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Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) Syndrome

Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), also known as multiple cutaneous and uterine leiomyomatosis or Reed’s syndrome, is a rare genetic condition that increases the risk of certain types of cancer. It is caused by a mutation of the fumarate hydratase (FH) gene, which is a tumour suppressor gene on chromosome one.

Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased risk of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.

HLRCC syndrome tends to affect the sexes equally, and is generally diagnosed between the ages of 18-53. However, anyone can develop this disease.

HLRCC is most commonly associated with the development of leiomyomas, however it has also been linked to other types of tumours. Some examples include:

  • Benign tumours, potentially including:
    • Cutaneous leiomyomas.
    • Uterine leiomyomas.
  • Renal cell carcinoma, most commonly papillary renal cell carcinoma.
  • Uterine leiomyosarcoma (rare).

Treatment

When cancers are detected, they are staged and graded based on size, metastasis, and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you. However, each patient with HLRCC will present with a unique disease behaviour, with varying tumour locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:

  • Type of tumours present.
  • Whether the tumours are malignant (cancerous) or benign (non-cancerous).
  • Tumour location.
  • Whether or not malignant tumours have metastasised.
  • Your age.
  • General health.
  • Your treatment preferences.

Your doctor may also recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.

Treatment options for tumours associated with HLRCC may include:

  • Surgery to remove as much of the tumour(s) as possible – these will vary based on tumour type and location.
  • Cryotherapy.
  • Ablation therapy.
  • Targeted therapy.
  • Clinical trials.
  • Palliative care.

Cancer Screening

Once a diagnosis of HLRCC has been confirmed, implementing a targeted screening plan becomes essential due to the increased risk of developing certain cancers.  The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them.  Some recommendations for HLRCC may include:

  • Annual physical examination.
  • Abdominal MRI starting from 8-10 years of age every 6-12 months.

Screening options for HLRCC may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.

Risk factors

HLRCC is caused by a genetic mutation of the fumarate hydratase (FH) gene, which is a type of tumour suppressor gene. It is an autosomal dominant disease, which means that you have a 50% chance of developing the condition if one of your parents carries the mutation.

Symptoms

The symptoms of HLRCC often vary by the type(s) of tumours present. General symptoms of HLRCC may include:

  • Firm, skin-coloured nodules.
  • Clusters of skin nodules.
  • Pain or tingling at the site(s) of the nodules.
  • Menorrhagia.
  • Menstrual pain.
  • Pelvic pressure.
  • Pelvic pain.
  • Haematuria.
  • Lower back pain.
  • Palpable mass in the lower back.

Symptoms related to specific tumours can be found on our knowledgebase.

Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.

Diagnosis

If your doctor suspects you have tumours associated with HLRCC they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.

  • Physical examination.
  • Pelvic examination.
  • Genetic testing.
  • Blood tests.
  • Urine tests.
  • Imaging tests, potentially including:
    • Ultrasound.
    • MRI (magnetic resonance imaging).
    • CT (computed tomography) scan.
  • Exploratory procedure, such as an endoscopy.
  • Biopsy, potentially including:
    • Endometrial (Pipelle) biopsy.
    • Hysteroscopy and D&C (dilation and curettage).

References

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