Cutaneous Clues to Renal Cell Carcinoma: Hereditary Leiomyomatosis and Renal Cell Carcinoma
May 2013 | Volume 12 | Issue 5 | Case Reports | 578 | Copyright © May 2013
Melissa A. Michelon MD,a Christle J. Layton MD,b Chad J. Jessup MD,b and Paul F. Lizzul MD PhD MBA MPHb
aSt. Vincent Hospital, Worcester, MA
bTufts Medical Center, Boston, MA
We present a case of a 33-year-old female who was incidentally found to have cutaneous leiomyomata during a routine skin examination. Further history revealed that she also suffered from uterine fibroids and that her mother had died at an early age from renal cell carcinoma. This case serves as a reminder of the often-subtle cutaneous clues, as well as the importance of a multidisciplinary approach, for early diagnosis of potentially fatal conditions. J Drugs Dermatol.
A 33-year-old female with a family history of melanoma presented to our dermatology clinic for a full skin examination. She was found to have multiple, grouped, reddish-brown dermal papules on her left shoulder and right thigh (Figure 1). These papules had been present for several years and were largely asymptomatic. Further questioning revealed a history of uterine leiomyomata for which she had previously undergone myomectomy. It was also noted that the patient’s mother had history of uterine leiomyomata and had died at age 46 years from renal cell carcinoma. Biopsies of the patient’s lesions were consistent with leiomyomata (Figure 2), and the patient was referred for further work-up. Genetic testing revealed a fumarate hydratase (FH) mutation and a computed tomography scan and ultrasound showed a 6-mm cystic lesion within the patient’s right kidney. The patient was also referred to the nephrology department for additional follow-up.
All these factors combined were suspicious for multiple cutaneous and uterine leiomyomatosis (MCUL), also known as Reed syndrome, or hereditary leiomyomatosis and renal cell cancer (HLRCC). This case is presented to illustrate the importance of history and physical examination and appropriate work-up for patients with cutaneous leiomyomata.
Reed syndrome, or MCUL (OMIM 150800), is a familial condition that predisposes patients to benign cutaneous leiomyomata and uterine fibroids. These patients may be at risk for development of renal cell carcinoma in a variant known as HLRCC. This autosomal dominant syndrome is linked to a germline mutation in the FH gene located on chromosome 1q42.3-q43.1 FH is an enzyme in the energy-producing tricarboxylic acid cycle and is thought to be involved in tumorigenesis, the mechanism of which is still being elucidated.2
Common cutaneous findings in patients with FH mutations are leiomyomata. Their sizes range from 0.5 to 2 cm, they can be single or multiple, and they are usually grouped, located on the shoulders, extremities, or trunk. Leiomyomata may be asymptomatic or painful, particularly with external stimuli such as cold or pressure.3 Treatment is largely symptomatic and includes excision, laser CO2 ablation, nitroglycerine, and nifedipine.4
Renal cell tumors in HLRCC are usually unilateral, solitary tumors and are predominantly type II papillary.5,6 These tumors seem to be more aggressive than those in other familial renal cancer syndromes, such as von Hippel-Lindau disease, hereditary papillary renal carcinoma, or Birt–Hogg–Dubé syndrome.7 Early detection is critical in order to screen for renal tumors because of their possibility of aggressiveness, in which prompt surgical intervention is crucial.6,8
Cutaneous manifestations may be the initial presentation in HLRCC, positioning dermatologists to play a critical role in the