Diagnosis Of Adult Granulosa Cell Tumor Research Articles

The impact of adjuvant platinum-based chemotherapy in early adult granulosa cell tumor of the ovaries: A meta-analysis of comparative studies.

5547 Background: Adult granulosa cell tumors (AGCT) are the most common type of malignant ovarian sex chord stromal tumors but only comprise 2 to 5 percent of all malignant ovarian neoplasms. Most granulosa cell tumors have an indolent growth pattern, and prognosis depends on the disease stage at diagnosis and the presence of residual disease after surgery. Though these tumors have metastatic potential, their tendency for late relapses is well documented. Despite the lack of supporting data, the National Cancer Centers Network recommends platinum-based adjuvant chemotherapy (AC) for Stage I with intermediate and high-risk features. Most studies have failed to show any benefit of AC with disease-free or overall survival. However, several of these studies were small, and some had short median follow-ups. Others included advanced stages and the juvenile variant of the disease. Therefore, we conducted this meta-analysis to evaluate the impact of AC on disease recurrence in a stage I enriched AGCT. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of AGCT, studies with a preponderance of stage I, comparative studies of AC versus none, and studies that reported recurrence rates. Studies that had a preponderance of advanced stages or juvenile variants were excluded. A meta-analysis using the fixed effects and random effects models was conducted. Results: Seven retrospective comparative studies with a total of 500 patients were included. The average median age was 47 years, and the average median follow-up was 58 months. Approximately 79% of the sample were stage I, and 79% of stage I were IC. Most AC regimens used were BEP and EP, though it varied among the regions. Platinum-based AC in early-stage AGCT failed to impact recurrence rates compared to clinical observation (HR=1.39, 95%CI 0.86-2.25, I2=48%, p=0.18). Conclusions: This is the first meta-analysis to show that adding platinum-based adjuvant chemotherapy to surgery does not improve the recurrence rate in early AGCT. Therefore, in the absence of evidence supporting any benefit of AC in this disease, recommendations to use AC should be re-evaluated, especially since the risk of platinum-based AC with or without Bleomycin is well-documented and carry potentially serious side effects.

Molecular assessment of testicular adult granulosa cell tumor demonstrates significant differences when compared to ovarian counterparts

Testicular adult granulosa cell tumor (AGCT) is a rare type of sex-cord stromal tumor that affects patients of a wide age range and has the potential for late metastasis. In the testis, the diagnosis of AGCTs often requires the exclusion of other more common types of sex-cord stromal tumors. Immunohistochemistry is of limited utility, being used mostly to confirm sex-cord lineage and to exclude other entities when morphology is not typical. Unlike ovarian AGCTs, which are molecularly homogeneous and harbor a specific activating FOXL2 mutation (c.7558C > T p.C134W) in >90% of cases, the molecular characteristics of testicular AGCTs remain largely unknown. In the current study, we analyzed 13 testicular AGCTs diagnosed at multiple institutions using massively parallel DNA sequencing to evaluate single nucleotide variants, copy number alterations, and structural variants. In all, 10/13 cases were sequenced successfully. Notably, the FOXL2 c.7558C > T (p.C134W) mutation was identified in only a single case (1/10, 10%). The remaining cases were molecularly heterogeneous, with largely nonrecurrent genetic variants. Putative driver events in individual cases included a well-characterized gain-of-function NRAS mutation, as well as inactivation of ATM and TP53, among others. The only highly recurrent finding was single copy loss of 22q (7/10 cases, 70%). Comparatively, the frequencies of FOXL2 c.7558C > T (p.C134W) and 22q loss in 12 metastatic ovarian AGCTs identified in our database were 92% (11/12) and 42% (5/12), respectively. The results of the present study suggest that testicular AGCTs are different from their ovarian counterparts in that they appear to be molecularly heterogeneous and only rarely harbor FOXL2 mutations.