A 52-year-old man from rural Maharashtra presents with progressive darkening and thickening of skin over the neck, axillae, and inframammary folds for 8 months. He reports associated weight loss of 6 kg over 3 months despite good appetite. On examination, the affected areas show velvety, hyperpigmented skin with exaggerated dermatoglyphics. His fasting blood glucose is 186 mg/dL, and HbA1c is 8.9%. Abdominal ultrasound reveals a heterogeneous mass in the pancreatic head. What is the most likely diagnosis underlying this cutaneous manifestation?

Explanation

## Clinical Diagnosis: Acanthosis Nigricans as Paraneoplastic Syndrome ### Presentation Analysis This patient presents with the classic triad of acanthosis nigricans (AN): velvety hyperpigmented skin with exaggerated skin markings in flexural areas (neck, axillae, inframammary folds). The key discriminating feature is the **concurrent finding of a pancreatic mass with weight loss and short symptom duration (8 months)**. ### Pathophysiology of Acanthosis Nigricans **Key Point:** Acanthosis nigricans is classified into three types based on etiology: | Type | Association | Mechanism | Frequency | |------|-------------|-----------|----------| | **Benign** | Obesity, PCOS, metabolic syndrome | Insulin resistance | 90% of cases | | **Malignant** | Gastric, lung, breast, pancreatic cancers | Tumor-derived growth factors (TGF-α, FGF) | 5–10% of cases | | **Drug-induced** | Nicotinic acid, corticosteroids, oral contraceptives | Medication-related | Rare | ### Why This Patient Has Malignant AN **High-Yield:** Malignant acanthosis nigricans typically presents with: 1. **Rapid onset** (< 1 year) — this patient: 8 months 2. **Associated systemic symptoms** — weight loss despite appetite 3. **Imaging evidence of malignancy** — pancreatic head mass 4. **Paraneoplastic mechanism** — tumor secretion of growth factors (not simple insulin resistance) **Clinical Pearl:** Pancreatic cancer is the **most common malignancy associated with acanthosis nigricans** in Indian populations, followed by gastric and lung cancers. The presence of a pancreatic mass on ultrasound makes this the definitive diagnosis. ### Differential Consideration: Type 2 Diabetes While the patient does have hyperglycemia (HbA1c 8.9%), benign AN from insulin resistance typically: - Develops **gradually over years** - Occurs in **obese patients** (no weight loss) - Has **no associated malignancy** - Responds to weight loss and glycemic control This patient's **rapid onset, weight loss, and imaging findings** point to malignant AN secondary to pancreatic adenocarcinoma. ### Management Implications **Mnemonic: PANG** — Pancreatic, Adenocarcinoma, Neoplastic, Growth factors Once malignant AN is suspected, urgent investigations include: - CA 19-9 tumor marker - CT chest/abdomen/pelvis for staging - Endoscopic ultrasound (EUS) with biopsy for tissue diagnosis - Multidisciplinary oncology consultation **Warning:** Do not attribute AN solely to the hyperglycemia; the pancreatic mass is the primary pathology driving the paraneoplastic syndrome.