damage
what is the cause of sudden cardiac death?
due to ischaemia-induced electrical instability
cardiac failure histology
- dilated heart
- scarring/thinning of walls
- fibrosis and replacement of ventricular myocardium
what is the abnormality in Hypertrophic Cardiomyopathy?
abnormality in beta-myosin heavy chain
what is the problem in restrictive cardiomyopathy?
impaired ventricular compliance
normal heart size = big atria
cause of chronic rheumatic valvular disease
immune cross reactivity with cardiac valves
mitral
histology of chronic rheumatic valvular disease
- thickening of valve leaflet
- commissures fuse
- thickening/shortening/fusion of chordae tendinae
causes of aortic regurgitation
- rigidity (rheumatic, degenerative)
- destruction (microbial endocarditis)
- disease of aortic valve ring (Marfan’s, AS, dissecting aneurysm)
true vs false aneurysm
true: all layers of wall dilate
false: extravascular haemotoma
describe the endothelium in liver
is discontinuous
no tight junctions
what do stellate cells do normally? Vs when activated?
normally = store Vit A activated = become myofibroblasts and lay down collagen
what is found in liver zone 3?
more metabolically active enzymes
what is the limiting plate?
ring of collagen around portal tract
what changes occur in liver injury?
- kupffer cells activated
- endothelial cells stick together = hard for blood to flow through
- BM-type collagens secreted into Space of Disse by activated Stellate cells
- hepatocytes lose microvilli
what happens in extrahepatic shunting?
blood never reaches liver
backlogs into sites of porto-systemic anastomosis
what happens in intrahepatic shunting?
blood goes through liver
does not come into contact with hepatocytes
blood = unfused and toxic
what histology do you see in acute hepatitis?
spotty necrosis
what determines the grade and stage in chronic hepatitis?
- grade = severity of inflammation
- stage = severity of fibrosis
what is interface hepatitis ?
AKA piecemeal hepatitis
inflammation crosses limiting plate
how does fibrosis stain? what would be seen in intrahepatic shunting?
stains blue
extends between portal tract and central vein
3 presentations of alcoholic liver disease
fatty liver
alcoholic hepatitis
cirrhosis
histology of alcoholic hepatitis
- ballooning of cells
- mallory denk bodies (pink deposits in cells)
- apoptosis
- pericellular fibrosis
why is zone 3 particularly vulnerable to damage?
hypoxic
most metabolically active
PBC
bile duct loss
chronic inflammation
granulomas
PSC
periductal bile fibrosis
leads to loss
Haemochromatosis gene
HFe gene on Chr 6
Wilsons Chromsome
Chr 13
where is the deficiency in A1AT?
deficiency in blood not hepatocytes
excess in hepatocytes, folds wrong and cannot leave = damage
hepatitis and emphysema
causes of hepatic granuloma
PBC
Drugs
TB
Sarcoidosis
exocrine and endocrine aspects of pancrea
exocrine: acini and ducts
endocrine: e.g. islets of Langherans
2 pathogenesis of acute pancreatitis
- Duct Obstruction (gallstone and alcohol)
2. Direct Acinar injury (all other causes)
how gallstone causes acute pancreatitis?
reflux of bile up pancreatic duct
damage to acini
release of enzyme
how alcohol causes acute pancreatitis?
spasm/oedema of Sphincter of Oddi
how does acute pancreatitis cause hypocalcaemia?
lipases released from inflamed pancreas = fat necrosis
Ca binds to free fatty acids = soaponification
what is a pseudocyst?
collection of fluid without epithelial lining
lined by fibrous tissue
rich in pancreatic enzymes/necrotic materal
IgG4 related disease (AI pancreatitis)
duct surrounded by loads of IgG4 expressing plasma cells
n.b. normal polyclonal response = different IgGs
different tumours of pancreas
- carcinomas: ductal (85%), acinar
- cystic neoplasms: serous cystadenoma, mucinous cystic neoplasm
- pancreatic neuro endocrine tumours
what 2 types of dysplastic ductal lesions can ductal carcinoma arise from?
- pancreatic intraductal neoplasia (PanIN)
- intraductal mucinous papillary neoplasm
ductal carcinoma mutation
K-Ras
pathology of ductal carcinoma
mucin secreting glands set in desmoplastic stroma (adenocarcinoma)
most commonly in head
cystic tumours features
serous/mucin secreting epithelium
2 different types of gallstone
- cholesterol (>50%): radiolucent (not seen on plain abdo X-ray)
- pigment: Ca salts of unconjugated bilirubin, radio-opaque
pathology of chronic cholecystitis
- chronic inflammation
- fibrosis
- diverticula: Rokitansky-Aschoff sinuses (gall bladder contracting against obstruction)
histology of body and fundus of stomach
- lined by gastric mucosa, columnar epithelium
- specialised glands in lamina propria (produce acids and enzymes)
- muscularis mucosa
which parts of the stomach are affected by H. pylori associated gastritis?
pyloric antrum/canal
how is the histology of antrum/pyloric canal different?
same histology except no specialised glands
are goblet cells normally seen in stomach?
goblet cells not normally seen in stomach
sign of intestinal metaplasia
Barrett’s oesophagus changes
squamous to columnar metaplasia
if goblet cells visible = intestinal metaplasia = much higher risk of Cancer
SCC of oesophagus
RFs and location
RFs: smoking, alcohol
mid/lower oesophagus, invades submucosa
causes of acute gastritis
- chemical (aspirin, alcohol, corrosives)
- infection (H. pylori)
causes of chronic gastritis (ABC)
- AI (anti-parietal cell)
- bacteria (H. pylori)
- chemical (NSAIDs, bile reflux)
what are the histological sign of MALT?
lymphoid follicles in stomach (not normal)
H.pylori induces lymphoid tissue in stomach
which form of H.pylori is associated with more chronic inflammation?
Cag-A +ve H. pylori
what are the 2 pathways that lead to GI cancer?
metaplasia - dyplasia e.g. oesophageal
adenoma-carcinpoma e.g. colon cancer
definition of ulcer
depth of tissue loss goes beyone=d muscularis mucosa into submucosa
gastric adenocarcinoma subtypes
- intestinal: well differentiated, big glands, containing mucin
- diffuse: poorly differentiated, no gland formation
types of diffuse adenocarcinoma
linitis plastica
signal ring cell carcinoma
what is lymphocytic duodenitis?
inflammatory changes (inc IELs) without architectural changes
what is the effect of ageing on skin?
fragile skin
little epidermis
collagen/elastic fibres poor quality
different inflammatory reaction patterns
- vesiculobullous (forms bullous)
- spongiotic (becomes oedematous)
- psoriasiform (thickened)
- lichenoid (sheeny plaque)
- vasculitis (ass/ w. vasculitides)
- granulomatous
features of bullous pemphigoid
- flexor surfaces
- tense bullae
- IgG and C3 attack BM (dermo-epidermal junction)
features of pemphigus vulgaris
- flaccid blisters
- IgG
- damage occuring within keratinocyte layers
- acantholysis
what is definition of acantholysis?
loss of intraceullular connections
= loss of cohesion between keratinocytes
features of pemphigus foliaceus
- thin bullae, not intact
- IgG mediated
- damage to outer layer of keratinocytes/stratum corneum
what is hyperparakeratosis?
thickening of skin on surface when you have been scratching
epidermis gets thicker
histology of eczema
spongiotic
oedema in between keratinocytes
plaque psoriasis histology
extensor silvery plaques
rapid turnover of cells = parakeratosis
no stratum granulosum = not enough time to form
Munro’s microabscesses (neutrophils) in epidermis
lichen planus presentation in mouth
Wickham striae
what histological finding can be seen in lichen planus and mycosis fungoides
band like lymphocytic infiltrate under epidermis
seborrhoeic keratosis
stuck on
horn cysts
what does BCCs arise from?
keratinocytes along bottom of epidermis
what is an SCC in situ called?
Bowen’s disease
what is Pagetoid spread?
melanocytes migrating up through epidermis
3 forms of urinary calculi
75%: calcium oxalate (due to hypercalciuria)
15%: struvite
5%: uric acid
features of struvite calculi
proteus infection (urease production) staghorn calculus
3 types of benign renal neoplasm
- papillary adenoma
- renal oncocytoma
- angiomyolipoma
types of renal cell carcinoma
- clear cell (70%)
- papillary (15%)
- chromophone (5%)
features of clear cell carcinoma
- lots of clear cells
- golden yellow tumour, haemorrhagic areas
- loss of Chr 3p
what are the cells that make up nephroblastoma?
malignant TRIPHASIC kidney tumour
- blastema = small round blue cells
- epithelial
- stromal
most common type of bladder carcinoma and RFs
transitional cell carcinoma
RFs: smoking, aromatic amines
Gleason score
most common pattern + worst pattern
features of testicular germ cell tumours
arise from germ cell neoplasia in situ
painless testicular lump
RFs for testicular germ cell tumours
undescended testes
LBW
5 subtypes of testicular germ cell tumours
- seminoma
- embryonal carcinoma
- post-pubertal teratoma
- yolk sack tumour
- choriocarcinoma (cytotrophoblasts + synctiotrophoblasts)
histology of seminoma
clear cells
prominate lymphocytic infiltrate
Tx of testicular germ cell tumours
platinum based chemo
composition of bone
- inorganic (Ca hydroxyapatite)
- organic (bone cells and matrix)
what is the location of the growth plates?
metaphysis
cortical bone features
long bones
mechanical/protective
cancellous bone features
vertebrae/pelvis
metabolic
osteocytes
osetoblast like cells
sit in lacunae
what cell are osteoclast percursors derived from?
monocytes
what are the 3 categories of metabolic bone disease?
- non-endocrine (e.g. age related osteoporosis)
- related to endocrine abnormality (e.g. vit D/PTH)
- disuse osteopaenia
what are the 2 types of osteomalacia?
vitamin D def
phosphate def
what is a brown cell tumour? associated with what?
hyperparathyroidism
multinucleated giant cells
what is Paget’s disease?
disorder of bone turnover
what re the stages of fracture repair?
- haemotoma at site (pro-callus)
- formation of fibrocartilaginous callus
- mineralisation of fibrocartiaginous callus
- remodelling of bone along weight bearing lines
what is salmonella osteomyelitis associated with?
SCD
x-ray changes in osteomyelitis
7 days: irregular subperiosteal new bone = involucrum
10-14 days: irregular lytic destruction
3-6 weeks: some areas of necrotic cortex detached = sequestra
lyme disease cause
tick bite from Ixodus dammini
organism: Borrelia burgdorferi
some symptoms of lyme disease
multisystem illness
inflammatory arthropathy
erythema chronicum migrans
histology of osteoarthritis
- cartilage degeneration
- fissuring
- abnormal matrix calcification
- osteophytes
- synovium inflamed, infiltration of inflammatory cells
what is RA?
severe chronic relapsing synovitis
characteristic deformities in RA
- radial deviation of wrist
- ulnar deviation of fingers
- swan neck and Botonniere deformity
- Z shaped thumbs
histology findings of RA
- proliferative synovitis
- pannus formation
- Grimley-Sokoloff cells
X-ray and Histology in Osteosarcoma
X-ray: lytic, elevated periosteum (Codman’s triangle)
Histology: malignant mesenchymal cells
X-ray and histology in Chrondrosarcoma
- X-ray: lytic with fluffy calcifications
- Histology: malignant chondrocytes
cause of Hirschsprung’s
absence of ganglion cells of myenteric plexus
associated genetic abnormality of Hirschsprung’s
RET proto-oncogene
secretory and exudative diarrhoea
- secretory: caused by toxin
- exudative: invasion and mucosal damage
associated skin lesions in Chrons
pyoderma gangrerosum
erythema multiforme
erythema nodosum
when can other parts of the bowel by caused in UC?
backwash ileilitis
terminal ileum inflamed
complications of UC
severe haemorrhage
toxic megacolon
adenocarcinoma
what are the tumours of colon/rectum?
- non neoplastic polyps
- neoplastic epithelial lesions (adenoma, adenocarcinoma, carcinoid tumour)
- mesenchymal lesions (stromal, lipoma, sarcoma)
- lymphoma
different non-neoplastic polyps
hyperplastic
inflammatory (pseudopolyp)
haemartomatous (jeuvenile, Peutz-Jeghers)
types of neoplastic polyp
tubular adenoma
tubulovillous adenoma
villous adenoma
RFs for cancer of a polyp
- size of polyp (>4cm)
- proportion of villous component
- degree of dysplastic change
familial syndromes characterised by polyps
- Peutz-Jeghers
- FAP (Gardner’s, Turcot)
- HNPCC
mutation in FAP
APC tumour suppressor on CHr 5q21
gene mutation in HNPCC
DNA mismatch repair gene
+ extra colonic cancers (e.g. endometrium, prostate, breast, stomach)
Duke’s staging
A: confined to bowel wall
B: through bowel wall
C: LN mets
D: distant mets
molecular mutation in lung adenocarcinoma
EGFR
ALK-1
molecular mutation in melanoma
BRAF
molecular mutation in breast
BRCA1/2
CERB-B2
molecular mutation in colon cancer
APC
KRAS
extra-axial tumours
coverings
tumours of bone, cranial soft tissue, meninges, nerves, metastatic deposits
intra-axial tumours
parenchyma
normal cell population of CNS/other cell types
WHO grading of CNS tumours
I: benign, long term survival
II: death > 5 yrs
III: death < 5 yrs
IV: death < 1 year
what are glial tumours and the 2 types?
most common primary tumour of CNS
- diffuse infiltration
- circumscribed glioma
diffuse infiltration types and genetics
adults
astrocytoma or oligodendrogliomas
genetics: IDH 1/2 mutations
circumscribed glioma type and genetic
- children
- MAPK mutation (BRAF)
- pilocystic astrocytoma = most common
pilocystic astrocytoma unique features and MRI
NF1
often cerebellar
piloid (hairy cell), Rosenthal fibres
MRI: well circumscribed, cystic and enhancing
astrocytoma features and MRI
- malignant progression –> eventually gliobastoma
- de novo glioblastoma = most aggressive/frequent
MRI: non-enhancing
features of glioblastoma multiforme
type 4
high cellularity and mitotic activity
features and histology of oligodenroglioma
long history of neuro signs
better prognosis than astrocytoma
histology: round cells with clear cytoplasm (fried eggs)
Meningioma features
MRI: extra-axial, contrast enhancing
focal symptoms
what is a medulloblastoma
originates from neuroepithelial precursors of cerebellum
small blue round cell tumour
which cancers metastasise to CNS? where are mets seen?
lung, breast, melanoma
seen at grey-white junction
what are the 2 main types of cerebral oedema?
- vasogenic: disruption of BBB
2. cytotoxic: secondary to cellular injury (hypoxia/ischaemia)
what is the flow of the CSF?
- choroid plexus pumps out of CSF
- goes into 3rd ventricle through intraventricular foramen
- goes down cerebral aqueduct into 4th ventricle
- down into medulla and central canal of spinal cord
how does CSF return back to systemic circulation?
CSF will circulate through subarachnoid space
and via arachnoid granules returns to systemic circulation
what are the 2 forms of hydrocephalus?
- non-communicating: obstruction to flow of CSF (usually involving cerebral aqueduct)
- communicating: NO obstruction, problem with reabsorption of CSF into venous sinuses (e.g. infection)
what is the normal ICP?
7-15mmHg
what is subfalcine herniation?
cortex pushed under rigid falx cerebri
what is transtentorial (uncal) herniation?
herniation of median temporal lobe through tentorial notch
what is tonsillar herniation?
tonsils (cerebellum) pushed through foramen magnum
what causes intra-parechymal haemorrhage?
due to rupture of small intraparenchymal vessel
usually due to HTN
what is a cavernous angioma?
closely packed vessels
no parenchyma interposed between vascular space
cavernous angioma vs AVM
similar to AVM but no brain substance wrapped up amongst vessels
where are most SAH?
most at internal carotid bifurcation
what is a contusion?
when brain collides with internal surface of skull
= bruising of surface
what is it called if pia mater is ruptures?
laceration
what is contrecoup damage?
rebound of brain after direct impact causes damage to opposite side of brain
what is the issue in prion protein?
prion protein change’s host protein into pathological form
histology in prion disease
spongiform encephalopathy = lots of vacuoles
features of vCJD and its cause
- sporadiac neuropsych
- cerebellar ataxia, dementia
- link to BSE (mad cow disease)
neuropathology of Alzheimer’s
- extracellular plaques (amyloid-beta)
- neurofibrillary tangles
- cerebral amyloid angiopathy (deposition of proteins in blood vessels)
- neuronal loss (cerebral atrophy)
how does tau cause Alzheimer’s?
hyperphosphorylated tau
intracellular accumulation
cell death
histology of Parkinson’s
- Lewy Bodies (alpha-synuclein)
- loss of dopaminergic cells from substantia nigra
- substantia nigra connects to basal ganglia
what staging system is used in Parkinson’s and Alzheimer’s?
Braak stages
3 main differentials for Parkinson’s?
- multiple system atrophy
- corticobasal degeneration
- progressive supranuclear palsy
which of these are tauopathies?
corticobasal degeneration
progressive supranuclear palsy
what is multiple system atrophy?
alpha-synucleinopathy
targets glial cell, tends to affect cerebellum
patient presents with fall
histology of Pick’s disease
- gliosis and neuronal loss
- balloon neurones
- Tau +ve Pick bodies
what are the 2 species of Tau in our brain?
3R and 4R
what is ARDS?
diffuse alveolar damage
phases to ARDS
- exudative phase (congested and leaky lungs)
- hyaline membranes
- organisation of exudates to form granulation tissue
acute histological changes in asthma
- bronchospasm
- oedema
- hyperaemia
- inflammation
chronic histological changes in asthma
- muscular hypertrophy
- airway narrowing
- mucus plugging
pathology in chronic bronchitis
- dilated airways
- mucus gland hyperplasia
- goblet cell hyperplasia
- mild inflammation
what is emphysema?
permanent loss of alveolar parenchyma distal to terminal bronchi
secondary to inflammation
emphysema in smoking vs A1AT
smoking = centrilobular damage A1AT = panacinar (damage throughout lungs)
what is bronchiectasis?
permanent abnormal dilation of bronchi with inflammation and fibrosis
infection = most common cause
complications of bronchiectasis
recurrent infection
haemoptysis
pulmonary HTN
amyloidosis
CF genetics
Chr 7
CFTR gene
Delta F508
what are the affects of CF on the different organs?
- GI: mec ileus, malabsorption
- Pancreas: pancreatitis, malabsorption
- liver: cirrhosis
- male: infertility
organisms affecting lungs in CF patients
S. pneumoniae
H. influenzae
P. aeruginosa
B. cepacia
Gram -ve causes of HAP
Klebsiella
Pseudomonas
Bronchopneumonia features
infection centred around airways
low virulence organisms
histopathology of lobar pneumonia
- congestive
- red hepatisation
- grey hepatisation
- resolution
what is a granuloma?
collection of macrophages and mutli-nucleate giant cells
what is pneumonitis?
interstitial inflammation
with lung cancers are near the airways?
SCC
with lung cancers are near the peripheral alveolar spaces?
mainly adenocarcinoma
what are the non-small cell carcinoma?
SCC
Adenocarcinoma
large cell carcinoma
which lung cancers is smoking associated with?
SCC
small cell
features of squamous cell carcinoma
- central
- arising from bronchial epithelium
- spreads locally, mets late
features of adenocarcinoma
- periphery
- glandular
- mets common and early
what is the pre-cursor lesion in lung adenocarcinoma?
atypical adenomatous hyperplasia
mutations in smokers
K-ras
DNA methylation issues
p53
mutations in non-smokers
EGFR
what are the features of large cell carcinoma?
poorly differentiated large cells
poorer prognosis
small cell carcinoma features
central, near bronchi
advanced disease, poor prognosis
paraneoplastic syndrome
histology in small cell carcinoma
small poorly differentiated
P53, RB1 mutation
adenocarcinoma main molecular changes
EGFR mutation
ALK translocation
Ros1 translocation