DISSEMINATED PERITONEAL LEIOMYOMATOSIS - CLONALITY ANALYSIS BY X-CHROMOSOME INACTIVATION AND CYTOGENETICS OF A CLINICALLY BENIGN SMOOTH-MUSCLE PROLIFERATION

Disseminated peritoneal leiomyomatosis (DPL, leiomyomatosis peritoneal is disseminata) Is a rare condition in which multiple histologically b enign smooth muscle tumorlets diffusely stud peritoneal and omental su rfaces in females, predominantly of reproductive age Although the dist ribution of these lesions suggests a metastatic process, DPL generally has a benign clinical course and has been regarded as a metaplastic p rocess, We assessed clonality of 42 tumorlets and 15 normal tissues fr om four females with DPI. by analyzing X chromosome inactivation as in dicated by the methylation status of the androgen receptor gene (HUMAR A), In each of the four patients, the same parental X chromosome was n onrandomly inactivated in all tumorlets, consistent with a metastatic unicentric neoplasm, or alternatively, selection for an X-linked allel e ill clonal multicentric lesions. Anomalous demethylation of the mark er for X inactivation (HUMARA) was associated with loss of heterozygos ity for markers spanning the X chromosome, or monosomy X, ill part of one leiomyomatous lesion, Biallelic demethylation of the HUMARA micros atellite polymorphism was also found in one intramural leiomyoma. Two of six DPL lesions karyotyped had cytogenetic abnormalities involving chromosomes 7, 12, anti 18, suggesting a pathogenesis in common with u terine leiomyomas.