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Alveolar Soft Part Sarcoma of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Cytogenetic Study of 10 Cases With Emphasis on its Distinction From Morphologic Mimics.

女性生殖道的腺泡状软组织肉瘤:10例病例的形态学、免疫组织化学和分子遗传学研究及与其具有相似组织学形态肿瘤的鉴别诊断。

Schoolmeester JK,Carlson J,Keeney GL,Fritchie KJ,Oliva E,Young RH,Nucci MR

Abstract

Alveolar soft part sarcoma (ASPS) is a morphologically distinctive neoplasm of unknown differentiation that bears a characteristic gene fusion involving ASPSCR1 and TFE3. ASPS can occur in the female genital tract, but is rare. Eleven cases with an initial diagnosis of ASPS at female genital tract sites were evaluated for their morphologic features and immunoprofile using a panel of antibodies (TFE3, HMB45, melan-A, smooth muscle actin, desmin, and h-Caldesmon). In addition, the presence of TFE3 rearrangement and subsequent ASPSCR1-TFE3 fusion were determined by fluorescence in situ hybridization. Ten tumors retained their classification as ASPS based on their morphologic appearance, immunohistochemical profile, and demonstration of ASPSCR1-TFE3 fusion. The remaining case was reclassified as conventional-type PEComa due to its pattern of HMB45, melan-A, and desmin positivity as well as absence of TFE3 rearrangement. Sites of the 10 ASPS were uterine corpus (3), cervix (2), uterus not further specified (2), vagina (2), and vulva (1). The age of the patients ranged from 15 to 68 years (mean 34 y, median 32 y). The tumors demonstrated a spectrum of morphologic features, but all had a consistent immunophenotype of strong TFE3 nuclear expression and lack of muscle (smooth muscle actin, desmin, h-Caldesmon) and melanocytic (melan-A, HMB45) markers, except focal positivity for HMB45 in 1. Follow-up was available for 4 patients ranging from 1 to 35 months (mean 15 mo, median 25 mo) and they were alive and had no evidence of recurrence or metastasis at last follow-up. Distinguishing ASPS from its morphologic mimics, particularly PEComa, is important due to increasingly efficacious targeted agents such as MET-selective and VEGF signaling inhibitors in the former and mTOR inhibition therapy in the latter.

摘要

腺泡状软组织肉瘤(ASPS)是一种起源未知、具有独特形态学特征的肿瘤,具有ASPSCR1和TFE3的特征性融合基因。 ASPS可发生在女性生殖道,但很罕见。本文对11例原诊断为女性生殖道部位的ASPS形态学特征进行总结研究,并使用一组抗体(TFE3、HMB45、melan-A、SMA、desmin和h-Caldesmon)评估其免疫表型。此外,通过荧光原位杂交检测TFE3重排和ASPSCR1-TFE3融合基因。根据其形态学、免疫组织化学表型和ASPSCR1-TFE3融合的表达,10例肿瘤诊断仍为ASPS。剩余1例由于其表达HMB45、melan-A和desmin并且缺乏TFE3重排,被重新分类为传统型PEComa。 10例ASPS的部位分别为为子宫体(3)、宫颈(2)、子宫未进一步明确(2)、阴道(2)和外阴(1)。患者年龄15〜68岁(平均34岁,中位年龄32岁)。肿瘤表现出一系列形态学特征,但均具有强TFE3核表达,肌标记(SMA,desmin,h-Caldesmon)和黑素细胞标记(melan-A,HMB45)阴性,1例局部表达HMB45。4例患者随访1〜35个月(平均15个月,中位25个月),并且在最后一次随访中都存活,没有复发或转移。区分ASPS与其形态学相似的肿瘤、特别是PEComa非常重要,因为前者可使用MET选择性靶向药和VEGF信号传导抑制剂,后者可使用mTOR抑制剂治疗。


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