Isolated Leptomeningeal Progression in a Patient with NTRK Fusion+ Uterine Sarcoma: A Case Report

While neurotrophic tropomyosin receptor kinase (NTRK) fusions represent rare oncogenic drivers (&#x3c;1% of solid cancers), the recent approval of NTRK inhibitors (larotrectinib and entrectinib) led to dramatic responses in patients with NTRK fusion+ tumors. Both drugs have phase I data, demonstrating efficacy in the central nervous system (CNS), including both primary brain tumors and brain metastases. We present a 29-year-old woman who was diagnosed with <i>NTRK3-SPECC1L</i> fusion+ undifferentiated uterine sarcoma and underwent resection, chemotherapy, and radiotherapy. Two years later, lung metastases were discovered. She was started on larotrectinib with complete response. She remained stable on larotrectinib until she presented with altered mental status and seizures. MRI demonstrated leptomeningeal enhancement, but because leptomeningeal progression from sarcoma is exceedingly rare and her symptoms improved dramatically with antiepileptics, these findings were initially attributed to seizures. After 2 unrevealing lumbar punctures and stable systemic imaging, a brain biopsy demonstrated metastatic sarcoma, still showing NTRK positivity. She underwent whole brain radiotherapy and was switched to entrectinib, but had clinical progression 1 month later and transitioned to hospice. This case demonstrates the efficacy of NTRK inhibitors in rare and aggressive cancer but highlights that these patients can develop isolated CNS progression even in the setting of CNS-penetrant drugs. CNS progression can occur if there is incomplete CNS drug penetration, discordance in molecular profiles between CNS and systemic disease, or acquired NTRK inhibitor resistance. In this case, CNS disease maintained the NTRK fusion status, but either inadequate CNS penetration or development of a resistance gene may explain the isolated CNS progression.

Development of an Algorithm To Differentiate Uterine Sarcoma From Fibroid Using MRI and LDH Levels

This study aimed to establish an evaluation method for detecting uterine sarcoma with 100% sensitivity using MRI and serum LDH levels. One evaluator reviewed the MRI images and LDH values of a total of 1801 cases, including 36 cases of uterine sarcoma and 1765 cases of uterine fibroids. The reproducibility of the algorithm was also examined using a test set of 61 cases, including 14 cases of uterine sarcoma, by four evaluators with different imaging experience and abilities. From the MRI images and LDH values of 1801 cases of uterine sarcoma and uterine fibroid, we found that all sarcomas were included in the group with high T2WI and either high T1WI, unclear margin, or high LDH value. In addition, when cases with DWI were examined, all sarcomas had high DWI. Among the 36 sarcoma cases, the group with positive findings in T2WI, T1WI, margin, and serum LDH levels all had a poor prognosis (p = 0.015). The reproducibility of the algorithm was examined by four evaluators, and the sensitivity of sarcoma detection ranged from 71–93%. We established an algorithm that is not uterine sarcoma if tumors in the myometrium with low T2WI and DWI.

Rhabdomyosarcoma of the uterus in an adult patient with osteopetrosis: a case report

Background Uterine sarcoma accounts for 3–7% of uterine malignant neoplasms. It is more aggressive than epithelial neoplasms, and patients have a poor prognosis. Rhabdomyosarcoma is classified as a heterologous uterine sarcoma. It is the most common soft tissue malignancy in children while rare in adults. In young patients, the majority of genital tract rhabdomyosarcomas occur in vagina; however, the most common site of gynecologic rhabdomyosarcoma is cervix followed by uterine corpus, in adults. Uterine corpus rhabdomyosarcoma is rare in adults. Diagnosis of pure rhabdomyosarcoma in uterus involves widespread and perfect sampling as well as precise histopathological evaluation to uncover any epithelial component. Case presentation Here we report a case of pure rhabdomyosarcoma of uterine corpus in a 60-year-old Iranian postmenopausal female who had osteopetrosis, presenting with 8-month heavy vaginal bleeding and a protruding cervical mass. She is alive on 18-month follow-up after treatment. Conclusions Rhabdomyosarcoma of uterine corpus is rare in adults. Diagnosis of pure rhabdomyosarcoma in uterus involves widespread and perfect sampling as well as precise histopathological evaluation to uncover any epithelial component. Treatment options in adult gynecological rhabdomyosarcoma are based on studies in younger patients, and more studies may help us choose the best approach for improving outcome.

Uterine Preservation Treatments in Sarcomas: Oncological Problems and Reproductive Results: A Systematic Review

Uterine sarcomas are rare cancers, sometimes diagnosed in women of childbearing age. Hysterectomy is the standard treatment in early stages. The option of lesion removal to save fertility is described in the literature, but it is still considered experimental. The objective of this systematic review is to report on the available evidence on the reproductive and oncological outcomes of fertility-sparing treatment in women with uterine sarcomas. PubMed, Scopus and Cochrane Central Register of Controlled Trials were searched between 1 January 2011 and 21 June 2021 for publications in English about women with uterine sarcoma treated with a fertility-sparing intervention. Thirty-seven studies were included for a total of 210 patients: 63 low-grade endometrial stromal sarcomas, 35 embryonal rhabdomyosarcomas of the cervix, 19 adenosarcomas, 7 leiomyosarcomas and 2 uterine tumors resembling an ovarian sex cord. Conservative treatment ensured pregnancy in 32% of cases. In terms of oncological outcomes, relapse was related to histology and the worst prognosis was reported for leiomyosarcoma, followed by low-grade endometrial stromal sarcoma, which relapsed in 71% and 54% of cases, respectively. The highest death rate was associated with leiomyosarcoma (57.1%). This study demonstrated that fertility-sparing treatments may be employed in selected cases of early stage uterine sarcoma.

FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation

Uterine sarcomas are rare but deadly malignancies without effective treatment. Immunotherapy is a promising new approach to treat these tumors but has shown heterogeneous effects in sarcoma patients. With the goal of identifying key factors for improved patient treatment, we characterized the tumor immune landscape in 58 uterine sarcoma cases with full clinicopathological annotation. Immune cell characterization revealed the overall prevalence of FOXP3+ cells and pro-tumor M2-like macrophages. Hierarchical clustering of patients showed four tumor type-independent immune signatures, where infiltration of FOXP3+ cells and M1-like macrophages associated with favorable prognosis. High CD8+/FOXP3+ ratio in UUS and ESS correlated with poor survival, upregulation of immunosuppressive markers, extracellular matrix (ECM)-related genes and proteins, and YAP activation. This study shows that uterine sarcomas present distinct immune signatures with prognostic value, independent of tumor type, and suggests that targeting the ECM could be beneficial for future treatments.

A ruptured ovarian cystadenofibroma presenting with life-threatening sepsis and an incidental synchronous endometrial stromal sarcoma

A woman in her 60s presented with a rare complication of an ovarian cyst which many clinicians may not consider at first presentation. She was admitted with life-threatening staphylococcus aureus sepsis. She presented shocked with a collapse following a 2-day history of diarrhoea, vomiting and pain in the right iliac fossa. She was taken to theatre where a ruptured, widely infarcted left ovarian serous cystadenofibroma was discovered with over 2 litres of purulent fluid exuding from the cyst into the abdomen. She had a left cyst removal, hysterectomy and bilateral salpingo-oophorectomy performed. Histological analysis and molecular gene testing of an incidentally discovered uterine neoplasm revealed an undifferentiated uterine sarcoma. She successfully recovered as an inpatient and was discharged under the care of an oncology team for ongoing management.