PLAG1-Rearranged Uterine Sarcomas: A Study of 11 Cases Showing a Wide Phenotypical Spectrum Not Limited to Myxoid Leiomyosarcoma-like Morphology

IF 7.1 1区 医学 Q1 PATHOLOGY
Michael Michal , Abbas Agaimy , Sabrina Croce , Gunhild Mechtersheimer , John M. Gross , Deyin Xing , Debra A. Bell , Sounak Gupta , Elaheh Mosaieby , Petr Martínek , Natálie Klubíčková , Květoslava Michalová , Jiří Bouda , Jindřich Fínek , Tahyna Hernandez , Michal Michal , J. Kenneth Schoolmeester , Ondrej Ondič
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引用次数: 0

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.”

PLAG1重排子宫肉瘤:对 11 例病例的研究显示了广泛的表型谱,而不局限于肌样雷氏肉瘤样形态。
最近在一部分子宫肌样白肌瘤(M-LMS)中发现了 PLAG1 基因融合。然而,我们也发现了一些PLAG1基因重排的子宫肉瘤(PLAG1-US),它们缺乏M-LMS样形态和/或任何平滑肌标记物的表达。为了更好地描述这些病例的临床病理特征,我们进行了多机构检索,结果发现了 11 例病例。患者年龄在34-72岁之间(平均57岁)。所有肿瘤均发生在子宫体部,大小为 6.5-32 厘米(平均 15 厘米)。最常见的分期为 pT1b(6 例),3 例为 pT1(未明确分期),pT2a 和 pT3b 期各 1 例。大多数患者仅接受了子宫切除术和附件切除术。7 例患者接受了随访(范围:7-71 个月;中位数:39 个月)。3例患者(随访7-21个月)无疾病迹象。剩下的 4 例患者中有 3 例在 55-71 个月内死于疾病,最后一例出现腹膜扩散,在 39 个月时转院接受姑息治疗。从形态上看,肿瘤在瘤间和瘤内表现出高度异质性。M-LMS样和上皮样LMS样形态分别出现在3个和5个原发肿瘤中,其余肿瘤大多表现为非描述性卵圆形/纺锤形细胞肉瘤。异常形态学发现包括基质明显透明化(3 例)、脂肪细胞分化并伴有模仿肌样脂肪肉瘤的区域(2 例)、骨肉瘤样分化(1 例)和未分化的多形性肉瘤样区域(1 例)。有丝分裂活跃度为 3-24 个/10 个高倍视野(平均:9 个),3/10 个病例出现坏死。3/11的病例未发现SMA、h-caldesmon或desmin的表达,而5/5的病例表达了PLAG1。通过 RNA 测序,确定了以下融合伙伴:PUM1、CHCHD7(各 n=2)、C15orf29、CD44、MYOCD、FRMD6、PTK2 和 TRPS1(各 n=1)。一个病例仅通过 FISH 发现 PLAG1 基因断裂。我们的研究结果表明,PLAG1-US 的形态学范围比以前报道的要广得多,包括但不限于 M-LMS 样形态,偶尔伴有异源(尤其是脂肪细胞)分化。由于目前难以准确界定其分化线,我们建议暂时使用 PLAG1 重组子宫肉瘤这一描述性名称。
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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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