Malignant peritoneal mesothelioma in a woman with bilateral ovarian serous borderline tumour: Potential interactions between the two diseases

We report a case of a 59-year-old woman with peritoneal malignant mesothelioma and no previous exposure to asbestos with a diagnosis of bilateral ovarian serous borderline tumour with peritoneal implants one year before. We discuss the histopathological and immunohistochemical findings to explain possible and potential interactions between the two diseases. To our knowledge, the association of both serous borderline ovarian tumour and malignant peritoneal mesothelioma has never been described before in the same woman and in such a tight temporal connection. This finding raises numerous issues about the origin of the two tumours and further biomolecular studies are needed to fully understand the carcinogenetic process. From a clinical point of view, this case report can be useful to gynaecologists because it leads to recommend a careful examination of the peritoneal cavity during a surgical resection of borderline serous tumour. Moreover, it may suggest performing a close follow-up associated with a careful surveillance of the patient, especially in the case of micropapillary pattern, to oncologists. A complete clinical approach could help to detect sooner possible relapses or other metachronous malignancies

Epithelial ovarian cancer is infiltrated by activated effector T cells co-expressing CD39, PD-1, TIM-3, CD137 and interacting with cancer cells and myeloid cells

IntroductionDespite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a strong need for better identifying local immune dynamics and immune-suppressive pathways limiting T-cell mediated anti-tumor immunity.MethodsIn this observational study we analyzed by immunohistochemistry, gene expression profiling and flow cytometry the antigenic landscape and immune composition of 48 EOC specimens, with a focus on tumor-infiltrating lymphocytes (TILs).ResultsActivated T cells showing features of partial exhaustion with a CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ surface profile were exclusively present in EOC specimens but not in corresponding peripheral blood or ascitic fluid, indicating that the tumor microenvironment might sustain this peculiar phenotype. Interestingly, while neoplastic cells expressed several tumor-associated antigens possibly able to stimulate tumor-specific TILs, macrophages provided both co-stimulatory and inhibitory signals and were more abundant in TILs-enriched specimens harboring the CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ signature.ConclusionThese data demonstrate that EOC is enriched in CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ T lymphocytes, a phenotype possibly modulated by antigen recognition on neoplastic cells and by a combination of inhibitory and co-stimulatory signals largely provided by infiltrating myeloid cells. Furthermore, we have identified immunosuppressive pathways potentially hampering local immunity which might be targeted by immunotherapeutic approaches

Fertility Preservation in Endometriosis Patients: Anti-Müllerian Hormone Is a Reliable Marker of the Ovarian Follicle Density

9noOBJECTIVE: To analyze the ovarian reserve via measurement of follicular density and anti-Müllerian hormone (AMH) in endometriosis patients participating to a clinical program of cortical ovarian cryopreservation. DESIGN: Retrospective analysis of serum AMH levels and prospective investigation of ovarian follicle number. SETTING: University Hospital. PATIENTS: Two hundred and two women with endometriosis and 400 controls. INTERVENTIONS: Blood samples and ovarian biopsies. MAIN OUTCOME MEASURES: Correlation of serum AMH levels and the number of non-growing follicles in the biopsied cortical tissues in endometriosis and control subjects, including age, type of AMH kit, and the laboratory performing the analysis as covariates. RESULTS: AMH levels were shown to decrease with age in untreated endometriosis patients (P < 1.0 × 10-5) but they were significantly lower in endometriosis compared to controls only in patients over 36 years old (P = 2.7 × 10-4). The AMH decrease was faster in endometriosis compared to controls (beta = 0.27, P = 4.0 × 10-4). Primordial follicle number decreased with the reduction of AMH levels in both cases and controls (beta = 0.3; P = 0.04). CONCLUSION: AMH is a reliable marker of ovarian reserve in endometriosis patients, and it can predict follicular density in women undergoing ovarian tissue cryopreservation.openopenGaravaglia, Elisabetta; Sala, Cinzia; Taccagni, Gianluca; Traglia, Michela; Barbieri, Caterina; Ferrari, Stefano; Candiani, Massimo; Panina-Bordignon, Paola; Toniolo, DanielaGaravaglia, Elisabetta; Sala, Cinzia; Taccagni, Gianluca; Traglia, Michela; Barbieri, CATERINA MARIA; Ferrari, Stefano; Candiani, Massimo; Panina Bordignon, Paola; Toniolo, Daniel

Malignant peritoneal mesothelioma in a woman with bilateral ovarian serous borderline tumour: Potential interactions between the two diseases

We report a case of a 59-year-old woman with peritoneal malignant mesothelioma and no previous exposure to asbestos with a diagnosis of bilateral ovarian serous borderline tumour with peritoneal implants one year before. We discuss the histopathological and immunohistochemical findings to explain possible and potential interactions between the two diseases. To our knowledge, the association of both serous borderline ovarian tumour and malignant peritoneal mesothelioma has never been described before in the same woman and in such a tight temporal connection. This finding raises numerous issues about the origin of the two tumours and further biomolecular studies are needed to fully understand the carcinogenetic process. From a clinical point of view, this case report can be useful to gynaecologists because it leads to recommend a careful examination of the peritoneal cavity during a surgical resection of borderline serous tumour. Moreover, it may suggest performing a close follow-up associated with a careful surveillance of the patient, especially in the case of micropapillary pattern, to oncologists. A complete clinical approach could help to detect sooner possible relapses or other metachronous malignancies

Stage I juvenile granulosa cell tumors of the ovary: A multicentre analysis from the MITO-9 study

OBJECTIVE: Juvenile type granulosa cell tumor (JGCTs) are extremely rare, mainly diagnosed in young women and pre-pubertal girls at stage I disease. Literature is scanty and guidelines regarding the optimal management are still controversial. The aim of this study is to add on the experience of the MITO group (Multicenter Italian Trials in Ovarian Cancer).METHODS: Clinicopathological data from patients with stage I JGCTs were retrospectively collected. Descriptive statistics were used to characterize the patient population. Clinicopathological features and treatment variables were evaluated for association with relapse.RESULTS: Seventeen patients were identified. Surgical approach was laparoscopic and open for 7 (41%) and 10 (59%) patients, respectively. Fertility sparing surgery (FSS) was performed in 15 patients (88%): unilateral salpingo-oophorectomy (USO) in 11 patients, cystectomy with subsequent USO in 2 patients and cystectomy alone in the remaining 2. Adjuvant chemotherapy was given in 2 cases. After a median follow up time of 80 months, no recurrences were registered.CONCLUSIONS: Given the available data, minimally invasive surgery is safe in stage I JGCTs. Because of the good prognosis and of the young age of patients, FSS can be chosen in most of the cases. The role of cystectomy deserves further validation. The need of adjuvant chemotherapy in stage I disease is still unclear, even if available data does not seem to support treatment over surveillance

Locally Performed HRD Testing for Ovarian Cancer? Yes, We Can!

Assessment of HRD status is now essential for ovarian cancer patient management. A relevant percentage of high-grade serous carcinoma (HGSC) is characterized by HRD, which is caused by genetic alterations in the homologous recombination repair (HRR) pathway. Recent trials have shown that not only patients with pathogenic/likely pathogenic BRCA variants, but also BRCAwt/HRD patients, are sensitive to PARPis and platinum therapy. The most common HRD test is Myriad MyChoice CDx, but there is a pressing need to offer an alternative to outsourcing analysis, which typically requires high costs and lengthy turnaround times. In order to set up a complete in-house workflow for HRD testing, we analyzed a small cohort of HGSC patients using the CE-IVD AmoyDx HRD Focus Panel and compared our results with Myriad&rsquo;s. In addition, to further deepen the mechanisms behind HRD, we analyzed the study cohort by using both a custom NGS panel that analyzed 21 HRR-related genes and FISH analysis to determine the copy numbers of PTEN and EMSY. We found complete concordance in HRD status detected by the Amoy and the Myriad assays, supporting the feasibility of internal HRD testing

Locally Performed HRD Testing for Ovarian Cancer? Yes, We Can!

Assessment of HRD status is now essential for ovarian cancer patient management. A relevant percentage of high-grade serous carcinoma (HGSC) is characterized by HRD, which is caused by genetic alterations in the homologous recombination repair (HRR) pathway. Recent trials have shown that not only patients with pathogenic/likely pathogenic BRCA variants, but also BRCAwt/HRD patients, are sensitive to PARPis and platinum therapy. The most common HRD test is Myriad MyChoice CDx, but there is a pressing need to offer an alternative to outsourcing analysis, which typically requires high costs and lengthy turnaround times. In order to set up a complete in-house workflow for HRD testing, we analyzed a small cohort of HGSC patients using the CE-IVD AmoyDx HRD Focus Panel and compared our results with Myriad’s. In addition, to further deepen the mechanisms behind HRD, we analyzed the study cohort by using both a custom NGS panel that analyzed 21 HRR-related genes and FISH analysis to determine the copy numbers of PTEN and EMSY. We found complete concordance in HRD status detected by the Amoy and the Myriad assays, supporting the feasibility of internal HRD testing

Role of Machine Learning (ML)-Based Classification Using Conventional 18F-FDG PET Parameters in Predicting Postsurgical Features of Endometrial Cancer Aggressiveness

Purpose: to investigate the preoperative role of ML-based classification using conventional 18F-FDG PET parameters and clinical data in predicting features of EC aggressiveness. Methods: retrospective study, including 123 EC patients who underwent 18F-FDG PET (2009&ndash;2021) for preoperative staging. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were computed on the primary tumour. Age and BMI were collected. Histotype, myometrial invasion (MI), risk group, lymph-nodal involvement (LN), and p53 expression were retrieved from histology. The population was split into a train and a validation set (80&ndash;20%). The train set was used to select relevant parameters (Mann-Whitney U test; ROC analysis) and implement ML models, while the validation set was used to test prediction abilities. Results: on the validation set, the best accuracies obtained with individual parameters and ML were: 61% (TLG) and 87% (ML) for MI; 71% (SUVmax) and 79% (ML) for risk groups; 72% (TLG) and 83% (ML) for LN; 45% (SUVmax; SUVmean) and 73% (ML) for p53 expression. Conclusions: ML-based classification using conventional 18F-FDG PET parameters and clinical data demonstrated ability to characterize the investigated features of EC aggressiveness, providing a non-invasive way to support preoperative stratification of EC patients