Hereditary leiomyomatosis and renal cell carcinoma: a case series and literature review

Abstract

Background Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genodermatosis characterized by cutaneous leiomyoma (CLM), uterine leiomyoma (ULM) and renal cell carcinoma (RCC). Five HLRCC patients are presented with a compiled database of published HLRCC cases to increase understanding of HLRCC. Furthermore, a surveillance program is suggested. Our review is based on a PubMed search which retrieved case reports and cohort studies published before November 2019. The search yielded 97 original papers with a total of 672 HLRCC patients. Results CLMs were present in 474 patients (71.5%), developed at the mean age of 28 years. Five patients had cutaneous leiomyosarcomas. ULMs were present in 356 women (83%), while two had uterine leiomyosarcoma. ULMs were diagnosed at a mean age of 32 years, with the youngest diagnosed at age 17 years. The most common surgical treatment for ULMs was hysterectomy, performed at a mean age of 35 years, with the youngest patient being 19 years old. RCCs were present in 189 patients (34.9%), of which half had metastatic disease. The mean age of diagnosis was 36 years with the youngest patient diagnosed with RCC at the age of 11 years. Conclusion We suggest a surveillance program for HLRCC including a dermatological examination once every 2 years, annual magnetic resonance imaging starting at the age of 10 years to monitor for early RCCs, annual gynecological examinations from the age of 15 years and counseling regarding risk of hysterectomy and family planning at the age of 18 years. CLMs are often the earliest manifestation of HLRCC, which is why recognizing these lesions, performing a biopsy, and making a prompt referral to genetic counseling is important in order to diagnose HLRCC early.

Hereditary renal cell tumors: Clinicopathologic importance

“…Approximately 71-100% of families with features suggestive of HLRCC demonstrate pathogenic variants [25,26,29]. Extrarenal manifestations include multiple cutaneous leiomyomas and early onset uterine leiomyomas and leiomyosarcomas.…”

Hereditary Leiomyomatosis and Renal Cell Cancer: Recent Insights Into Mechanisms and Systemic Treatment

“…Hereditary leiomyomatosis and renal cell cancer (HLRCC), also known as leiomyomatosis and renal cell cancer (LRCC), is a rare autosomal dominant disorder in which the affected individuals have a higher risk of developing cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC) (1). HLRCC, estimated to have an estimated incidence of approximately 1 in 200,000, is caused by inactivating mutations in the fumarate hydratase (FH) gene (2)(3)(4)(5)(6).…”

“…There is a tendency to develop into uterine and cutaneous leiomyomas as well as papillary RCC in individuals with HLRCC, and approximately 15% to 30% of HLRCC patients develop kidney cancer ( 4 – 6 , 10 , 11 ). According to the latest analysis of 672 HLRCCs, 71.5% of patients had skin leiomyomas, 83% of women had uterine leiomyomas, and 34.9% of patients had RCCs ( 1 ). Furthermore, uterine leiomyomas appeared in 79% to 100% of women carrying the FH mutation ( 6 , 11 , 12 ).…”

A novel pathogenic variant of the FH gene in a family with hereditary leiomyomatosis and renal cell carcinoma

“…Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a newly emerging hereditary tumor syndrome with an autosomal dominant inheritance pattern characterized by cutaneous leiomyoma, uterine leiomyoma, and renal cell carcinoma (RCC) 1 . More than 300 families with HLRCC have been reported to date, although the condition may be underdiagnosed 2 , 3 . Loss-of-function germline variants of the FH gene, which is located on chromosome 1q43 and encodes fumarate hydratase, cause HLRCC 4 .…”

“…Loss-of-function germline variants of the FH gene, which is located on chromosome 1q43 and encodes fumarate hydratase, cause HLRCC 4 . The incidence of RCC in FH pathogenic variant carriers is estimated to be approximately 15–20% with a median age of onset of 35–44 years 3 , 5 , 6 ; however, a substantial number of FH pathogenic variant carriers can develop RCC at a very young age. Actually, a case of a seven-year-old boy with HLRCC-associated RCC was recently reported 7 .…”