keratoacanthoma

**Definition and epidemiology** - Common, keratinocyte-derived neoplasm, usually considered a well-differentiated variant of cutaneous SCC. - Typically seen in fair-skinned, older adults (age >50), with a male predominance. - Arises on sun-exposed skin: face, dorsal hands, and forearms.

**Pathophysiology and risk factors** - Arises from hair follicle epithelium. Chronic UV exposure is the main risk factor. - Other associations: HPV (proposed), immunosuppression, trauma or other skin injury, tar and chemical carcinogen exposure, and smoking. - Associated genetic syndromes: - Muir-Torre syndrome (a Lynch syndrome variant): sebaceous neoplasms plus multiple keratoacanthomas and visceral cancers, especially colorectal. - Ferguson-Smith syndrome: multiple self-healing epitheliomas (TGFBR1 mutation). - Grzybowski syndrome: eruptive keratoacanthomas. - BRAF inhibitors (vemurafenib, dabrafenib) cause keratoacanthomas and cutaneous SCCs through paradoxical MAPK activation in cells with RAS mutations.

**Clinical course (classic triad of phases)** 1. **Proliferative phase:** very rapid growth over 2-8 weeks. 2. **Mature phase:** a stable, firm, dome-shaped, skin-colored or erythematous nodule with a central keratin plug or crater. 3. **Involution phase:** spontaneous regression over about 4-6 months, leaving an atrophic or depressed scar.

**Histology** - Cup-shaped (crateriform) lesion with a central keratin-filled crater. - "Lipping" or buttressing of epidermis at the edges. - Proliferation of well-differentiated squamous cells with abundant glassy, eosinophilic cytoplasm. - Minimal nuclear atypia, but occasional mitoses. - A mixed inflammatory infiltrate is present. - Features favoring SCC: deep invasion, marked atypia, perineural invasion, and an asymmetric or infiltrative base. - Histology can be indistinguishable from SCC, so pathology review of the whole lesion (excisional or deep shave) is important.

**Management** - Surgical excision is preferred because it confirms the diagnosis and rules out SCC. - Alternatives: curettage and electrodesiccation, Mohs surgery (for facial or other critical sites), intralesional methotrexate or 5-FU, topical 5-FU, and radiation. - Observation for spontaneous regression is generally not favored because of the risk of misdiagnosing SCC. - Prognosis is excellent. Rare cases show perineural invasion, local recurrence, or metastasis, which are more likely if the lesion is really an SCC.

**High-yield board points** - Buzzwords: "rapidly growing dome-shaped nodule with central keratin plug that regresses spontaneously" in an older, sun-exposed patient. - Rapid growth over weeks distinguishes it from the slower-growing basal cell carcinoma (pearly papule with telangiectasias). - Multiple keratoacanthomas plus sebaceous tumors point to Muir-Torre syndrome. - A patient on a BRAF inhibitor who develops rapidly growing skin lesions is likely to have keratoacanthomas or SCC. - Treat as SCC. It is not truly benign.