Copyright @ 2006 International Society of Gynecological Pathologists. Unauthorized reproduction of this article is prohibited. Original Article Clinical and Pathological Predictive Factors in Women with Adult-type Granulosa Cell Tumor of the Ovary Jeannine Villella, M.D., Francois R. Herrmann, M.D., M.P.H., Sadhana Kaul, M.D., Shashikant Lele, M.D., David Marchetti, M.D., Joan Natiella, M.T., Kunle Odunsi, M.D., Ph.D., and Paulette Mhawech-Fauceglia, M.D. Summary: Granulosa cell tumor (GCT) is a rare neoplasm hallmarked by a very indolent course and late recurrences. Although numerous clinical and pathological parameters have been implicated as prognostic factors for GCT, their role remains controversial. We performed a retrospective study at our institution where we identified 48 patients with GCT from our tumor registry. Demographic and clinical course information was recorded from the medical record. Twenty of 48 formalin-fixed, paraffin-embedded blocks were retrieved from archived specimens. Pathological para- meters such as nuclear atypia, mitotic count, Ki-67 index using immunohistochemistry, and quantitative DNA ploidy were performed. DNA aneuploidy by quantitative method was associated with patients’ overall survival. The degree of nuclear atypia, mitotic count, Ki-67 index, and DNA aneuploidy was not predictive of tumor recurrence. Multi- institutional collaboration is imperative to create a comprehensive national database for investigation into ways that may better indicate prognosis in these patients. Key Words: GCT—Clinical parameters—DNA ploidy—Ki-67—Prognosis. Granulosa cell tumor (GCT) of the ovary is a rare neoplasm, accounting for 2% to 3% of all ovarian can- cers. More than 60% of cases present in the perimeno- pausal or early postmenopausal period, with a median age at diagnosis between 50 and 54 years (1). Symptoms and clinical presentations vary depending on the patient’s age and reproductive status. The most common presenting sign is bleeding, and menorrhagia is the most common presentation in premenopausal women. These tumors have a propensity to be large, with most exceeding 10 cm; thus, pain can also be a frequent symptom. Adult GCT is most frequently unilateral and may rupture or cause adnexal torsion, further exacerbating painful symptoms. More than 75% of GCTs are diagnosed as International Federation of Gynecology and Obstetrics stage I, and only 6% are stage IV (2). Although GCT has been con- sidered to be of low-grade malignancy, 10% to 50% of the patients develop recurrences presenting as late as 20 to 30 years after initial diagnosis. Numerous studies have shown that stage, size, age, mitotic count, nuclear atypia, Ki-67 index, and p53 may be good prognostic factors in predicting disease outcome in women with GCT (2 Y 14). In addition, some authors reported an association between DNA aneuploidy, per- centage of S-phase, and tumor behavior (15,16). Despite these claims, prognostic factors, namely, DNA ploidy, are subject to debate. In the present study, we conducted a retrospective review of GCT at our institution to evaluate the role of some debated prognostic factors, specifically DNA ploidy, in predicting disease outcome. From the Department of Gynecologic Oncology Surgery (J.V., S.L., D.M., K.O.), Roswell Park Cancer Institute, Buffalo, New York; De- partment of Geriatrics and Rehabilitation (F.R.H.), Geneva University Hospital, Geneva, Switzerland; and Department of Pathology and Labo- ratory Medicine (S.K., J.N., P.M.F.), Roswell Park Cancer Institute, Buffalo, New York. Address correspondence and reprint requests to Paulette Mhawech- Fauceglia, MD, Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton streets, Buffalo, NY 12463. E-mail: pmhawech1@yahoo.com International Journal of Gynecological Pathology 26:154–159, Lippincott Williams & Wilkins, Baltimore Ó 2007 International Society of Gynecological Pathologists 154 DOI: 10.1097/01.pgp.0000228143.52054.46