Hereditary Leiomyomatosis and Renal Cell Cancer

Abstract

Hereditary leiomyomatosis and renal cell cancer is a genodermatosis with an autosomal dominant inheritance pattern. It is a tumour predisposition syndrome characterized by cutaneous and uterine leiomyomas, and increased susceptibility to develop renal cell carcinoma. There are 200-300 families with hereditary leiomyomatosis and renal cell carcinoma reported worldwide, but the syndrome is believed to be underdiagnosed. Cutaneous leiomyomas are small smooth muscle tumours that tend to grow over time. Larger lesions, in particular, can cause pain or itching. Uterine leiomyomas have a high penetrance in women with hereditary leiomyomatosis and renal cell cancer. They frequently cause symptoms, and surgical intervention is often necessary. Hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinomas have a high potential to metastasize. Patients are diagnosed by genetic testing if a pathogenic mutation is demonstrated in the gene encoding fumarate hydratase. Immunohistochemistry may be a useful diagnostic approach in patients without a detectable pathogenic mutation. Diagnosed patients should be monitored for renal tumours in a lifelong surveillance programme.

Keywords: cancer surveillance; cutaneous leiomyomas; hereditary leiomyomatosis; renal cell carcinoma; uterine leiomyomas.

Fig. 1

Presentations of cutaneous leiomyomas. (A) Small cluster of reddish cutaneous leiomyomas (CLM) with 1 prominent lesion and 2 surrounding smaller lesions located on the upper trunk of a 35-year-old woman with genetically verified hereditary leiomyomatosis and renal cell cancer (HLRCC). (B) A single CLM on the upper arm of a woman with HLRCC. (C) Clusters of CLMs in the woman’s mother.

Fig. 2

Surgical excision of cutaneous leiomyomas on the chest of a 20-year-old patient under current investigation for hereditary leiomyomatosis and renal cell cancer. (A) Cutaneous leiomyomas prior to surgical excision. (B) Keloid formation following surgical excision.

Fig. 3

Immunohistochemical staining of a cutaneous leiomyoma in a hereditary leiomyomatosis and renal cell cancer patient. Tumour cells are fusiform with small clear uniform nuclei. The tumour tissue predominantly consists of smooth muscle cells with positive staining for smooth muscle markers alpha-smooth muscle actin (ASMA), desmin and vimentin. (A) Haematoxylin and eosin staining of cutaneous leiomyoma. (B) ASMA staining of cutaneous leiomyoma. Original magnification x40.