BMC Geriatrics

ATM, BLM, and CDH1 gene co-mutations in a high-grade endometrial stromal sarcoma patient with multiple abdominal cavity metastases: a case report and literature review

Abstract Background High-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed. Case presentation A 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib. Conclusions Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS.

Predictive determinants of CIN II + lesions in women over 65 years old: the contribution of HPV, colposcopy, and double immunostaining techniques

Cervical intraepithelial neoplasia grade II or higher (CIN II+) is hard to diagnose in women over 65 years of age since age-related anatomical changes take place, and there is a paucity of data. The aim of the study was to identify predictive clinical, virological, colposcopic, and immunohistochemical predictors of CIN II + lesions in this less studied population. We retrospectively analyzed 364 postmenopausal women aged ≥ 65 years who underwent colposcopy due to abnormal cytology and/or positive human papillomavirus (HPV) test results. Data included HPV test results, cytology, colposcopic findings, biopsy results, and p16/Ki67 dual immunostaining. Univariate logistic regression was used to determine risk factors associated with CIN II+. CIN II + lesions were detected in 6.0% of the patients (n = 22). 100% of the CIN II + cases were p16/Ki67 positive and 0% were in negative-staining cases (p < 0.001). CIN II + prevalence was significantly higher among HPV-positive women (9.9%) compared with HPV-negative women (0.7%) (p < 0.001). Among HPV genotypes, HPV 18 was associated with the highest CIN II + rate (20%). Being sexually active (OR: 4.847; p = 0.002), persistent HPV infection (OR: 1.512; p = 0.013), HPV positivity (OR: 16.602; p = 0.006), HPV 18 infection (OR: 5.042; p = 0.033), and pathologic colposcopic findings (OR: 5.503; p = 0.007) were all significantly associated with CIN II + lesions. In women aged ≥ 65 years, CIN II + lesions are strongly linked to HPV positivity, persistent infection, high-risk types such as HPV 18, dual p16/Ki67 positivity, and abnormal colposcopy. This argues for individualized, multimodal cervical screening in elderly women, combining HPV genotype-based risk stratification, biomarker triage (p16/Ki-67), and clinical factors to improve detection and reduce unnecessary procedures.

Hemophagocytic lymphohistiocytosis following pembrolizumab and bevacizumab combination therapy for cervical cancer: a case report and systematic review

Abstract Background Programmed cell death protein 1 (PD-1) checkpoint inhibitors such as pembrolizumab are novel therapeutics used to treat various advanced malignancies. Immune-related adverse events are common, among the most serious of these toxicities is hemophagocytic lymphohistiocytosis (HLH), which is a life-threatening disorder of unbridled immune activation but has not been properly established. Methods We have procured the first case of hemophagocytic lymphohistiocytosis as an aftermath of treatment with pembrolizumab from the Sir Run Run Shaw Hospital, Zhejiang University, China. In a pursuit to enhance the understanding of this condition, a comprehensive systematic review was performed encompassing all reported instances of ICI-associated Hemophagocytic lymphohistiocytosis within the realms of PubMed and Embase databases. Results We detail the recovery of a cervical cancer patient with a history of psoriasis who developed HLH after combined pembrolizumab and bevacizumab treatment. Remarkably, tumor lesions exhibited substantial and sustained regression. From an analysis of 52 identified Immune Checkpoint Inhibitor (ICI)-related HLH cases, we discovered that HLH often occurred within the first two treatment cycles and approximately 20% of these patients had a history of autoimmune-related diseases. Despite a 15% mortality rate, the majority of patients experienced positive outcomes. Notably, in instances of recovery from HLH, 80% showed positive tumor outcomes. Even after discontinuation of ICI treatment, tumor control persisted in some cases. Conclusion We identified the first case of HLH caused by ICI treatment in cervical cancer and summarized the possible occurrence factors of these cases, the treatment outcomes of HLH, and the impact on tumor outcomes.