Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

Histopathology1 Tarush Gupta Question on MS Teams pollHowareyoufeelingabouthistopathology?(MSTeams Poll) • Most content out of all the path specialities • ONLY 15 SBAs, 15 VSAs and 2 CPQs (32 questions total) • You do NOT NEED to know tissue slides and specimens • Caveat = buzzwords in questions • TOP TIP = learn the most common cause • 3 key questions: 1. How is disease caused? 2. What can you see in diseased tissue? 3. How does this correlate with clinical findings?Lecturecontent TOPICS COVERED TOPICS NOT COVERED Gynae (overlap with O&G) Heart Breast Lungs Brain GI & HPB Bone Renal & Urology Skin 10 quizzes (1 SBA & 1 VSA in each)Gynae + VulvaQUIZ1(SBA&VSA) 1) What is the mechanism of action by which HPV 16 & 18 cause cervical cancer? a) Activating oncogene b) Inhibiting oncogene c) Activating tumour suppressor genes d) Inhibiting tumour suppressor genes e) Genetic translocation 2) A 31 year old woman comes to her GP with non-specific abdominal pain. This occurs once a month and lasts for several days each time. There is no intermenstrual bleeding, she is not sexually active and is not taking any contraceptives. An USS of the abdomen reveals a unilateral hypoechoic mass on the left ovary. What is the most likely diagnosis?Definitions Cellular process Definition Example Hyperplasia ↑ no. of cells Parathyroid hyperplasia Hypertrophy ↑ size of cells HOCM, LVH Metaplasia Reversible change Barrett’s oesophagus from one cell type to another Dysplasia ↓ grading of cells i.e. Cervix replacement of normal cells with abnormal cells Basement membrane intact Neoplasia Uncontrolled abnormal Benign or malignant growth of cells and tissuesVulvalintraepithelialneoplasia(VIN) Vulva = vaginal opening, labia majora, labia minora, clitoris Graded as VIN 1-3 Normal epithelium Usual type VIN risk factors: • HPV 16/18 • Smoking • Immunosuppression Differentiated type VIN risk factors: • Lichen sclerosis Proliferation of • PROGRESSION TO SCC epithelial cellsVulvalandvaginalcarcinoma Squamous cell carcinoma (95%) Primary vulval carcinoma (95%) Clear cell (5%) Squamous cell carcinoma Adenocarcinoma Visible, painless lesion May be ulcerated Difficulty urinating Itching, irritation FLAWS Older women Teenagers Lichen sclerosis COCP Cervicalintraepithelialneoplasia(CIN) Columnar TZ SquamousGradingCINusinghistology Key criteria = depth of dysplasia (rule of 1/3rds) Invasion of basement membrane = CANCERCervicalcancer SCC (80%) Adenocarcinoma (20%) i.e. from columnar cells HPV infection COCP Risk factors High parity Immunosuppression SmokingHPVinfection16&18 Cytological and Latent Activated histological changes HPV encodes E6 and E7 proteins which inactivate 2 tumour suppressor genes (TSGs) • E6 inactivates p53 • E7 inactivates Retinoblastoma gene (Rb) = PROLIFERATION OF EPITHELIUMCervicalcancerscreening All women aged 25-49 offered smear test every 3 years, women aged 50- 75 offered every 5 years Check for HPV SMEAR If HPV +ve → cytology Colposcopy CLINICEndometriumMalignancy Benign Malignant Fibroids a.k.a. leiomyoma (NOTAdenocarcinomas (90%) TECHNICALLY CANCER) • Endometriod (80%) • Non-endometriod (20%)Fibroids Benign tumour of myometrium Common 40% in women over 40 Pathophysiology – oestrogen dependent growth *Enlarge during pregnancy **Regress during menopause Bundmuscle cellshEndometriosis Presence of endometrial tissue outside the endometrium • Myometrium (adenomyosis) • Ovary • Fallopian tubes • Uterine ligaments • Bladder • Colon • Peritoneum Caused by vascular or lymphatic dissemination of endometrial cellsEndometriosis Red-blue / brown vesicles Endometrial tissue is “Powder burns” darker hence appearance of Endometriomas on ovaries “powder burns” ”chocolate cysts” Extremely Endometrialcarcinoma irregular Adenocarcinomas (80%) SCC (20%) Endometriod Non-endometriod Epidemiology 80% 20% Peri-menopausal women Post-menopausal women ↑ Lifetime oestrogen exposure Types Secretory Papillary Endometriod Clear cell Mucinous Serous Pathophysiology Related to oestrogen Unrelated to oestrogen excess excess Mutations PTEN > 50% (TSG) PTEN, P53, HER-2 “Sarah Eats Meat, Paul Can’t Stand (it)”Pelvicinflammatorydisease 3 key features: 1.Ascending infection ascending from vagina and cervix to uterus and Fallopian tubes and ovaries 2.Inflammation (e.g. endometritis, salpingitis) 3.Formation of adhesions Fitz-Hugh Curtis syndrome • 10% • Unknown aetiology • RUQ pain due to peri- hepatitis • Buzzword – “violin-strings” peri-hepatic lesionsPIDcauses Ascending STI e.g. IUD N. gonorrhoea C. trachomatis Causative organisms External contamination Others e.g. abortion, TB TOP Schistosomiasis S. aureusOvariancancer&cysts Leading cause of death from gynae malignancies Peak incidence 75-84 yrs 90% are epithelial tumoursOvarian lesion Type Description Physiological cysts Follicular Commonest type (most common) Due to non-rupture of the dominant follicle or failure of atresia in a non-dominant follicle Commonly regress after several menstrual cycles Corpus luteum During the menstrual cycle if a pregnancy doesn’t occur the corpus luteum Common in early breaks down and disappears. If this doesn’t happen the corpus luteum may pregnancy become filled with blood or fluid and become a corpus luteal Most likely to present with intraperitoneal bleeds Benign germ cell Dermoid cyst a.k.a mature cystic teratomas, usually lined with epithelial tissue and so contain tumours (most common skin appendages, hair and teeth benign tumonur) Most common benign ovarian tumour in women under 30 Associated with torsion Rokitansky’s protuberance Malignant germ cell Dysgerminoma Most common malignant ovarian cancer in younger women tumours Sensitive to radiotherapy Benign epithelial Serous cystadenoma The most common benign epithelial tumour which bares resemblance to the tumour most common type of ovarian cancer Histology: columnar epithelium, psammoma bodies Mucinous 2ndmost common benign epithelial tumour cystadenoma Typically very large and become massive May cause pseudomyxoma peritonei Histology: mucin secreting cells Malignant epithelial Endometriod Co-exist with endometrial cancer and endometriosis (Ca125 ↑↑) tumours carcinoma Histology: tubular glands Clear cell carcinoma Associated with endometrioma Histology: clear cells, hobnail appearance Sex-cord tumours Granulosa/theca cell Secrete oestrogen → PMB, IMB, endometrial cancer, breast cancer, breast tumours enlargement. Histology: Call-exner bodies Sertoli/Leydig cell Secrete androgens → virilization, defeminization, breast atrophy, hirsutism, tumours enlarged clitorisQUIZ2(SBA&VSA) 1) A 40 year old nulliparous woman with BMI 32 presents with cyclical dysmenorrhea and heavy menstrual bleeding. What is the biopsy most likely to show? a) Cervical intraepithelial neoplasia b) Bundles of smooth muscle cells c) Powder burns d) Dense “violin-string” adhesions e) Rokitansky protuberances 2) A young woman presents to the colposcopy clinic after an abnormal smear test which showed reduced differentiation of squamous epithelium lining the cervix. What name is given for the pathological process underlying this change?Break(1minute)BreastQUIZ2(SBA&VSA) 1) A 62 year old woman has follow-up in The Breast Clinic after mammography detected microcalcifications in the left breast. There are no palpable lumps, no nipple inversion or changed to underlying skin. No axillary lymph nodes are palpable. She is currently asymptomatic. What is the most likely diagnosis? a) Fibroadenoma b) Fibrocystic disease c) Radial scar d) Ductal carcinoma in situ e) Lobular carcinoma in situ 2) What is the single best prognostic indicator for breast cancer?Breastlumps •Mastitis •Fibroadenoma •Fat necrosis •Fibrocystic disease •Duct ectasia Benign Inflammatory breast lumps Malignant Proliferative breast lumps •Intraductal papilloma •Ductal (DCIS / •Radial scar Invasive) •Usual epithelial •Lobular (LCIS / hyperplasia Invasive) •Flat epithelial atypia •Paget’s disease •In situ lobular neoplasiaANYONEWITHALUMP,BLOODYDISCHARGE,NIPPLE INVERSIONORSKINCHANGES Collects sample of < 35yrs cells Collects core of tissue > 35yrsFNAvscorebiopsy FNA Cells spread across a slide, stained, and coded Looking at individual cells independent of each other Coded from C1 (inadequate sample), C2 (benign), C3 (atypia), C4 (suspicious of malignancy) to C5 (malignant) Core biopsy Intact tissue removed and analysed for architecture and cellular detail Looking at whole segment of tissue, basement membrance, cell-cell interactions Coded B1 (normal), B2 (benign), B3 (uncertain), B4 (suspicious) to B5 (malignant). B5a = DCIS, B5b = invasive carcinomaInflammatory:Mastitis Mastitis – erythematous, tender breast, fevers Lactational – within 6 weeks post-partum due to milk stasis, may have a cracked nipple Non-lactational – not currently breast-feeding Abundance of neutrophilsInflammatory:Mastitis Management: Conservative – warm compresses, analgesia, elevation, continue breastfeeding bilaterally If unresolved after 12-24hrs Medical – oral antibiotics (usually Fluclox as S. aureus most common organism) Abscess = fluctuant swelling, swinging fevers • Rx: IV antibiotics and incision & drainage (I&D)Inflammatory:Fatnecrosis An inflammatory disease to damaged adipose tissue Buzzwords in SBAs: trauma to breast, previous radiotherapy, unilateral underlying mass Damaged fat lobulesBenign:Fibroadenoma Benign neoplasm of a lobule with 2 components: • Fibro– (stomal) • Glandular (epithelial) Stromal proliferation Most common lump in women 20-40 Oestrogen driven → cyclical pain, regress during menopause Buzzwords: • Single 1-5cm, unilateral, spherical, well demarcated, firm/rubbery, painless • Mobile a.k.a. “breast mouse” Management: • < 3 cm → conservative • > 3 cm → surgical excisionPhyllodestumour Aggressive malignant fibroepithelial neoplasms arising from breast stroma i.e. malignant version of fibroadenomas EXTREMELY RARE • 2 in every 1 million women • > 50 yrs • Comes up surprisingly often… Structurally similar to fibroadenomas Key buzzwords are: • Artichoke appearance • Frond-like • BranchingBenign:Fibrocysticdisease Fluid filled sacs in breast Fluid filled cysts Common – 7% of women, peri-menopausal Buzzwords: • Single or multiple “lumpiness”, unilateral or bilateral, cyclical pain • Well demarcated, fluctuant, transilluminable, clear nipple discharge RED FLAGS: 1. FNA is blood-stained 2. Core biopsy reveals complex cystic contentsBenign:Ductectasia Blockage of milk ducts → dilatation Peri-post menopausal women Duct dilatation Buzzwords: • SMOKERS Proteinaceous material inside the duct • Sub/peri-areolar mass • Firm, thick yellow-green discharge Nipple discharge contains macrophages and proteinaceous material Summarytable Fibroadenoma Phyllodes tumour Breast cyst Duct ectasia Definition Benign neoplasm of a Aggressive fibroepithelialFluid filled sacs in the Dilatation of milk ducts due lobule; arising from fibro neoplasms arising from breast to blockage (stromal) and glandular breast stroma (adenomal) epithelium Epidemiology MOST COMMON LUMP > 50yrs Common 7% of women Peri/post-menopausal IN WOMEN 20-40yrs Peri-menopausal (50yrs) Risk factors: SMOKING, multiparity Site-size Single unilateral 1-5cm Clinically and Single or multiple Sub-areolar mass May be bilateral and radiologically similar to Unilateral or bilateral Nipple inversion multiple (RARE) fibroadenomas Increase in size during Pain correlates with pregnancy & menstrual menstrual cycle cycles as they are oestrogen driven Colour- Well demarcated, Well demarcated, clear Firm, thick yellow-green- consistency spherical, firm, smooth, nipple discharge white nipple discharge. May rubbery lead to local infection if ducts get infected → inflammatory symptoms and abscess formation Tender- Painless Painless Tender transillumina Transilluminable ble Fluctuance- Mobile “Breast mouse” Fluctuant/mobile Fixed fixed [BUZZWORD]Proliferativelesions:Intraductalpapilloma Benign neoplasms growing within the ducts of breast – “well defined nodule within a duct” Peri-post menopausal women 2 types: 1. Peripheral → small ductules affected → clinically silent with subareolar mass 2. Central → large ductules affected → blood or clear nipple discharge Dilated ductule with papillary massProliferativelesions:Radialscar Benign sclerosing lesion caused by impaired healing post-injury Buzzwords: Central, fibrous, stellate areaProliferative:Pre-malignancy A diverse group of intraductal proliferative lesions associated with an increased risk of developing subsequent invasive breast carcinoma Usually ASYMPTOMATIC Pre-malignant neoplasms Risk of breast cancer Usual epithelial hyperplasia 1-2x Flat epithelial atypia 4x In situ lobular neoplasia 7-12xBreastcancer • Commonest cancer in UK affecting 1/7 females • Rare under 35s, increasing with age Lifetime Genetics oestrogen Lifestyle exposure BRCA 1/2 Early menarche (Autosomal Alcohol Dominant) Late menopause Family History Nulliparity Smoking +Ve Late first child Li Fraumeni Poor diet syndrome COCP Types Non-invasive Invasive Ductal carcinoma in situInvasive ductal (DCIS – 3-5%) carcinoma (85%) Lobular carcinoma in Invasive lobular situ (LCIS – 1%) carcinoma (10%) Paget’s disease (2%) Limited to ducts/lobules by Malignant epithelial tumours which basement membrane infiltrate breast, and have capacity to metastasize DCIS → microcalcifications LCIS → usually incidental finding Ductal → big, pleomorphic cells Invasive → cells in chains/single file Histology: ducts filled with atypical Tubular → well-formed tubules epithelial cells Mucinous → extracellular mucinNottinghamGradingsysem Graded /3 for following 3 criteria (total /9): 1. Nuclear pleomorphisms 2. Tubule formation 3. Mitotic activity Grade 1 = well differentiated (<5) Grade 2 = moderately differentiated (6-7) Grade 3 = poorly differentiated (8-9) All breast cancers assessed for ER, PR and HER-2 status **Important in medical management e.g. Tamoxifen is anti-ER in breast, Herceptin is a monoclonal Ab to HER-2QUIZ4(SBA&VSA) 1) A 34 year old nulliparous woman presents to her GP after noticing a small lump in her right breast while she was showering. The lump is 2cm, spherical, mobile and painless. Her father had colon cancer and her sister had ovarian cancer. She currently takes COCP, omeprazole and metformin. What is the most appropriate management of the patient? a) Detailed clinical history, examination, USS breasts b) Detailed clinical history, examination, mammography breasts c) Detailed clinical history & examination, USS breasts, FNA d) Detailed clinical history & examination, mammography breasts, FNA e) Detailed clinical history & examination, USS breasts, core biopsy 2) A 55 year old woman with Beurger’s disease presents to her GP with a swollen right breast, sub-areolar mass and green nipple discharge. Core biopsy reveals dilated breast ducts and complex cellular proteinaceous material. What is the most likely diagnosis?Break(1minute)NeuroQUIZ5(SBA &VSA) 1) A 64 year old man presents with a 2 month history of functional decline, personality changes, and vomiting first thing in the morning. MRI of the brain revealed a single lesion in the parietal with high mitotic activity, high cellularity and poor differentiation. What is the most likely diagnosis? a) Pilocytic astrocytoma b) Glioblastoma multiforme c) Meningioma d) Ependyoma e) Oligodendroglioma 2) An 8 year old boy has headaches worse in the morning, associated with vomiting on waking. His school teacher also claims he has become quieter at school and struggles to follow lessons. An MRI reveals a singe 2x3cm lesion in the parietal lobe. What type of brain cancer is he most likely to have? Stroke / TIA Tumours Chronic Raised ICP Neurodegenerative (Hydrocephalus disease and herniation) Stoke/TIA Stroke – a focal neurological deficit of presumed vascular origin that lasts more than 24 hrs TIA - a focal neurological deficit of presumed vascular origin that resolves within 24 hrs Ischaemic (80%) Haemorrhagic (20%) Atherosclerosis Vasculitis Hypertension Sub arachnoid haemorrhage Thromboembolic (e.g. AF) Diabetes Cavernous angiomas AV malformation (recurrent low (< 50yrs) pressure bleed)Ischaemicstroke Ischaemia – lack of oxygen supply to tissue Infarction – death of tissue due to lack of oxygen supply InfarctHaemorrhagicstroke:Non-traumatic Intraparenchymal haemorrhage 50% due to HTN Common site = basal ganglia Subarachnoid haemorrhage 85% from ruptured berry aneurysms (assn with PCKD) Common locations – bifurcation of internal carotid, posterior communicating arteries Buzzword “hyperattenuation around the Circle of Willis” If CT –ve then do LP at 12hrs to look for xanthochromia and oxyhaemoglobinHaemorrhagicstroke:Traumatic Extradural haemorrhage Fracture of pterion caused by trauma (e.g. RTA, punch to temples etc) Rupture of middle meningeal artery Buzzword – “lemon” shape Subdural haemorrhage Prev Hx of minor head trauma Rupture of bridging veins Alcoholics, anti-coagulations, elderly Buzzword – “banana”, crescent shapeTraumaticbraininjury Single largest cause of death in under 45s RED FLAGS – • Otorrhoea • Rhinorrhoea • “Straw-coloured” fluid (CSF) from nose or ears • Battle’s sign Diffuse axonal injury - shear tensile forces tearing axons apart in midline structures like Corpus callosum, rostral brainstem and septum pellucidum • Commonest cause of traumatic coma Contusions – collisions between brain and skull • Coup – impact of brain on skull • Countercoup – injury to opposite side of brainBraintumoursBraintumours Primary tumours originate within the CNS • Extra-axial – cranium, soft tissue, Genetics PMH meninges, nerves • Intra-axial – glia, neurons, neuroendocrine cells FH of brain cancer Cancer Secondary tumours are mets from other parts of the body NF 1/2 • Commonest form of brain tumour • Sources: lung, skin, and breast • Well demarcated, solitary nodules Tuberous Radiotherapy sclerosis • POOR PROGNOSISTumourgrades Staging = how far the tumour has spread Grading = how differentiated the tumour cells are compared with native cells e.g. Grade 1 = well differentiated, Grade 4 = poorly differentiated For brain cancer: • Grade 1 → benign • Grade 2 → >5 yrs survival • Grade 3 → 1-5 yrs survival • Grade 4 → <1yr survivalAstrocytomas Astrocytes are the most abundant cell type within CNS Pilocytic Diffuse glioma (G2- Glioblastoma astrocytoma (G1) 3) multiforme (G4) • 0 – 20 years • 20 – 40 years • 50+ years • Indolent, • MOST childhood COMMON, AGGRESSIVE, PRIMARY TUMOUR IN ADULTS Grade 2 Grade 3 Grade 4 Grade 1Braincancerbuzzwords Type Location Buzzword Meningioma Meninges / arachnoid cells Psammoma bodies Medulloblastoma Cerebellum Children, squint (embryonal) Ependyoma Posterior fossa Tuberous sclerosis Craniopharyngioma Pituitary sella Inferior bitemporal hemianopia Pituitary tumour Pituitary sella Superior bitemporal hemianopia If primary tumour: • Surgical resection • Radiotherapy • NOT chemotherapy as most do not penetrate BBBNeurodegenerativediseases:Dementia A global impairment of cognitive function and personality without impairment of consciousness. This impairment goes beyond what might be expected from normal ageing. The 5A’s: Amnesia Apraxia Aphasia Agnosia Anomia Alzheimer’s > vascular > Lewy body > frontotemporalAlzheimer’s Aetiology has 2 key theories: 1. Accumulation of β-amyloid plaques outside neurons interferes with neuronal communication 2. Hyperphosphorylation of Tau proteins leads → dissociation of Tau from neuron microfilaments → formation of neurofibrillary tangles β-amyloid plaques Tau tanglesMedial temporal lobes and hippocampus most commonly affected Global atrophy BRAAK staging used to stage Alzheimer’sBuzzwords Type Characteristics Buzzword Vascular Mini strokes Step-wise deterioration Lewy body Dx – Parkinson’s Little people/animals running around Fluctuating course Frontotemporal Younger patient 40-60 Personality change Strong +ve FHx Disinhibition Dx – Huntington’s Overeating disease Emotional bluntingParkinson’sdisease Depletion of dopaminergic neurons projecting from basal ganglia to the substantia nigra Pathophysiology: • Alpha synuclein mutation → misfolds (=Lewy bodies) • Accumulation of Lewy bodies in nigrostriatal pathway → Parkinson’s • Peripheral ganglia → motor retardation • Olfactory bulb → early loss of smell Lewy bodies MelaninParkinson’s+syndromes Parkinson’s + Buzzwords Vascular Parkinson’s PD + cardiovascular RFs Drug-induced Parkinson’s PD + Bilateral symptoms Multiple system atrophy (MSA) PD + autonomic dysfunction Progressive supranuclear palsy PD + vertical gaze dysfunction (PSP) Corticobasal dysfunction PD + alien limbs phenomenonHydrocephalusRaisedICPandHerniationQUIZ6(SBA &VSA) 1) A 76 patient is diagnosed with terminal brain metastasis. Where has the likely primary tumour originated from? a) Liver b) Kidney c) Lung d) Prostate e) Colon 2) A 67 year old man has difficulty getting up out of a chair. On examination he has a shuffling gait and cog-wheel rigidity. Cranial nerve examination reveals a deficit in CN 1. Accumulation of which protein is responsible for this man’s presentation?Break(1minute)BoneQUIZ7(SBA &VSA) 1) An 8 year old boy is referred to the endocrine clinic because he is 155cm and has irregular brows macules and patches on his back and torso. He also finds it difficult to walk and has intermittent bone bain. X- ray reveals bilateral shepherd’s crook deformity of the femurs and biopsy shows trabecular Chinese letter patterns. What is the cause of his skeletal problems? a) McCune – Albright syndrome b) Osteosarcoma c) Ewing’s sarcoma d) Klippel – Trenaunay syndrome e) West syndrome 2) What is the most common malignant bone cancer in adults?FracturesFracturerepairOsteoarthritis X-ray features Loss of joint space Osteophytes Subchondral sclerosis Subchondral cystsRheumatoidarthritis Inflammation of the synovium Genetic predisposition: • HLA DR-4 • PADI 2&4 increase citrullination of proteins • PTPN 2 suppresses T cell activation Rheumatoid factor / T-cell and B- anti-CCP binds to cell inflammatory Pannus Carbonege and receptors on synovial proliferation, markers formation destruction membrane angiogenesisRheumatoidarthritis 5 key features on histology: 1. Synovitis Sockerhoff cells 2. Proliferation of synoviocytes 3. Thickening of synovial membranes 4. Inflammatory cell infiltrates 5. Fibrin depositionOsteomyelitis 1 week 3-6 weeks Irregular sub- 1-2 weeks periosteal new Irregular lytic Detachment of bone formation destruction necrotic cortex (involucrum) (sequestra)GoutvsPseudogout Buzzword: “Rat-bite” erosions Buzzword: White lines of chondrocalcinosisBonecancerbasics Benign Malignant Acute periosteal No periosteal reaction reaction Thick endosteal Border between lesion reaction and normal bone Irregular bone Regular bone formation formation Intraosseous and Extraosseous and regular calcification irregular calcifiation Malignantbonetumours Name Epidemiology Bone Histology [BUZZWORDS] X-ray Appearance Malignant mesenchymal Adolescence Very rare – 60% cells Elevated periosteum Osteosarcoma Knee (60%) ALP +ve (Codman’s triangle) less rare than Replacement of bone marrow Sunburst appearance lung cancer with trabecular bone Axial skeleton Chondrosarcoma >40 yrs Femur/tibia/ Malignant chondrocytes Lytic lesion with fluffy (proliferation of cartilage) calcification, pelvis <20yrs Long bones, Ewing’s sarcoma HIGHLY Sheets of small round cells Onion skinning of periosteum MALIGNANT pelvis Giant cell Osteoclasts and stromal cells “Soap bubble appearance” Lytic/lucent lesions right up to (borderline 20-40yrs F>M Knee- epiphysis malignancy) “Giant multi-nucleate articular surface osteoclasts”Benignbonetumours:Fibrousdysplasia Bone is replaced by fibrous tissue Assn with McCune-Albright syndrome • Triad of: fibrous dysplasia, café au lait spots and precocious puberty • SEE PAEDS “Soap-bubble” osteolysis “Shepherd’s crook Chinese letters deformity”QUIZ8(SBA&VSA) 1) A 50 year old publican presents to A&E with an stutely painful big toe. There is erythematous tenderness over the 1 metatarso-phalangeal joint. An aspirate of the joint is taken and viewed under polarized light. Which of the findings is consistent with the likely diagnosis? a) Rhomboid shaped crystals, positively birefringent b) Needle shaped crystals, positively birefringent c) Rhomboid shaped crystals, negatively birefringent d) Needle shaped crystals, negatively birefringent e) Apple-green birefringence 2) A 45 year old woman has pain in her hands that lasts for 45 minutes every morning. X-ray of the hands shows joint subluxation, soft tissue swelling and erosions at the joint margins. Proliferation of which cell type is responsible for the woman’s presentation?Break(1minute)Skin Layers of epidermis: Stratum corneum Stratum granulosum Stratum spinosum Stratum basaleQUIZ9(SBA&VSA) 1) A patient is diagnosed with malignant melanoma, which of the following is associated with the worst prognosis? a) Asymmetry b) 3 colours c) Irregular borders d) 10mm width e) 4 mm depth 2) A 87 year old woman has multiple blisters on her arms. These are extremely painful and burst when she touches them. MCS of blister fluid is negative for microbes, crystals or blood. Biopsy of the skin shows intraepidermial acantholysis. What is the diagnosis? Eczema / Psoriasis Inflammatory Bullous Dermatology disease BCC / SCC / Cancer MMEczemaa.k.a.dermatitis Aetiology: 1. Inside-out theory – auto-immune IgE sensitization leads to skin barrier dysfunction 2. Outside-in theory – allergen exposure leads to IgE dysfunction Mutations in filaggrin gene T1 hypersensitivity – atopic dermatitis T4 hypersensitivity – contact dermatitis (e.g. jewellery, watches, shoes etc.) ↑ eosinophils Eczema Thickening of epidermis Fluid collection in epidermis (spongiosis)Psoriasis 1. T4 T-cell hypersensitivity reaction within the epidermis 2. T-cell recruitment and release of inflammatory cytokines e.g. TNF-a 3. Keratinocyte hyperproliferation 4. Epidermal thickening Buzzwords: “Parakeratosis” Auspitz sign – rubbing causes bleeding Psoriasistypes Type Feature Chronic plaque Most common, extensor surfaces Flexural Flexural surfaces Guttate “Rain-drop” lesions on back and torso 2 weeks after GABHS throat infection Erythrodermic/pustular EMERGENCY Koebner phenomenon Forms at sites of traumaBullouspemphigoid Bullous pemphigoid affects flexural surfaces in the elderly population IgG Abs and C3 bind to hemidesmosomes (adhesion molecules) in basement membrane of epidermis → epidermis lifts off → fluid accumulates in space a.k.a. subepidermal bulla Histology: eosinophilia, linear deposition of IgG along basement membrancePemphigusvulgaris Pemphigus vulgaris are a type of blister that start in the mouth before spreading to other parts of the body IgG to desmoglein 1 & 3 (adhesion molecules) between keratinocytes in stratum spinosum → acantholysis a.k.a. intraepidermal bulla These bulla rupture easily, in comparison with bullous pemphigoidPemphigusfoliaceus Affects elderly population IgG against desmoglein in epidermis → detachment of superficial keratinocytesSummarytable Bullous Pemphigus Pemphigus pemphigoid vulgaris foliaceus Key mediator IgG and C3 IgG IgG Target Hemidesmosomes Desmoglein 1 & 3 Desmoglein Layer of skin Basement Stratum spinosum Stratum corneum membrane of epidermis Result Subepidermal bulla Intraepidermal bulla Detachment of superficial keratinocytes Skincancer:Skincancers Basal cell carcinoma Squamous cell carcinoma Melanoma Epidemiology 70% 20% 10% Risk factors 1. UV exposure: • Long exposed periods in the sun • > 6 sunburns • Sunbeds 2. ↑ Age 3. Exposure to ionizing radiation/prev radiotherapy 4. Type 1-2 skin types on Fitzpatrick scale 5. FHx +ve 6. Immuno-suppression – transplant, innumodeficiencies 7. VAX (vitiligo, albinism, xoderma pigmentosum) 8. FAMMM (familial atypical malignant mole melanoma) Presentation Basal cells in stratum basale Epidermal keratinocytes Superficial spreading (90%) – these are keratinocyte Locally invasive – mod mets Nodular precursors Lentigo meligna Slowly growing NOTE: Marjolin’s ulcer Acral lentiginous (soles, palms) Locally invasive – rarely mets Appearance “Well defined, pearly rolled “Hyperkeratotic, crusting, ABCDEs (Asymmetry, irregular edges, shiny, fine ulcerated and rolled edges” borders, colours >2, diameter telangiectasia” >6mm, evolving BRESLOW’S THICKNESS Prognosis EXCELLENT OK BAD Pre-malignant 1. Nevoid basal cell carcinoma 1. Solar/actinic keratosis Melanocytic naevi conditions (Gorlin-Goltz syndrome) 2. Bowen’s disease (SCC in Seborrhoeic keratosis situ) BCC Melanoma SCCQUIZ10(SBA&VSA) 1) A 14 year old boy has 6 months of intermittent erythematous, purple scaly plaques on the flexural surfaces of his elbows and knees. There is also white spots and splitting of the nail. What would be seen on biopsy of the plaques? a) Filaggrin gene mutation b) Spongiosis c) Hyperparakeratosis d) Epidermal necrolysis e) Rain-drop lesions 2) What is the most common type of malignant melanoma?Finalthoughts