Differential Diagnosis for Acanthosis Nigricans in a 52-Year-Old Woman

Single Most Likely Diagnosis

• Malignancy-associated acanthosis nigricans: Given the patient's age, smoking history, and the presence of acanthosis nigricans without obesity or diabetes, a malignancy should be considered as a potential cause. The long history of smoking increases the risk of various cancers.

Other Likely Diagnoses

• Familial acanthosis nigricans: Although less common, familial forms can occur without insulin resistance or obesity. However, this would typically present at a younger age.
• Drug-induced acanthosis nigricans: Certain medications, such as niacin, can cause acanthosis nigricans. The patient's medication history should be reviewed.
• Hormonal disorders: Polycystic ovary syndrome (PCOS), Cushing's syndrome, and other hormonal imbalances can lead to acanthosis nigricans, even in the absence of obesity. Normal glucose levels do not rule out these conditions entirely.

Do Not Miss Diagnoses

• Gastric adenocarcinoma: This is a classic, though rare, cause of malignant acanthosis nigricans. Given the potential severity, it must be considered and ruled out, especially in a smoker.
• Other internal malignancies: Lung, breast, and colon cancers can also be associated with acanthosis nigricans. The patient's smoking history increases the risk of lung cancer.

Rare Diagnoses

• Autoimmune disorders: Rarely, autoimmune conditions can lead to acanthosis nigricans. These would be considered if other causes are ruled out and there are suggestive symptoms or findings.
• Genetic syndromes: Certain genetic syndromes, such as Berardinelli-Seip congenital lipodystrophy, can cause acanthosis nigricans, but these are extremely rare and typically present with other distinctive features.