Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a tumor predisposition syndrome that increases the risk for a triad of features: cutaneous leiomyomas (smooth muscle tumors of the skin), uterine leiomyomas (more commonly referred to as uterine fibroids), and renal cell cancer. An estimated 76% of patients present with single or multiple cutaneous leiomyomas distributed over the trunk and extremities, and more rarely on the face and neck. The skin findings manifest at a mean age of 25 years. Uterine leiomyomas are present in almost all women with HLRCC and occur at a younger age than in the general population. Uterine fibroids are generally large and numerous. Renal tumors occur in ~10-16% of patients with HLRCC, with a median age at detection of 44 years. Most tumors are classified as 'type 2' papillary renal cancer, although tubulo-papillary, tubular, and solid tumor types have been described. The renal tumors are typically unilateral, solitary, and more aggressive than those associated with other hereditary cancer syndromes.
The differential diagnosis for HLRCC includes Von Hippel-Lindau (VHL) syndrome and Birt-Hogg-Dubé (BHD) syndrome, both of which are associated with an increased risk for renal cancer. BHD syndrome may present with cutaneous fibrofolliculomas, a skin feature reminiscent of cutaneous leiomyomas in HLRCC. Mutations in the SDHB gene associated with Hereditary Paraganglioma-Pheochromocytoma Syndrome have also been reported in patients with apparently isolated familial renal cell carcinoma.