Leiomyomatosis hereditary with renal cell carcinoma

Author:Prof. Dr. med. Peter Altmeyer

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Last updated on: 07.04.2024

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Synonym(s)

Hereditary leiomyomatosis and renal cell cancer syndromes; Hereditary leiomyomatosis renal cell cancer syndrome; Hereditary leiomyomatosis - renal cell carcinoma - syndrome; HLRCC

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DefinitionThis section has been translated automatically.

Very rare, autosomal dominant inherited systemic disease ( OMIM 605839) with multiple leiomyomas of the skin and uterus associated with papillary renal cell carcinoma.

EtiopathogenesisThis section has been translated automatically.

The disease is caused by germline mutations of the FH gene(fumarate hydratase gene). The FH gene is located on chromosome 1 (1q42.3-43), consists of 10 exons and codes for the enzyme of the citric acid cycle, fumarate hydratase. Of the 155 mutations detected, 58% are missense mutations, 27% are frameshift mutations, and 9% are nonsense mutations. A correlation between the genotype of the FH mutation and the phenotype could not be established so far.

The mutations lead to an accumulation of fumarate, which in turn leads to an increase in HIF via various mechanisms. This in turn leads to an increase in HIF(hypoxia-induced factor) via various mechanisms. The increased HIF level induces the transcription of growth factors such as VEGF (vascular endothelial growth factor) and GLUT-1 (glucose-transporter type 1), a condition that leads to the corresponding tumor proliferation in the present genetic disposition.

ManifestationThis section has been translated automatically.

First occurrence between the ages of 20 and 30; progression in size and number over time.

Clinical featuresThis section has been translated automatically.

The leading symptom of HLRCC are cutaneous, rarely solitary, but mostly multiple, grouped, also arranged in stripes, 0.2 - 1.0 cm large, skin-colored to brownish, often pressure painful nodules and plaques. Leiomyomas are found in approximately 75% of patients with this syndrome. Leiomyomas of the uterus occur in almost all affected women. In addition, renal cell carcinomas are diagnosed in about 15% of affected patients (usually unilateral, solitary, and aggressive in course). Uterine sarcomas, prostate carcinomas and breast carcinomas have also been described in combination with HLRCC.

DiagnosisThis section has been translated automatically.

In patients with cutaneous leiomyomatosis, molecular genetic testing is indicated. If this confirms a mutation of the FH gene, close tumor screening is indicated for family members who are also genetically affected.

Diagnostic criteria for hereditary leiomyomatosis, adapted from Schmidt et al.

Main criteria (high probability of the presence of hereditary leiomyomatosis):

  • - Multiple cutaneous leiomyomas with at least one confirmatory histologic finding
  • Secondary criteria (suspected presence of hereditary leiomyomatosis)
  • -Solitary cutaneous leiomyoma with positive family history
  • -Early occurrence of papillary renal cell carcinoma type II
  • -Multiple, early-onset (<40 years), symptomatic uterine leiomyomas

Definitive diagnosis

  • - Molecular genetically proven germline mutation of the FH gene

LiteratureThis section has been translated automatically.

  1. Bruce H et al (2009) Cutaneous manifestations of internal malignancy. Cancer J Clin 59: 73-98
  2. Frank J et al (2011) Hereditary metabolic diseases with cutaneous manifestation. Dermatologist 62: 98-106
  3. Patel VM et al (2017) Hereditary leiomyomatosis and renal cell cancer syndrome: An update and review.
    J Am Acad Dermatol77: 149-158.
  4. Valero T et al (2016) Painful nodules. J Dtsch Dermatol Ges 14: 627-629

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Last updated on: 07.04.2024