Background Endometrial cancer (EC) is a heterogeneous disease comprising four molecular subtypes, one of which is mismatch repair-deficient (MMRd). Immunohistochemical (IHC) evaluation of MMR proteins typically reveals the loss of paired MMR protein expression. However, concurrent loss of all four MMR proteins, known as the null phenotype, is extremely rare and has been reported only in a few colorectal, gastric, and small bowel adenocarcinomas. The mechanisms underlying this unusual MMR IHC pattern remain unclear. Case Report We describe a patient with EC showing concurrent loss of all four MMR proteins by IHC. Molecular analysis revealed hypermethylation of the MutL homolog 1 (MLH1) promoter and somatic mutations in MutS homolog 2 (MSH2). Germline genetic testing identified no pathogenic variants, suggesting that the MMR alterations were acquired somatically. To the best of our knowledge, this is the first reported case of EC with the null MMR phenotype. The coexistence of MLH1 promoter hypermethylation and MSH2 mutations suggests that multiple mechanisms of MMR disruption may occur within a single tumor. Conclusion This case highlights the importance of recognizing unusual MMR IHC profiles in EC and performing molecular analyses to clarify the underlying genetic and epigenetic alterations. Although MMR deficiency can result from different mechanisms, including MLH1 promoter hypermethylation, Lynch syndrome, and somatic mutations, multiple mechanisms may coexist in an individual tumor. Accurate characterization of MMR deficiency is clinically relevant because MMR-deficient tumors are often microsatellite instability-high and may be eligible for immune checkpoint inhibitor therapy.
[Background] Low-grade endometrial stromal sarcoma (LG-ESS) generally follows an indolent clinical course, and high-grade transformation during disease progression is rare. [Case Presentation] We report a 44-year-old woman with Birt–Hogg–Dubé (BHD) syndrome who developed rapid transformation of LG-ESS to high-grade endometrial stromal sarcoma (HG-ESS). The patient underwent surgery for a presumed uterine leiomyoma and was diagnosed with FIGO stage IA LG-ESS. Six months after surgery, a vaginal cuff recurrence was detected and rapidly progressed despite letrozole treatment. Cytoreductive surgery was performed, and the recurrent tumor was diagnosed as HG-ESS. Re-review of the primary specimen revealed no high-grade component. Comprehensive genomic profiling of the recurrent tumor identified a ZC3H7B–BCOR fusion and MDM2 amplification, in addition to the germline pathogenic FLCN variant associated with BHD syndrome. Doxorubicin achieved a partial response, but the disease subsequently progressed during further treatment. This case demonstrates exceptionally rapid transformation from LG-ESS to BCOR-rearranged HG-ESS within 6 months. Although the temporal acquisition of the BCOR rearrangement could not be established because molecular testing was not performed on the primary tumor, the marked morphologic and clinical progression supports substantial tumor evolution. The identification of BCOR rearrangement and MDM2 amplification may provide insight into the aggressive clinical course. [Conclusions] This case highlights the potential value of comprehensive genomic profiling in recurrent ESS and suggests that MDM2 inhibitors may represent a future treatment strategy for selected patients.
Objective To describe the demographic and clinical characteristics of patients with gestational trophoblastic neoplasia (GTN) managed at the Gestational Trophoblastic Disease Referral Center of Amazonas (RC-GTD Amazonas) and to assess the impact of the center's restructuring on treatment outcomes. Methods This ambispective cohort study included women treated for GTN at RC-GTD Amazonas, AM, Brazil, between 2011 and 2022. Patients were grouped according to treatment period: before (2011–2019) and after (2020−2022) the center's restructuring. Demographic, clinical, and treatment data were collected from medical records. Outcomes included treatment characteristics, loss to follow-up, chemotherapy regimen changes, and mortality. Results A total of 29 patients were treated, 11 before and 18 after restructuring. Most patients were young, of low socioeconomic status, and self-identified as parda or Indigenous. Post-molar GTN accounted for 76% of cases. After restructuring, there was a marked reduction in chemotherapy regimen changes and a significant decrease in loss to post-molar follow-up. Pre-treatment hCG levels were higher post-restructuring, likely reflecting more systematic and timely assessment. Overall mortality was 17%, with no significant difference between periods. All fatal cases were high-risk GTN and associated with advanced disease, treatment delay, and metastatic involvement. Hemorrhagic shock due to vaginal metastases was the leading cause of death. Conclusion The restructuring of RC-GTD Amazonas improved treatment standardization and patient follow-up, even during the COVID-19 pandemic. Although mortality was unchanged, the findings highlight the importance of organized referral pathways, early diagnosis, and institutional preparedness to manage acute complications in geographically complex and resource-limited settings.
Objective Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion with variable risk of concurrent endometrial carcinoma. Identifying predictors of endometrial carcinoma in women with EIN without pathological suspicion of carcinoma may improve surgical planning. Methods A retrospective cohort study of patients with EIN who underwent hysterectomy between 2014 and 2024. Preoperative clinical and diagnostic variables were evaluated as predictors of concurrent endometrial carcinoma and incorporated into a multivariable logistic regression model to construct a nomogram. Model discrimination was assessed using the area under the receiver operating characteristic curve. Ridge and Firth penalized regression were performed as sensitivity analyses. Results The final cohort included 124 women, of whom 18 (14.5%) had concurrent endometrial carcinoma. Type 2 diabetes mellitus was associated with increased odds of concurrent carcinoma (adjusted OR 4.18, 95% CI 1.11–15.69). Hysteroscopy-guided sampling or dilation and curettage was associated with lower odds compared with pipelle biopsy (adjusted OR 0.11, 95% CI 0.02–0.50). A nomogram incorporating age, body mass index, type 2 diabetes mellitus, and diagnostic modality demonstrated an AUC of 0.828 (95% CI 0.725–0.931) and an optimism-corrected AUC of 0.784. Penalized sensitivity analyses yielded consistent findings. Conclusion A simple preoperative nomogram based on routinely available clinical variables showed promising discrimination for concurrent endometrial carcinoma in women with EIN. Prospective and external validation in independent cohorts is required before clinical implementation.
Objective While cancer treatment requires a significant time commitment, the objective time spent does not necessarily reflect a patient's perceived time burden. To understand which specific aspects of care are most burdensome, we sought to quantify frustration with time spent on various cancer care-related tasks among individuals receiving treatment for advanced ovarian or metastatic breast cancer. Methods Upon enrolling in a longitudinal study, 83 participants completed a baseline survey regarding frustration with time spent on cancer care tasks. Frustration was measured on a scale of 0 (not at all frustrating) to 10 (extremely frustrating) for cancer care-related activities including travel, waiting, appointments, and logistical tasks. Scores were compared by employment status, dependent status, and distance from the cancer clinic using Wilcoxon rank-sum and Kruskal-Wallis tests. Results Median frustration scores for most tasks were low, but ranges were wide. Activities associated with the greatest frustration included number of trips to the cancer center, travel time per trip, wait times, and paperwork. Participants receiving disability benefits reported high frustration with nearly all tasks. Additionally, participants with dependents reported greater frustration with the number of trips, paperwork, time off work, and organizing dependent care. Participants living 30+ miles from the cancer center reported more frustration with travel time per trip and arranging transportation. Conclusion Time-related frustrations in cancer care are not uniform and more heavily impact participants who are on disability, have dependents, or experience geographic barriers. Individualized care coordination and optimized systemic workflows may minimize care-related time burden for these vulnerable populations.
