A 48-year-old Indian man with a 15-year history of Type 2 diabetes mellitus presents with progressive velvety thickening and hyperpigmentation of the skin over his neck, axillae, and groin for 6 months. He is on metformin and glibenclamide. His HbA1c is 7.8% and BMI is 28 kg/m². Over the past 3 months, he has developed rapid worsening of the skin lesions despite improved glycaemic control. On examination, the affected areas show marked papillomatosis with exaggerated ridges. There is no lymphadenopathy. Abdominal examination reveals a firm, irregular hepatomegaly. What is the most appropriate next investigation?

Explanation

## Acanthosis Nigricans: Malignancy Screening ### Clinical Context This patient presents with **acanthosis nigricans in the setting of rapid progression despite improved glycaemic control**, combined with **hepatomegaly**. These features raise concern for **paraneoplastic acanthosis nigricans** (malignancy-associated), which requires urgent investigation. **Key Point:** While acanthosis nigricans is most commonly associated with insulin resistance and Type 2 DM, **5–10% of cases are paraneoplastic**. Red flags for malignancy include: - Rapid onset or sudden worsening - Absence of obesity or metabolic syndrome - Associated systemic symptoms (weight loss, hepatomegaly, lymphadenopathy) - Older age at presentation ### Paraneoplastic Acanthosis Nigricans: Malignancies | Malignancy | Frequency | Notes | |-----------|-----------|-------| | **Gastric adenocarcinoma** | 60–70% | Most common in Asia | | Lung cancer | 15–20% | Squamous cell > adenocarcinoma | | Breast cancer | 10–15% | Often advanced stage | | Ovarian cancer | 5–10% | Poor prognosis | | Lymphoma | 5% | Hodgkin and non-Hodgkin | | Hepatocellular carcinoma | 3–5% | Especially in cirrhotic patients | **High-Yield:** In an Asian patient (India) with acanthosis nigricans and hepatomegaly, **gastric cancer** is the most likely occult malignancy. Hepatomegaly suggests hepatic metastases or primary HCC. ### Investigation Strategy ```mermaid flowchart TD A[Acanthosis Nigricans + Red Flags]:::outcome --> B{Metabolic or Paraneoplastic?}:::decision B -->|Metabolic: Obese, DM, PCOS| C[Manage insulin resistance]:::action B -->|Paraneoplastic: Rapid onset, hepatomegaly, age >40| D[Urgent malignancy screening]:::urgent D --> E[Contrast-enhanced CT abdomen/pelvis]:::action E --> F[Tumour markers: CEA, CA 19-9]:::action F --> G{Findings?}:::decision G -->|Positive| H[Endoscopy ± biopsy]:::action G -->|Negative| I[Reassess; consider PET-CT]:::action ``` **Clinical Pearl:** The **hepatomegaly** in this patient is the critical finding. Combined with rapid worsening of acanthosis nigricans despite glycaemic control, it mandates imaging to exclude hepatocellular carcinoma or metastatic disease. ### Why Contrast-Enhanced CT? 1. **Detects hepatic lesions** (HCC, metastases) 2. **Evaluates gastric wall thickening** (gastric cancer is most common paraneoplastic cause in Asia) 3. **Assesses lymph nodes** (staging) 4. **Identifies ascites** (peritoneal involvement) **Mnemonic:** **RAPID WORSENING + HEPATOMEGALY = RULE OUT MALIGNANCY** (even in diabetics with known acanthosis nigricans).