A 68-year-old woman from Mumbai presents with sudden onset of velvety, hyperpigmented plaques over the neck, axillae, and inframammary folds over 3 months. She has no significant past medical history, BMI 22 kg/m², normal fasting glucose, and no family history of diabetes. Physical examination reveals extensive acanthosis nigricans with keratotic papules. What is the most appropriate next step in management?

Explanation

## Clinical Red Flags for Malignancy-Associated Acanthosis Nigricans This patient has several **alarm features** that mandate urgent malignancy screening: ### Red Flag Recognition | Feature | This Patient | Significance | |---------|--------------|---------------| | Age | 68 years | Peak age for malignancy-associated AN | | Onset | Sudden (3 months) | Rapid progression suggests malignancy | | BMI | 22 (normal) | Rules out insulin resistance | | Fasting glucose | Normal | Excludes metabolic etiology | | Extent | Extensive, keratotic | Severe phenotype associated with cancer | | Risk factors | None | Metabolic causes ruled out | **High-Yield:** **Malignancy-associated acanthosis nigricans** occurs in 5–10% of AN cases but is a paraneoplastic syndrome with 90% cancer prevalence. It is the **most common cutaneous paraneoplastic syndrome** and demands urgent investigation. ## Malignancy Associations **Mnemonic: GALL** — **G**astric cancer (most common), **A**denopathy/Lymphoma, **L**ung cancer, **L**iver cancer (hepatocellular carcinoma) Other associations: breast, ovarian, endometrial, pancreatic, and colorectal cancers. ## Screening Algorithm for Malignancy-Associated AN ```mermaid flowchart TD A[Acanthosis Nigricans]:::outcome --> B{Red flags present?}:::decision B -->|Yes: Age >40, rapid onset, no metabolic risk| C[Comprehensive malignancy screening]:::action B -->|No: Obesity, diabetes, young age| D[Metabolic management]:::action C --> E[Chest X-ray, abdominal ultrasound]:::action E --> F[Upper and lower endoscopy]:::action F --> G[Tumor markers: CEA, CA 19-9]:::action G --> H{Malignancy found?}:::decision H -->|Yes| I[Oncology referral and treatment]:::urgent H -->|No| J[Repeat screening in 6-12 months]:::action D --> K[Weight loss, glycemic control]:::action ``` **Clinical Pearl:** In malignancy-associated AN, the skin lesions often improve after successful cancer treatment, confirming the paraneoplastic nature. This is a marker of disease activity and prognosis. ## Why Other Options Fail - **Reassurance alone** is dangerous; a 68-year-old with rapid-onset AN and no metabolic risk factors has ~90% probability of underlying malignancy. - **Metformin** is ineffective because the etiology is not insulin resistance. - **Topical agents** do not address the underlying cancer and delay critical diagnosis. **Warning:** Failure to screen for malignancy in a high-risk patient with acanthosis nigricans represents a missed opportunity for early cancer detection and is a common examination trap.