ZC3H7A/B::BCOR fusion fibromyxoid sarcoma of soft tissue: an emerging aggressive sarcoma overlapping with malignant ossifying fibromyxoid tumors

TL;DR

A rare and aggressive soft tissue sarcoma linked to ZC3H7A/B::BCOR gene fusions is described, with poor patient outcomes and overlapping features with other bone-related tumors.

Contribution

The paper expands the clinicopathological profile of ZC3H7A/B::BCOR fusion sarcomas in soft tissue and highlights their aggressive behavior.

Findings

Seven soft tissue tumors with ZC3H7A/B::BCOR fusions showed varied histology and aggressive clinical outcomes.

Most tumors lacked ossification and were immunoreactive for S100, cyclin D1, and SATB2.

Three of four followed patients died of disease, indicating poor prognosis.

Abstract

BCOR-rearranged sarcomas constitute ultra-rare tumors. Among these, ZC3H7A/B::BCOR sarcomas are less common and are primarily reported as a subset of high-grade endometrial stromal sarcomas, as well as in the spectrum of malignant ossifying fibromyxoid tumors (OFMTs). Herein, we present the clinicopathological, immunohistochemical, and molecular profiles of seven soft tissue tumors exhibiting ZC3H7A/B::BCOR fusions. The patient’s age ranged from 13 to 65 years (median = 38). Locations were neck (2) and one case each in the paraspinal region, scalp, gluteal region, chest wall, and thigh. Histologically, the tumors were composed of round to polygonal or spindle-shaped cells with a variable amount of fibromyxoid stroma, lacking bone shell or ossification, leading to a range of initial differential diagnoses. Immunohistochemically, the tumor cells were positive for S100 (5/6), cyclin D1 (2/3), SATB2 (2/3), BCOR (2/4), and TLE1 (1/3) while negative for MUC4 (0/6), keratin (0/5), EMA (0/4), desmin (0/6), CD34 (0/6), SMA (0/5), SOX10 (0/5), and melanoma cocktail (0/2). Targeted RNA sequencing revealed ZC3H7B::BCOR fusions in six tumors (four with ZC3H7Bex10::BCORex6 and one each ZC3H7Bex12::BCORex7 and ZC3H7Bex12::BCORex6). One tumor revealed a ZC3H7Aex10::BCORex6 fusion. All seven tumors were resected, mostly with clear margins (5/7), including two patients who received adjuvant therapy. Three of four patients with available follow-up (mean = 45 months) died of disease, while one patient was alive with multiple bone metastases. This series comprises seven additional ZC3H7A/B::BCOR soft tissue sarcomas associated with aggressive clinical outcomes. Whether this aggressive sarcoma represents a molecular subtype of malignant OFMT or a genetic variant of BCOR-rearranged sarcomas remains to be further verified.

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