A 52-year-old Indian man presents with progressive darkening and thickening of skin over his neck, axillae, and groin for the past 8 months. He reports associated weight loss of 6 kg over 3 months and mild pruritus. On examination, the affected areas show velvety, hyperpigmented plaques with exaggerated skin markings. His fasting blood glucose is 186 mg/dL, and HbA1c is 9.2%. Abdominal examination reveals a palpable epigastric mass. What is the most likely underlying diagnosis?

Explanation

## Clinical Presentation & Diagnosis **Key Point:** Acanthosis nigricans (AN) presenting with weight loss, constitutional symptoms, and an epigastric mass in a middle-aged patient is highly suspicious for **malignancy-associated acanthosis nigricans (MAAN)**, particularly gastric cancer. ### Pathophysiology of Acanthosis Nigricans 1. **Insulin-resistant form** (90% of cases) - Associated with obesity, type 2 DM, PCOS, metabolic syndrome - Hyperinsulinemia drives keratinocyte proliferation via IGF-1 receptors - Usually benign prognosis 2. **Malignancy-associated form** (10% of cases) - Paraneoplastic syndrome caused by circulating growth factors (TGF-α, FGF) - Rapid onset, often precedes cancer diagnosis - Associated with weight loss, constitutional symptoms - **Most common malignancies:** gastric cancer (60%), lung, breast, ovarian, lymphoma ### Red Flags for Malignancy in This Case | Feature | Significance | |---------|-------------| | **Rapid progression (8 months)** | Suggests paraneoplastic etiology | | **Weight loss (6 kg/3 months)** | Constitutional symptom; not typical of simple insulin resistance | | **Palpable epigastric mass** | Direct evidence of gastric pathology | | **Age 52 years** | MAAN typically presents in 4th–6th decade | | **Velvety texture with exaggerated markings** | Classic morphology of AN | **Clinical Pearl:** While this patient has hyperglycemia and AN, the **combination of rapid onset, weight loss, and epigastric mass** makes malignancy the most likely underlying diagnosis. Gastric adenocarcinoma is the most common malignancy associated with AN in Asian populations. **High-Yield:** MAAN often appears **acutely** and is accompanied by **systemic symptoms**. Always investigate for occult malignancy in AN patients with: - Rapid onset (< 1 year) - Weight loss - Age > 40 years - Absence of obesity or metabolic syndrome ### Diagnostic Approach ```mermaid flowchart TD A[Acanthosis Nigricans]:::outcome --> B{Clinical Features?}:::decision B -->|Gradual onset + Obesity/DM/PCOS| C[Insulin-Resistant AN]:::outcome B -->|Rapid onset + Weight loss + Age > 40| D[Malignancy-Associated AN]:::outcome D --> E[Investigate for cancer]:::action E --> F[Gastric, lung, breast, ovarian]:::outcome C --> G[Manage metabolic disorder]:::action ``` **Next Steps:** Upper GI endoscopy with biopsy is indicated to confirm gastric adenocarcinoma.