Soft tissue sarcoma with ZC3H7B::BCOR fusion in a male mimicking low-grade fibromyxoid sarcoma - A case report.

Diagnosis of soft tissue tumors is often challenging, given the large number of entities, often with non-specific or overlapping morphology. Although morphology still plays an important part in diagnostic process, additional studies including immunohistochemistry and molecular genetics are often needed to arrive at correct diagnosis. We report a case of 61-year-old male with subcutaneous tumor in right hip area, that was surgically removed. The tumor was composed of uniform bland spindle cells in mild to moderately cellular myxoid nodules, with limited areas of collagenization and the diagnosis of low grade fibromyxoid sarcoma was made. The tumor recurred 3 years after the initial diagnosis and the new sample showed a high-grade round cell sarcoma with limited residual low-grade areas and non-specific immunoprofile after extended immunohistochemical work-up. Molecular analysis demonstrated ZC3H7B::BCOR fusion. Sarcomas with ZC3H7B::BCOR fusion occurring outside of uterus are exceedingly rare. A comprehensive review of previously published cases and a short discussion about classification of the entity is provided, together with data about morphology and immunoprofile of the lesions. The case also underscores the necessity of extended work up of soft tissue tumors with unusual immunohistochemical or morphological features in order to accurately assess their biological potential.

ZC3H7B-BCOR High-Grade Endometrial Stromal Sarcoma with a Mucoid Grossly Feature: A Case Report and Literature Review.

We report on a 50-year-old postmenopausal woman who presented with abnormal uterine bleeding and pelvic pain due to a uterine solid mass grew from the uterine fundus to the cervix and with so far undescribed obviously gelatinous grossly change, which was suspected of myxoid leiomyosarcoma in intraoperative diagnosis. Morphologically, the tumor cells displayed haphazard fascicles of uniform mild-to-moderate heteromorphic spindle cell component with significant and abundant myxoid stroma, forming signet ring cells and microcysts. Immunohistochemically, the tumour cells were diffusely positivefor CD10 and cyclin D1 and negative for Desmin and SMA, but the expression of BCOR staining was not present. The FISH study showed a positive BCOR gene break probe, and the RNA sequencing revealed an identified reciprocal fusion gene ZC3H7B-BCOR. The case was finally diagnosed as ZC3H7B-BCOR high-grade endometrial stromal sarcoma. Tumor recurrence occurred rapidly on the pelvic peritoneal and vaginal 2 months after resection. In conclusion, these findings further support ZC3H7B-BCOR HGESS has a poor prognosis and molecular testing of uterine mesenchymal tumors with myxoid matrix and unusual grossly presentation is recommended to avoid misdiagnosis.

Update on Endometrial Stromal Tumours of the Uterus.

Endometrial stromal tumours (ESTs) are rare, intriguing uterine mesenchymal neoplasms with variegated histopathological, immunohistochemical and molecular characteristics. Morphologically, ESTs resemble endometrial stromal cells in the proliferative phase of the menstrual cycle. In 1966 Norris and Taylor classified ESTs into benign and malignant categories according to the mitotic count. In the most recent classification by the WHO (2020), ESTs have been divided into four categories: Endometrial Stromal Nodules (ESNs), Low-Grade Endometrial Stromal Sarcomas (LG-ESSs), High-Grade Endometrial Stromal Sarcomas (HG-ESSs) and Undifferentiated Uterine Sarcomas (UUSs). ESNs are clinically benign. LG-ESSs are tumours of low malignant potential, often with indolent clinical behaviour, with some cases presented with a late recurrence after hysterectomy. HG-ESSs are tumours of high malignant potential with more aggressive clinical outcome. UUSs show high-grade morphological features with very aggressive clinical behavior. With the advent of molecular techniques, the morphological classification of ESTs can be integrated with molecular findings in enhanced classification of these tumours. In the future, the morphological and immunohistochemical features correlated with molecular categorisation of ESTs, will become a robust means to plan therapeutic decisions, especially in recurrences and metastatic disease. In this review, we summarise the morphological, immunohistochemical and molecular features of ESTs with particular reference to the most recent molecular findings.

ZC3H7B-BCOR high-grade endometrial stromal sarcoma may present as myoma nascens with cytoplasmic signet ring cell change.

We report on 51-year-old woman who presented with brown discharge and postcoital bleeding due to myoma nascens-like polypoid mass distending cervical canal. Histologically, the tumor consisted of high-grade spindle cell component with up to 15 mitotic figures per 10 HPF and also low-grade leiomyoma-like areas with focal myxoid change and so far undescribed cytoplasmic signet ring cell change. Immunohistochemically Desmin, actin, and h-caldesmon were negative. Conversely, BCOR positive expression was coupled with Cyclin D1 positivity and was antibody clone dependent. The molecular NGS and FISH study identified reciprocal fusion gene ZC3H7B-BCOR. In conclusion, these findings further support the idea of routine reflex molecular testing of uterine mesenchymal tumors with unusual clinical presentation or in case malignancy is suspected. Lastly, we suggest ZC3H7B-BCOR rearranged high-grade endometrial stromal sarcoma might be considered as a tumor suitable for BCL6-targeted treatment.

Ossifying fibromyxoid tumor: morphology, genetics, and differential diagnosis.

Ossifying fibromyxoid tumor (OFMT) is a soft tissue neoplasm of uncertain differentiation and intermediate (rarely metastasizing) biologic potential, with typical morphologic features, of an encapsulated, lobulated tumor comprising uniform polygonal cells within fibromyxoid stroma, which is surrounded by or contains metaplastic bone, classically as a peripheral rim of lamellar bone. Ossifying fibromyxoid tumor can arise at almost any site, although most frequently occurs within the extremities and trunk. Although most behave in a benign fashion, tumors can rarely show atypical or malignant features. It is now established that OFMTs represent translocation-associated tumors, with up to 85% associated with recurrent gene rearrangements, mostly involving the PHF1 gene (including in typical, atypical, and malignant neoplasms), with EP400-PHF1 in approximately 40% of tumors, and ZC3H7B-BCOR, MEAF6-PHF1, and EPC1-PHF1 fusions also described. Correct diagnosis is clinically important to ensure correct treatment and prognostication, both to avoid overdiagnosing OFMT as a malignant neoplasm such as osteosarcoma and also because of the propensity for aggressive behavior in a small number of OFMT. We review OFMT, with emphasis on the morphologic spectrum, recent molecular genetic findings, and the differential diagnosis.