Defining the relationship between ovarian adult granulosa cell tumors and synchronous endometrial pathology: Does ovarian tumor size correlate with endometrial cancer?

OBJECTIVE: The main feature of adult granulosa cell tumors (AGCT) is their capacity to secrete hormones, with nearly all of them capable of synthesizing oestradiol. The primary goal of this study is to identify synchronized endometrial pathologies, particularly endometrial cancer, in AGCT patients who had undergone a hysterectomy. MATERIALS AND METHODS: The study cohort comprised retrospectively of 316 AGCT patients from 10 tertiary gynecological oncology centers. AGCT surgery consisted of bilateral salpingo-oophorectomy, hysterectomy, peritoneal cytology, omentectomy, and the excision of any suspicious lesion. The median tumor size value was used to define the relationship between tumor size and endometrial cancer. The relationship between each value and endometrial cancer was evaluated. RESULTS: Endometrial intraepithelial neoplasia, or hyperplasia with complex atypia, was detected in 7.3% of patients, and endometrial cancer in 3.1% of patients. Age, menopausal status, tumor size, International Federation of Gynecology and Obstetrics stage, ascites, and CA-125 level were not statistically significant factors to predict endometrial cancer. There was no endometrial cancer under the age of 40, and 97.8% of women diagnosed with endometrial hyperplasia were over the age of 40. During the menopausal period, the endometrial cancer risk was 4.5%. Developing endometrial cancer increased to 12.1% from 3.2% when the size of the tumor was >150 mm in menopausal patients (p = 0.036). CONCLUSION: Endometrial hyperplasia, or cancer, occurs in approximately 30% of AGCT patients. Patients diagnosed with AGCT, especially those older than 40 years, should be evaluated for endometrial pathologies. There may be a relationship between tumor size and endometrial cancer, especially in menopausal patients.

Is adjuvant chemotherapy necessary for 2014 FIGO stage IC adult granulosa cell tumor?: Multicentric Turkish study.

AIM: The aim of our study is to examine the clinical, surgical, and pathological factors of stage 1C adult granulosa cell tumor (AGCT) patients and to investigate the effects of adjuvant therapy on recurrence and survival rates in this patient group. METHODS: Out of a total of 415 AGCT patients treated by 10 tertiary oncology centers participating in the study, 63 (15.2%) patients with 2014 FIGO stage IC constituted the study group. The FIGO 2014 system was used for staging. Patient group who received adjuvant chemotherapy was compared with patient group who did not receive adjuvant chemotherapy in terms of disease-free survival (DFS), and disease-specific survival. RESULTS: The 5-year DFS of the study cohort was 89%, and the 10-year DFS was 85%. Those who received adjuvant chemotherapy and those who did not were similar in terms of clinical, surgical and pathological factors, except for peritoneal cytology. In the univariate analysis, none of the clinical, surgical or pathological factors were significant for DFS. Adjuvant chemotherapy and type of treatment protocol had no impact on DFS. CONCLUSION: Adjuvant chemotherapy was not associated with improved DFS and overall survival in stage IC AGCT. Multicentric and randomized controlled studies are needed for early stage AGCT in order to confirm these results and reach accurate conclusions.

Prognostic factors of adult granulosa cell tumors of the ovary: a Turkish retrospective multicenter study.

OBJECTIVE: To define the clinical, histopathological features and the prognostic factors affecting survival in patients with adult granulosa cell tumors of the ovary (AGCT). METHODS: A 322 patients whose final pathologic outcome was AGCT treated at nine tertiary oncology centers between 1988 and 2021 participated in the study. RESULTS: The mean age of the patients was 51.3±11.8 years and ranged from 21 to 82 years. According to the International Federation of Gynecology and Obstetrics 2014, 250 (77.6%) patients were stage I, 24 (7.5%) patients were stage II, 20 (6.2%) patients were stage III, and 3 (7.8%) were stage IV. Lymphadenectomy was added to the surgical procedure in 210 (65.2%) patients. Lymph node involvement was noted in seven (3.3%) patients. Peritoneal cytology was positive in 19 (5.9%) patients, and 13 (4%) had metastases in the omentum. Of 285 patients who underwent hysterectomy, 19 (6.7%) had complex hyperplasia with atypia/endometrial intraepithelial neoplasia, and 8 (2.8%) had grade 1 endometrioid endometrial carcinoma. It was found that 93 (28.9%) patients in the study group received adjuvant treatment. Bleomycin, etoposide, cisplatin was the most commonly used chemotherapy protocol. The median follow-up time of the study group was 41 months (range, 1-276 months). It was noted that 34 (10.6%) patients relapsed during this period, and 9 (2.8%) patients died because of the disease. The entire cohort had a 5-year disease-free survival (DFS) of 86% and a 5-year disease-specific survival of 98%. Recurrences were observed only in the pelvis in 13 patients and the extra-abdominal region in 7 patients. The recurrence rate increased 6.168-fold in patients with positive peritoneal cytology (95% confidence interval [CI]=1.914-19.878; p=0.002), 3.755-fold in stage II-IV (95% CI=1.275-11.063; p=0.016), and 2.517-fold in postmenopausal women (95% CI=1.017-6.233; p=0.046) increased. CONCLUSION: In this study, lymph node involvement was detected in 3.3% of patients with AGCT. Therefore, it was concluded that lymphadenectomy can be avoided in primary surgical treatment. Positive peritoneal cytology, stage, and menopausal status were independent prognostic predictors of DFS.

Clinicopathological features of atypical glandular cells, not otherwise specified, on cervicovaginal pap smears.

OBJECTIVE: The Papanicolaou (Pap) smear test is a standard screening test that detects cervical lesions and cancers. In this multicentric study, we performed a retrospective analysis of cytological results associated with atypical glandular cells, not otherwise specified (AGC-NOS). METHODS: We retrospectively reviewed Pap smear tests that resulted as AGC-NOS. A total of 254 women who underwent colposcopy due to a Pap smear result of AGC-NOS were included the study between 2003 and 2021. The ages, Pap smear results, HPV results if any, colposcopic biopsy results, endocervical and endometrial pathology results, and management of these patients were analysed. RESULTS: Two hundred fifty-four patients with AGC-NOS Pap smear results were included in the study. A total of 70 (27.6%) patients had cervical and endometrial premalignant or malignant lesions. Malignancy was observed in 17 (6.7%) patients (endometrium, n = 11 [4.3%]; cervix, n = 6 [2.4%]). Isolated premalignant or malignant lesions of the cervix and endometrium were detected in 57 (22.4%) and 12 (4.7%) patients, respectively. CONCLUSIONS: Patients diagnosed with AGC-NOS should undergo a careful evaluation with all clinicopathological features. Because cancer of the cervix and endometrium is not rare in patients diagnosed with AGC-NOS, colposcopic examination with endocervical sampling should be a priority based on a cervicovaginal smear. Endometrial sampling is also required according to the patient's clinic, age, and examination characteristics.

Post-recurrence survival analysis of patients with pulmonary recurrence from gynaecologic cancers: a multi-institutional analysis of 122 patients.

In this retrospective study, patients with epithelial gynaecologic cancer with pulmonary recurrence (PR) were evaluated from five national gynaecologic oncology clinics. Patients with a diagnosis of primary endometrial, ovarian/fallopian tube/peritoneal, cervical or vaginal/vulvar tumours who developed an initial PR were included in the study A total of 122 patients were included in the study. The median follow-up time after recurrence was 7.5 (range, 1-84) months. The 2-year PRS was 48% in the main cohort. The risk of death was more than seven times higher in patients who did not receive salvage chemotherapy compared with those who did (hazard ratio: 7.6, 95% CI: 3.0-18.9; p < .001). When squamous cell carcinoma was compared with the other tumour types, the risk of death increased more than three times (hazard ratio: 3.7, 95% CI: 1.4-9.6; p = .007).IMPACT STATEMENTWhat is already known on this subject? Pulmonary recurrence (PR) from gynaecologic malignancies is rare and can cause major clinical problem. Therefore, defining the clinical and pathologic characteristics and recurrence patterns are essential.What the results of this study add? This study demonstrates non-squamous subtype and salvage chemotherapy at PR were associated with improved survival.What of these findings for clinical practice and/or further research? To the best of our knowledge, our study is the largest study to investigate the clinico-pathologic characteristics, recurrence patterns, treatment options, and post-recurrence survival (PRS) in patients with PR from epithelial gynaecologic cancers. Future research should examine the underlying causes of these findings.

Which factors predict parametrial involvement in early stage cervical cancer? A Turkish multicenter study.

OBJECTIVE: To evaluate the clinical and pathological factors for predicting the parametrial involvement (PI) in early stage cervical cancer. STUDY DESIGN: This study included 406 patients with type III radical hysterectomy + pelvic ±â€¯para-aortic lymphadenectomy and FIGO stage I and II cervical adenocarcinoma, squamous type, and adenosquamous type cervical cancer. RESULTS: The entire cohort of patients had lymphadenectomy performed. Early stage cervical cancer patients were evaluated. FIGO 2014 stage, uterine invasion, LVSI, surgical border involvement, vaginal metastasis, stromal invasion and lymph node metastasis were found to be effective for PI on univariate analyses. However; age, tumor type and tumor size did not determine the parametrial invasion. LVSI (HR: 4.438, 95%CI: 1.771-11.121; p = 0.001), lymph node metastases (HR: 2.418, 95%CI: 1.207-4.847; p = 0.013) and vaginal involvement (HR: 4.109, 95%CI: 1.674-10.087; p = 0.02) are independent prognostic factors on multivariate analysis. CONCLUSION: Lymph node metastases, LVSI and surgical border involvement are independent prognostic factors for PI in early stage cervical cancer patients. Therefore, less radical surgical approaches for early stage tumors with no nodal spread, negative LVSI and no surgical border involvement are applicable.

Cytoreductive surgery in advanced stage malignant ovarian germ cell tumors.

INTRODUCTION: To evaluate the survival effect of cytoreductive surgery in advanced stage malignant ovarian germ cell tumors (MOGCT). MATERIAL AND METHODS: Clinicopathological data of patients with MOGCT that were treated between 1991 and 2014. Maximal debulking was defined as no gross residual tumor after primary or recurrence surgery; optimal and suboptimal debulking were used for patients with residual tumors of ≤1cm and >1cm, respectively. RESULTS: In total, 31 patients with advanced stage MOGCT were analyzed. The median age at diagnosis was 21 (14-57) years. The median follow-up duration was 64.1 months. Of these 31 patients; 7 patients underwent sub-optimal debulking, 5 patients had optimal surgery and 18 had maximal debulking. Five-year DFS according to surgical resection rates were 29% in suboptimal debulking group, 75% in optimal debulking group and 93% in maximal cytoreduction group (p<0.001). Three of seven patients who underwent sub-optimal debulking were died of disease, however no deaths were seen in patients with optimal and maximal debulking. Five-year OS was 32% in suboptimal debulking group, and 100% in optimal and maximal debulking groups (p=0.001). DISCUSSION: The benefit of cytoreductive surgery is less well-established in MOGCT of ovary compared to ovarian tumors of epithelial origin due to rareness of this histological subtype. Patients with MOGCT are usually younger and preservation of fertility is an important issue which may lead to suboptimal procedures, sometimes in exchange for diminished survival. Our data demonstrated that maximal cytoreduction should be aimed in patients with advanced stage MOGCT, as it is significantly associated with improved overall survival.

Hormone therapy following surgery in low-grade endometrial stromal sarcoma: Is it related to a decrease in recurrence rate?

BACKGROUND: Low-grade endometrial stromal sarcoma (LGESS) is, in most cases, a slow-growing malignancy; however, it is related with high recurrence rates. The aim of this study is to determine which factors may be associated with the recurrence rate of LGESS. METHODS: The clinicopathological features and treatment options in 37 patients with LGESS were evaluated. RESULTS: All patients underwent the hysterectomy and bilateral salpingo-oophorectomy. Additionally, lymphadenectomy was performed in 56.8% (n = 21) of the patients. Among the patients who underwent lymphadenectomy, 14.3% (n = 3) had lymph node metastasis. The disease was limited to the uterus in 75.7% of patients. Treatment following surgery was radiotherapy in three patients, chemotherapy in seven patients, hormone therapy in 12 patients, and chemotherapy plus hormone therapy in one patient. Megestrol acetate was used in all patients who received hormone therapy. Median follow-up time was 96 months. The 5-year disease-free survival and disease-specific survival were 72% and 97%, respectively. The recurrence rate was 27%. Only hormone therapy following surgery was significantly associated with a lower recurrence rate, even in patients with stage 1 disease. None of the patients treated with hormone therapy following surgery had recurrence, whereas recurrence occurred in 38.5% of the patients who underwent surgery only (p = 0.039). CONCLUSION: Hormone therapy after surgery should be considered a viable option for decreasing the LGESS recurrence rate, regardless of the disease stage.

Prognostic factors and oncological outcomes of ovarian yolk sac tumors: a retrospective multicentric analysis of 99 cases.

PURPOSE: To investigate the clinico-pathological prognostic factors and treatment outcomes in patients with ovarian yolk sac tumors (YST). METHODS: A multicenter, retrospective department database review was performed to identify patients with ovarian YST who underwent surgery between 2000 and 2017 at seven Gynecologic Oncology Centers in Turkey. RESULTS: The study group consisted of 99 consecutive patients with a mean age of 23.9 years. While 52 patients had early stage (stage I-II) disease, the remaining 47 patients had advanced stage (stage III-IV) disease. The uterus was preserved in 74 (74.8%) of the cases. The absence of gross residual disease following surgery was achieved in 76.8% of the cases. Of the 54 patients with lymph node dissection (LND), lymph node metastasis was detected in 10 (18.5%) patients. Of the 99 patients, only 3 patients did not receive adjuvant therapy, and most of the patients (91.9%) received BEP (bleomycin, etoposide, cisplatin) chemotherapy. Disease recurred in 21 (21.2%) patients. The 5-year disease-free survival (DFS) and overall survival (OS) in the entire cohort were 79.2% and 81.3%, respectively. In multivariate analysis, only residual disease following initial surgery was found to be significantly associated with DFS and OS in patients with ovarian YST (p = 0.026 and p = 0.001, respectively). CONCLUSIONS: Our results demonstrate the significance of achieving no visible residual disease in patients with ovarian YST. Fertility-sparing approach for patients with no visible residual disease affected neither DFS nor OS. Although high lymphatic involvement rate was detected, the benefit of LND could not be demonstrated.

Recurrence in Uterine Tumors with Ovarian Sex-Cord Tumor Resemblance: A Case Report and Systematic Review.

OBJECTIVE: The aim of this study was to evaluate the prognostic factors of recurrence in uterine tumors resembling ovarian sex-cord tumors (UTROSCT) and to determine clinical-pathological characteristics, treatment options and outcome. MATERIAL AND METHOD: An electronic literature search was conducted from 1976 to 2018. After the comprehensive evaluation and conjunction with our case, the study included 79 cases. RESULTS: The median age at initial diagnosis was 49 years (range; 16-86 years). The age was under 40 years in 21 (26.6%) patients. Whereas 68 patients underwent at least hysterectomy, 9 patients had organ sparing surgery. There was necrosis in 4 (5.1%) patients, atypia in 16 (20.3%) patients, and infiltrative tumor border in 34 (43%) patients. At least one mitosis per 10 high power fields was determined in 36 (45.5%) patients. The tumor involved at least part of the myometrium in 54 (68.3%) patients. Median follow-up time was 30 months (range; 3-296 months). Recurrence was determined in 5 (6.3%) patients. The disease free survival (DFS) was significantly related only to surgery type. None of the pathologic features were associated with DFS. The 5-year DFS was 86% and 96% in patients who underwent organ sparing surgery or not, respectively (p=0.038). CONCLUSION: The accurate pathologic diagnosis of UTROSCT has great value in shaping surgical management and management during the follow-up period. Organ sparing surgery was related to poor DFS. Although recurrence is rare, it should be kept in mind for patients with UTROSCT.

Prognostic factors and treatment outcomes in surgically-staged non-invasive uterine clear cell carcinoma: a Turkish Gynecologic Oncology Group study.

OBJECTIVE: To assess the prognosis of surgically-staged non-invasive uterine clear cell carcinoma (UCCC), and to determine the role of adjuvant therapy. METHODS: A multicenter, retrospective department database review was performed to identify patients with UCCC who underwent surgical treatment between 1997 and 2016 at 8 Gynecologic Oncology Centers. Demographic, clinicopathological, and survival data were collected. RESULTS: A total of 232 women with UCCC were identified. Of these, 53 (22.8%) had surgically-staged non-invasive UCCC. Twelve patients (22.6%) were upstaged at surgical assessment, including a 5.6% rate of lymphatic dissemination (3/53). Of those, 1 had stage IIIA, 1 had stage IIIC1, 1 had stage IIIC2, and 9 had stage IVB disease. Of the 9 women with stage IVB disease, 5 had isolated omental involvement indicating omentum as the most common metastatic site. UCCC limited only to the endometrium with no extra-uterine disease was confirmed in 41 women (73.3%) after surgical staging. Of those, 13 women (32%) were observed without adjuvant treatment whereas 28 patients (68%) underwent adjuvant therapy. The 5-year disease-free survival rates for patients with and without adjuvant treatment were 100.0% vs. 74.1%, respectively (p=0.060). CONCLUSION: Extra-uterine disease may occur in the absence of myometrial invasion (MMI), therefore comprehensive surgical staging including omentectomy should be the standard of care for women with UCCC regardless of the depth of MMI. Larger cohorts are needed in order to clarify the necessity of adjuvant treatment for women with UCCC truly confined to the endometrium.