HLRCC is characterized by the occurrence of cutaneous leiomyomas, uterine leiomyomas, and/or renal cell tumors. The severity of the disease varies greatly within the same family and between families.
These skin manifestations, which usually occur on the trunk or extremities, less frequently on the head and neck, appear as skin-colored or light-brown papules or nodules. The average age when they occur is 25 (with a range of 10-47 years), whereby the number and size of the leiomyomas increase with age. Leiomyomas are typically described as painful. The pain may be intensified due to cold, heat, or touching.
The number of cutaneous leiomyomas associated with the HLRCC varies a lot – either multiple leiomyomas or only one single leiomyoma may occur. The complete absence of any skin manifestations is possible as well.
Uterine leiomyomas occur in approximately 80% of female HLRCC patients. Compared to the population as a whole, uterine leiomyomas associated with an HLRCC occur earlier, at an average age of 30 (with a range of 18-52 years), meaning that surgical interventions such as myomectomies or hysterectomies are performed at a much younger age (35 years on average) as well. The leiomyomas are typically large and numerous and frequently cause irregular and severe menstrual bleeding along with abdominal pain.
The renal diseases that occur as part of HLRCC are type 2 papillary or tubular/papillary renal cell carcinomas and collecting duct carcinomas. Most of these tumors are unilateral and solitary and prove to be more aggressive than other hereditary renal cell carcinomas. Renal cell carcinomas occur in approximately 10-16% of HLRCC patients, whereby the average age is 41 at the time of diagnosis. Symptoms may include hematuria, low back pain, or a palpable space-occupying lesion, although an asymptomatic progression is possible as well.