A 52-year-old man from rural Maharashtra presents with progressive darkening and thickening of skin over the neck, axillae, and groin for 8 months. On examination, he has velvety, hyperpigmented plaques with exaggerated skin markings. He reports a 6 kg weight loss over the past 3 months and persistent abdominal discomfort. Fasting blood glucose is 186 mg/dL. Abdominal ultrasound reveals a heterogeneous mass in the pancreatic head. What is the most likely diagnosis underlying his skin findings?

Explanation

## Clinical Diagnosis: Acanthosis Nigricans Associated with Malignancy ### Key Clinical Features This patient presents with the classic triad of acanthosis nigricans (AN): 1. Velvety, hyperpigmented plaques with exaggerated skin markings 2. Predilection for intertriginous areas (neck, axillae, groin) 3. Associated with systemic malignancy (pancreatic adenocarcinoma) ### Pathophysiology of Malignancy-Associated AN **High-Yield:** Acanthosis nigricans in an adult with rapid onset and associated constitutional symptoms (weight loss, abdominal pain) should raise suspicion for underlying malignancy in ~90% of cases. Pancreatic cancer is the most common malignancy associated with AN in India. **Key Point:** The skin lesions result from: - Insulin-like growth factor (IGF) secretion by tumor cells - Activation of IGF-1 receptors on keratinocytes - Epidermal hyperplasia and melanin deposition - This is a paraneoplastic syndrome ### Differential Diagnosis in This Case | Feature | Pancreatic CA | Type 2 DM | Addison Disease | Hemochromatosis | |---------|---------------|----------|-----------------|------------------| | **Onset** | Rapid (months) | Gradual (years) | Variable | Gradual | | **Weight loss** | Prominent | Absent | Present | Absent | | **Abdominal mass** | Yes (imaging) | No | No | No | | **Skin pattern** | Velvety, AN | AN if obese | Diffuse bronzing | Bronze/slate | | **Glucose** | Often elevated | Elevated | Normal/low | Normal | **Clinical Pearl:** The presence of a pancreatic mass on imaging + rapid-onset AN + weight loss + hyperglycemia = malignancy-associated AN until proven otherwise. ### Malignancy-Associated AN: Epidemiology **Mnemonic: MALIGNANCY CANCERS** — Common associations: - **M**astoid/Mouth cancers (oral, pharyngeal) - **A**denocarcinomas (gastric, pancreatic, lung) - **L**ung cancer - **I**ntestinal (colorectal) - **G**astric cancer - **N**eoplasms of breast, ovary - **A**bdominal (pancreatic > gastric > colorectal) - **N**on-Hodgkin lymphoma - **C**ervical, endometrial - **Y**ellow nail syndrome (lung cancer association) In this case, **pancreatic adenocarcinoma** is the most likely culprit given the imaging finding and clinical presentation. ### Management Approach ```mermaid flowchart TD A[Acanthosis Nigricans diagnosis]:::outcome --> B{Malignancy-associated?}:::decision B -->|Rapid onset + constitutional symptoms| C[Urgent malignancy screening]:::action B -->|Gradual onset + obesity/DM| D[Metabolic evaluation]:::action C --> E[Imaging: CT abdomen/pelvis]:::action C --> F[Tumor markers: CEA, CA 19-9]:::action E --> G{Mass found?}:::decision G -->|Yes| H[Oncology referral + biopsy]:::action G -->|No| I[Consider lymphoma, occult malignancy]:::action ``` **Warning:** Do NOT assume AN in an adult is simply metabolic. Always screen for malignancy, especially if onset is rapid or weight loss is present.