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PA33.4 | Common Skin Tumors & Morphology — SDL Guide (Part 3)

Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) of the skin is the second most common skin cancer. Unlike BCC, it has real metastatic potential (5–10% overall, higher for lesions arising in scars, chronic ulcers, or mucosae). It arises from epidermal keratinocytes.

Pathogenesis: UV-induced TP53 mutation (also HPV in genital/mucosal SCC). Sequence: normal skin → AK (SCC in situ/Bowen) → invasive SCC.

Clinical features: Firm, fleshy, erythematous papule or plaque that may ulcerate, crust, or form a cutaneous horn. Sun-exposed sites (lip, ear, dorsum of hand) are classic. Marjolin's ulcer = SCC arising in a chronic scar or burn — higher metastatic risk.

Two-panel clinical illustration showing Panel A: a close-up of the lower lip with a squamous cell carcinoma lesion labeled with ulceration, keratotic crust, indurated border, and irregular border; and Panel B: a schematic cross-section through the lesion identifying the ulcer floor, keratotic debris, indurated dermis, and normal surrounding epithelium. — **Panel A:** Ulceration (central excavated crater), Keratotic crust (whitish-grey scaly surface debris), Indurated border (raised firm peripheral rim), Irregular border (jagged outer margin of lesion). **Panel B:** Ulcer floor (absent epithelium centrally), Keratotic debris (surface layer), Indurated dermis — fibrotic zone beneath the raised border, Normal surrounding squamous epithelium on either side.

Histological features:
1. Invasive nests and cords of atypical squamous cells breaching the basement membrane into the dermis (this breach defines invasion; contrast with Bowen disease).
2. Dyskeratosis: individual cell keratinization (eosinophilic cells with dense cytoplasm).
3. Keratin pearls (squamous eddies): concentric whorls of keratinizing cells — the hallmark of well-differentiated SCC.
4. Intercellular bridges (desmosomes) visible between cells.
5. Mitoses, including atypical mitoses.

Three-panel H&E histology diagram of well-differentiated squamous cell carcinoma showing low-power invasive nests with keratin pearls and dermal invasion (Panel A), high-power detail of a keratin pearl with dyskeratotic cell (Panel B), and high-power view of intercellular bridges between atypical squamous cells (Panel C). — **Panel A:** Invasive tumor nests, keratin pearls (squamous eddies), dermal invasion arrow, dermo-epidermal junction breach, surrounding fibrous stroma. **Panel B:** Concentric lamellar keratin pearl whorls, central amorphous keratin core, dyskeratotic cell (pyknotic nucleus, bright eosinophilic cytoplasm), peripheral palisading atypical cells. **Panel C:** Intercellular bridges (desmosomes) between adjacent atypical squamous cells, pleomorphic nuclei with prominent nucleoli, individual cell keratinization.

Grading: Well-differentiated = prominent keratin pearls; moderately differentiated = some keratinization; poorly differentiated = minimal keratinization, marked pleomorphism.

Melanoma

Melanoma is the most dangerous skin tumor — despite representing only 4% of skin cancers, it accounts for >75% of skin cancer deaths. It arises from melanocytes and has high metastatic potential.

Pathogenesis: UV-driven BRAF mutation (in ~60% of cases, the V600E hotspot) is the initiating event for most cutaneous melanomas. Loss of CDKN2A (p16) drives progression. Dysplastic nevi are precursors in a subset.

Clinical recognition (ABCDE rule):
- Asymmetry
- Border — irregular, notched
- Color — variegated (multiple shades of brown, black, red, white, blue)
- Diameter — >6 mm
- Evolution — changing lesion

Two-panel diagram: Panel A shows a clinical illustration of superficial spreading melanoma with labeled ABCDE features (asymmetry axis, notched border, color zones, diameter reference, and evolution arrow); Panel B is a reference table listing the ABCDE melanoma criteria with descriptors. — **Panel A:** Superficial spreading melanoma lesion with labeled arrows: (A) Asymmetry dashed axis, (B) Irregular/notched border at multiple points, (C) Color zones — tan, brown, black, pink with swatches, (D) Diameter >6 mm with measurement arrow and 6 mm reference circle, (E) Evolution indicator with growth arrow. **Panel B:** ABCDE reference table — five rows each with criterion letter, name, and one-line clinical descriptor; light gray background, sans-serif typeface.

Major subtypes:
- Superficial spreading melanoma (70%): most common; radial growth phase before vertical growth.
- Nodular melanoma (15–30%): predominantly vertical growth from the start; worst prognosis.
- Lentigo maligna melanoma: on sun-damaged facial skin of elderly; slow radial growth phase.
- Acral lentiginous melanoma: palms, soles, subungual; most common in dark-skinned populations.

Histological features:
1. Atypical melanocytes at the DEJ and ascending into the epidermis (pagetoid spread — single cells or nests within the upper epidermis).
2. Vertical growth phase: invasion into the dermis with large, pleomorphic melanocytes and prominent nucleoli.
3. Loss of maturation in the deep component (deep cells remain large).
4. Mitoses in the dermis.
5. Tumour-infiltrating lymphocytes (TILs) brisk or absent.

Three-panel H&E histology diagram of superficial spreading melanoma showing pagetoid spread of atypical melanocytes through the epidermis, irregular nests at the dermal-epidermal junction, and a vertical growth phase nodule invading the dermis, with high-power insets of each key feature. — **Panel A:** Full-thickness H&E cross-section: stratum corneum, epidermis with pagetoid spread (scattered atypical melanocytes at all levels), atypical melanocyte nests at DEJ, vertical growth phase nodule in dermis, surrounding collagen. **Panel B:** High-power zoom of epidermis: keratinocytes, individual atypical melanocytes with pale cytoplasm and irregular nuclei scattered through spinous and granular layers — illustrating classic pagetoid scatter pattern. **Panel C:** High-power zoom of dermal nodule: sheets of pleomorphic melanoma cells, vesicular nuclei, prominent nucleoli, mitotic figures, compressed papillary dermal collagen — illustrating vertical growth phase invasion.

Breslow thickness: The single most important prognostic factor — measured in millimeters from the top of the granular layer to the deepest invasive cell. ≤1 mm = excellent prognosis; >4 mm = high risk of systemic spread.

CLINICAL PEARL

BCC vs SCC vs Melanoma — the three-question shortcut for the practical exam:

Is there peripheral palisading + retraction cleft? → BCC.
Are there keratin pearls + intercellular bridges + basement membrane breach? → SCC.
Is there pagetoid spread + pleomorphic melanocytes + loss of maturation? → Melanoma.

Never forget: BCC almost never metastasizes; SCC metastasizes in ~5–10%; Melanoma is highly aggressive. Getting the diagnosis right changes management entirely.

Dermatofibroma and Cutaneous Metastases

Dermatofibroma (fibrous histiocytoma) is a common, benign dermal nodule found predominantly on the lower legs of young to middle-aged women. Its exact nature (reactive vs neoplastic) is debated.

Clinical features: Firm, tan-brown, slightly raised nodule that dimples inward on lateral compression (Fitzpatrick's dimple sign) — a useful bedside test.

Histological features:
1. Proliferation of spindle cells (fibroblasts and histiocytes) in the dermis, arranged in a storiform (cartwheel) pattern.
2. The overlying epidermis is hyperplastic with downward extension into the dermis ("induction" of the overlying epidermis).
3. Siderophages (hemosiderin-laden macrophages) are often present.
4. The lesion is poorly circumscribed and blends with surrounding dermal collagen (trapping of collagen bundles at the periphery).

Two-panel H&E histology illustration of dermatofibroma showing low-power storiform spindle-cell pattern with hyperplastic epidermis in Panel A and high-power cartwheel arrangement of spindle cells with trapped collagen bundles in Panel B. — **Panel A:** Hyperplastic epidermis (thickened with elongated rete ridges), Storiform (cartwheel) pattern (curved bracket over central dermal proliferation), Spindle cells (leader lines to individual elongated cells), Trapped collagen bundles (arrows to peripheral eosinophilic strands). **Panel B:** Spindle cell fascicles (radiating curved arrays of elongated nuclei), Fibrous center (pale central zone of each cartwheel nodule), Cartwheel schematic inset (simplified spoke-and-hub diagram for conceptual orientation).

Cutaneous metastases are skin deposits from internal malignancies. They appear as firm, non-tender, rapidly growing dermal or subcutaneous nodules, often multiple.

Common primary sources:
- Women: breast (most common), colon, ovary
- Men: lung (most common), colon, kidney

Special patterns:
- Sister Mary Joseph nodule: umbilical metastasis from GI or pelvic cancer — an ominous sign of peritoneal spread.
- Carcinoma en cuirasse: diffuse skin induration from breast cancer permeating the dermal lymphatics — resembles a leather breastplate.

Histology: The skin biopsy shows adenocarcinoma cells (or whatever the primary histotype) in the dermis, without connection to the overlying epidermis — this epidermal sparing distinguishes metastasis from a primary skin adnexal tumor.