Antonescu Cristina R, Kao Yu-Chien, Xu Bin, Fujisawa Yumi, Chung Catherine, Fletcher Christopher D M, Graf Nicole, Suurmeijer Albert J, Zin Angelica, Wexler Leonard H, Ferrari Andrea, Bisogno Gianni, Alaggio Rita
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, ROC.
Mod Pathol. 2020 Sep;33(9):1669-1677. doi: 10.1038/s41379-020-0557-5. Epub 2020 May 5.
Until recently, undifferentiated round cell sarcomas (URCS) in infants have been considered a wastebasket diagnosis, composed of various pathologic entities and lacking consistent genetic alterations. The recent identification of recurrent BCOR internal tandem duplications (ITD) and less common alternative YWHAE-NUTM2B/E fusions in half of infantile URCS and the majority of so-called primitive myxoid mesenchymal tumors of infancy (PMMTI) suggests a common pathogenesis with clear cell sarcoma of the kidney which also harbors the same genetic alterations. These tumors also share a similar morphology and immunoprofile, including positivity for BCOR, cyclin D1, and SATB2. In this study, we investigate the largest cohort to date of genetically confirmed URCS and PMMTI with BCOR ITD or YWHAE fusions to better define their morphologic spectrum and clinical behavior. Twenty-eight cases harbored BCOR ITD and five YWHAE fusions, occurring in 29 infants and 4 children, 19 males and 14 females. Microscopically, 20 were classified as URCS and 13 as PMMTI. Follow-up was available in 25 patients, with 14 (56%) succumbing to their diseases at a mean duration of 18-months follow-up (range: 2-62). Six patients remained with no evidence of disease at a mean follow-up of 63 months (range: 4-192), four patients were still alive with disease (mean follow-up: 46 months, range: 4-120), and one died of other causes. Local recurrence and distant metastasis were each observed in 11/25 (44%) of the patients. The overall survival was 42% at 3 years and 34% at 5 years (median survival: 26 months). There was no statistically significant survival difference between cases diagnosed as URCS and PMMTI and between those with BCOR ITD and YWHAE fusions.
直到最近，婴儿未分化圆形细胞肉瘤（URCS）一直被视为一种“垃圾桶诊断”，它由各种病理实体组成，且缺乏一致的基因改变。最近在半数婴儿URCS和大多数所谓的婴儿原始黏液样间叶肿瘤（PMMTI）中发现了复发性BCOR内部串联重复（ITD）以及较少见的YWHAE-NUTM2B/E融合，这提示其与同样存在相同基因改变的肾透明细胞肉瘤有共同的发病机制。这些肿瘤还具有相似的形态学和免疫表型，包括BCOR、细胞周期蛋白D1和SATB2呈阳性。在本研究中，我们调查了迄今为止最大的一组经基因确认的伴有BCOR ITD或YWHAE融合的URCS和PMMTI队列，以更好地界定其形态学谱和临床行为。28例存在BCOR ITD，5例存在YWHAE融合，发生于29例婴儿和4例儿童，其中男性19例，女性14例。显微镜下，20例被分类为URCS，13例为PMMTI。25例患者有随访资料，14例（56%）在平均18个月的随访期内（范围：2 - 62个月）因病死亡。6例患者在平均63个月的随访期内（范围：4 - 192个月）无疾病证据，4例患者仍患有疾病存活（平均随访：46个月，范围：4 - 120个月），1例死于其他原因。25例患者中有11例（44%）出现局部复发和远处转移。3年总生存率为42%，5年为34%（中位生存期：26个月）。诊断为URCS和PMMTI的病例之间以及存在BCOR ITD和YWHAE融合的病例之间，生存率无统计学显著差异。
