VHL Deficiency in the Female Genital Tract
CJ Bechert, SB Shively, N Yuldasheva, S Glasker, A Vortmeyer. University of Texas Medical Branch, Galveston, TX; National Institute of Neurological Disorders and Stroke, Bethesda, MD; National Cancer Institute, Bethesda, MD; Albert-Ludwigs Universitt, Freiburg, Germany; Yale University School of Medicine, New Haven, CT
Background: von Hippel-Lindau (VHL) disease is an autosomal dominant neoplasia syndrome that results from a germline mutation in the VHL tumor suppressor gene (3p26-p25). Affected individuals are at risk for developing various tumors, benign and malignant, most notably renal cell carcinoma (clear cell type). Papillary cystadenomas of the broad ligament also known as adnexal papillary cystadenoma of probable mesonephric origin (APMO) have been rarely reported and are regarded as the female counterpart of the male epididymal cystadenoma. These lesions form in remnant mesonephric duct tissue, typically embedded in the broad ligament. Recognition of these lesions is critical not only for its association with VHL disease but also for its diagnostic confusion with metastatic renal cell carcinoma and other primary tumors.
Design: Tumor and precursor cells were microdissected and subjected to loss of heterozygosity (LOH) analysis. Control samples were obtained from the matched normal tissue on the same histological slide. The samples were analyzed for LOH with the microsatellite markers D3S1038 and D3S1110 flanking the VHL gene on chromosome 3p25. Additionally, the expression of hypoxia-inducible factors (HIF 1) and (HIF 2) was investigated by immunohistochemistry.
Results: We identified broad ligament cystadenomas with deficiency at VHL gene locus (3p26-p25). PCR based LOH analysis of microdissected tumor cells, revealed a loss of the wildtype copy of the VHL gene. Adjacent normal tissue microdissected from the same slide did not reveal LOH (negative control). As expected for VHL deficient cells, neoplastic epithelium expressed HIF 1 and HIF 2 as well as HIF downstream targets CAIX and GLUT-1.
Conclusions: Results of microdissection with LOH analysis confirm that VHL broad ligament cystadenomas are unique, VHL deficient lesions of the female genital tract that can be useful clinically as an indicator for initiating VHL patient screening workups. Furthermore, awareness and recognition of this unique lesion can prevent misdiagnosis as metastatic renal cell carcinoma.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 142, Monday Morning