Abstract：
PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine sarcomas lacking M-LMS-like morphology and/or any expression of smooth muscle markers. To better characterize their clinicopathologic features, we performed a multiinstitutional search that yielded 11 cases. The patients ranged in age from 34 to 72 years (mean, 57 years). All tumors arose in the uterine corpus, ranging in size from 6.5 to 32 cm (mean, 15 cm). The most common stage at presentation was pT1b (n = 6), and 3 cases had stage pT1 (unspecified), and 1 case each presented in stages pT2a and pT3b. Most were treated only with hysterectomy and adnexectomy. The follow-up (range, 7-71 months; median, 39 months) was available for 7 patients. Three cases (7-21 months of follow-up) had no evidence of disease. Three of the 4 remaining patients died of disease within 55 to 71 months, while peritoneal spread developed in the last patient, and the patient was transferred for palliative care at 39 months. Morphologically, the tumors showed a high intertumoral and intratumoral heterogeneity. M-LMS-like and epithelioid leiomyosarcoma-like morphology were present in 3 and 5 primary tumors, respectively, the remaining mostly presented as nondescript ovoid or spindle cell sarcomas. Unusual morphologic findings included prominently hyalinized stroma (n = 3), adipocytic differentiation with areas mimicking myxoid liposarcoma (n = 2), osteosarcomatous differentiation (n = 1), and undifferentiated pleomorphic sarcoma-like areas (n = 1). The mitotic activity ranged from 3 to 24 mitoses per 10 high-power fields (mean, 9); 3 of 10 cases showed necrosis. In 3 of 11 cases, no expression of smooth muscle actin, h-caldesmon, or desmin was noted, whereas 5 of 5 cases expressed PLAG1. By RNA sequencing, the following fusion partners were identified: PUM1, CHCHD7 (each n = 2), C15orf29, CD44, MYOCD, FRMD6, PTK2, and TRPS1 (each n = 1). One case only showed PLAG1 gene break by fluorescence in situ hybridization. Our study documents a much broader morphologic spectrum of PLAG1-rearranged uterine sarcomas than previously reported, encompassing but not limited to M-LMS-like morphology with occasional heterologous (particularly adipocytic) differentiation. As it is currently difficult to precisely define their line of differentiation, for the time being, we suggest using a descriptive name \"PLAG1-rearranged uterine sarcoma.\"
摘要：
最近在子宫粘液样平滑肌肉瘤（M-LMS）的一部分中发现了PLAG1基因融合。然而,我们曾遇到PLAG1重排子宫肉瘤(PLAG1-US)缺乏M-LMS样形态和/或任何平滑肌标志物表达的病例.为了更好地描述他们的临床病理特征，我们进行了多机构检索,共11例.患者的年龄范围为34-72岁（平均：57）。所有肿瘤都出现在子宫体，大小从6.5-32厘米（平均：15）。最常见的表现阶段是pT1b（n=6），3例pT1期（未指明），1例pT2a和pT3b期各出现。大多数仅通过子宫切除术和附件切除术治疗。对7例患者进行了随访（范围：7-71个月；中位数：39个月）。3例（随访7-21个月）没有疾病证据。剩下的4名患者中有3名在55-71个月内死于疾病，而最后一次发生腹膜扩散，并在39个月时接受姑息治疗。形态学上,肿瘤表现出高度的瘤间和瘤内异质性.在3和5个原发肿瘤中存在M-LMS样和上皮样LMS样形态，分别,其余大部分表现为非描述性卵圆形/梭形细胞肉瘤。异常的形态学发现包括明显透明的基质（n=3），脂肪细胞分化与类似黏液样脂肪肉瘤的区域（n=2），骨肉瘤分化（n=1）和未分化的多形性肉瘤样区域（n=1）。有丝分裂活性范围为3-24个有丝分裂/10个高倍场（平均值：9），3/10例出现坏死。在3/11案例中，无SMA表达,注意到h-caldesmon或desmin，5/5例表达PLAG1。通过RNA测序，确定了以下融合伙伴：PUM1，CHCHD7（每个n=2），C15orf29,CD44,MYOCD,FRMD6、PTK2和TRPS1(各n=1)。1例仅FISH显示PLAG1基因断裂。我们的研究记录了比以前报道的PLAG1-US更广泛的形态学光谱，包括但不限于M-LMS样形态,偶尔具有异源(特别是脂肪细胞)分化。由于目前很难准确定义它们的差异化路线，暂时,我们建议使用PLAG1重排子宫肉瘤的描述性名称.
