## Malignancy Association in Acanthosis Nigricans **Key Point:** Gastric adenocarcinoma is the most frequent underlying malignancy in adult-onset acanthosis nigricans, accounting for approximately 40–60% of paraneoplastic cases. ### Frequency by Cancer Type | Malignancy | Frequency in AN | Geographic Variation | |---|---|---| | Gastric adenocarcinoma | 40–60% | Higher in Asia, India | | Lung cancer (squamous) | 15–25% | Higher in Western populations | | Breast carcinoma | 10–15% | Variable | | Lymphoma | 5–10% | Rare | | Colorectal cancer | <5% | Rare | **Clinical Pearl:** In India and other Asian populations, gastric cancer is the predominant association, making gastric malignancy screening essential in any adult presenting with acanthosis nigricans. **High-Yield:** The association is strongest with **adenocarcinomas**, particularly those of the gastrointestinal tract. Squamous cell carcinomas are less commonly associated than adenocarcinomas. ### Pathophysiology The exact mechanism is unclear but likely involves: - Circulating growth factors (IGF-1, TGF-α) secreted by the tumour - Activation of insulin-like growth factor receptors on keratinocytes - Stimulation of epidermal proliferation and melanin production **Warning:** Not all acanthosis nigricans is malignancy-associated. Insulin resistance (obesity, PCOS, type 2 diabetes) is actually the most common cause overall, but when malignancy is present, gastric cancer dominates in adult populations. 
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