Department of Pathology, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic.
Department of Pathology and Molecular Genetics, Bioptical Laboratory, Ltd., Plzen, Czech Republic.
Mod Pathol. 2021 Apr;34(4):770-785. doi: 10.1038/s41379-020-00684-8. Epub 2020 Oct 4.
The knowledge of clinical features and, particularly, histopathological spectrum of EWSR1-PATZ1-rearranged spindle and round cell sarcomas (EPS) remains limited. For this reason, we report the largest clinicopathological study of EPS to date. Nine cases were collected, consisting of four males and five females ranging in age from 10 to 81 years (average: 49 years). Five tumors occurred in abdominal wall soft tissues, three in the thorax, and one in the back of the neck. Tumor sizes ranged from 2.5 to 18 cm (average 6.6 cm). Five patients had follow-up with an average of 38 months (range: 18-60 months). Two patients had no recurrence or metastasis 19 months after diagnosis. Four patients developed multifocal pleural or pulmonary metastasis and were treated variably by surgery, radiotherapy, and chemotherapy. The latter seemed to have little to no clinical benefit. One of the four patients was free of disease 60 months after diagnosis, two patients were alive with disease at 18 and 60 months, respectively. Morphologically, low, intermediate, and high-grade sarcomas composed of a variable mixture of spindled, ovoid, epithelioid, and round cells were seen. The architectural and stromal features also varied, resulting in a broad morphologic spectrum. Immunohistochemically, the following markers were most consistently expressed: S100-protein (7/9 cases), GFAP (7/8), MyoD1 (8/9), Pax-7 (4/5), desmin (7/9), and AE1/3 (4/9). By next-generation sequencing, all cases revealed EWSR1-PATZ1 gene fusion. In addition, 3/6 cases tested harbored CDKN2A deletion, while CDKN2B deletion and TP53 mutation were detected in one case each. Our findings confirm that EPS is a clinicopathologic entity, albeit with a broad morphologic spectrum. The uneventful outcome in some of our cases indicates that a subset of EPS might follow a more indolent clinical course than previously appreciated. Additional studies are needed to validate whether any morphological and/or molecular attributes have a prognostic impact.
EWSR1-PATZ1 重排梭形和圆形细胞肉瘤（EPS）的临床特征，尤其是组织病理学谱，仍然有限。因此，我们报告了迄今为止最大的 EPS 临床病理研究。共收集了 9 例病例，包括 4 名男性和 5 名女性，年龄 10 至 81 岁（平均年龄 49 岁）。5 例肿瘤发生于腹壁软组织，3 例发生于胸腔，1 例发生于颈后。肿瘤大小 2.5 至 18cm（平均 6.6cm）。5 例患者获得随访，平均随访时间 38 个月（范围 18-60 个月）。2 例患者在诊断后 19 个月无复发或转移。4 例患者发生多发性胸膜或肺转移，分别接受手术、放疗和化疗治疗，后者似乎没有临床获益。4 例患者中有 1 例在诊断后 60 个月时无疾病，2 例患者在 18 个月和 60 个月时仍有疾病，分别存活。形态上，低、中、高级别肉瘤由梭形、卵圆形、上皮样和圆形细胞的可变混合组成。结构和基质特征也不同，导致形态学谱广泛。免疫组化染色结果显示，以下标记物表达最为一致：S100 蛋白（9 例中的 7 例）、GFAP（8 例中的 7 例）、MyoD1（9 例中的 8 例）、Pax-7（5 例中的 4 例）、结蛋白（9 例中的 7 例）和 AE1/3（9 例中的 4 例）。通过下一代测序，所有病例均显示 EWSR1-PATZ1 基因融合。此外，3/6 例检测到 CDKN2A 缺失，1 例检测到 CDKN2B 缺失和 TP53 突变。我们的研究结果证实，EPS 是一种临床病理实体，尽管形态学谱广泛。我们部分病例的良好结局表明，与之前认为的相比，某些 EPS 可能具有更惰性的临床病程。需要进一步的研究来验证任何形态学和/或分子特征是否具有预后影响。
