Malignant skin tumors Notes

NOTES NOTES MALIGNANT TUMORS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Malignant cutaneous lesions due to abnormal/uncontrolled growth of epithelial cells SIGNS & SYMPTOMS ▪ ≥ one multiple visible cutaneous tumors ▪ Melanoma can present noncutaneously (e.g. ocular, mucosal) DIAGNOSIS TREATMENT LAB RESULTS Histological analysis ▪ Confirms diagnosis, establishes tumor grade MEDICATIONS Biopsy ▪ Confirms diagnosis, establishes tumor grade SURGERY OTHER DIAGNOSTICS OTHER INTERVENTIONS ▪ Dermatological examination with dermatoscope, TNM staging ▪ Breslow thickness ▫ Distance of tumor cell from basal layer of epidermis 24 OSMOSIS.ORG ▪ Immunomodulators ▪ Surgical excision ▪ Electrodesiccation, curettage of lesion ▪ Radiation therapy

Chapter 5 Malignant Skin Tumors BASAL-CELL CARCINOMA osms.it/basal-cell_carcinoma PATHOLOGY & CAUSES CAUSES ▪ Most common type of skin cancer; emerges from basal cells found in lower epidermis ▪ Slow growing, can infiltrate surrounding tissue, rarely metastasizes ▪ UV radiation: direct DNA damage (pyrimidine dimers) → alters DNA structure → mutations, carcinogenesis if tumor suppressor gene involved ▪ Gorlin syndrome: numerous basal cell carcinomas due to mutation of PTCH1 gene TYPES RISK FACTORS Nodular ▪ Pearly circular cystic pigmented nodule Infiltrative ▪ Invades dermis Micronodular ▪ Solid white-coloured lesion Morpheaform ▪ Flat white-yellowish waxy lesion Superficial ▪ Erythematous plaque, usually on upper trunk ▪ Arsenic exposure; immunodeficiency; fair skin, albinism; xeroderma pigmentosum; risk increases with age; high exposure to UV radiation SIGNS & SYMPTOMS ▪ Presents on face, periocular, neck, scalp (i.e. sun-exposed areas) ▪ Newly discovered lesion ▫ Pearly elevated patch of skin ▪ Does not heal within four weeks ▪ Dimpled at midpoint ▪ Grows slowly ▪ May bleed (esp. when poked/knocked) ▪ Painless, may itch ▪ Dilated blood vessels (telangiectasia) ▪ Ulcerated lesion ▫ Brown-black pigmentation in crater of lesion DIAGNOSIS LAB RESULTS Figure 5.1 The clinical appearance of a basal-cell carcinoma on the nose of an elderly individual. The tumor is nodular with central ulceration and pearly borders. Skin biopsy/histopathology ▪ Basal cells form clusters called islands with peripheral palisading nuclei OSMOSIS.ORG 25

TREATMENT MEDICATIONS ▪ Topical 5-fluorouracil/imiquimod SURGERY ▪ Electrodesiccation, curettage; complete surgical excision; cryosurgery; Mohs surgery Figure 5.2 The histological appearance of a basal-cell carcinoma. Malignant darkstaining, basaloid cells infiltrate the dermis. There is clefting at the junction between the tumor and the dermis. OTHER DIAGNOSTICS ▪ Radiation, photodynamic therapy OTHER DIAGNOSTICS ▪ Dermatoscopy ▫ Scattered vascular pattern, telangiectasias, hemorrhage-ulceration, hypopigmented areas with blue-grey ovoid nests, red dots/globules MELANOMA osms.it/melanoma PATHOLOGY & CAUSES ▪ Malignant skin cancer, arises from melanocytes ▪ Occurs most commonly on skin ▫ Rarely: mouth, eyes, gastrointestinal (GI) tract ▪ Can arise from ▫ Preexisting mole ▫ De novo lump: nodular melanoma (most dangerous) Variants ▪ Superficial spreading melanoma ▪ Lentigo maligna melanoma ▪ Nodular melanoma ▪ Acral lentiginous melanoma 26 OSMOSIS.ORG Figure 5.3 A malignant melanoma exhibiting pigment production.

Chapter 5 Malignant Skin Tumors Growth phases ▪ Radial growth phase (< 1mm thick) ▫ Grows laterally along epidermis, superficial dermis; does not spread ▫ Rarely metastasizes; good prognosis if detected ▪ Vertical growth phase (> 1mm thick) ▫ Grows deeper into dermis, beyond ▫ Invasive, able to metastasize through lymph/blood vessels CAUSES ▪ DNA damage caused by ultraviolet (UV) light exposure (e.g. sun, tanning beds) ▪ Genetic mutations in MC1R, CDKN2A, BRAF genes RISK FACTORS Immunosuppression Numerous moles Family history of melanoma Syndromes ▫ Dysplastic nevus syndrome, xeroderma pigmentosum, albinism, Gorlin syndrome ▪ Exposure/overexposure to UV light (e.g. sun, tanning beds) ▫ Esp. if blistering/occurring early in life; more common in people with fair skin ▪ ▪ ▪ ▪ ▫ See tables: American Joint Committee on Cancer Guideline for TMN staging of melanoma ▪ Histopathological evaluation for tumor grade OTHER DIAGNOSTICS ▪ Dermatological examination using dermatoscope ▫ Classic melanoma: mnemonic ABCDE ▫ Nodular melanoma: mnemonic EFG MNEMONIC: ABCDE Appearance of classic melanoma Asymmetry Border irregularities Color variation Diameter: 6 mm Enlargement MNEMONIC: EFG Appearance of nodular melanoma Elevated Firm to touch Growing COMPLICATIONS ▪ Metastazes most commonly to lymph nodes, skin, subcutaneous tissue → lungs, liver, brain SIGNS & SYMPTOMS ▪ New skin lesion/change pre-existing lesion: color, shape, size irregularities; ulcerations, pruritus, bleeding ▪ Nausea, vomiting, loss of appetite, fatigue DIAGNOSIS LAB RESULTS Figure 5.4 The clinical appearance of a malignant melanoma. It is darkly pigmented with an irregular border. Full-thickness, sentinel node biopsy ▪ Tumor staging OSMOSIS.ORG 27

TREATMENT MEDICATIONS ▪ Immunotherapy in case of metastases SURGERY ▪ Surgical excision ▫ Wide margin excision (1–3cm of normal tissue depending on depth of invasion) ▪ Excision if sentinel node biopsy is positive 28 OSMOSIS.ORG OTHER INTERVENTIONS ▪ Early detection for good prognosis (depends directly on depth of invasion) ▪ Radiation/chemotherapy in case of metastases

Chapter 5 Malignant Skin Tumors Figure 5.5 The gross pathology of the heart in a case of metastatic melanoma. SQUAMOUS-CELL CARCINOMA (SCC) osms.it/squamous-cell_carcinoma PATHOLOGY & CAUSES ▪ Second most common type of skin cancer ▪ Epidermal keratinocytes acquire antiapoptotic properties → frequent mitosis RISK FACTORS ▪ Immunosuppression, chronic UV exposure, fair skin, albinism, xeroderma pigmentosa, tobacco use (increases risk of lip/oral SCC), arsenic exposure (rare) CAUSES ▪ UV radiation (e.g. sun, tanning beds) ▪ HPV infection ▪ Genetic mutations ▫ Deletion of tumor progression locus 2 (Tpl2) gene ▪ Preceding skin lesions (e.g. actinic keratosis, other melanomas) ▫ Actinic keratosis: precancerous skin lesion; rough, scaly patch caused by chronic, long-term sun exposure ▪ Bowen’s disease (AKA squamous cell carcinoma in situ) Figure 5.6 An ulcerated squamous cell carcinoma on the nose of a middle-aged individual. OSMOSIS.ORG 29

COMPLICATIONS ▪ Significant risk of metastasis SIGNS & SYMPTOMS ▪ Most commonly found on sun-exposed areas (e.g. head, nose, neck) ▪ Small rough scaly nodule (slow growing) ▫ Nodule expands → center necroses → evolves into ulcer covered by red growing plaque → frequently scales, easily bleeds ▪ Chronic draining sinuses DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Assess surrounding tissue invasion (soft tissue, bones, lymph nodes), metastasis Dermatoscopy, excisional/incisional biopsy of subcutaneous tissue ▪ Microscopic features: hyperkeratosis, nuclear atypia ▪ See tables: American Joint Committee on Cancer Guideline for TMN staging of cutaneous squamous-cell carcinoma MRI ▪ Evaluate vital structures (neural, vascular invasions) TREATMENT MEDICATIONS ▪ Topical immunomodulators SURGERY ▪ Surgical excision ▪ Mohs surgery: microscopic procedure removing thin layers of affected tissue, examining under microscope until cancerfree tissue reached ▪ Electrodessication, curettage 30 OSMOSIS.ORG OTHER INTERVENTIONS ▪ Chemotherapy, radiotherapy, photodynamic therapy

Chapter 5 Malignant Skin Tumors Figure 5.7 The histological appearance of well-differentiated squamous cell carcinoma of the skin. It is composed of polygonal cells with eosinophilic cytoplasm which produce keratin pearls. OSMOSIS.ORG 31