Mass-Forming Endometriosis Shows HMGA1 and HMGA2 Rearrangements
F Medeiros, ARC Araujo, M Erickson-Johnson, PC Kashyap, CP Crum, M Nucci, P Dal Cin, X Wang, DA Bell, AM Oliveira. Mayo Clinic, Rochester, MN; Hospital Universitario Onofre Lopes, Natal, RN, Brazil; Brigham and Women's Hospital, Boston, MA
Background: Endometriosis is a common gynecological disorder characterized by ectopic endometrium associated with pelvic pain and infertility. The pathogenesis is unclear and several genetic, endocrine, immune and environmental agents have been extensively studied as potential causative factors. Previous studies have demonstrated clonality in endometriotic cysts and indicated a wide range of cytogenetic and molecular genetic aberrations in endometriosis; however, consistent somatic genetic alterations have not been identified. Rarely, endometriosis presents as a mass lesion with an infiltrative pattern reminiscent of malignancy. Herein, we describe the cytogenetic and molecular genetic findings of a series of mass-forming endometriosis.
Design: One index case of pulmonary endometriosis underwent conventional cytogenetics analysis. Additional 16 cases of tumor-forming endometriosis were investigated by fluorescence in situ hybridization (FISH) for HMGA1 and HMGA2 loci. FISH was performed on paraffin-embedded thin tissue sections using custom-designed probes.
Results: The index patient presented with a lung nodule. Histopathologic examination revealed the presence of endometrial glands and stroma. Conventional cytogenetics analysis demonstrated the following karyotype: 46,XX, t(5;6)(q13;p21). Molecular cytogenetic analysis revealed HMGA1 rearrangement. A second patient with a large abdominal mass during pregnancy that was composed of markedly decidualized endometrial stroma and endometrioid glands. FISH revealed an HMGA1 rearrangement exclusively in the stromal component. Faced with these findings we evaluated additional cases of mass forming endometriosis for both HMGA1 and HMGA2 rearrangements. Of the 15 additional cases evaluated, 2 (13%) had HMGA2 but not HMGA1 rearrangements. Rearrangements were exclusively found in the stromal component.
Conclusions: Mass-forming endometriosis is an uncommon subset of endometriosis that harbors HMGA1 or HMGA2 rearrangements in up to 23% of cases (4 of 17). This finding supports the concept that endometriosis is clonal and that rearrangement of specific genes (HMGA1/2) likely contributes to neoplastic outgrowth. The role of HMGA1/2 in this process, and in the distinction of benign from more aggressive forms of endometriosis, bears further study.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 163, Tuesday Afternoon