Endometrial stromal sarcoma (ESS) is a rare malignant tumor of uterine mesenchyme, accounting for 15–20% of uterine sarcomas. It is classified into low-grade (LG-ESS) and high-grade (HG-ESS) subtypes, each defined by distinct histopathological and molecular features. LG-ESS exhibits slow progression, resembling proliferative-phase endometrial stroma, with genetic alterations like JAZF1-SUZ12 fusions. HG-ESS is more aggressive, characterized by high mitotic activity, necrosis, and genetic markers such as BCOR internal tandem duplication, often leading to advanced-stage diagnosis. Surgical resection is the cornerstone for managing early-stage ESS. A total hysterectomy with bilateral salpingo-oophorectomy (BSO) is recommended to prevent recurrence. Fertility-preserving approaches may be considered in LG-ESS but are associated with high recurrence rates. Lymphadenectomy is not routinely performed, given its limited prognostic value. HG-ESS, due to its aggressiveness, often requires additional treatment, including chemotherapy. Adjuvant therapy varies by subtype. LG-ESS responds well to hormonal treatments such as aromatase inhibitors and progestins, while tamoxifen is contraindicated. HG-ESS, lacking hormonal receptor expression, is managed with chemotherapy, often incorporating doxorubicin-based regimens. Radiotherapy may improve local control in select cases but shows limited impact on overall survival. Advanced-stage ESS treatment focuses on complete cytoreduction, supplemented by systemic therapies. Hormonal therapy remains the standard for advanced LG-ESS, whereas HG-ESS relies on chemotherapy. Prognosis depends on the subtype and stage. LG-ESS has favorable outcomes, with five-year survival exceeding 90% in early stages, but recurrent disease remains common. HG-ESS is associated with poorer survival due to its aggressive nature. Advances in molecular profiling offer promising avenues for personalized therapies, integrating genomic insights with targeted treatments to improve outcomes in this rare malignancy.

This study aimed to assess intra-operative, short-term, and long-term morbidity and develop a score predicting post-operative complications after pelvic exenteration for gynecologic cancer. This was a retrospective, multi-center, international study conducted in tertiary referral centers for gynecologic oncology. The inclusion criteria included cervical, vaginal, vulvar, or endometrial cancer; anterior/total pelvic exenteration performed between January 2005 and March 2023; curative/palliative intent; with or without laterally extended endopelvic/pelvic resection. Logistic regression adjusted for co-variables and a score predictive of severe post-operative complications based on the multi-variable analysis were developed. A total of 862 patients were included. Seven patients (0.8%) had severe intra-operative complications, and no patient experienced intra-operative death. A total of 225 patients (26.1%) had severe early post-operative complications and 27 (3.1%) died within 30 days. The most frequent severe early post-operative complications were pelvic abscess/collection (23.4%) and urostomy leak/fistula (13.4%). A total of 87 patients (10.1%) had severe late post-operative complications, and 16 patients (1.8%) died between 31 and 180 days. The most frequent severe late post-operative complications were pelvic abscess/collection (21.6%) and benign ureteric stricture (13.5%). Risk factors independently associated with severe early and late post-operative complications were no previous recurrences, American Society of Anesthesiologists score >1, total pelvic exenteration, infra-levator pelvic exenteration, laterally extended endopelvic/pelvic resection; and infra-levator pelvic exenteration and laterally extended endopelvic/pelvic resection, respectively. The COREPEX predictive score identified 4 groups with significantly different risk of severe post-operative complications (p < .001). Patients undergoing anterior or total pelvic exenteration have a low risk of intra-operative but a remarkable risk of major post-operative complications. No intra-operative death was recorded, and post-operative mortality was low. The COREPEX score predicting the risk of post-operative complications can be used to counsel patients and for future studies.

Women with vulvar cancer are considerably older than those with other gynaecological malignancies, raising concerns about the tolerability of radical surgery. Yet, for locally advanced or recurrent disease, pelvic exenteration may be the only curative option. Robust evidence to guide decision-making in this population is lacking. This multicentre observational cohort study used data from the COREPEX registry including women who underwent anterior or total pelvic exenteration between 2005 and 2023 across 20 European tertiary referral centres. The primary outcome was overall survival (OS); secondary outcomes were progression-free survival (PFS) and major postoperative complications. Associations were assessed using multivariable Cox and binomial regression models adjusted for relevant covariates. Among 861 women, 79 (9.2%) had vulvar cancer. Median follow-up was 49 months for OS and 40 months for PFS. Women with vulvar cancer were older and more often overweight. Five-year OS was 32% (95% CI, 19-46) in vulvar cancer versus 29% (95% CI, 25-34) in other cancers, adjusted HR 1.05 (95% CI, 0.75-1.46). Five-year PFS was 34% versus 29%, adjusted HR 0.96 (95% CI, 0.69-1.34). Major complications occurred in 33% vs 29%, adjusted RR 1.12 (95% CI, 0.77-1.58). Lymph node metastases, positive margins, and recurrent or persistent disease independently predicted poorer survival. Despite their older age, women with vulvar cancer had survival and morbidity comparable to those with other gynaecological malignancies. These findings support pelvic exenteration as a curative option for selected women with vulvar cancer when complete resection is feasible.

Non–islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by excessive secretion of incompletely processed insulin–like growth factor–2 (IGF–2) from tumor cells. This leads to severe, refractory hypoglycemia. A 67–year–old woman presented with stage IIIC high-grade ovarian carcinoma associated with severe hypoglycemia at diagnosis, and at recurrence. Laboratory tests showed suppressed insulin and C–peptide levels, with an elevated IGF–2/IGF–1 ratio, consistent with NICTH. The patient underwent primary surgery followed by adjuvant platinum-based chemotherapy and maintenance therapy with bevacizumab and olaparib. This comprehensive treatment approach led to remission of both the carcinoma and the associated severe paraneoplastic hypoglycemia. The relapse of the disease was accompanied by a recurrence of hypoglycemia, refractory to medical treatement, which ultimately led to the patient’s death. This represents the first reported case of HGSOC with NICTH, emphasizing the complexity of ovarian cancer presentations and the importance of early diagnosis and comprehensive management in rare paraneoplastic conditions.