Benign metastasizing leiomyoma: clonality, telomere length and clinicopathologic analysis

Mod Pathol. 2006 Jan;19(1):130-40. doi: 10.1038/modpathol.3800504.

Abstract

Benign metastasizing leiomyoma is a rare condition affecting women with a history of uterine leiomyomata and is characterized by multiple histologically benign pulmonary smooth muscle tumors. Speculations on its pathogenesis include a benign uterine leiomyoma colonizing the lung, a metastatic low-grade uterine leiomyosarcoma, and primary pulmonary leiomyomatosis. To elucidate its pathogenesis, we analyzed the clinical, pathological and immunohistochemical features, clonality, and telomere length of multiple lung and uterine tumors in three patients with benign metastasizing leiomyoma. In all cases, pulmonary tumors had benign histology and immunohistochemical profiles (estrogen receptor positive, progesterone receptor positive, and very low proliferative index) identical to uterine leiomyoma. In eight tumors from three patients, clonality was assessed by analyzing the variable length of the polymorphic CAG repeat sequence within the human androgen receptor gene. In the two informative patients pulmonary and uterine tumors showed identical patterns of androgen receptor allelic inactivation, indicating that they were clonal. The telomere length measured by fluorescence in situ hybridization in pulmonary leiomyomas of all three patients were either long or very long and were identical to the uterine counterparts, indicating significant telomere shortening is not a crucial step for developing metastases. Our evidence supports the notion that benign metastasizing leiomyoma is clonally derived from benign-appearing uterine leiomyomas.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Clone Cells / chemistry
  • Clone Cells / metabolism
  • Clone Cells / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Leiomyoma / genetics
  • Leiomyoma / metabolism
  • Leiomyoma / pathology*
  • Lung / diagnostic imaging
  • Lung / pathology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Receptors, Androgen / genetics
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Telomere / genetics
  • Tomography, X-Ray Computed
  • Trinucleotide Repeats / genetics
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / pathology*
  • X Chromosome Inactivation / genetics

Substances

  • Receptors, Androgen
  • Receptors, Estrogen
  • Receptors, Progesterone