Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL.
Department of Pathology and Laboratory Medicine, Massachusetts General Hospital, Harvard University, Boston, MA.
Hum Pathol. 2019 Aug;90:45-53. doi: 10.1016/j.humpath.2019.05.001. Epub 2019 May 9.
The classification of bone neoplasms composed of small round cells is experiencing a transformation after the discovery of various gene fusion rearrangements that determine diagnosis, behavior, and response to therapy. We present herein 4 new cases of small round cell tumor of the bone that harbor NFATc2 rearrangements involving either EWSR1 or FUS genes. We studied the clinical presentation, pathologic features, genetics (FISH, targeted RNA sequencing) and outcome in these 4 patients. We also reviewed the literature describing similar cases. All our patients were male. The median age at diagnosis was 33.5 years. All tumors presented in long bones of the extremities as a large destructive mass with a mean size of 12.5 cm. All cases were hypercellular with prominent collagenous stroma and consisted of small to medium size round cells arranged in cords, thin trabeculae, and pseudoacinar structures. Most cases showed focal or diffuse membrane staining for CD99; whereas S100, synaptophysin and chromogranin were negative. EMA showed cytoplasmic staining in one case. Genetic studies identified EWSR1-NFATc2 fusion in 3 cases, and FUS-NFATc2 fusion in one case. Two patients were treated with neoadjuvant chemotherapy using Ewing sarcoma regimens, and surgical excision was performed on 3 patients; necrosis was minimal. Follow-up is limited; after a median follow-up of 8.7 months, one patient developed local recurrence and metastases to the lungs. Poorly differentiated round cell sarcoma with EWSR1/FUS-NFATc2 fusions are uncommon. The tumors have consistent clinical findings, morphology, and immunoprofile that in combination are distinctive and differ from that of Ewing sarcoma. Importantly, these tumors do not respond to Ewing sarcoma chemotherapy regimens.
小圆形细胞肿瘤的分类在发现各种基因融合重排后正在发生转变，这些重排决定了诊断、行为和对治疗的反应。我们在此介绍了 4 例新的骨小圆细胞肿瘤病例，这些肿瘤存在涉及 EWSR1 或 FUS 基因的 NFATc2 重排。我们研究了这 4 例患者的临床表现、病理特征、遗传学（FISH、靶向 RNA 测序）和预后，并复习了描述类似病例的文献。所有患者均为男性，中位发病年龄为 33.5 岁。所有肿瘤均表现为四肢长骨的大破坏性肿块，平均大小为 12.5cm。所有肿瘤均为细胞丰富性，伴显著胶原性基质，由小至中等大小的圆形细胞排列成条索状、薄小梁状和假腺泡状结构。大多数病例显示 CD99 的局灶性或弥漫性膜染色；而 S100、突触素和嗜铬粒蛋白为阴性。EMA 在 1 例中显示细胞质染色。遗传学研究在 3 例中发现了 EWSR1-NFATc2 融合，在 1 例中发现了 FUS-NFATc2 融合。2 例患者采用尤文肉瘤方案进行新辅助化疗，3 例患者进行了手术切除；坏死程度轻微。随访时间有限；在中位随访 8.7 个月后，1 例患者出现局部复发和肺转移。低分化小圆细胞肉瘤伴 EWSR1/FUS-NFATc2 融合较为罕见。这些肿瘤具有一致的临床发现、形态学和免疫表型，联合起来具有独特性，与尤文肉瘤不同。重要的是，这些肿瘤对尤文肉瘤化疗方案没有反应。
