Malignant ovarian germ cell tumors are rare and diverse malignancies, accounting for approximately 5% of all ovarian cancers. Primarily affecting young women, these tumors present unique challenges, particularly in balancing effective treatment with fertility preservation. Early diagnosis is common due to the rapid tumor growth and symptoms such as abdominal pain and distension, leading to favorable prognoses when combined with the high chemosensitivity of platinum-based regimens. Fertility-sparing surgery is the cornerstone of treatment for stage I disease, often followed by close surveillance to minimize the long-term toxicities of chemotherapy. Pathology is pivotal for diagnosis, incorporating immunohistochemical markers to differentiate malignant ovarian germ cell tumors subtypes, including dysgerminomas, yolk sac tumors, and immature teratomas. Advanced imaging modalities like ultrasound, magnetic resonance imaging, and computed tomography are essential for staging, monitoring treatment response, and detecting recurrences. Despite high cure rates, long-term follow-up is crucial to manage late toxicities, such as gonadal dysfunction and secondary malignancies. Recurrent malignant ovarian germ cell tumors present significant therapeutic challenges. High-dose chemotherapy with stem-cell transplantation offers promise in select cases, while the role of secondary cytoreductive surgery and radiotherapy is limited to specific indications. Emerging targeted therapies and novel approaches, such as KIT inhibitors for dysgerminomas with KIT mutations, remain experimental, with limited success reported so far. The rarity and heterogeneity of malignant ovarian germ cell tumors impede large-scale research efforts, underscoring the need for greater understanding of their molecular and genetic landscape to develop more effective and personalized therapies.

Nodal status is one of the most important prognostic factors for patients with apparent early stage endometrial cancer. The role of retroperitoneal staging in endometrial cancer is controversial. Nodal status provides useful prognostic data, and allows to tailor the need of postoperative treatments. However, two independent randomized trials showed that the execution of (pelvic) lymphadenectomy increases the risk of having surgery-related complication without improving patients’ outcomes. Sentinel node mapping aims to achieve data regarding nodal status without increasing morbidity. Sentinel node mapping is the removal of first (clinically negative) lymph nodes draining the uterus. Several studies suggested that sentinel node mapping is not inferior to lymphadenectomy in identifying patients with nodal disease. More importantly, thorough ultrastaging sentinel node mapping allows the detection of low volume disease (micrometastases and isolated tumor cells), that are not always detectable via conventional pathological examination. Therefore, the adoption of sentinel node mapping guarantees a higher identification of patients with nodal disease than lymphadenectomy. Further evidence is needed to assess the value of various adjuvant strategies in patients with low volume disease and to tailor those treatments also on the basis of the molecular and genomic characterization of endometrial tumors.

Mutations in genes encoding for proteins along the RAS-RAF-MEK-ERK pathway have been detected in a variety of tumor entities including ovarian carcinomas. In the recent years, several inhibitors of this pathway have been developed, whose antitumor potential is currently being assessed in different clinical trials. Low grade serous ovarian carcinoma, is a rare gynecological tumor which shows favorable overall survival, compared to the general ovarian cancer population, but worrying resistance to conventional chemotherapies. The clinical behavior of low grade serous ovarian carcinoma reflects the different gene profile compared to high-grade serous carcinoma: KRAS/BRAF mutations. BRAF inhibitors as single agents were approved for the treatment of BRAF mutated tumors. Nevertheless, many patients face progressive disease. The understanding of the mechanisms of resistance to BRAF inhibitors therapy and preclinical studies showing that BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors combined therapy delays the onset of resistance compared to BRAF inhibitor single agent, led to the clinical investigation of combined therapy. The aim of this paper is to review the efficacy and safety of the combination of BRAF plus MEK inhibitors on ovarian carcinomas, in particularly focusing on low grade serous ovarian carcinoma.

Nodal status is one of the most important prognostic factors for patients with apparent early stage endometrial cancer. The role of retroperitoneal staging in endometrial cancer is controversial. Nodal status provides useful prognostic data, and allows to tailor the need of postoperative treatments. However, two independent randomized trials showed that the execution of (pelvic) lymphadenectomy increases the risk of having surgery-related complication without improving patients’ outcomes. Sentinel node mapping aims to achieve data regarding nodal status without increasing morbidity. Sentinel node mapping is the removal of first (clinically negative) lymph nodes draining the uterus. Several studies suggested that sentinel node mapping is not inferior to lymphadenectomy in identifying patients with nodal disease. More importantly, thorough ultrastaging sentinel node mapping allows the detection of low volume disease (micrometastases and isolated tumor cells), that are not always detectable via conventional pathological examination. Therefore, the adoption of sentinel node mapping guarantees a higher identification of patients with nodal disease than lymphadenectomy. Further evidence is needed to assess the value of various adjuvant strategies in patients with low volume disease and to tailor those treatments also on the basis of the molecular and genomic characterization of endometrial tumors.

Mutations in genes encoding for proteins along the RAS-RAF-MEK-ERK pathway have been detected in a variety of tumor entities including ovarian carcinomas. In the recent years, several inhibitors of this pathway have been developed, whose antitumor potential is currently being assessed in different clinical trials. Low grade serous ovarian carcinoma, is a rare gynecological tumor which shows favorable overall survival, compared to the general ovarian cancer population, but worrying resistance to conventional chemotherapies. The clinical behavior of low grade serous ovarian carcinoma reflects the different gene profile compared to high-grade serous carcinoma: KRAS/BRAF mutations. BRAF inhibitors as single agents were approved for the treatment of BRAF mutated tumors. Nevertheless, many patients face progressive disease. The understanding of the mechanisms of resistance to BRAF inhibitors therapy and preclinical studies showing that BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors combined therapy delays the onset of resistance compared to BRAF inhibitor single agent, led to the clinical investigation of combined therapy. The aim of this paper is to review the efficacy and safety of the combination of BRAF plus MEK inhibitors on ovarian carcinomas, in particularly focusing on low grade serous ovarian carcinoma.

Nodal status is one of the most important prognostic factors for patients with apparent early stage endometrial cancer. The role of retroperitoneal staging in endometrial cancer is controversial. Nodal status provides useful prognostic data, and allows to tailor the need of postoperative treatments. However, two independent randomized trials showed that the execution of (pelvic) lymphadenectomy increases the risk of having surgery-related complication without improving patients’ outcomes. Sentinel node mapping aims to achieve data regarding nodal status without increasing morbidity. Sentinel node mapping is the removal of first (clinically negative) lymph nodes draining the uterus. Several studies suggested that sentinel node mapping is not inferior to lymphadenectomy in identifying patients with nodal disease. More importantly, thorough ultrastaging sentinel node mapping allows the detection of low volume disease (micrometastases and isolated tumor cells), that are not always detectable via conventional pathological examination. Therefore, the adoption of sentinel node mapping guarantees a higher identification of patients with nodal disease than lymphadenectomy. Further evidence is needed to assess the value of various adjuvant strategies in patients with low volume disease and to tailor those treatments also on the basis of the molecular and genomic characterization of endometrial tumors.

Mutations in genes encoding for proteins along the RAS-RAF-MEK-ERK pathway have been detected in a variety of tumor entities including ovarian carcinomas. In the recent years, several inhibitors of this pathway have been developed, whose antitumor potential is currently being assessed in different clinical trials. Low grade serous ovarian carcinoma, is a rare gynecological tumor which shows favorable overall survival, compared to the general ovarian cancer population, but worrying resistance to conventional chemotherapies. The clinical behavior of low grade serous ovarian carcinoma reflects the different gene profile compared to high-grade serous carcinoma: KRAS/BRAF mutations. BRAF inhibitors as single agents were approved for the treatment of BRAF mutated tumors. Nevertheless, many patients face progressive disease. The understanding of the mechanisms of resistance to BRAF inhibitors therapy and preclinical studies showing that BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors combined therapy delays the onset of resistance compared to BRAF inhibitor single agent, led to the clinical investigation of combined therapy. The aim of this paper is to review the efficacy and safety of the combination of BRAF plus MEK inhibitors on ovarian carcinomas, in particularly focusing on low grade serous ovarian carcinoma.

The World Health Organization (WHO) classified the novel coronavirus (i.e., coronavirus disease 2019 [COVID-19]) as a global public health emergency. COVID-19 threatens to curtail patient access to evidence-based treatment. Medicine is changing, basically due to the limited available resources. In the field of gynecologic oncology, we have to re-design our treatments' paradigm. During COVID-19 pandemic outbreak, the highest priority is to achieve the maximum benefit from less demanding procedures. Extensive procedures should be avoided, in order to reduce hospitalization and postoperative events that might increase the in-hospital spread of the virus. There are ongoing concerns on the use of laparoscopic procedures, related to the possible contamination of the staff working in the operation room.Other minimally invasive techniques, including, vaginal surgery as well as robotic-assisted and isobaric procedures would be preferred over laparoscopy. A fair allocation of resources is paramount adequate treatments.

Objective: Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changes in cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), and the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of gynecologist oncologists and to assess the implementation of containment measures against COVID-19 diffusion. Methods: The survey consisted of a self-administered, anonymous, online questionnaire. Thesurvey was sent via email to all the members of the SIGO, and MITO groups on April 7, 2020, and was closed on April 20, 2020. Results: Overall, 604 participants completed the questionnaire with a response-rate of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize in-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10%–15%), and to perform less radical surgical procedures (20%–25%) during COVID-19 pandemic. Conclusions National guidelines should be implemented to further promote the safety of patients and health care providers. International cooperation is of paramount importance, as heavily affected nations can serve as an example to find out ways to safely preserve clinical activity during the COVID-19 outbreak.

Objective: Uterine serous carcinoma (USC) is a rare highly aggressive disease. In the present study, we aimed to investigate the survival implication of the systematic lymphadenectomy in patients who underwent surgery for apparent early-stage USC. Methods: Consecutive patients with apparent early-stage USC surgically treated at six Italian referral cancer centers were analyzed. A comparison was made between patients who underwent retroperitoneal staging including at least pelvic lymphadenectomy “LND” vs.those who underwent hysterectomy alone “NO-LND”. Baseline, surgical and oncological outcomes were analyzed. Kaplan- Meier curves were calculated for disease-free survival (DFS) and disease-specific survival (DSS). Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). Results: One hundred forty patients were analyzed, 106 LND and 34 NO-LND. NO-LND group (compared to LND group) included older patients (median age, 73 vs.67 years) and with higher comorbidities (median Charlson Comorbidity Index, 6 vs. 5) (p<0.001). No differences in terms of recurrence rate (LND vs. NO-LND, 33.1% vs. 41.4%; p=0.240) were observed. At Cox regression analysis lymphadenectomy did not significantly influence DFS (HR=0.59; 95% confidence interval [CI]=0.32–1.08; p=0.09), and DSS (HR=0.14; 95% CI=0.02–1.21; multivariable analysis p=0.07). Positive node was independently associated with worse DFS (HR=6.22; 95% CI=3.08–12.60; p<0.001) and DSS (HR=5.51; 95% CI=2.31– 13.10; p<0.001), while adjuvant chemotherapy was associated with improved DFS (HR=0.38;95% CI=0.17–0.86; p=0.02) and age was independently associated with worse DSS (HR=1.07;95% CI=1.02–1.13; p<0.001). Conclusions Although lymphadenectomy did not show survival benefits in patients who underwent surgery for apparent early-stage USC, the presence of lymph node metastasis was the main adverse prognostic factors, supporting the prognostic role of the retroperitoneal staging also in this histological subtype.