Nonmelanocytic Malignant Skin Tumors.pdf

Nonmelanocytic Malignant Skin Tumors Actinic Keratosis Small rough spots and may have cutaneous horn Biopsy needed to confirm diagnosis (to rule out BCC, SCC) Microscopic features of Stratum corneum: o Hyperkeratosis o Parakeratosis o Dermal elastosis UV Radiation Complete Carcinogen Tumor initiator...

Nonmelanocytic Malignant Skin Tumors Actinic Keratosis Small rough spots and may have cutaneous horn Biopsy needed to confirm diagnosis (to rule out BCC, SCC) Microscopic features of Stratum corneum: o Hyperkeratosis o Parakeratosis o Dermal elastosis UV Radiation Complete Carcinogen Tumor initiator and promoter Causes DNA dmg and p53 mutation 3 components: o UV-A (400nm) § Longest wavelength § Reaches dermis § Indirect DNA dmg o UV-B (320nm) § Absorbed by epidermis § Most carcinogenic o UV-C (100 nm) § Shortest wavelength § Absorbed by atmosphere ozone Basal Cell Carcinoma Develops early in pts w nevoid basal cell carcinoma Seen on sun-exposed skin Risk factors: o UV (tanning, phototherapy) o Gene mutations o Arsenic exposure o Albinism Pathogenesis: o PTCH gene- protein patched homolog 1 o UV damage for p53 and PTCH gene Appear as papule or nodule w telangiectasia Microscopic Features: o Nodular: nodules in the dermis o Superficial: Multifocal growth from the epidermis o Presence of: § Palisading and peritumoral clefting § Can be multifocal, superficial Treatment and Prognosis: o Surgery o Radiation therapy o Photodynamic therapy o Pharmacologic therapy: Hedgehog pathway inhibitors Hedgehog Proteins Involved in: o cell specification o Patterning of cell proliferation and differentiation o Regulation of cell proliferation and differentiation 3 types: Sonic Hedgehog Indian Hedgehog Desert Hedgehog SHH Most potent and most often expressed Causes severe congenital malformation Causes nevoid basal cell carcinoma syndrome Modifications of signaling may lead to tumor of various origin o Basal cell carcinomas (BCCs) in skin o Medulloblastomas in brain o Gliomas in brain o Rhabdomyosarcomas in muscle o Pancreatic and small cell lung cancers Squamous Cell Carcinoma Derived from keratinocytes in epidermal layer Risk Factors: HPV 5/8 infection Often white plaque (leukoplakia) May have induration, ulceration, hemorrhage Microscopic Features: o Graded according to degree of differentiation o Various histological patterns: § Conventional § Acantholytic § Clear cell § Desmoplastic § Lymphoepitheliomatous § Spindle cell § Verrucous § Warty SCC in situ o Full thickness keratinocyte atypia o NO invasion o Well differentiated in conventional type § Malignant SC invades dermis § Keratin pearls present Acantholytic SCC o Malignant SC invade dermis o Loss of intercellular connection (Acantholysis) Acantholysis Merkel Cell Carcinoma Uncommon but aggressive neuroendocrine tumor Associated with: o Merkle cell polyomavirus o UV o Immunosuppression Clinical Presentation: o Painless nodules o Rapid growing o Differential diagnoses including SCC, BCC, keratoacanthoma, melanoma (Biopsy needed for diagnosis) Microscopic features: o Monotonous round tumor cells o Scant eosinophilic cytoplasm o Round and vesicular nuclei o Granular and dusty chromatin in the nuclei o Express neuroendocrine markers: § CD56 § Chromogranin § Synaptophysin § Cytokeratin 20 (CK20) o Differential diagnoses including lymphoma (CD45+), Metastatic small cell carcinoma (TTF1+ if from lung) Monotonous round tumor cells Mycosis Fungoides Most common type of cutaneous T cell lymphoma (Clonal CD4+ T cells) Diagnosis/Differential: Other T cell lymphomas, Hodgkin lymphoma and dermatitis Four stages: o Patch: Pruritic, with erythematous or hypopigmented macules/patches Microscopic feature: clonal CD4+ T cells o Plaque: Usually pruritic, thickened plaques that may resemble psoriasis Microscopic feature: Clustered in epidermis o Tumoral: Large irregular lumps develop from plaques Microscopic feature: Dense dermal infiltrates with cerebriform nuclei o Sézary syndrome § Commonly erythroderma § Lymphadenopathy § Neoplastic T cells w cerebriform nuclei (Sézary cells) Microscopic feature: Tumor cells found in peripheral blood These tumor cells are positive for CD4 and negative for CD8