"Hereditary Leiomyomatosis and Renal Cell Carcinoma" – What Is It?
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a disease caused by mutations, i.e., genetic changes in the FH gene. It is characterized by the occurrence of benign tumors of the skin (cutaneous leiomyomas), benign tumors of the uterus (uterine leiomyomas), and/or malignant renal tumors (renal cell carcinomas).
How Is "Hereditary Leiomyomatosis and Renal Cell Carcinoma" Diagnosed?
Suspected Diagnosis
The presence of multiple leiomyomas (benign tumors) of the skin should suggest HLRCC. In addition, HLRCC is suspected in the presence of ≥2 of the following findings:
- Symptomatic and/or multiple leiomyomas (benign tumors) of the uterus requiring surgery before the age of 40
- A certain form of kidney cancer (type 2 papillary renal cell carcinoma) before the age of 40
- A first-degree relative with one of the above criteria
Clinical Diagnosis
The diagnosis of HLRCC is considered confirmed when a mutation, i.e., genetic change in the FH gene, is detected in combination with one of the following clinical findings:
- Multiple leiomyomas of the skin if there is no family history of HLRCC
- 1 cutaneous leiomyoma, if HLRCC occurs in the family
- ≥1 of the following malignant renal tumors: collecting duct carcinoma, tubulo-papillary or type 2 papillary renal cell carcinoma (regardless of familial occurrence)
Genetic Diagnostics
Genetic detection is carried out by identifying a mutation, i.e., a genetic change in the FH gene.
What Is the Risk of Cancer?
HLRCC patients are significantly more likely to develop malignant kidney tumors (renal cell carcinomas). The disease is also characterized by the occurrence of benign skin tumors (cutaneous leiomyomas) and benign tumors of the uterus (uterine leiomyomas). The severity of the disease can vary greatly from patient to patient.
Renal Cell Carcinomas
Renal cell carcinomas, i.e., malignant kidney tumors, occur in around 10-16% of patients with HLRCC. Most of these tumors are localized on one side, occur singly, and are more aggressive than other hereditary renal cell carcinomas. The average age at diagnosis is 41 years. Clinical signs of renal cell carcinoma may include blood in the urine, lower back pain, or a palpable mass on one flank. However, it is also possible for these tumors to cause no symptoms at all.
Leiomyomas of the Skin
These skin manifestations, which usually occur on the trunk, arms, and legs but less frequently on the head and neck, appear as skin-colored or light-brown nodules. The average age of onset is 25 years (interval 10-47 years), with leiomyomas increasing in number and size with age. Leiomyomas are typically described as painful. This pain can be intensified by cold, heat, or touch.
The number of leiomyomas on the skin in the context of HLRCC is variable, so several leiomyomas or only a single leiomyoma can occur. The absence of skin manifestations is also possible.
Leiomyomas of the Uterus
Uterine leiomyomas occur in around 80% of female HLRCC patients. Compared to the general population, uterine leiomyomas in the context of HLRCC occur earlier with an average age of 30 years (interval 18-52 years), so surgical measures such as removal of the tumors or hysterectomies are also performed at a much younger age (35 years on average). Leiomyomas are typically large and numerous and often cause irregular and heavy menstrual bleeding as well as pain in the lower abdomen.
What Is Known About the Development of "Hereditary Leiomyomatosis and Renal Cell Carcinoma "?
Hereditary leiomyomatosis and renal cell carcinoma are caused by mutations, i.e., genetic changes in the FH gene. This gene codes for the FH protein, which normally causes the degradation of another protein (HIF) and thus inhibits the release of growth factors.
If the FH gene is now present in an altered form, the FH protein is also not produced correctly. As a result, the HIF protein cannot be broken down properly, leading to an accumulation of the HIF protein. The increased release of growth factors can lead to the development of benign and malignant tumors.
HLRCC can be passed on from parents to their children. The inheritance is autosomal dominant. The genetic change in the FH gene can also occur as a spontaneous or new mutation, known as a de novo mutation.
Is There Any Form of Treatment Available?
Leiomyomas of the Skin
Die Therapie der Leiomyome der Haut ist schwierig. Folgende Optionen bestehen:
- Chirurgische Entfernung einzelner schmerzhafter Läsionen
- Kälte- und/oder Lasertherapie
- Medikamentöse Therapien können den Schmerz reduzieren.
Leiomyomas of the Uterus
- Medication: Anti-hormonal and pain therapy before surgery to reduce the size of the leiomyomas and/or temporarily as symptomatic therapy
- Surgical removal of leiomyomas as uterus-preserving surgical therapy
- Surgical removal of the uterus
Kidney Carcinomas
- Early surgical removal: complete removal of the affected kidney should be considered due to the aggressiveness of the tumor.
Diagnosis of " Hereditary Leiomyomatosis and Renal Cell Carcinoma" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnose Hereditary Leiomyomatosis and Renal Cell Carcinoma. Wie geht es weiter?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
To date, there are no standardized screening recommendations. The American Association for Cancer Research suggests the following procedure:
- Annual MRI of the kidneys from the age of 8
- Annual skin examination by a pediatrician or dermatologist from the time of diagnosis
- Annual gynecological examination, if necessary with ultrasound, from the first gynecological presentation, but at the latest from the age of 20 or if symptoms occur
Hereditary Leiomyomatosis and Renal Cell Carcinoma – What You Can Do Yourself
You Should Pay Attention to This
You should consult a doctor as soon as changes occur on the skin, especially in the form of painful nodules. In addition, symptoms such as back pain, bloody urine, or masses in the flank area should be noticed and reported to a doctor. You should also urgently consult a doctor if you experience any other new abnormalities or complaints, e.g., irregular or heavy periods or pain in the abdomen.
Further Information
Patients can also register for the CPS register at any time or have this done by the doctors looking after them.
Any further questions?
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