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PA33.4 | Common Skin Tumors & Morphology — SDL Guide (Part 2)

Melanocytic Nevi — Junctional, Compound, and Intradermal

Melanocytic nevi ('moles') are benign neoplasms of nevus cells — modified melanocytes that grow in nests. The three-stage classification reflects a proposed migration of nevus cells from the epidermis into the dermis as the lesion matures.

The nevus maturation sequence:

1. Junctional nevus — nevus cell nests confined to the dermo-epidermal junction (DEJ). Clinically: flat, uniformly pigmented brown macule. Histologically: nests of nevus cells at the DEJ only, without intradermal component.

1. Compound nevus — nests at the DEJ and in the dermis. Clinically: slightly raised, pigmented papule. This is the most common type.

1. Intradermal nevus — nests entirely within the dermis, no junctional component. Clinically: dome-shaped, flesh-coloured or lightly pigmented papule, often pedunculated. Histologically: upper dermal nests of large cells, lower dermal cells become smaller and spindled (maturation — an important feature distinguishing benign from malignant).

Melanocytic Nevi — Histological Classification (H&E)

Maturation is the key concept: in benign nevi, the deeper the cells go, the smaller they become (neuroid differentiation). Loss of maturation (deep cells remain large) is a feature of melanoma.

Dysplastic (atypical/Clark's) nevus is a clinically and histologically atypical nevus that may be a melanoma precursor. Clinical (ABCDE clues): Asymmetry, irregular Border, variegated Color, Diameter >6 mm, Evolution. Histologically: architectural disorder (bridging of nests, lentiginous growth), cytological atypia, a fibroplastic stroma, and a sparse lymphocytic infiltrate.

Histology of Dysplastic Nevus (H&E) — Architectural and Cytological Features

Premalignant Lesions — Actinic Keratosis and Bowen Disease

Actinic keratosis (AK) is a UV-induced intraepidermal dysplasia — the most common precancerous lesion of the skin. It progresses to invasive SCC in ~8–20% of cases if untreated.

Clinical features: Rough, scaly, erythematous macule or thin plaque on sun-exposed skin (face, scalp, dorsum of hands) in older, fair-skinned individuals. The 'sandpaper' texture on palpation is a useful clinical clue.

Histology:
- Dysplastic keratinocytes in the lower layers of the epidermis (sparing the upper layers and adnexal epithelium — important distinction from Bowen disease).
- Parakeratosis (nucleated cells in the stratum corneum) alternating with orthokeratosis.
- Solar elastosis in the dermis (thick, amorphous, blue-grey elastin on H&E — the hallmark of cumulative sun damage).

Histology of Actinic Keratosis (H&E)

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Bowen disease (SCC in situ) is full-thickness epidermal dysplasia — the entire epidermis is replaced by atypical keratinocytes, but the basement membrane remains intact (no dermal invasion). Think of it as AK that has spread upward to involve the full thickness.

Clinical features: Sharply demarcated, scaly, erythematous plaque, often on the trunk or extremities, not necessarily sun-exposed.

Histology (the 'windswept' or 'wind-blown' pattern):
- Full-thickness epidermal atypia: dysplastic cells at all levels.
- Disordered maturation: loss of normal cell polarity ('windswept' appearance).
- Koilocyte-like cells and multinucleated keratinocytes possible.
- Intact basement membrane (the critical feature — invasion = SCC).

Bowen Disease (SCC In Situ): Histological Comparison with Normal Epidermis (H&E)

AK vs Bowen at a glance:

Feature	Actinic Keratosis	Bowen Disease
Extent of dysplasia	Basal/parabasal layers	Full thickness
Adnexal epithelium	Spared	Involved
Sun exposure relationship	Strong	Variable
Progression risk to SCC	8–20%	Higher

Basal Cell Carcinoma

Basal cell carcinoma (BCC) is the most common cancer in humans (lifetime risk ~30% in fair-skinned populations). It arises from the basal layer of the epidermis and almost never metastasizes, but it is locally destructive.

Pathogenesis: UV-induced mutation of PTCH1 (patched-1) gene → unregulated Hedgehog signaling → sustained proliferation.

Clinical features (nodular BCC — the most common subtype): Pearly, translucent papule or nodule with telangiectatic vessels on the surface, with a rolled (everted) border and possible central ulceration ('rodent ulcer'). Almost exclusively on sun-exposed skin of the head and neck.

Nodular Basal Cell Carcinoma — Clinical Features and Cross-section

Histological features (key pattern):
1. Nests and cords of basaloid cells (small, dark nuclei, scant cytoplasm) extending from the epidermis into the dermis.
2. Peripheral palisading of cells at the edge of each nest (cells align like soldiers in a row).
3. Stromal retraction artifact: a cleft between the tumor nest and surrounding stroma (important — do not confuse with true invasion).
4. Myxoid/mucinous stroma.
5. Mitoses are present but apoptosis is also prominent.

Nodular BCC — H&E Histology: Peripheral Palisading and Stromal Retraction Cleft

Subtypes in brief:
- Nodular BCC (most common): discrete nests, as above.
- Superficial BCC: buds of basaloid cells attached to the epidermis, spreading laterally.
- Morpheaform (sclerosing) BCC: thin cords of cells in a dense fibrous stroma — the most aggressive, highest recurrence rate.