Case Of Adult Granulosa Cell Tumor Research Articles

Clinical characteristics and prognosis of ovarian juvenile granulosa cell tumors

Objective: To analyze the clinical characteristics, treatments, and prognosis of patients with ovarian juvenile granulosa cell tumor (JGCT). Methods: Clinical and pathological data, and follow-up information of 34 patients diagnosed with JGCT from 2000 to 2021 were collected from the surveillance, epidemiology, and end results (SEER) database. A retrospective analysis was conducted to summarize the patients' clinical and pathological characteristics, treatments, and prognosis. Propensity score matching (PSM) was used to match the JGCT cases with adult granulosa cell tumor (AGCT) cases in SEER database. A total of 96 patients with ovarian granulosa cell tumor (OGCT), including 32 cases of JGCT and 64 cases of AGCT, were enrolled in a matched cohort analysis. Univariate and multivariate Cox regression analysis were performed on the matched cohort to explore the risk factors for overall survival. Kaplan-Meier curves and the log-rank test were used to compare the survival outcomes between JGCT and AGCT. Results: (1) The median age at diagnosis for the 34 JGCT patients was 19.5 years (ranged: 1-48 years), with 3 patients aged ≤10 years, 16 patients aged 11-20 years, 11 patients aged 21-30 years, and 4 patients aged >30 years. Tumors originated unilaterally in 33 patients, with only 1 case originating bilaterally. The maximum tumor diameter was recorded in 26 patients, with a median size of 12.4 cm (ranged: 3.5-40.0 cm). According to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system, 19 patients were diagnosed with stage Ⅰ (including 10 cases with stage Ⅰa and 9 cases with stage Ⅰc), 4 patients with stage Ⅱ, 8 patients with stage Ⅲ, and 3 patients with stage Ⅳ. Two patients did not undergo surgery for the resection of lesions. Stage Ⅰ patients (15/19) underwent fertility-sparing surgery, while stage Ⅱ-Ⅲ patients underwent either fertility-sparing surgery or cytoreductive surgery (6 cases each). Stage Ⅳ patients underwent cytoreductive surgery (2 cases). Lymph node dissection was performed in 10 patients, among which only 1 patient with positive lymph nodes metastasis. None of the 34 patients received radiotherapy, while 18 patients received adjuvant chemotherapy (included neoadjuvant chemotherapy and postoperative adjuvant chemotherapy). The proportion of stage Ⅰ patients receiving adjuvant chemotherapy was relatively low, with only 4 out of 19 patients (including 2 out of 10 cases for stage Ⅰa and 2 out of 9 cases for stage Ⅰc). The proportions of patients receiving adjuvant chemotherapy for stages Ⅱ, Ⅲ and Ⅳ were 3 out of 4 cases, 8 out of 8 cases, and 3 out of 3 cases, respectively. The follow-up ended in December 2021, with 20 patients alive and 14 dead. The survival rate for ovarian JGCT patients was 59% (20/34). Among them, the survival rate for stage Ⅰ patients was 16/19, while for stage Ⅱ-Ⅳ patients, it was 4/15; there was a statistically significant difference (P=0.002). Among stage Ⅱ-Ⅲ patients, the survival rate at the end of follow-up was 1/6 for those who underwent fertility-sparing surgery, compared to 3/6 for those who underwent cytoreductive surgery (P=0.546). (2) For the 96 OGCT patients after matching using the PSM method, 64 ovarian AGCT patients had 5 deaths and 59 survivors during the follow-up period, the survival rate was 92% (59/64) at the end of follow-up. In contrast, among the 32 ovarian JGCT patients, 13 died and 19 survived, resulting in a survival rate of 59% (19/32) at the end of follow-up, which was statistically significant difference for the AGCT group (P<0.001). Univariate Cox analysis revealed that histology, extent of surgery, chemotherapy, postoperative tumor residual status, and stage all significantly affected the survival outcomes of OGCT patients (all P<0.05). Multivariate Cox analysis revealed that variables with significant statistical differences were histology and stage. The median survival time for JGCT patients was 126 months, while AGCT patients median survival time was not reached with a statistically significant between the two groups (P<0.001). Conclusions: Ovarian JGCT predominantly occur in adolescents and young women. Lymph node metastasis is relatively rare, and treatment primarily involves surgery and adjuvant chemotherapy. Most ovarian JGCT patients are diagnosed at stage Ⅰ, with a favorable prognosis. Fertility-preserving surgery is recommended, involving salpingo-oophorectomy on the affected side plus comprehensive staging surgery, or a second surgery to achieve comprehensive staging. For stage Ⅱ-Ⅳ ovarian JGCT patients, the prognosis is relatively poor, and fertility-preserving surgery should be considered with caution. The prognosis of ovarian JGCT patients is worse than that of ovarian AGCT patients.

An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers.

The current knowledge about the immunohistochemical features of adult granulosa cell tumor (AGCT) is mostly limited to the "traditional" immunohistochemical markers of sex cord differentiation, such as inhibin, calretinin, FOXL2, SF1, and CD99. Knowledge about the immunohistochemical markers possibly used for predictive purpose is limited. In our study, we focused on the immunohistochemical examination of 290 cases of AGCT classified based on strict diagnostic criteria, including molecular testing. The antibodies used included 12 of the "diagnostic" antibodies already examined in previous studies, 10 antibodies whose expression has not yet been examined in AGCT, and 7 antibodies with possible predictive significance, including the expression of HER2, PD-L1, CTLA4, and 4 mismatch repair (MMR) proteins. The results of our study showed expression of FOXL2, SF1, CD99, inhibin A, calretinin, ER, PR, AR, CKAE1/3, and CAIX in 98%, 100%, 90%, 78%, 45%, 41%, 94%, 82%, 26%, and 9% of AGCT, respectively. GATA3, SATB2, napsin A, MUC4, TTF1, and CD44 were all negative. PTEN showed a loss of expression in 71% of cases and DPC4 in 4% of cases. The aberrant staining pattern (overexpression) of p53 was found in 1% (3/268) of cases, 2 primary tumors, and 1 recurrent case. Concerning the predictive markers, the results of our study showed that AGCT is microsatellite stable, do not express PD-L1, and are HER2 negative. The CTLA4 expression was found in almost 70% of AGCT tumor cells.

Adult Granulosa Cell Tumor With High-grade Transformation: Report of a Series With FOXL2 Mutation Analysis.

Adult granulosa cell tumor (AGCT) is a low-grade malignant neoplasm with a significant propensity for late recurrence and metastasis. Almost all AGCTs are composed of cells with bland nuclear features and even when these tumors recur or metastasize, the nuclear features are almost always low-grade. We report 5 cases of AGCT in patients aged 37 to 88 years composed of areas of typical AGCT with low-grade morphology admixed with areas of high-grade morphology, with marked nuclear atypia, often with bizarre multinucleate cells and high mitotic activity; this is the first reported series of high-grade transformation in AGCTs. The high-grade areas often morphologically closely resembled juvenile granulosa cell tumor with abundant eosinophilic cytoplasm, significant mitotic activity, and intermediate sized follicles. Four cases were FIGO stage IA at diagnosis and 1 was stage IIIC with omental involvement. FOXL2 mutation analysis of both the morphologically low-grade and high-grade areas in 4 of 5 cases confirmed the presence of missense point mutation, c.402C>G, p.(Cys134Trp), providing conclusive evidence that the high-grade component represents transformation of typical AGCT rather than the coexistence of another sex cord-stromal tumor, such as juvenile granulosa cell tumor, which has been suggested for such neoplasms. In 3 of 4 cases where immunohistochemistry was undertaken, there was a striking difference between the p53 staining in the low-grade and high-grade components with wild-type staining in the former and diffuse mutation-type immunoreactivity in the latter, suggesting that TP53 mutation is likely to play a role in high-grade transformation. TP53 mutation analysis covering exons 4 to 10 was undertaken in 4 cases and TP53 mutations were identified in the high-grade component of 2 of the cases. In 1 case, there was diffuse block-type p16 staining in the high-grade component. Follow-up in the 4 stage IA neoplasms revealed no evidence of tumor recurrence in 3 (6 to 9 mo follow-up) while the other patient developed mediastinal, peritoneal, and pulmonary metastasis 17 months after diagnosis. High-grade transformation is uncommon in AGCTs and given that one of our cases was advanced stage at diagnosis, another exhibited widespread metastasis within a short period and there have been occasional case reports of aggressive behavior in AGCTs with high-grade transformation, this event may herald an aggressive clinical course.

Granulosa Cell Tumor of the Ovary: A Retrospective Study of 31 Cases and a Review of the Literature.

Background Adult granulosa cell tumors (AGCTs) are the most common sex cord-stromal tumors. Unlike epithelial ovarian tumors, they occur in young women and are usually detected at an early stage. The aim of this study was to report the clinical and pathological characteristics of AGCT patients and to identify the prognostic factors. Methods All cases of AGCTs, treated at Salah Azaïz Institute between 1995 and 2010, were retrospectively included. Kaplan-Meier's statistical method was used to assess the relapse-free survival and the overall survival. Results The final cohort included 31 patients with AGCT. The mean age was 53 years (35–73 years). Patients mainly presented with abdominal mass and/or pain (61%, n = 19). Mean tumor size was 20 cm. The majority of patients had a stage I disease (61%, n = 19). Two among 3 patients with stage IV disease had liver metastasis. Mitotic index was low in 45% of cases (n = 14). Surgical treatment was optimal in almost all cases (90%, n = 28). The median follow-up time was 14 years (1–184 months). Ten patients relapsed (32%) with a median RFS of 8.4 years (6.8–9.9 years). Mean overall survival was 13 years (11–15 years). Stage I disease and low-to-intermediate mitotic index were associated with a better prognosis in univariate analysis (resp., p = 0.05 and p = 0.02) but were not independent prognostic factors. Conclusion GCTs have a long natural history with common late relapses. Hence, long active follow-up is recommended. In Tunisian patients, hepatic metastases were more frequent than occidental series. The prognosis remains good and initial staging at diagnosis is an important prognostic factor.

Recurrence of adult granulosa cell tumor of the ovary: experience at a tertiary care center

Adult granulosa cell tumor (AGCT) is the most common ovarian sex cord stromal tumor with a favorable prognosis. However, a subset of patients develop recurrence. We retrieved and reviewed 156 cases of AGCT reported between 1992 and 2012. The ages ranged from 20 to 84 years (mean, 48 years). The size of the tumor ranged from 0.8 to 25 cm (mean, 10 cm). Histologically, all tumors were composed of round or polygonal cells with indented or grooved nuclei, eosinophilic cytoplasm, and well defined cell borders. A diffuse pattern was seen in the majority followed by microfollicular, trabecular and macrofollicular. The mitotic figures ranged from 2 to a maximum of 21/10 HPFs. Focal necrosis were seen in 17 cases. Associated simple hyperplasia of endometrium was seen in 9 cases, complex hyperplasia in 2, and endometrioid adenocarcinoma of the endometrium in 3 cases. Recurrence was seen in 8 cases with a follow-up of 2 to 19 years (mean, 6 years). The recurrent tumors were mostly >5 cm and sites included the same adnexal site and contralateral ovary, omentum, mesentery of small bowel, abdominal wall, uterine and fallopian tube serosa, lymph nodes, pelvis, and appendix. Histologically, recurrent tumors exhibited a diffuse histologic pattern and a mitotic count of 6.8 as compared to 3.3 in primary tumors. In conclusion, a tumor size of >5 cm and a diffuse histologic pattern were associated with increased recurrence risk. The recurrent tumors hadz increased mitotic figures compared with primary tumors. Appendix, a very rare site of recurrence was seen in one of our cases.

Adult granulosa-cell tumor of the ovary: a retrospective study of 45 cases.

This study describes 45 cases of adult granulosa-cell tumors seen in our institution between 1976 and 1993. The median age was 46.5 years (12-77) and 18 women were postmenopausal. Vaginal bleeding was present in one-third of cases; other complaints were abdominal pain (28%) and the presence of a pelvic mass (47%). The tumor size was variable (<3 cm to 30 cm, median 11.5 cm). FIGO stages were: stage I: 30 (73%) (19 Ia, seven Ic, four I unknown); stage II: seven (17%) (two IIa, five IIC); stage III: three (7%) (one IIIb, two IIIc). Two adenocarcinomas and 13 cases of hyperplasia were found in 25 endometrial samples available. The initial therapy for all the cases was surgery, consisting in 34 patients of hysterectomy, bilateral salpingo-oophorectomy, +/- tumor resection. Sixteen patients received adjuvant therapy as well: chemotherapy (CT) alone for 12, radiotherapy (RT) alone for two, and CT + RT for two patients. Among the 39 patients who achieved a complete response after initial therapy, 15 patients have relapsed (pelvic recurrences) (38.5%) including six stage Ia (three received only conservative surgery). All the recurrent tumors were resected and 14/15 had CT (13/14 with cisplatin). The overall survival rate was 77.2% at 5 years, 66.5% at 10 years, and 41.2% at 20 years. A statistically significant difference was found between the survival of patients with stage Ia disease (75% at 10 and 15 years) and that of other patients (60% at 10 years, and <50% at 15 years). Serum estradiol and serum inhibin were measured in some patients and the results are described.