A 52-year-old man with a 10-year history of type 2 diabetes presents with velvety, hyperpigmented plaques over the neck, axillae, and inframammary folds. He is concerned about malignancy. Which investigation is most appropriate to establish the diagnosis of acanthosis nigricans and rule out underlying malignancy?

Explanation

## Diagnostic Approach to Acanthosis Nigricans ### Role of Skin Biopsy **Key Point:** Skin biopsy is the gold standard for confirming acanthosis nigricans histologically and ruling out malignant transformation or other dermatoses. **Histopathological Features:** - Hyperkeratosis (often papillomatous) - Acanthosis (thickened epidermis) - Hyperpigmentation of basal layer - Preserved dermal–epidermal interface - Absence of malignant cells ### Why Biopsy is Essential **Clinical Pearl:** While acanthosis nigricans is clinically recognizable in most cases, biopsy becomes crucial when: 1. Diagnosis is uncertain 2. Rapid onset or atypical morphology raises concern for malignancy-associated variant 3. Patient anxiety about malignant potential is high 4. Lesions show unusual features (erosion, ulceration, bleeding) **High-Yield:** Acanthosis nigricans can be associated with internal malignancy in 5–10% of cases (gastric, lung, breast, ovarian cancers). Biopsy helps exclude malignant infiltration or paraneoplastic transformation. ### Differential Diagnosis on Histology | Feature | Benign Acanthosis Nigricans | Malignancy-Associated | Pseudoacanthosis Nigricans | |---------|------------------------------|----------------------|---------------------------| | Epidermal thickening | Marked | Marked | Minimal | | Dermal infiltrate | Absent | Present (lymphocytes, tumor cells) | Absent | | Basal pigmentation | Increased | Increased | Normal | | Atypia | None | May be present | None | **Warning:** Clinical appearance alone cannot reliably distinguish benign from malignancy-associated acanthosis nigricans; histology is mandatory for definitive diagnosis.