j0305257 8th special pathology practice Bones Soft tissue Skin j0305257 BONES j0305257 Osteomyelitis û purulent – tendency to chronicity ð staphylococcus, E. coli, Klebsiella, salmonella, gonococcus, … ð û entry of infection: ð hematogenous (bacteriemia, sepsis) ð from adjacent tissues (ORL, teeth) ð direct implantation (orthopedic surgery, trauma) û û difficult healing ð slow diffusion of ATB into bones… sugical drainage necessary û û complications ð pathological fracture, sepsis, purulent arthritis j0305257 Osteomyelitis û acute stage: û flegmonous intertrabecular inflammation, necrosis û subperiostal abscess → bone ischemia, skin draining sinus possible û û subacute and chronic stage: ð separation of necrotic parts of the bone as sequestrum • free foreign bodies eliminated through sinus • sequestrum may be surrounded by reactive new bone growth – involucrum, persistent infection û û tbc ostitis: immunosuppressed, endemic regions; spine, chronic destruction j0305257 Chronic purulent osteomyelitis osteomyelit3, 100x.jpg j0305257 Chronic purulent osteomyelitis osteomyelit2, 200x.jpg 1 2 1Osteoclast 2Inflammatory infiltrate (mainly plasma cells, neutrophils) j0305257 Osteitis fibrosa cystica û von Recklinghausen`s disease, now rare û û primary or secondary hyperparathyreoidism → ↑osteoclastic bone resorption→ pathological fractures, „brown tumor“ û û stage: ð osteoclastic resorption ð fibrous phase ð cystic phase – pseudocysts due to resorbed haematomas j0305257 Brown tumor – osteitis fibrosa cystica WHO-Bone Tumours_04 1 Pseudocyst 2 Haemosiderin 3 Multinucleated osteoclast-like cell 4 Spindle cells 1 2 3 4 j0305257 Selected BONE TUMORS j0305257 Giant-cell tumor of the bone û histogenesis (?? undifferentiated mesenchymal cells, marrow stromal cell) û û characteristic X-ray, localization ð poorly demarcated bone destructive (osteolytic) lesion in the meta- or epiphysis of a long bone at the age of 20-40. ð ð û Gross: ðsoft brown-red tumor, often with central hemorrhage ðlocally destructive growth, metastases in 10% (lungs) j0305257 obrbbtu-mi2 Giant cell bone tumor j0305257 Giant-cell tumor of the bone femur WHO-Bone Tumours_05 1 Limited bone destruction 2 Tibia 1 1 2 copy j0305257 Giant-cell tumor of the bone û micro: ð 2 cell types: • uniform population of mononuclear cells - proliferating. • giant multinucleated cells – osteoclast-like (100 nuclei) ð often hemorrhage, fibrosis and necrosis • diff.dg.: „brown tumor“ inosteitis fibrosa cystica j0305257 Giant-cell tumor of the bone OBN2, 200xsuper.jpg j0305257 Giant-cell tumor of the bone OBN2, 400xsuper.jpg j0305257 Osteochondroma û„exostosis“ û on the metaphysis of the long/flat bones û often during the period of skeletal growth û û gross: û bone prominence covered with cartilage – growthplate-like û û micro: ð benign hyaline cartilage on the surface → enchondral ossification and lamellar bone formation ðintertrabecular bone marrow (adipous, haematopoetic) j0305257 Osteochondroma osteochondrom3, přehled20x.jpg j0305257 Osteochondroma osteochondrom2, přehled40x.jpg j0305257 Osteochondroma osteochondrom1, 100x.jpg j0305257 Osteosarcoma (OSA) û bone matrix producing malignant cells ûprimary: typically in childhood - adolescence ð mostly during accelerated skeletal growth period ð û secondary osteosarcoma possible in Paget disease, post-radiation û û localization ð long bone metaphyses (femur, tibia, humerus), especially in knee region (Codmann`s triangle on the X-ray) û û divided according to their biological behavior ð low-grade (LG) – more commonly peripheral growth ð high-grade (HG) – more commonly central growth j0305257 Image072 Osteosarcoma – Codman`s triangle copy j0305257 HG OSA û micro: ðirregular atypical osteoblasts → tumorous osteoid ðfrequent mitoses ðsignificantly dilated vascular spaces ðpossible presence of cartilage or fibrous bone elements • osteoblastic, chondroblastic, fibroblastic variant û û blood-borne micrometastases often present at the time of diagnosis (bones, lungs) ðpoor prognosis without treatment, with overt meta, recurrent ðchemotherapy + surgery (avoiding amputation) ð j0305257 Osteosarcoma OSA1, 100x.jpg 1 3 2 1Osteoid matrix 2Neoplastic osteoblasts 3Bone trabeculae j0305257 Osteosarcoma OSA3, 200x.jpg j0305257 Osteosarcoma P0073.jpg Neoplastic osteoblasts j0305257 Chondrosarcoma û typically in adulthood (after age of 20, mostly in 4th-6th decade) û û localization ð pelvis, femur, shoulder region û û micro ð nodules of neoplastic cartilaginous tissue ð neoplastic chondroblasts with anisonucleosis, hyperchromasia, binucleate ð calcification, necrosis common ð myxoid change of cartilaginous matrix possible û û prognosis ð better than HG OSA ð slow proliferative activity common (surgery mostly) j0305257 Chondrosarcoma chondrosa, 100x.jpg j0305257 Chondrosarcoma chondrosa, 200x.jpg j0305257 Ewing‘s sarcoma/PNET û group of small blue round-cell sarcomas, with detectable specific chromosome translocation ð improved prognosis thanks to aggresive CHT ð 5-year survival for metastatic disease (lungs, bones) is only 25% û û typical in children and young adults û most often localized in bone marrow, but any other localization possible û û molecular genetic changes: ð balanced translocation of EWSR1 (localized on 22nd chromosome) and ETS gene family → fusion genes →abnormal cell proliferation + survival •t(11;22)/ EWSR1-FLI – the most common (90%) •t(21;22)/EWSR1-ERG – in 5-9% j0305257 Ewing‘s sarcoma/PNET û gross: ð X-ray: osteolytic destructive lesion localized in diaphysis of a long bone + lamelated or “onion skin” type periosteal reaction ð whitish necrotic focus – may resemble purulent osteomyelitis ð fragile, necrotic, hemorrhagic tumor in soft tissues and in affected organs û û micro: ð uniform round cells ð formation of rosettes, pseudorosettes ð necrosis ð mitoses j0305257 Ewing‘s sarcoma Ew6_sval_100x immature cell infiltration of skeletal muscle j0305257 Ewing‘s sarcoma Ew4_400x Ew4a_200xCD99 Tumor cell nuclei with dispersed chromatine Right: anti-CD99 j0305257 Ewing‘s sarcoma FISH: split ( ) EWSR1 gene on chromosome 22, normal locus EWS ( ) j0305257 JOINTS, SOFT TISSUES j0305257 Arthritis uratica - gout û defective uric acid metabolism ðmonosodium urate crystals • in joint cartilage, in synovial membrane, in soft tissues surrounding joint (big toe joints…) û û acute gouty arthritis ð acute synovial membrane inflammation • neutrophils, free oxygen radicals, inflammatory synovial membrane damage… • û chronic gouty arthritis ð after repeated acute attacks ð tophus • aggregates of urate crystals surrounded by giant cell granuloma j0305257 Arthritis uratica – tophus dna1, přehled40x.jpg j0305257 Arthritis uratica – tophus dna3, 200x.jpg j0305257 Arthritis uratica – tophus urát, 200x.jpg urát, 400x.jpg Needle-shaped urate crystals j0305257 Myositis ossificans ûtumor-like reactive nodular fibroblastic lesion ûmetaplastic ossification of skeletal muscle following inflammation (diff.dg. x extraskeletal osteosarcoma) û û mostly in young sportsmen, proximal limbs û û often trauma anamnesis (→ deep haematoma) û û X-Ray: central clearing with ossified border û û micro: ð central fibroblastic proliferation + hemosiderin ð metaplastic ossification and regressive muscle changes in the periphery j0305257 Myositis ossificans WHO-Bone Tumours_01 1 Caput femoris 2 Collum femoris 3 Calcified structure in skeletal muscle 1 2 3 copy j0305257 Myositis ossifficans WHO-Bone Tumours_02 1 Fibrous tissue proliferation in muscle 2 Newly formed lamellar bone trabeculae 1 2 j0305257 Undifferentiated pleomorphic sarcoma (Malignant fibrous histiocytoma, MFH) û û high-grade sarcoma û û 30% of all soft tissue sarcomas ð may occur in dermis and subcutaneous tissue û û often in the thigh region û û mostly in older males û û diagnosis per exclusionem ð after elimination of any other poorly differentiated mesenchymal or neuroectodermal tumor j0305257 „MFH“ û gross: ðwhitish tumor, „ fish-flesh“ appearance on cut section ð û micro: ðexcessive pleomorphism of tumor cells and cellular architectonics ðbizarre multinucleate cells ðfrequent mitotic activity, necrosis ðvariants: • pleomorphic • inflammatory • giant-cell j0305257 MFH – high grade undifferentiated pleomorphic sarcoma NEO078 Pleomorphic nuclei of neoplastic cells j0305257 maligní fibrózní histiocytom Pleomorphic nuclei of neoplastic cells, frequent mitotic activity (atypical mitoses) MFH – high grade undifferentiated pleomorphic sarcoma j0305257 Synovial sarcoma û in fact not from synovial cells – original cell unclear û û usually balanced translocation t (X;18) û û typical in adolescents and young adults (15 – 40s) û û mostly in deep soft tissues of upper or lower limbs û j0305257 Synovial sarcoma û therapy: ðresection + CHT, RT ð û aggressive tumor ðlung, bones metastases ð5-year survival 25 – 85 % û û micro: ðBiphasic variant • spindle cells + epithelial component (glandular formations, strands of epithelial cells) ðMonophasic variant • spindle cells j0305257 Synovial sarcoma synovial sarcoma mikro.jpg Biphasic variant: spindle cells + glandular formations j0305257 Synovial sarcoma FISH: split ( ) gene SS18, normal locus SS18( ) j0305257 SKIN - INFLAMMATION j0305257 Skin changes - terms û hyperkeratosis ð thickened stratum corneum, often associated with marked stratum granulosum ð û parakeratosis ð imperfect keratinization characterized by retention of the nuclear remnants in the stratum corneum, stratum granulosum often missing ð û dyskeratosis ðabnormal monocellular keratinization (disordered or premature) occuring within individual cells or groups of cells below the stratum granulosum – intraepidermal keratin foci ð û acanthosis ð hyperplasia of the stratum spinosum ð û papillomatosis ð hyperplasia of papillary dermis with elongation of the dermal papillae j0305257 Psoriasis ûchronic inflammatory dermatosis (epidermal hyperproliferation) genetic susceptibility (HLA) + unknown trigger factor;T-cell mediated, TNF, increased epidermal cell proliferation and turnover ûtypical localizations: ðelbows, knees, extensor surfaces of the skin ðgeneralization possible ûsometimes associated with arthropathy, myopathy, enteropathy, etc. û j0305257 Psoriasis ûgross: ðwell demarcated pink to red plaques ðcovered by silvery parakeratotic scales ûmicro: ðhyperkeratosis, parakeratosis •stratum granulosum thinned or absent ðacanthosis •thinned suprapapillary layer of dermis, papillary oedema ðneutrophils in the stratum corneum – microabscesses ðchronic dermal inflammatory infiltrate û j0305257 00887+ Psoriasis copy j0305257 Psoriasis copy psor-ma j0305257 psoriáza1, 100x.jpg Psoriasis 1 2 3 4 1Acanthosis 2Papillomatosis, papillary oedema 3Hyperkeratosis, parakeratosis 4Microabscesses 5Dermal chronic inflammation 5 j0305257 Psoriasis psoriáza, mikroabsces, 200x.jpg microabscess j0305257 Lichen ruber planus û chronic disease of skin and mucous membranes û localization ð wrist, volar side of forearm, lower leg (crus) û gross ð pruritic skin-colored polygonal shaped flat-topped papulae ð may fuse to form purple plaques ðoral – white reticular lesions û j0305257 Lichen ruber planus û micro: ðhyperkeratosis without parakeratosis, thickened stratum granulosum ðirregular acanthosis, disperse necrotic keratinocytes ðinterface dermatitis – cell-mediated cytotoxic immune reaction – degeneration + destruction of basal keratinocytes, saw-tooth profile ðdense infiltrate of lymphocytes along the dermoepidermal junction + melanin incontinence (pigment in melanophages) ðx lichenoid infiltrate j0305257 01067+ Lichen ruber planus copy j0305257 00155+ 1 hyperkeratosis without parakeratosis 2 acanthosis 3 vacuolar degeneration at dermoepidermal junction 4 lymphocytes 5 thickened stratum granulosum Lichen ruber planus 1 2 3 4 5 j0305257 Urticaria (hives) û dermal (interstitial) edema û û very sparse superficial perivascular and interstitial infiltrate consisting of mononuclear cells with neutrophils and sometimes with eosinophils û û dermographism û j0305257 01141+ 00715+ Urticaria (dermographism) copy j0305257 00420+ • mild perivascular infiltrates with presence of eosinophils and neutrophils • normal epidermis Urticaria j0305257 Blistering (bullous) diseases û sites of blister formation: ð subcorneal ð suprabasal ð subepidermal ð û causes: ð acantholysis (dissolution of the intercellular bonds of the stratum spinosum) ð spongiosis (intercellular edema of the epidermis) ð balooning and reticular degeneration ð cellular vacuolization of the basal cell layer ð necrotic blisters j0305257 Epidermolysis bullosa û group of non-inflammatory blistering disorders û inherited defects in structural proteins lending mechanical stability to the skin ûblisters on the skin + mucosal membranes due to minimal trauma (pressure, rubbing) û dg. ð IF ðELMI ðmolecular-genetic methods ð j0305257 Epidermolysis bullosa A, B: large erosions C: collagen VII absence in the dermo-epidermal junction (IF) D: collagen VII - positive control (IF) A B C D j0305257 Pemphigus vulgaris û life threatening disease, may start at any age (more common 4-6th decade) û repeated attacks û acantholysis → large blisters formation û→→→ loss of fluids, proteins; secondary infection ûauto-antibodies → dissolution of desmosomes û suprabasal blisters (skin+mucosa – oral), frequent eosinophils û immunofluorescence ðintercellular IgG deposits between keratinocytes j0305257 00863+ Pemphigus vulgaris copy j0305257 00075+ 1 acantholytic blister 2 eosinophils 3 suprabasal acantholysis, round acantholytic cells Pemphigus vulgaris 1 2 3 j0305257 Bullous pemphigoid û chronic skin disease û benign affection (x pemphigus vulgaris) û patients mostly over 60 years; skin +/- mucosa û subepidermal tense nonacantholytic blister, numerous eosinophils (better healing) û immunofluorescence: deposits of Ig, C3 along the basement membrane, fibrin û j0305257 00102+ 1 subepidermal blister – basal layer vacuolization, fibrin and eosinophils 2 inflammatory infiltrate (presence of eosinophils) 1 2 Bullous pemphigoid j0305257 Herpes simplex û recurrent disease, painful erythematous vesicles, often erosive û û localization ð lip border ð anogenital region j0305257 00100+ Herpes simplex j0305257 Dermatitis herpetiformis Duhring û chronic skin disease, urticaria + groups of vesicles û dietary gluten hypersensitivity û (possible association with celiac disease) û extreme pruritus (+ scratching excoriations) û intrapapillary edema, subepidermal blister û numerous neutrophils (at the tips of dermal papillae) û immunofluorescence: ðsubepidermal IgA deposition û j0305257 1 1 1 Dermatitis herpetiformis û û 01255+ Intrapapillary edema and neutrophilic accumulation (small subepidermal vesicles) j0305257 Granulomas û chronic skin disease û dense accumulation of modified histiocytes in dermis û histology: •epitheloid granulomas •palisading granulomas •inflammatory granulomas • aetiology: ð infectious: mycobacteria, fungi ð non-infectious: foreign body ð uncertain immune-mediated origin j0305257 Granuloma annulare û acquired chronic skin disease of unknown aetiology û û usually self-limited (even spontaneously) û û multiple round lesions with elevated borders û û micro: ðpalisading granuloma in the dermis • poorly demarcated • centered to foci of necrobiosis (degenerated collagen) j0305257 00249+ 2 1Necrobiosis 2Histiocytes Granuloma annulare 1 j0305257 Necrobiosis lipoidica û acquired chronic skin disease û often associated with diabetes mellitus, females û û localization: ð crural region of legs û û micro: ð large areas of necrobiosis ð surrounding rim of histiocytes ð positive lipid stain j0305257 00328+ 1 areas of necrobiosis 2 rim of histiocytes Necrobiosis lipoidica 1 2 j0305257 Rheumatoid nodules û patients with rheumatoid arthritis û û localization: ðmostly extensor sites of limbs, but it can occur elsewhere (+ extracutaneous localization – diff. dg. x tumors) û û nodules (mm-5cm) localized deep in dermis û û micro: ð large palisading granulomas around fibrinoid necrosis j0305257 00350+ 1 fibrinoid necrosis 2 palisading histiocytes Rheumatoid nodules 1 2 j0305257 Foreign body granuloma û epithelioid granulomas surrounding foreign material ûmultinucleated giant cells û foreign material can often be visualized by polarized light û process often associated with purulent inflammation û û example: ðSchloffer`s pseudotumor around suture material û j0305257 Schloffer`s pseudotumor stehový granulom1, 1000x.jpg 1 2 2 1Suture 2Giant multinucleated cells j0305257 Schloffer`s pseudotumor stehový granulom1, 200x.jpg j0305257 û chronic autoimmune multisystem disease ð kidney, skin, joints, lungs, heart, serosal membranes, mucous membranes, CNS û û clinic: ðacute onset ðsubacute ðchronic (insidious onset) Lupus erythematosus j0305257 Systemic lupus erythematosus SLE û etiology: ðfailure of the self-tolerance mechanism ðgenetic predisposition + unknown trigger ðCMV?, EBV?, hereditary factors, female hormones? û clinic: ðremitting, relapsing disease ðfever, muscle pain, arthralgia – diff. dg. x sepsis! ðseizures- diff. dg. x epilepsy! ðantinuclear and antiphospholipid antibodies, anemia, leukopenia, thrombocytopenia j0305257 SLE û skin: ð involved in 80% of patients ð specific: maculopapular exanthema in face (“butterfly pattern”); UV-sensitive ð nonspecific: chronic skin ulcers ð û heart: ð pericarditis, myocarditis ð Libman-Sacks verrucous non-bacterial endocarditis ð û lungs: ð pleuritis, lupus pneumonitis j0305257 SLE û kidney: ð lupus nephritis ð û CNS involvement ð various symptoms û hematologic disorders: ð anemia, leukocytopenia, lymphocytopenia, thrombocytopenia, antiphospholipid antibodies ð û joint involvement ð arthralgia, migrating polyarthritis, joint deformity, diff. dg. x rheumatoid arthritis j0305257 SLE û micro: ð hyperkeratosis ð atrophy of the basal epidermal layer ð dermal edema ðperiadnexal lymphocytic infiltrate j0305257 Discoid lupus erythematosus û form of lupus limited to the skin û û anitinuclear antibody positivity in 70% ð negative SLE specific antibodies ð û clinic: ð chronic disease, relapsing and remitting ð transform in systemic form in 5-10% of patients (after 10-20 years) j0305257 SLE – exanthema (“butterfly pattern”) j0305257 00215+ 1 vacuolar degeneration 2 mild lymphocytic infiltrate SLE – acute form 1 2 j0305257 00571+ SLE – Immunofluorescence (lupus band) j0305257 SKIN - TUMORS j0305257 Verruca vulgaris û caused by HPV (type 2, less often type 1, 4, 7…) û transmission: direct contact, autoinoculation ûmost frequent localization: fingers, feet û û gross: ð warty papule with a rough surface , gray-white to tan, skin color û û micro: ð papillomatous (verrucous) epidermal hyperplasia with acanthosis, hyperkeratosis and parakeratosis ð intracytoplasmatic viral inclusions ð reactive mononuclear infiltrate in dermis and interstitium j0305257 Plantar verruca verrplant-ma j0305257 Verruca vulgaris vulgární veruka 2, přehled40x.jpg Papillomatosis + hyperkeratosis + parakeratosis j0305257 Verruca vulgaris detail parakeratozy, 100x.jpg Parakeratosis j0305257 Condyloma accuminatum û caused by HPV, mainly type 6,11 etc. - localized in anogenital region û sexually transmitted disease ð venereal wart, incubation time 2-3 months û gross: ð wart-like (often multiple) lesion in typical localization û micro: ð koilocytes • cells with shrinked dark nuclei surrounded with empty “halo”, bi- or multinucleated cells ð hyper-, para- and dyskeratosis j0305257 Condyloma accuminatum condylomata2, přehled20x.jpg j0305257 Condyloma accuminatum condylomata2, 100x.jpg j0305257 Condyloma accuminatum condylomata2, 200x.jpg j0305257 Seborrheic keratosis û common benign cutaneous tumor û û gross: ð well demarcated hyperpigmented papule of “greasy waxy appearance” ð û micro: ð hyperkeratosis, papillomatosis, acanthosis ð formation of „horn“ cysts filled with keratin lamellae ð variable melanin pigmentation often present j0305257 seboroicka-veruka-spanek seboroicke-veruky-dyskeratozy-zada Seborrheic keratosis j0305257 Seborrheic keratosis seborh, přehled20x.jpg j0305257 Seborrheic keratosis seborh,100x.jpg j0305257 Actinic keratosis • intraepidermal dysplasia - precancerosis • occurs at sites of chronic sun exposure û (head, neck, shoulder…) • • gross: • areas of thickened, rough skin + small excoriations, atrophy û • micro: • dysplasia up to variable layer of the epidermis (starts at basal layer) • atrophy + hyperkeratosis, parakeratosis + dense chronic inflammatory infiltrate in superficial dermis j0305257 aktinicke-keratozy-celo Actinic keratosis j0305257 Actinic keratosis ker-sol-7764-00-he-10x 1 atypical keratinocytes 2 epidermal atrophy 3 hyperkeratosis, parakeratosis 4 inflammatory infiltrate 1 2 3 4 j0305257 Basal cell carcinoma û locally aggressive carcinoma (rarely metastasize) û typically at the sites of chronic sun exposure û ûgross: ð flat / nodular lesion of skin color; erythematous plaque (superficial BCC) ð may contain melanin pigment ð often central ulceration û micro: ð hyperchromatic dark basaloid cell nests ð peripheral palisading ð mitoses frequent, ð stroma shrinks away from the tumor nests, creating clefts or separation artifacts j0305257 ca-baso-ulc-detail1 Basal cell carcinoma j0305257 Superficial basal cell carcinoma BCC-supf-ma j0305257 Superficial basal cell carcinoma BCC-supf-mi j0305257 Basal cell carcinoma bazaliom1, 100x.jpg j0305257 Basal cell carcinoma bazaliom2a, 200x.jpg j0305257 Squamous cell carcinoma ûUV light, HPV, chronic ulcers + wounds, chemical carcinogenes û û gross: ð sharply demarcated scaling plaques, sm. elevated or nodular lesion of firm consistency ð possible ulceration û û micro: ðtumor cells arranged in cords and nests • cells on the edge of nests smaller, to the centre increased cytoplasmic volume (~ stratum spinosum) • atypical mitoses at all levels of epidermis • variabler keratinization, dyskeratosis, keratine pearls • intercellular bridges j0305257 ca-spino-ucho Squamous cell carcinoma j0305257 02444-1 Squamous cell carcinoma j0305257 Melanocytic lesions û Benign: ð freckles (ephelides) ð benign lentigo ð pigmented nevus ð spindle and epitheloid cell nevus (Spitz nevus) ð atypical (dysplastic) nevus û Malignant melanoma: ð lentigo maligna ð superficial spreading melanoma ð nodular melanoma ð acral lentiginous melanoma ð û j0305257 Pigmented nevus û benign tumor, congenital or acquired û congenital nevus usually larger (esthetic surgery) û micro: ðjunctional nevi • groups of pigmented cells (= nests) grow in dermoepidermal junction ðcompound nevi • nests grow in junction zone and into the underlying dermis (in dermis arranged also in cords) ðintradermal nevi • nests/cords only in the dermis û j0305257 01 Melanocytic lesions copy j0305257 Pigmented nevus nevi-pigmentosi-detail j0305257 Intradermal pigmented nevus nevus-id-7463-00-he-2,5x 1.Melanocytes 2.Papillary dermis separating nests of melanocytes and epidermis 1 1 2 j0305257 Intradermal pigmented nevus nevus-id-7463-00-he-10x j0305257 Compound pigmented nevus smíšený névus2, 200x.jpg smíšený névus, 400x.jpg j0305257 Malignant melanoma û origin: ðmalignization of preexisting nevi ðde novo ð û localization: ðskin ðmucous membranes ðmeninges ðeye j0305257 Malignant melanoma û gross: ð similarity to congenital nevus at early stage ð irregular borders ð variegation of color within a pigmented lesion ð ulceration, darkening, bleeding at late stages ð ðclinic ABCD rule • Assymetry • irregular Border • uneven Colour • Diameter > 6mm j0305257 Malignant melanoma û micro: ð assymetry ð atypical pleomorphic epitheloid or spindle cells ð large hyperchromatic nuclei with prominent nucleoli ð mitoses (atypically localized) ð irregular rough granular pigmentation • forms with complete absence of pigment possible ð immunoprofile: • melan A, HMB-45, S-100 ð ð • j0305257 24_06 Clark 1 2 3 4 5 do tuku Depth of melanoma invasion by Clark copy j0305257 24_07 Depth of melanoma invasion by Breslow (mm) copy j0305257 Melanoma – prognostic factors û thickness of lesion by Breslow (groups of 1-2-4 mm) û depth of invasion by Clark (in TNM) û ulceration û mitotic rate û parcial regression (worse prognosis) û presence of tumor-infiltrating lymphocytes û lymphovascular invasion û females - longer survival û longer survival by localization on limbs ðexcept of subungual and plantar form (acral lentiginous melanoma – worse prognosis) û j0305257 Malignant melanoma û 3 growth phases: ð melanoma in situ (intraepidermal phase) ð ð radial growth phase - superficial MM • superficial growth within epidermal layers associated with invasion into the papillary dermis • ð vertical growth phase – nodular MM • downward invasion into the reticular dermis • clone of cells with metastatic potential j0305257 Lentigo maligna û severe intraepidermal melanocytic dysplasia – melanoma in situ; may progress – lentigo maligna melanoma û gross: ð irregular pigmented lesion, mostly localized on the face û û micro: ð atypical melanocytes single in dermoepidermal junction and in all layers of the epidermis ð epidermal atrophy and basophilic collagen degeneration j0305257 lentigo-maligna-suborbit Lentigo maligna melanoma j0305257 Lentigo maligna melanoma mm-in-situ-6398-92-he-20x 1 irregular nests in the junction zone 2 melanocytes in all epidermal layers (pagetoid spread) 1 2 1 j0305257 Malignant melanoma radial growth phase - SSM DSCN1896 j0305257 Malignant melanoma radial growth phase - SSM ssm-4852-96-he-10x 1. Irregulary distributed nests in junction zone 2. Single melanocytes in upper epidermal layers 3. Lymphocytic infiltrate 4. Invasion into papillary dermis (Clark 3) 1 2 3 4 j0305257 Malignant melanoma vertical growth phase û SSM + nodular clone of melanoblasts with vertical growth û worse prognosis ûgross: ðirregular variably pigmented macule + prominent nodule û micro: SSM + different neoplastic clone, bigger nest with vertical growth j0305257 melanom-nodularni-detail Malignant melanoma vertical growth phase with nodularity j0305257 Malignant melanoma – nodular MM û growth zone in the dermis û û metastasizes, depends on prognostic factors ð first into lymph nodes, later hematogenous spreading into literally any organ/tissue ð radical excision û û gross: ðnodule of various color ð û micro: ð tumorous melanocytes forming nodule of various size in the dermis • tumor cells differ from radial growth component (new tumorous clone) – most often epitheloid appearance • maturation to the base of the lesion absent j0305257 mm-nodul-799-93-he-1,25x Large tumor infiltrating fat tissue, without horizontal growth component; local enormous melanin production Malignant melanoma – nodular MM j0305257 MM2, 100x.jpg Local melanin production Malignant melanoma vertical growth phase – nodular MM j0305257 MM3, 400x.jpg MM4, 400x.jpg Atypical melanoblasts, prominent nucleoli Malignant melanoma nodular MM j0305257 Malignant melanoma liver metastases mts MMjátra.jpg j0305257 Image049