TFE3重排的头颈部肿瘤:22 例病例横跨肺泡软组织肉瘤和 PEComa 之间的形态连续性,突显基因型多样性。

IF 4.5 1区 医学 Q1 PATHOLOGY
Abbas Agaimy, Michael Michal, Ali Abdelsatir, Azza A Abdelsatir, Sawsan Abdulrahim, Jan Laco, Stephan Ihrler, Lars Tögel, Robert Stoehr, Justin A Bishop, Nasir Ud Din, Michal Michal
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引用次数: 0

摘要

TFE3重排是组织遗传学、地形学和生物学上多种肿瘤的特征。TFE3 融合除了是肺泡软组织肉瘤(ASPS)和肺透明细胞间质瘤的普遍定义特征外,在肾细胞癌、血管周上皮样细胞瘤(PEComa)、上皮样血管内皮瘤和骨化性纤维瘤中也有报道。TFE3相关肿瘤在头颈部罕见,可能会给诊断带来挑战。我们在此描述了 22 例 TFE3 融合性肿瘤,11 男 11 女,年龄从 4 岁到 79 岁(中位 25 岁),涉及头颈部不同部位:鼻窦腔(8 例)、舌(4 例)、口腔/咽部(3 例)、唾液腺(2 例)、眼眶(2 例)、软组织或未指明部位(3 例)。根据形态学和髓母细胞免疫表型,10 例为 ASPS,7 例为 PEComa(3 例黑色素瘤,均为鼻窦瘤),5 例为 ASPS 和 PEComa 的中间(不确定)组织学重叠。所有病例的TFE3免疫组化均呈均匀的强阳性。在16例成功检测的病例中,14例(88%)的靶向RNA测序/FISH检测证实了TFE3融合。ASPSCR1是ASPS中最常见的融合伙伴(5例中有4例);1例ASPS有罕见的VCP::TFE3融合。6 例成功检测的 PEComas 有肾细胞癌和 PEComas 中已知的融合伙伴(NONO、PRCC、SFPQ 和 PSPC1)。不确定的肿瘤分别有ASPSCR1::TFE3(n = 2)和U2AF2::TFE3(n = 1)融合。这一专门研究 TFE3 阳性头颈部肿瘤的大型系列研究表明,最近提出的 TFE3 相关间叶肿瘤的形态学重叠谱系。虽然所有的 PEComas 都是鼻窦肿瘤,但 ASPS 却从来不是鼻窦肿瘤,而且发生在头颈部的不同部位,并偏爱舌部。不定型(PEComa-like)类别在分子上与 ASPS 更为相似,但与典型的 ASPS 相比,在年龄、性别和解剖分布上都有所不同。我们报告 VCP 是 ASPS 的新型融合伙伴,而 PSPC1 则是 PEComa 的新型 TFE3 融合伙伴(在一个 PEComa 中检测到)。未来的研究将揭示这些高度重叠的肿瘤最合适的术语亚型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TFE3-rearranged Head and Neck Neoplasms: Twenty-two Cases Spanning the Morphologic Continuum Between Alveolar Soft Part Sarcoma and PEComa and Highlighting Genotypic Diversity.

TFE3 rearrangements characterize histogenetically, topographically, and biologically diverse neoplasms. Besides being a universal defining feature in alveolar soft part sarcoma (ASPS) and clear cell stromal tumor of the lung, TFE3 fusions have been reported in subsets of renal cell carcinoma, perivascular epithelioid cell tumor (PEComa), epithelioid hemangioendothelioma and ossifying fibromyxoid tumors. TFE3-related neoplasms are rare in the head and neck and may pose diagnostic challenges. We herein describe 22 TFE3 fusion neoplasms affecting 11 males and 11 females aged 4 to 79 years (median, 25) and involving different head and neck sites: sinonasal cavities (n = 8), tongue (n = 4), oral cavity/oropharynx (n = 3), salivary glands (n = 2), orbit (n = 2), and soft tissue or unspecified sites (n = 3). Based on morphology and myomelanocytic immunophenotype, 10 tumors qualified as ASPS, 7 as PEComas (3 melanotic; all sinonasal), and 5 showed intermediate (indeterminate) histology overlapping with ASPS and PEComa. Immunohistochemistry for TFE3 was homogeneously strongly positive in all cases. Targeted RNA sequencing/FISH testing confirmed TFE3 fusions in 14 of 16 successfully tested cases (88%). ASPSCR1 was the most frequent fusion partner in ASPS (4 of 5 cases); one ASPS had a rare VCP::TFE3 fusion. The 6 successfully tested PEComas had known fusion partners as reported in renal cell carcinoma and PEComas (NONO, PRCC, SFPQ, and PSPC1). The indeterminate tumors harbored ASPSCR1::TFE3 (n = 2) and U2AF2::TFE3 (n = 1) fusions, respectively. This large series devoted to TFE3-positive head and neck tumors illustrates the recently proposed morphologic overlap in the spectrum of TFE3-associated mesenchymal neoplasms. While all PEComas were sinonasal, ASPS was never sinonasal and occurred in diverse head and neck sites with a predilection for the tongue. The indeterminate (PEComa-like) category is molecularly more akin to ASPS but shows different age, sex, and anatomic distribution compared with classic ASPS. We report VCP as a novel fusion partner in ASPS and PSPC1 as a novel TFE3 fusion partner in PEComa (detected in one PEComa). Future studies should shed light on the most appropriate terminological subtyping of these highly overlapping tumors.

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来源期刊
CiteScore
10.30
自引率
5.40%
发文量
295
审稿时长
1 months
期刊介绍: The American Journal of Surgical Pathology has achieved worldwide recognition for its outstanding coverage of the state of the art in human surgical pathology. In each monthly issue, experts present original articles, review articles, detailed case reports, and special features, enhanced by superb illustrations. Coverage encompasses technical methods, diagnostic aids, and frozen-section diagnosis, in addition to detailed pathologic studies of a wide range of disease entities. Official Journal of The Arthur Purdy Stout Society of Surgical Pathologists and The Gastrointestinal Pathology Society.
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