Comparison of proliferation indices in primary adult-type granulosa cell tumors of the ovary and their corresponding metastases : an analysis of 14 cases

Adult-type granulosa cell tumors (GCTs) of the ovary are generally low-grade malignancies, but late metastases are relatively common. Limited data suggest that recurrent GCTs may exhibit altered morphology and/or biologic behavior, but few studies have directly compared primary and recurrent tumors in individual patients. Fourteen GCTs in which histologic material was available from both the primary tumor and one or more metastases were reviewed, and the mitotic index (MI) and Ki-67 labelling index (KI) were evaluated using carefully specified methodology. The findings were also correlated with the time interval to tumor recurrence. The median interval to first recurrence was 6.6 years (range: 2.2 to 12.2 yr). There were only minor differences in tumor morphology between the primary and metastatic GCTs. None of the cases exhibited high-grade (sarcomatoid) transformation. There was a wide range in MI and KI in the GCTs and no consistent correlation was seen between these indices in the paired primary and recurrent neoplasms. There was also no association between the MI and the KI and the time interval to metastasis. In conclusion, metastatic GCTs generally maintain their morphologic features even after multiple recurrences over many years. Cellular proliferation in GCT is variable, and there is no uniform alteration in proliferation indices between paired primary and metastatic lesions. Therefore, data derived from the analysis of primary GCT may not always be applicable to recurrent tumors. These findings may have implications for management including the potential response of GCT to adjuvant therapies.