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(American Journal of Pathology. 2001;159:825-829.)
© 2001 American Society for Investigative Pathology

Short Communications

Familial Cutaneous Leiomyomatosis Is a Two-Hit Condition Associated with Renal Cell Cancer of Characteristic Histopathology

Maija Kiuru^*, Virpi Launonen^*, Marja Hietala, Kristiina Aittomäki^*, Outi Vierimaa, Reijo Salovaara^*¶, Johanna Arola^¶, Eero Pukkala^||, Pertti Sistonen^**, Riitta Herva and Lauri A. Aaltonen^*

From the Department of Medical Genetics,^*
Biomedicum Helsinki, and the Department of Pathology,^¶
Haartman Institute, University of Helsinki, Helsinki; the Departments of Clinical Genetics,
and Medical Genetics,
Turku University Hospital, Turku; the Departments of Clinical Genetics
and Pathology,
Oulu University Hospital, Oulu; the Finnish Cancer Registry,^||
Institute for Statistical and Epidemiological Cancer Research, Helsinki; and the Finnish Red Cross Blood Transfusion Service,^**
Helsinki, Finland

Little has been known about the molecular background of familial multiple cutaneous leiomyomatosis (MCL). We report here a clinical, histopathological, and molecular study of a multiple cutaneous leiomyomatosis kindred with seven affected members. This detailed study revealed strong features of a recently described cancer predisposition syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC). The family was compatible with linkage to the HLRCC locus in 1q. Also, all seven cutaneous leiomyomas derived from the proband and analyzed for loss of heterozygosity displayed loss of the wild-type allele, confirming the association with a susceptibility gene in chromosome 1q. One individual had had renal cell cancer at the age of 35 years. This tumor displayed a rare papillary histopathology, which appears to be characteristic for HLRCC. The derived linkage, loss of heterozygosity, and clinical data suggest that MCL and HLRCC are a single disease with a variable phenotype. The possibility that members of leiomyomatosis families are predisposed to renal cell cancer should be taken into account.

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