Histopathology Part 4- (p183-207- Breast, Cerebral, Neurodegenerative, Bone, Skin + Miscellaneous) Flashcards
How does acute mastitis present?
Painful
Red breast
Fever
Either lactational or non-lactational
What causes lactational and non-lactational acute mastitis?
Lactational- staphylococcal infection (often polymicrobial)
Non-lactational- secondary to duct ectasia
Treatment of lactational acute mastitis?
Continued expression of milk + antibiotics +/- surgical drainage
Treatment of non-lactational acute mastitis?
Abx + treatment of duct ectasia
Who does mammary duct ectasia usually occur in?
Multiparous 40-60yo women
Smokers- biggest RF
How does duct ectasia present?
Poorly defined palpable periareolar mass with thick white nipple secretions
What is the pathophysiology of duct ectasia?
Dilatation in one or more of the larger lactiferous ducts, which fill with a stagnant brown or green secretion, which may discharge.
These fluids irritate surrounding tissue leading to periductal mastitis or even abscess and fistula formation
Which condition mimics the mammographic appearance of cancer?
Duct ectasia
What would you see on cytology for duct ectasia?
Proteinaceous material
Inflammatory cells
What is fat necrosis of the breast?
Inflammatory reaction to damaged adipose tissue (can be delayed 10y from trauma)
How does fat necrosis of the breast present?
Painless breast mass which can mimic carcinoma by displaying skin tethering or nipple retraction
What is fibrocystic disease/fibroadenosis?
Breast lumpiness
Common group of changes caused by exaggerated hormone response:
Cystic- small cysts form by dilation of lobules and contain fluid
Fibrosis- secondary to cyst rupture
Adenosis- increased number of acini per lobule
What would you see on histology for gynaecomastia?
Epithelial hyperplasia
Finger-like projections into ducts
What is a fibroadenoma commonly referred to as?
A breast mouse- spherical and freely mobile
What is the most common benign breast tumour?
Fibroadenoma
When do fibroadenomas usually occur?
Reproductive period- usually 20-30y
What has a strong influence over fibroadenomas?
Hormones- increase in size during pregnancy and calcify after menopause
What is a duct papilloma?
Benign papillary tumour within the duct system of the breast
How does duct papilloma present?
Bloody discharge
No lump
Where does breast cancer rank in the most common cancers in women?
Numero uno
Women’s lifetime risk of breast cancer?
1 in 8
In which age range is breast cancer more common?
75-80y
What are the risk factors for breast cancer?
Susceptibility genes- BRCA1/2 Hormone exposure- early menarche, late menopause, OCP, HRT etc Advancing age FH Race (Caucasian most likely) Obesity Smoking Alcohol
How does breast cancer present?
Hard fixed lump
Paget’s disease (eczema of nipple then areola- normal eczema never affects the nips)
Peau d’orange
Nipple retraction
What is the breast cancer screening programme in the UK?
47-73yo women are invited every 3y for mammography
What is breast carcinoma in situ?
Neoplastic epithelial proliferation limited to ducts (DCIS) or lobules (LCIS) by basement membrane
How is breast carcinoma histologically subcategorised?
Ductal- can’t be classified into one of the others, most common
Lobular- cells in single file chains/strands
Tubular- well formed tubules with low grade nuclei
Mucinous- abundant extracellular mucin
What is the triple assessment for breast cancer?
Examination
Radiological exam- mammography/USS/MRI)
FNA + cytology
What are all neoplastic breast lesions assessed for?
Oestrogen receptor, progesterone receptor and HER2 receptor status
How does ER/PR/HER2 receptor status influence prognosis?
ER/PR positive- good as responds to tamoxifen
HER2 positive- bad prognosis
What is tamoxifen’s MOA?
Mixed agonist/antagonist of oestrogen at its receptor
What is herceptin/trastuzumab?
Monoclonal Ig to Her2
What is it important to monitor in herceptin treatment?
LVEF as it is toxic to myocardium
Where do phyllodes tumours arise from?
Interlobular stroma with increased cellularity and mitoses
What are the main differences between male and female breast cancer?
Lesions easier to find due to smaller breasts but lack of awareness may postpone treatment
Presence of gynaecomastia may mask condition
Diagnosis made later in males
Lesions less contained as don’t have to travel far to infiltrate
Almost 1/2 of male b cancer patients are stage III or IV
What is an infarction?
An area of tissue death due to lack of oxygen
What is the most common cause of a cerebral infarction?
Cerebral atherosclerosis
RFs for strokes and TIAs?
Smoking, DM, HTN, FH, past TIAs, OCP, PVD, ETOH, hyperviscosity e.g. sickle cell or polycythaemia vera
Symptoms and signs of stroke?
Sudden onset FAST Numbness Loss of vision Dysphagia
Symptoms and signs of TIA?
<24h
Amaurosis fugax- painless temporary loss of vision
Carotid bruit
Commonest area affected in a stroke?
MCA
Investigations for stroke/TIA?
CT/MRI (infarct vs haemorrhage) for stroke
Carotid US for TIA
Vascular risk- BP, FBC, ESR, U+E, glu, lipids, CXR, ECG, carotid doppler
Stroke/TIA management?
Aspirin +/- dipyridamole
Thrombolytics (if <3h) for stroke
+/- carotid endarterectomy
Long term- HTN, lipid reducing, anticoag
How would a stroke affecting the anterior cerebral artery (ACA) present?
Contralateral leg paresis
Sensory loss
Cognitive deficits (apathy, confusion, poor judgement)
How would a stroke affecting the MCA present?
Contralateral weakness and sensory loss of face and arm
Cortical sensory loss
Contralateral homonymous hemianopia or quadrantopia
If dominant hemisphere- aphasia
If non-dominant- neglect
Eye deviation towards side of lesion and away from weak side
How would a stroke affecting the PCA present?
Contralateral hemianopia or quadrantopia
Midbrain findings- CNIII and IV palsy/pupillary changes, hemiparesis
Thalamic findings- sensory loss, amnesia, decreased level of consciousness
Bilateral- cortical blindness or prosopagnosia
How would a stroke affecting the basilar artery present?
Proximal- impaired extraocular movement, vertical nystagmus, reactive miosis, hemi or quadriplegia, dysarthria, locked-in syndrome, coma
Distal- somnolence (sleepy), memory and behaviour abnormalities, oculomotor impairment
What type of haemorrhages are commonly non-traumatic?
Intraparenchymal
Subarachnoid
What is the common site for intraparenchymal haemorrhage?
Basal ganglia
What are responsible for 85% of subarachnoid haemorrhages?
Ruptured berry aneurysms
How does a SAH present?
Thunderclap headache
Vomiting
LoC
Usually in F <50
Patients with which conditions are at increased risk of SAH?
Polycystic kidney disease
Ehler’s Danlos
Aortic coarctation pts
Which cerebral haemorrhages are usually due to trauma?
Extradural
Subdural
Traumatic parenchymal
Which artery is involved in an extradural haemorrhage?
Middle meningeal artery ruptures
How does a subdural typically present?
Prev history of minor trauma -> damaged bridging veins with slow venous bleed, often elderly/alcoholic, associated with brain atrophy and fluctuating consciousness
Six types of brain herniation?
Uncal Central- transtentorial Cingulate- subfalcine Transcalvarial Upward tonsilar
Which organism most commonly causes meningitis in newborns-3m olds?
Group B strep (90% in first 5 days)
E. Coli and Listeria monocytogenes as well
Which organisms most commonly causes meningitis in 1m-6y olds?
Neisseria meningitidis, streptococcus pneumoniae, haemophillus influenza type B
Which organisms most commonly causes meningitis in >6yo olds?
N. meningitidis, strep pneumoniae, mumps (pre-MMR vaccine)
Which viruses cause meningitis?
Enteroviruses (80%), CMV, Arbovirus, HSV (most common in adults)
What RFs are there for meningitis?
Young
HIV
Immunocompromised
Environmental- crowding, poverty + close contact with affected individuals
What would you see in the CSF for bacterial/pyogenic meningitis (appearance, predominant cell, cell count, glucose, protein and presence of bacteria in smear or culture)?
Appearance- turbid Predominant cell- polymorphs e.g. neutrophils Cell count- 90-1000+ Glucose- low <40 Protein- high >250 Bacteria in smear and culture
What would you see in the CSF for TB meningitis (appearance, predominant cell, cell count, glucose, protein and presence of bacteria in smear or culture)?
Appearance- fibrin web Predominant cell- mononuclear e.g. lymphocytes Cell count- 10-1000 Glucose- low <40 Protein- high 50-500 Bacteria often not in smear
What would you see in the CSF for viral meningitis (appearance, predominant cell, cell count, glucose, protein and presence of bacteria in smear or culture)?
Appearance- clear Predominant cell- mononuclear e.g. lymphocytes Cell count- 50-1000 Glucose- normal Protein- normal or high <100 Bacteria often not in smear
Symptoms of viral encephalitis?
Drowsiness Seizures Behavioural changes Headache Fever
Viruses that cause viral encephalitis?
Enteroviruses HSV VZV Arboviruses Adenoviruses HIV Mumps Rubella Rabies
Are most brain tumours primary or secondary tumours?
Secondary
Which cancers are the most common primaries for secondary brain tumours?
Lung
Breast
Malignant melanoma
Commonest type of primary brain tumour?
Astrocytomas
Which familial syndromes are associated with CNS tumours?
Von Hippel Lindau- hemangioblastoma of cerebellum, brainstem and spinal cord
Tuberous sclerosis- giant cell astrocytoma
NF type 1- neurofibroma astrocytoma
NF type 2- Meningioma, ependydoma, astrocytoma
Li-Fraumeni- astrocytoma, primitive neuroectodermal tumour
Turcot syndrome- glioblastoma multiforme, medulloblastoma, pineoblastoma
MEN 1- pituitary adenoma
What is the common pathogenic mechanism behind neurodegenerative diseases e.g. dementia?
Accumulation of misfolded proteins (intra or extra-cellular
What are the four As of dementia?
Amnesia
Aphasia- language disorder
Apraxia- unable to do skills
Agnosia- unable to recognise people, objects
What is the pathological misfolded protein in Alzheimer’s disease?
Tau
Beta-amyloid
What is the pathological misfolded protein in Lewy body dementia?
Alpha-synuclein
Ubiquitin
What is the pathological misfolded protein in corticobasal degeneration?
Tau
What is the pathological misfolded protein in frontotemporal dementia linked to Chr 17?
Tau
What is the pathological misfolded protein in Pick’s disease?
Tau
What changes occur to the brain during Alzheimer’s
Generalised atrophy of the brain
Widened sulci
Narrowed gyri
Enlarged ventricles (temporal and frontal especially)
Senile plaques of beta-amyloid protein and neurofibrillary tangles of tau protein
How is Alzheimer’s diagnosed?
Clinical diagnosis
PET and MRI may help
How is Alzheimer’s treated?
Symptomatic:
Anti-cholinesterases
nAChR agonists
Glutamate antagonists
How can Lewy Body Dementia be differentiated from Alzheimer’s?
Psychological disturbances- visual hallucinations- small people or animals
Day to day fluctuations
Signs of Parkinsonism (very similar)
Recurrent falls and syncope
What is the pathology of Parkinson’s disease?
Death of dopaminergic neurones in substantia nigra -> reduced stimulation of the motor cortex by the basal ganglia
How does Parkinsons present?
TRAP Tremor Rigidity Akinesia Postural instability
What is the pathology of multiple sclerosis?
Autoimmune demyelinating disease with plaques
How does multiple sclerosis commonly present?
20-40yo, focal sx e.g. optic neuritis, poor coordination
Aetiology of osteoporosis?
Age-related or secondary to systemic disease/drugs
Disease features of osteoporosis?
Decreased bone mass- >2.5 SD below normal (1-2.5=osteopenia)
Symptoms of osteoporosis?
Low impact fractures- NOF or Colles’
Pain
RF for osteoporosis?
Age Smoking F Poor diet Low BMI
Changes of x ray for osteoporosis?
Usually none
Histology of osteoporosis?
Loss of cancellous bone
Biochemical changes of osteoporosis (Ca, PO4, ALP)?
All normal
Aetiology of osteomalacia/rickets?
Low dietary vit D
low sunlight
Malabsorption of vit D
Genetic causes
What is osteomalacia/rickets?
Decreased bone mineralisation
Symptoms of osteomalacia?
Bone pain/tenderness
Proximal muscle weakness
Symptoms of Rickets?
Bone pain Bowing tibia Rachitic rosary Frontal bossing Pigeon chest Delayed walking
Changes of x ray for osteomalacia?
Looser’s zones (pseudofractures)
Splaying of metaphysis
Histology of osteomalacia?
Excess of unmineralised bone
Biochemical changes of osteomalacia/Rickets (Ca, PO4, ALP)?
Ca- Normal or low
Decreased PO4
Increased ALP
Aetiology of primary hyperparathyroidism?
Parathyroid adenoma
Hyperplasia
Carcinoma
MEN
Disease features of primary hyperparathyroidism?
Excess PTH production -> Ca reabsorption and PO4 excretion
Bone changes of osteitis and fibrosa cystica
Symptoms of primary hyperparathyroidisim?
Hypercalcaemia- Moans, stones. bones and groans Depression Renal stones Bone pain and fractures Constipation Pancreatitis Polydipsia Polyuria
X Ray changes in primary hyperparathyroidism?
Brown’s tumours
Salt and pepper skull
Subperiosteal resorption in phalanges
Histology of primary hyperparathyroidism?
Osteitis fibrosa cystica (aka brown tumour)
Biochemical changes of primary hyperparathyroidism (Ca, PO4, ALP)?
Increased Ca
Decreased or normal PO4
Increased or normal ALP
Increased PTH
Aetiology of Paget’s?
Disorder of bone turnover
Disease features of Paget’s?
Lytic and sclerotic lesions
Symptoms of Paget’s?
Bone pain Microfractures Nerve compression Skull changes increase head size Deafness High output cardiac failure
RF for Paget’s?
> 50 + Caucasian
X ray changes in Paget’s?
Mixed lytic and sclerotic
Skull- osteoporosis circuscripta, cotton wool
Vertebrae- picture frame, ivory vertebra
Pelvis- sclerosis and lucency
Histology of Paget’s?
Huge osteoclasts with >100 nuclei
Mosaic pattern of lamellar bone
Biochemical changes of Paget’s (Ca, PO4, ALP)?
Normal Ca
Normal PO4
Massively raised ALP
Aetiology of renal osteodystrophy?
All skeletal changes associated with CKD- osteitis fibrosa cystica, osteomalacia, osteosclerosis, adynamic bone disease, osteoporosis
Biochemical changes of renal osteodystrophy (Ca, PO4, ALP)?
Low Ca
High PO4
Secondary hyperparathyroidism
What is the main way to differentiate between gout and pseudogout?
Gout has negatively birefringent crystals
Pseudogout has positively birefringent crystals
What are RFs of gout?
Increased dietary purine intake
ETOH
Diuretics
Inherited metabolic abnormalities
What is the aetiology of pseudogout?
Idiopathic
HyperPTH
Hypothyroid
Wilsons
Which joints are affected in gout?
Great toe- MTP, lower extremities
What are the clinical features of gout?
Hot swollen red and exquisitely painful joint
Tophus (s/c urate deposits) is pathognomic lesion
What is the crystal type in gout?
Urate crystals
Needle shaped
What is the crystal type in pseudogout?
Calcium pyrophosphate crystals
Rhomboid shaped
How do you manage gout?
Acute- Colchicine
Long term- Allopurinol
Conservative- reduce alcohol and purine intake e.g. sardines or liver
Management of pseudogout?
NSAIDs or intra-articular steroids
What causes osteomyelitis ?
Haematogenous spread or local infection e.g. post-trauma
Mainly bacterial and occasionally fungal
Which organism most commonly causes osteomyelitis in adults and which most commonly cause it in children?
Adults- S.Aureus
Children- haemophillus influenza, GBS
How does osteomyelitis present?
Pain, swelling and tenderness
General features of malaise, fever, chills + leukocytosis
In what condition would you see Heberden’s and Bouchard’s nodes?
Osteoarthritis
Heberden’s- DIPJ
Bouchard’s- PIPJ
X ray features of osteoarthritis?
LOSS Loss of joint space Osteophytes Subchondral sclerosis Subchondral cysts
How does rheumatoid arthritis present?
Slowly progressive
Symmetrical in small joints of hands and feet- spares DIPJ
Characteristic deformities of rheumatoid arthritis?
Swan neck and Boutonniere deformity of fingers
Radial deviation of wrist and ulnar deviation of fingers
Z shaped thumb
How can you differentiate benign and malignant bone disease on xray?
Benign- No periosteal reaction, thick endosteal reaction, well developed bone formation, intraosseous and even calcification
Malignant- Acute periosteal triangle- Codman’s triangle, onion skin, sunburst, broad border between lesion and normal bone, varied bone formation, extraosseous and irregular calcification
Name some malignant bone tumours?
Osteosarcoma
Chondrosarcoma
Ewing’s sarcoma
Giant cell
Who does osteosarcoma and Ewing’s sarcoma affect?
Adolescents
Where is most commonly affected by osteosarcoma?
Knee- 60%
What is seen on histology of osteosarcoma?
Malignant mesenchymal cells
ALP +ve
What is the X-ray appearance of osteosarcoma?
Codman’s triangle- elevated periosteum
Sunburst appearance
Which bones does chondrosarcoma affect?
Axial skeleton
Femur/tibia/pelvis
X-ray appearance of chondrosarcoma?
Lytic lesion with fluffy calcification
Which bones does Ewing’s sarcoma affect?
Long bones
Pelvis
What is seen on histology of Ewing’s sarcoma?
Sheets of small round cells
CD99 +ve
T 11:22 translocation
X-ray appearance of Ewing’s sarcoma?
Onion skinning of periosteum
Who does giant cell malignancy tend to affect?
20-40y
F>M
Where in the body does giant cell malignancy commonly occur?
Knee- epiphysis
What is seen on histology of giant cell malignancy?
Osteoclast-type multinucleate giant cells on background of splindle/ovoid cells
X-ray appearance of giant cell malignancy?
Lytic/lucent lesions right up to articular surface
What benign bone tumours are there?
Osteoid osteoma Osteoma- Enchondroma Osteochondroma Fibrous dysplasia Simple bone cyst Osteoblastoma
Any knowledge about osteoid osteoma?
Adolescents
M>F
Affects tibia diaphysis/proximal femur
Small benign bone forming lesion, night pain
X-ray- Radiolucident NIDUS with sclerotic rim ‘BULLS EYE’
Any knowledge about osteoma?
Middle age
Head and neck
Bony outgrowths attached to normal bone
Gardner syndrome- GI polyps, multiple osteomas + epidermoid cysts
Any knowledge about enchondroma?
Often in HANDS
Benign tumours of cartilage
Ollier’s syndrome- multiple enchondromas
Maffuci’s syndrome- multiple enchondromas and haemangiomas
X-ray- Lytic lesion, cotton wool calcification
Which benign bone tumour is most common?
Osteochondroma- cartilage capped bony outgrowth
Where do osteochondromas commonly occur?
Metaphysis of long bones near tendon attachment sites
Any knowledge on fibrous dysplasia?
Femur
Bit of bone replaced by fibrous tissue
Chinese letters on histology- misshapen bone trabeculae
X-ray- soap bubble osteolysis, Shepherd’s crook deformity
Any knowledge on simple bone cyst?
Humerus or femur
Fluid filled unilocular
X-ray- Lytic and well defined
What is the stratum corneum?
Outermost layer of epidermis, consisting of keratinised cells
What is hyperkeratosis?
Increase in stratum corneum/keratin
What is parakeratosis?
Nuclei in stratum corneum
What is acanthosis?
Increase in stratum spinosum
What is acantholysis?
Decrease in cohesion between keratinocytes
What is spongiosis?
Intracellular edema
What is lentiginous?
Linear pattern of melanocyte proliferation within epidermal basal cell layer
5 layers of epidermis?
S corneum S lucidum- only in hands + feet S granulosum S spinosum S basale
What is dermatitis/eczema?
Terms used to describe a group of disorders with same histology and presenting with inflamed dry itchy rashes
What is the histology of all types of dermatitis/eczema?
DISCA Acute: Dilated dermal capillaries Inflammatory infiltrate in dermis Spongiosis
Chronic:
Crusting, scaling
Acanthosis
Different types of dermatitis?
Atopic
Contact
Seborrhoeic
Where does atopic dermatitis commonly affect in infants and older?
Infants- face and scalp
Older- flexural area
What type of hypersensitivity reaction is contact dermatitis?
Type IV
What causes seborrhoeic dermatits?
Inflammatory reaction to a yeast
What is psoriasis?
A common chronic inflammatory dermatosis with well-demarcated red scaly plaques- cells have increased proliferation rate
What is the commonest form of psoriasis?
Chronic plaque affecting extensor surfaces and scalp
What is Auspitz’ sign?
Rubbing psoriatic plaques causes pinpoint bleeding
What is Koebner phenomenon?
Lesions form at sites of trauma
What is seen on histology for psoriasis?
Parakeratosis, loss of granular layer, clubbing of rete ridges giving test tubes in a rack appearance, Munro’s microabscesses
Pathophysiology of chronic plaque psoriasis?
Type IV T cell hypersensitivty reaction
What are other forms of psoriasis and how do they typically present?
Flexural- seen in later life, groin, natal cleft and submammary areas
Guttate- rain drop plaques, children, seen 2w post STREP
Erythrodermic/pustular- severe widespread, systemic symptoms, can be limited to hands and feet (palmo-plantar)
What nail changes are seen in psoriasis?
Pitting
Onycholysis
Subungal keratosis
What are lesions like in lichen planus?
6ps Pruritic Purple Polygonal Papules Plaques Pearl sheen White network on surface called Wickam's striae
Where is lichen planus usually seen?
On inner surface of wrists but can affect oral mucosa
Histology of lichen planus?
Hyperkeratosis with saw-toothing of rete ridges and basal cell degeneration
What lesions are seen in erythema multiforme and where?
Annular target lesions
Most commonly on extensor surfaces of hands and feet
Can be a combination of macules, papules, weals, vesicles, bullae and petechiae
Causes of erythema multiforme?
Infections- e.g. HSV, mycoplasma Drugs- SNAPP: Sulphonamides NSAIDs Allopurinol Penicillin Phenytoin
Which condition is dermatitis herpetiformis associated with (not herpes lol)?
Coeliac
Pathophysiology of dermatitis herpetiformis?
IgA Abs bind to basement membrane -> subepidermal bulla
Clinical features of dermatitis herpetiformis?
Itchy vesicles on extensor surfaces of elbows and buttocks
Histology of dermatitis herpetiformis?
Microabscesses which coalesce to form subepidermal bullae
Neutrophil and IgA deposits at tips of dermal papillae
Pathophysiology of pemphigoid?
IgG Abs bind to hemidesmosomes of basement membrane -> subepidermal bulla
Pathophysiology of pemphigus?
IgG Abs bind to desmosomal proteins -> intraepidermal bulla
How can you easily differentiate between pemphigoid and pemphigus?
PemphigoiD- Deep bullae
PemphiguS- Superficial bullae
Clinical features of pemphigoid?
Large tense bullae on erythematous base
Often on forearms, groin and axillae
Elderly
Do not rupture as easily as pemphigus
Histology of pemphigoid?
Subepidermal bulla with eosinophils
Linear deposition of IgG along basement membrane
Clinical features of pemphigus?
Bullae are easily ruptured
Found on skin and mucosal membranes
Histology of pemphigus?
Intraepidermal bulla
Netlike pattern of intracellular IgG deposits
Acantholysis
What are seborrhoeic keratosis?
Benign rough waxy plaques with a ‘stuck on’ appearance
What is an actinic keratosis?
Rough sandpaper-like scaly lesion on sun-exposed area
Histology of actinic keratosis?
SPAIN Solar elastosis Parakeratosis Atypia/dysplasia Inflammation Not full thickness
What is a keratoacanthoma?
Rapidly growing dome shaped nodule which may develop necrotic crusted centre
Grows over 2-3w and clears spontaneously
Histology of keratoacanthoma?
Similar to SCC- difficult to distinguish
Characteristics of Bowen’s disease?
Intraepidermal squamous cell carcinoma in situ
Flat red scaly patches on sun-exposed areas
Histology of Bowen’s disease?
Full thickness atypia/dysplasia
Basement membrane intact- not invading the dermis
When does Bowen’s disease become an SCC?
When it invades the dermis
What is referred to as a ‘rodent’ ulcer?
BCC
Characteristics of a BCC?
Pearly surface often with teleangiectasia
Histology of BCC?
Mass of basal cells pushing down into dermis
Palisading
What is a mole?
A benign melanocytic naevus
Histology of melanoma?
Atypical melanocytes, initially grow horizontally in epidermis (radial growth phase) then vertically into dermis (vertical growth phase) which produces Buckshot appearance
Most important prognostic factor in melanoma?
Breslow thickness
Subtypes of melanoma?
Lentigo maligna melanoma- sun exposed area of elderly
Superficial spreading malignant melanoma- irregular borders with colour variation
Nodular malignant melanoma
Acral lentiginous melanoma- palms, soles and subungal areas
How can you differentiate between Stevens Johnson syndrome and Toxic Epidermal Necrolysis?
Sheets of skin detachment- <10% BSA= SJS, >30%= TEN
What commonly causes SJS and TEN?
Drugs- Sulphonamide antibiotics, anticonvulsants
How does pityriasis rosea typically present?
Salmon pink rash appears first (Herald patch) followed by ovule macules in Christmas tree distribution
Post-virus
What type of hypersensitivity reaction is involved in SLE?
Type III
RFs for SLE?
In pts with classical complement deficiencies
Drug induced
Afro-Caribbeans
F>M
HLA association of SLE?
HLA DR3
Autoantibody involved in SLE?
ANA (95%)
Anti dsDNA
Anti-Sm
Anti-histone
Histology of SLE?
LE bodies Kidney- CNS- small vessel angiopathy Spleen- onion skin lesions Heart- Libman-Sack endocarditis
Diagnostic criteria for SLE?
4 of 11 ACR criteria- SOAP BRAIN MD Serositis Oral ulcers Arthritis Photosensitivity Blood disorders (AIHA, ITP, leucopenia) Renal involvement ANA +ve Immune phenomena Neuro symptoms Malar rash Discoid rash
HLA association of scleroderma?
HLA DR5 + DRw8
Autoantibody in limited and diffuse scleroderma?
Limited- anti-centromere
Diffuse- anti-Scl70, fibrillarin, RNA pol I, II, III
PM-Scl
Histology of limited scleroderma?
Increased collagen in skin and organs
Onion skin thickening of arterioles
Histology of diffuse scleroderma?
Inflammation within or around muscle fibres
Signs and symptoms of limited scleroderma?
Skin changes on face and distal to elbows and knees
Calcinosis Raynaud's Esophogeal dysmotility Sclerodactyly Telangiectasia
Signs and symptoms of diffuse scleroderma?
Skin changes can occur anywhere
Widespread organ involvement
Pulmonary fibrosis association
Autoantibody in polymyositis + dermatomyositis?
Anti Jo-1 (tRNA synthetase)
Signs and symptoms of polymyositis + dermatomyositis?
Proximal muscle weakness
Increased CK + abnormal EMG
DM has cutaneous features- heliotrope rash + Gottron papules
Name some large vessel vasculitides?
Takayasu’s arteritis
Temporal arteritis
Name some medium vessel vasculitides?
Polyarteritis nodosa
Kawasaki’s
Buerger’s disease
Name some small vessel vasculitides?
Wegener’s granulomatosis
Churg Strauss
Microscopic polyangiitis
Henoch Schonlein Purpura
What is Takayasu’s arteritis also referred to as?
Pulseless disease- absent pulse, bruits and claudication
Increased in Japanese women
Key features of temporal arteritis?
Elderly Scalp tenderness Temporal headache Increased ESR Overlap with polymyalgia rheumatica
Histology of temporal arteritis?
Granulomatous transmural inflammation + giant cells + skip lesions
Key features of polyarteritis nodosa?
Renal involvement main feature
Spares lungs
30% have Hep B
Microaneurysms on angiography
Key features of Kawasaki’s?
Children <5 Fever>5d Rash- red palms and soles Conjunctivitis Inflammation of lips, mouth or tongue (STRAWBERRY) Cervical LNs Coronary arteries may be involved
Key features of Buerger’s disease?
Heavy smokers usually men >35 Inflammation of arteries of extremities Pain Ulceration of toes, feet and fingers Angiogram- corkscrew appearance from segmental occlusive lesions
Key features of Wegener’s granulomatosis?
Triad of
URT- sinusitis, epistaxis, saddle nose
LRT- cavitation, pulmonary haemorrhage
Kidneys- crescentic glomerulonephritis
cANCA +ve
Key features of Churg Strauss?
Asthma, allergic rhinitis
Eosinophillia
Later systemic involvement
pANCA +ve
Key features of microscopic polyangiitis?
Pulmonary renal syndrome- pulmonary haemorrhage and glomerulonephritis
pANCA +ve
Key features of Henoch Schonlein purpura?
IgA mediated vasculitis In children <10 Preceding URTI Palpable purpuric rash- lower limb extensors + buttocks Colicky abdo pain Glomerulonephritis Arthritis Orchitis
What is amyloidosis?
Multisystem disorder caused by abnormal folding of proteins that are deposited as amyloid fibrils in tissues. disrupting their normal function
What is the primary form of amyloidosis?
AL- deposition of amyloid L protein
Key features of AL amyloidosis
Most associated with plasma cell dyscrasias and with paraproteins e.g. MM
Most have monoclonal Ig, free light chains in serum and urine (Bence Jones) and increased bone marrow plasma cells
What is the secondary form of amyloidosis?
AA amyloidosis- Amyloid A (an acute phase protein) secondary to chronic infection and inflammation e.g. autoimmune disease- RA, ank spond, IBD, chronic disease- TB, IVDU+ non-immune- RCC, Hodgkin’s
Clinical features of amyloidosis?
Caused by amyloid deposits in various organs-
Kidney- nephrotic syndrome (most common presentation)
Heart- conduction defects, HF, cardiomegaly
Liver/spleen- hepatosplenomegaly
Tongue- macroglossia in 10%
Neuropathies- inc carpal tunnel
How can amyloidosis be identified by staining?
Apple green birefringence with Congo red stain under polarised light (otherwise pink/red)
What is sarcoidosis?
A multisystem disease of unknown cause, commonly affecting young adults, characterised by non-caseating granulomas in many tissues
What is seen on histology of sarcoidosis?
Non-caseating granulomas, also get Schaumman and asteroid bodies (inclusion of protein and calcium)
How is sarcoidosis most commonly detected?
Routine CXR - bilateral hilar lymphadenopathy and pulmonary infiltrates leading to fine nodular shadowing in mid zones
Most seek help with SOB, cough, chest pain + night sweats
Extrapulmonary manifestations of sarcoidosis?
Skin- erythema nodosum, lupus pernio, skin nodules
LNs
Joints- arthritis + bone cysts
Eyes- anterior uveitis
Liver/spleen- hepatosplenomegaly
Blood- leukopenia/anaemia
Hypercalcaemia/hypercalcuria -> renal calculi + nephrocalcinosis
Heart- dysrhythmias, cardiomyopathy, conduction defects
CNs
Constitutional symptoms- FLAWS
How is sarcoidosis diagnosed?
Exclusion
Ix- Raised Ca, ESR + ACE, transbronchial biopsy