骨和软组织未分化圆形细胞肉瘤的临床病理特征：试图阐明 CK（+）肉瘤。
Clinicopathologic features of undifferentiated round cell sarcomas of bone & soft tissues: An attempt to unravel the & -positive sarcomas.
机构信息
Department of Surgical Pathology, Tata Memorial Hospital; Division of Molecular Pathology & Translational Medicine, Tata Memorial Hospital, Homi Bhabha National Institute (Deemed to be University), Mumbai, Maharashtra, India.
Department of Surgical Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India.
出版信息
Indian J Med Res. 2019 Dec;150(6):557-574. doi: 10.4103/ijmr.IJMR_2144_18.
BACKGROUND & OBJECTIVES: Certain genetically defined undifferentiated round cell sarcomas, namely BCOR-CCNB3 and CIC-DUX4 positive, have been described. Here we present detailed clinicopathologic features and molecular results in such cases.
METHODS
Fifty one cases of undifferentiated round cell sarcomas, including 32 cases, tested for BCOR-CCNB3 and CIC-DUX4 fusions, by reverse transcription polymerase chain reaction technique and 44 tumours, for CCNB3 immunostaining, were analyzed.
RESULTS
Twenty seven (52.9%) tumours occurred in males and 24 (47%) in females; in soft tissues (38; 74.5%), commonly, trunk and extremities and bones (13; 25.4%), frequently, femur and tibia. Five of 32 (15.6%) tested cases were positive for BCOR-CCNB3 fusion and seven (21.8%) for CIC-DUX4 fusions. Histopathologically, CIC-DUX4-positive sarcomas comprised nodular aggregates of round to polygonal cells, containing hyperchromatic nuclei, prominent nucleoli and moderate cytoplasm, with focal myxoid stroma and variable necrosis, in certain cases. BCOR-CCNB3- positive sarcomas mostly comprised diffusely arranged, round to oval to short spindly cells with angulated nuclei, vesicular chromatin, inconspicuous nucleoli and interspersed vessels. Immunohistochemically, tumour cells were positive for MIC2 in 24 of 49 (48.9%) and CCNB3 in 12 of 44 (27.2%) cases. Four of five BCOR-CCNB3-positive sarcomas showed CCNB3 immunostaining and 6 of 7 CIC-DUX4-positive sarcomas displayed WT1 immunostaining. Most patients (27/37) (72.9%) underwent surgical resection and chemotherapy. Median overall survival was 12 months, and disease-free survival was seven months.
INTERPRETATION & CONCLUSIONS: Undifferentiated round cell sarcomas are rare; mostly occur in soft tissues of extremities, with CIC-DUX4 positive, as these are relatively more frequent than BCOR-CCNB3 positive sarcomas. CCNB3 and WT1 are useful immunostains for triaging such cases for BCOR-CCNB3 and CIC-DUX4 fusion testing, respectively. Overall, these are relatively aggressive tumours, especially CIC-DUX4-positive sarcomas.
背景与目的
某些具有特定遗传定义的未分化圆形细胞肉瘤，如 BCOR-CCNB3 和 CIC-DUX4 阳性肉瘤，已有相关描述。本文主要介绍这些病例的详细临床病理特征和分子结果。
方法
对 32 例经逆转录聚合酶链反应技术检测为 BCOR-CCNB3 和 CIC-DUX4 融合阳性的未分化圆形细胞肉瘤和 44 例进行 CCNB3 免疫染色的肿瘤病例进行分析。
结果
27 例（52.9%）肿瘤发生在男性，24 例（47%）发生在女性；38 例（74.5%）发生在软组织，常见于躯干和四肢，13 例（25.4%）发生在骨骼，常见于股骨和胫骨。32 例检测病例中有 5 例（15.6%）为 BCOR-CCNB3 融合阳性，7 例（21.8%）为 CIC-DUX4 融合阳性。组织病理学上，CIC-DUX4 阳性肉瘤由圆形到多边形细胞的结节状聚集组成，含有深染核、明显核仁及中等量细胞质，伴有局灶性黏液样基质和不同程度的坏死，某些病例可见。BCOR-CCNB3 阳性肉瘤主要由弥漫排列的圆形到椭圆形至短梭形细胞组成，具有成角核、泡状染色质、不明显核仁及穿插的血管。免疫组织化学染色显示，24 例（48.9%）中肿瘤细胞 MIC2 阳性，12 例（27.2%）中 CCNB3 阳性。5 例 BCOR-CCNB3 阳性肉瘤中有 4 例 CCNB3 免疫染色阳性，7 例 CIC-DUX4 阳性肉瘤中有 6 例 WT1 免疫染色阳性。大多数患者（27/37）（72.9%）接受了手术切除和化疗。中位总生存期为 12 个月，无病生存期为 7 个月。
结论与解释
未分化圆形细胞肉瘤较为罕见；多发生于四肢软组织，以 CIC-DUX4 阳性为主，较 BCOR-CCNB3 阳性肉瘤更为常见。CCNB3 和 WT1 是用于筛选此类病例进行 BCOR-CCNB3 和 CIC-DUX4 融合检测的有用免疫标记物。总体而言，这些肿瘤是相对侵袭性的，尤其是 CIC-DUX4 阳性肉瘤。
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