A 48-year-old woman with no significant past medical history presents with sudden onset of velvety, hyperpigmented plaques in the neck and axillae over 3 months. She denies diabetes or obesity. Which investigation should be prioritized to identify a potential underlying malignancy?

## Acanthosis Nigricans and Occult Malignancy ### Clinical Context: Rapid Onset Without Metabolic Risk Factors **Key Point:** Rapid onset of acanthosis nigricans in a non-obese, non-diabetic patient is a red flag for underlying malignancy until proven otherwise. Skin biopsy followed by systemic screening is the appropriate next step. ### Malignancy-Associated Acanthosis Nigricans (MAAN) **High-Yield:** MAAN accounts for 5–10% of all acanthosis nigricans cases and is associated with: - **Most common:** Gastric adenocarcinoma (40–60% of cases) - **Other associations:** Lung, breast, ovarian, endometrial, lymphoma - **Key feature:** Often precedes cancer diagnosis by months to years ### Diagnostic Algorithm for Suspected MAAN ```mermaid flowchart TD A[Acanthosis Nigricans diagnosed clinically]:::outcome --> B{Metabolic risk factors?}:::decision B -->|Yes: DM, obesity| C[Benign metabolic form likely]:::outcome B -->|No or rapid onset| D[High suspicion for MAAN]:::urgent D --> E[Skin biopsy]:::action E --> F{Histology consistent?}:::decision F -->|Yes| G[Systemic malignancy screening]:::action G --> H[CT chest/abdomen/pelvis]:::action G --> I[Upper GI endoscopy]:::action G --> J[Age-appropriate cancer screening]:::action H --> K[Identify and treat cancer]:::outcome ``` ### Why Biopsy First? **Clinical Pearl:** Biopsy confirms the diagnosis and provides histological evidence of benign vs. malignancy-associated features before embarking on expensive systemic screening. ### Systemic Screening Investigations | Investigation | Rationale | Priority | |---------------|-----------|----------| | CT chest/abdomen/pelvis | Detects gastric, lung, pancreatic, ovarian cancers | High | | Upper GI endoscopy | Gastric cancer is most common association | High | | Colonoscopy | Colorectal cancer screening | Medium | | Mammography/Ultrasound breast | Breast cancer association | Medium | | Tumor markers (CEA, CA 19-9) | Supportive but not diagnostic | Low | **Warning:** Do NOT delay biopsy and malignancy screening in a patient with rapid-onset acanthosis nigricans without metabolic risk factors. Prognosis improves with early cancer detection.