Lecture #182: Pathology: Skin Tumors

What is the classic appearance of seborrheic keratosis?

Well-demarcated tan-to-brown velvety plaques with a “stuck-on” appearance.

What mutation is commonly associated with seborrheic keratosis?

Activating FGFR3 mutations.

What is the Leser-Trelat sign?

Rapid increase in seborrheic keratoses associated with underlying adenocarcinoma.

What histologic feature is characteristic of seborrheic keratosis?

Horn cysts filled with keratin within sheets of benign basaloid cells.

What body areas are commonly affected by acanthosis nigricans?

Flexural regions including axillae, neck folds, and groin.

What condition is benign acanthosis nigricans commonly associated with?

Obesity and insulin resistance/diabetes.

What malignancy is classically associated with malignant acanthosis nigricans?

Gastrointestinal adenocarcinoma.

What histologic changes are seen in acanthosis nigricans?

Hyperkeratosis with hyperpigmentation of the basal layer without melanocyte hyperplasia.

What is another name for a fibroepithelial polyp?

Skin tag or acrochordon.

What is the classic appearance of a fibroepithelial polyp?

A soft lesion attached by a thin stalk.

What conditions are associated with fibroepithelial polyps?

Obesity, diabetes, pregnancy, and intestinal polyposis.

What is the histology of a fibroepithelial polyp?

Fibrovascular core covered by benign squamous epithelium.

What causes epithelial inclusion cysts?

Invagination and cystic expansion of epidermis or hair follicles.

What is the classic clinical appearance of an epithelial inclusion cyst?

Firm, movable, dome-shaped flesh-colored lesion.

What fills epithelial inclusion cysts histologically?

Keratin.

What is actinic keratosis?

A premalignant squamous dysplasia caused by chronic sun exposure.

What skin type is most commonly affected by actinic keratosis?

Lightly pigmented individuals.

What is the classic texture of actinic keratosis?

Rough sandpaper-like lesions.

What is a cutaneous horn?

Excessive keratin production projecting from actinic keratosis.

What histologic findings characterize actinic keratosis?

Basal layer atypia, hyperkeratosis, parakeratosis, and solar elastosis.

What is solar elastosis?

UV-induced damage causing gray-blue thickening of the superficial dermis from abnormal elastin and collagen.

What cancer can arise from actinic keratosis?

Squamous cell carcinoma.

What tumor suppressor mutation is associated with progression from AK to SCC?

p53 dysfunction.

What is the second most common cancer in the world?

Squamous cell carcinoma.

What is the major risk factor for squamous cell carcinoma?

Chronic UV exposure causing DNA damage.

What are histologic hallmarks of squamous cell carcinoma?

Keratin pearls, hyperkeratosis, intercellular bridges, nodules, and ulceration.

What are keratin pearls?

Concentric layers of keratinized squamous cells seen in SCC.

What is the most common invasive cancer in humans?

Basal cell carcinoma.

What signaling pathway is activated in basal cell carcinoma?

Hedgehog signaling pathway.

What mutation is classically associated with basal cell carcinoma?

Loss of function mutation in PTCH1.

What syndrome predisposes to multiple basal cell carcinomas?

Gorlin syndrome.

What is the classic appearance of basal cell carcinoma?

Pearly papules with telangiectasias and rolled borders.

What histologic finding is classic for basal cell carcinoma?

Peripheral palisading of basaloid tumor nests.

How often does basal cell carcinoma metastasize?

Rarely metastasizes but is locally aggressive.

What treatment options are used for basal cell carcinoma?

Surgical excision, Mohs surgery, cryotherapy, imiquimod, and 5-FU.

What is a solar lentigo?

A benign melanocytic hyperplasia occurring on sun-exposed skin.

What is the histologic growth pattern of solar lentigo?

Linear melanocyte proliferation along the dermoepidermal junction.

What are the typical clinical features of benign melanocytic nevi?

Symmetric, smooth-bordered, uniformly pigmented lesions usually under 6 mm.

What mutations are commonly seen in melanocytic nevi?

BRAF or NRAS mutations.

What is a congenital nevus?

A nevus present at birth that may rarely develop melanoma.

What is a blue nevus?

A dark blue-black dermal melanocytic proliferation.

What is a Spitz nevus?

A rapidly growing dome-shaped nevus commonly seen in children.

What is a halo nevus?

A nevus surrounded by depigmentation due to autoimmune melanocyte destruction.

What is a dysplastic nevus?

An atypical melanocytic lesion that may indicate increased melanoma risk.

What mutations are associated with dysplastic nevi?

BRAF or NRAS activation with CDKN2A loss.

What are the clinical features of dysplastic nevi?

Larger than 5 mm with irregular borders and variable pigmentation.

What histologic feature called “bridging” is seen in dysplastic nevi?

Fusion of adjacent melanocyte nests across rete ridges.

What is the deadliest skin cancer?

Melanoma.

What are the ABCDEs of melanoma?

Asymmetry, Border irregularity, Color variation, Diameter >6 mm, and Evolution.

What are the two growth phases of melanoma?

Radial growth phase and vertical growth phase.

Which melanoma growth phase is associated with metastasis?

Vertical growth phase.

What is the most common subtype of melanoma?

Superficial spreading melanoma.

Which melanoma subtype has the worst prognosis due to early vertical growth?

Nodular melanoma.

Which melanoma subtype is most common in non-white patients?

Acral lentiginous melanoma.

What histologic features suggest melanoma?

Pagetoid spread, dermal mitoses, cytologic atypia, ulceration, and asymmetry.

What is Breslow depth?

Measurement of melanoma thickness from the granular layer to deepest tumor invasion.

What is the most important prognostic factor in melanoma?

Breslow depth.

What stage of melanoma has distant metastases?

Stage IV.

What immune checkpoint inhibitors are used to treat melanoma?

Ipilimumab, nivolumab, and pembrolizumab.

What targeted therapy is used for melanoma with BRAF V600E mutations?

BRAF inhibitors.