A 52-year-old obese woman presents with dark, velvety thickening of skin over the neck, axillae, and inframammary folds. Laboratory investigations reveal fasting blood glucose of 186 mg/dL and HbA1c of 8.2%. Regarding acanthosis nigricans in this patient, all of the following are true EXCEPT:

Explanation

## Pathophysiology of Acanthosis Nigricans **Key Point:** Acanthosis nigricans is NOT a primary melanin disorder but rather a cutaneous manifestation of insulin resistance and associated metabolic dysfunction. ### Correct Mechanism The pathogenesis involves: 1. Hyperinsulinemia and insulin resistance 2. Activation of insulin-like growth factor (IGF) receptors on keratinocytes and fibroblasts 3. Epidermal hyperplasia and dermal papillomatosis 4. Secondary hyperpigmentation due to increased melanin transfer, NOT primary melanin deposition ### Histopathological Features - **Acanthosis** (epidermal thickening) - **Papillomatosis** (dermal projections) - **Hyperkeratosis** (thickened stratum corneum) - Mild melanin increase in basal layer (secondary, not primary) ### Clinical Associations | Feature | Details | |---------|----------| | **Metabolic** | Type 2 DM, obesity, PCOS, insulin resistance | | **Malignancy-associated** | Gastric cancer (most common), lung, breast, lymphoma | | **Presentation** | Pruritic, velvety, dark plaques; flexural distribution | | **Onset** | Often precedes diabetes diagnosis by months to years | **High-Yield:** The lesions are NOT due to melanin toxicity or direct deposition—they result from keratinocyte proliferation driven by hyperinsulinemia and IGF signaling. **Clinical Pearl:** In a patient with acanthosis nigricans and no obvious metabolic risk factors, malignancy screening (especially gastric cancer in Asian populations) is warranted.