带有EWSR1::PATZ1的软组织肉瘤是最近公认的具有可变形态和异质性免疫组织化学特征的实体。我们研究了17个这样的肿瘤。肿瘤发生在12名男性和5名女性(中位年龄50岁,范围15-71岁),胸腹软组织受累(14例,82%),下肢(2例;12%)和舌头(1例;6%),范围为0.7-11.3厘米(中位数:4.7厘米)。除一名患者外,所有患者均接受了完整的手术切除;7例还接受了新辅助化学/放射疗法治疗。所有病例均显示EWSR1::PATZ1肉瘤的典型特征,包括均匀的圆形到纺锤状的细胞,纤维粘液样基质,纤维带,透明血管,和假肺泡/微囊空间。不寻常的特征,在一个子集的案例中看到,包括出现退行性核异型,上皮样细胞形态学,成熟脂肪,丰富的横纹肌母细胞,高有丝分裂活性,细胞性和核异型性增加的病灶。免疫组化阳性结果为:desmin(16/17,94%),MyoD1(13/14,93%),肌原蛋白(6/14,43%),GFAP(10/10,100%),S100蛋白(15/17,88%),SOX10(7/13,46%),角蛋白(10/17,59%),CD99(4/11,36%),H3K27me3(保留表达9/9,100%),p16(无表达;1/4,25%)和p53(野生型3/3,100%)。融合事件包括EWSR1外显子8::PATZ1外显子1(14/17,82%),EWSR1外显子9::PATZ1外显子1(2/17,12%)和EWSR1外显子7::PATZ1外显子1(1/17,6%)。没有评估的肿瘤具有CDKN2A/B和/或TP53或MDM2扩增的改变。临床随访(16例患者:中位数,13.5个月;范围:1-77个月)显示1例患者发生远处转移(出现时转移),无局部复发。在最后的随访中,14例患者无病,1患有疾病,1人死于疾病(13个月时),1个有不确定的肺结节。我们得出的结论是,EWSR1::PATZ1的形态谱比以前认识到的要宽。虽然需要更多的长期随访,这些非常罕见的肉瘤的预后可能比以前报道的更有利。
Soft tissue sarcomas harboring EWSR1::PATZ1 are a recently recognized entity with variable morphology and a heterogeneous immunohistochemical profile. We studied 17 such tumors. The tumors occurred in 12 men and 5 women (median age, 50 years; range, 15-71 years), involved the thoracoabdominal soft tissues (14 cases; 82%), lower extremities (2 cases; 12%), and tongue (1 case; 6%), and ranged from 0.7 to 11.3 cm (median, 4.7 cm). All but 1 patient received complete surgical resection; 7 were also treated with neoadjuvant chemo/radiotherapy. All cases showed typical features of EWSR1::PATZ1 sarcoma, including uniform round to spindled cells, fibromyxoid matrix, fibrous bands, hyalinized vessels, and pseudoalveolar/microcystic spaces. Unusual features, seen in a subset of cases, included degenerative-appearing nuclear atypia, epithelioid cytomorphology, mature fat, abundant rhabdomyoblasts, high mitotic activity, and foci with increased cellularity and nuclear atypia. Positive immunohistochemical results were desmin (16/17, 94%), MyoD1 (13/14, 93%), myogenin (6/14, 43%), GFAP (10/10, 100%), S100 protein (15/17, 88%), SOX10 (7/13, 54%), keratin (10/17, 59%), CD99 (4/11, 36%), H3K27me3 (retained expression 9/9, 100%), p16 (absent expression 1/4, 25%), and p53 (wild type 3/3, 100%). Fusion events included EWSR1 exon 8::PATZ1 exon 1 (14/17, 82%), EWSR1 exon 9::PATZ1 exon 1 (2/17, 12%), and EWSR1 exon 7::PATZ1 exon 1 (1/17, 6%). No evaluated tumor had alterations of CDKN2A/B and/or TP53, or MDM2 amplification. Clinical follow-up (16 patients: median, 13.5 months; range, 1-77 months) showed distant metastases in 3 patients (1/3 at time of presentation) and no local recurrences. At the time of last follow-up, 14 patients were disease free, 1 was alive with disease, 1 was dead of disease (at 13 months), and 1 had an indeterminant pulmonary nodule. We conclude that the morphologic spectrum of EWSR1::PATZ1 is broader than has been previously appreciated. Although more long-term follow-up is needed, the prognosis of these very rare sarcomas may be more favorable than previously reported.