Cutaneous Signs and Syndromes Associated With Internal Malignancies

Claudia C. Ramirez, MD; Brian Berman, MD, PhD


Skinmed. 2005;4(2):84-92. 

In This Article

Acanthosis Nigricans and Birt-Hogg-Dube Syndrome

Acanthosis nigricans (AN) is characterized by a diffuse, velvety thickening and hyperpigmentation of the skin. The major flexures are most commonly involved, for example, the neck, axillae, groin, and antecubital fossae, but the knuckles may also be affected.[1] AN can be associated with an internal malignancy but may also occur as a familial form, associated with endocrine disorders, insulin resistance, and obesity and may be induced by medications such as corticosteroids.

AN associated with an internal malignancy differs from other forms of AN primarily having more pronounced hyperkeratosis, hyperpigmentation, mucosal, and mucocutaneous junction involvement and weight loss.[2] AN most often occurs simultaneously with the underlying malignancy,[3] but it can precede by 5 years other symptoms of a malignancy. In 80%-90% of cases, the cancer, usually adenocarcinoma, is abdominal (gastrointestinal [GI] and genitourinary tract) with the stomach being the primary site for the tumor in 60% of cases.[4,5] Other associated sites are the uterus, liver, esophagus, prostate, pancreas, colon, kidney, ovary, and rectum.

Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant genodermatosis characterized by the development of small, dome-shaped papules on the face, neck, and upper trunk. It has been associated with renal neoplasms and spontaneous pneumothorax.

Zbar et al.[6] identified risk factors for renal tumors in 98 patients with BHD syndrome. The odds ratio for renal tumor in these patients was 9.3, whereas family members of patients with BHD syndrome had an odds ratio of 6.9. Chromophobe renal carcinoma, an uncommon type of renal cancer, was the predominant type of renal cancer found.