Malignant acanthosis nigricans with enhanced expression of fibroblast growth factor receptor 3.

Sir, Fibroblast growth factor receptor 3 (FGFR3) belongs to the transmembrane tyrosine kinase receptors (1). Con-stitutive activating FGFR3 germline mutations cause genetic syndromes with acanthosis nigricans (AN) (2–5). In addition to hereditary forms of AN, some sporadic forms are known. Among these, the lesions linked with malignancy are called malignant acanthosis nigricans (MAN), which are more severe and more extensive than other sporadic forms of AN. We describe here two cases of MAN and examine the role of the FGFR3 signalling pathway in MAN. PATIENTS AND METHODS Case 1. A 68-year-old Japanese man presented in October 1999 with a 4-month history of darkening and thickening of the skin on his face, neck, axillae, groin, hands and feet. On physical examination he had velvety hyperpigmented plaques on the face (Fig. 1) neck, axillae, groin, and dorsal and palmar aspects of his hands and feet. Soft papillomas and warty nodules studded the affected surface. Thickening and papillation without hyperpigmentation was evident on the lips, gingiva, and hard plate. A skin biopsy specimen taken from his axillae revealed hyperkeratosis and mild acanthosis with dermal papillomatosis. A gastroscopy showed a Borrmann type 4 tumour located in the cardiac part of the stomach, and histological examination revealed a poorly differentiated adenocarcinoma. We diagnosed this case as MAN. He underwent a palliative gastrectomy in November 1999, because the gastric cancer had directly invaded the diaphragm, and his para-aortic lymph nodes were swollen. His skin improved after the operation, but subsequently worsened again with the development of metastatic lesions. He died in April 2000 with peritoneal dissemination. Case 2. A 70-year-old Japanese man presented in January 2004 with a 4-month history of darkening and thickening of the skin on his face. On physical examination, he had velvety hyperpigmented plaques on the face neck, axillae, and dorsal aspects of his hands. Soft papillomas and warty nodules studded the affected surface. His oral mucosa gradually became diffusely thick, and both palms became diffusely hyperkeratotic. A gastroscopy showed a Borrmann type 1 tumour located in the greater curvature of the stomach, and histological examination revealed a poorly differentiated adenocarcinoma. This case was also diagnosed as MAN. He underwent a total gastrectomy for the proximal gastric cancer in March 2004. He received Tegafur after the operation. His abdominal lesions currently remain in remission 4 years after surgical removal. His skin lesions have been improving since the operation. In order to elucidate …