Department of Pathology.
Biomedical Center, Charles University Faculty of Medicine in Pilsen.
Am J Surg Pathol. 2018 Oct;42(10):1325-1333. doi: 10.1097/PAS.0000000000001109.
Three cases of superficial acral fibroblastic spindle cell neoplasms with EWSR1-SMAD3 fusion have been recently reported. Their differential diagnosis is broad, primarily comprising rare tumors from the fibroblastic/myofibroblastic category. The aim of this report is to present 4 new cases of this entity and to discuss the appropriate differential diagnosis. Also, as the ERG antibody seems to be a characteristic marker for these tumors, we analyzed ERG immunostaining characteristics in potential mimics of this entity. All cases in our cohort occurred in women aged 5 to 68 years (mean, 36.5 y). Two were located on the hand, 1 on foot, and the last case arose on the calf. The tumor size ranged from 1 to 1.5 cm in the greatest dimension, with a mean size of 1.2 cm. Except for one recent case, follow-up was available, ranging from 7 to 18 years (mean, 11.7 y), with a recurrence noted in 1 case after 10 years. All tumors were subcutaneous and showed 2 main components. One consisted of bland, spindled cells with elongated nuclei which were round when observed on the cross-section. These cells mostly grew in relatively hypercellular, well-organized, and intersecting fascicles. The second component was prominently hyalinized and paucicellular, but lacked calcifications. Both components showed either a distinct zonation pattern, or they were randomly intermingled with each other. In all 3 analyzable tumors, next-generation sequencing showed EWSR1-SMAD3 gene fusion in each case. By fluorescence in situ hybridization, one tested case also revealed unbalanced rearrangement of the EWSR1 gene. All 4 cases showed strong, diffuse nuclear expression of ERG, whereas none of the mimics stained with this antibody except for weak to moderate staining in calcifying aponeurotic fibromas (9/10 cases). Two tumors showed focal weak to moderate expression of SAT-B2. The 4 herein presented cases further broaden the clinicopathologic spectrum of tumors with EWSR1-SMAD3 gene fusion. They also confirm that they represent a novel entity for which we propose the name EWSR1-SMAD3-rearranged fibroblastic Tumor. Our study also proves that in the context of fibroblastic/myofibroblastic tumors, ERG immunohistochemistry is a relatively specific marker for these neoplasms.
最近报道了三例具有 EWSR1-SMAD3 融合的浅表肢端纤维母细胞性梭形细胞肿瘤。其鉴别诊断范围广泛，主要包括纤维母细胞/肌纤维母细胞来源的罕见肿瘤。本报告的目的是介绍该实体的 4 个新病例，并讨论适当的鉴别诊断。此外，由于 ERG 抗体似乎是这些肿瘤的特征性标志物，我们分析了该实体潜在模拟物的 ERG 免疫染色特征。我们队列中的所有病例均发生于年龄为 5 至 68 岁的女性（平均年龄 36.5 岁）。其中 2 例位于手部，1 例位于足部，最后 1 例发生于小腿。肿瘤最大径范围为 1 至 1.5cm，平均大小为 1.2cm。除了 1 例近期病例外，均获得随访，随访时间为 7 至 18 年（平均 11.7 年），1 例在 10 年后复发。所有肿瘤均位于皮下，表现出 2 种主要成分。一种由拉长的圆形细胞核组成，细胞核呈梭形，在横切面上观察时呈圆形。这些细胞主要在相对富含细胞、组织良好和交叉的束状结构中生长。第二种成分明显玻璃样变和细胞稀少，但缺乏钙化。这两种成分表现出明显的分带模式，或者彼此随机混合。在所有 3 例可分析的肿瘤中，下一代测序均显示每种肿瘤均存在 EWSR1-SMAD3 基因融合。通过荧光原位杂交，1 例检测病例还显示 EWSR1 基因的不平衡重排。所有 4 例病例均显示 ERG 的强弥漫性核表达，而除钙化性腱膜纤维瘤（10/10 例）有弱至中度染色外，无其他模拟物染色。2 例肿瘤显示 SAT-B2 局灶性弱至中度表达。本文报道的 4 例病例进一步拓宽了具有 EWSR1-SMAD3 基因融合的肿瘤的临床病理谱。它们还证实，它们代表一种新的实体，我们建议将其命名为 EWSR1-SMAD3 重排纤维母细胞瘤。我们的研究还证明，在纤维母细胞/肌纤维母细胞性肿瘤中，ERG 免疫组化是这些肿瘤的相对特异性标志物。
