Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Genes Chromosomes Cancer. 2020 Oct;59(10):575-583. doi: 10.1002/gcc.22877. Epub 2020 Jul 6.
Gene fusions resulting in oncogenic activation of various receptor tyrosine kinases, including NTRK1-3, ALK, and RET, have been increasingly recognized in soft tissue tumors (STTs), displaying a wide morphologic spectrum and therefore diagnostically challenging. A subset of STT with NTRK1 rearrangements were recently defined as lipofibromatosis-like neural tumors (LPFNTs), being characterized by mildly atypical spindle cells with a highly infiltrative growth in the subcutis and expression of S100 and CD34 immunostains. Other emerging morphologic phenotypes associated with kinase fusions include infantile/adult fibrosarcoma and malignant peripheral nerve sheath tumor-like patterns. In this study, a large cohort of 73 STT positive for various kinase fusions, including 44 previously published cases, was investigated for the presence of an LPFNT phenotype, to better define the incidence of this distinctive morphologic pattern and its relationship with various gene fusions. Surprisingly, half (36/73) of STT with kinase fusions showed at least a focal LPFNT component defined as >10%. Most of the tumors occurred in the subcutaneous tissues of the extremities (n = 25) and trunk (n = 9) of children or young adults (<30 years old) of both genders. Two-thirds (24/36) of these cases showed hybrid morphologies with alternating LPFNT and solid areas of monomorphic spindle to ovoid tumor cells with fascicular or haphazard arrangement, while one-third (12/36) had pure LPFNT morphology. Other common histologic findings included lymphocytic infiltrates, staghorn-like vessels, and perivascular or stromal hyalinization, especially in hybrid cases. Mitotic activity was generally low (<4/10 high power fields in 81% cases), being increased only in a minority of cases. Immunoreactivity for CD34 (92% in hybrid cases, 89% in pure cases) and S100 (89% in hybrid cases, 64% in pure cases) were commonly present. The gene rearrangements most commonly involved NTRK1 (75%), followed by RET (8%) and less commonly NTRK2, NTRK3, ROS1, ALK, and MET.
基因融合导致各种受体酪氨酸激酶的致癌激活，包括 NTRK1-3、ALK 和 RET，已在软组织肿瘤（STT）中越来越多地被发现，具有广泛的形态学谱，因此具有诊断挑战性。最近，具有 NTRK1 重排的 STT 亚组被定义为脂肪纤维瘤样神经肿瘤（LPFNT），其特征为轻度非典型梭形细胞，在皮下组织中具有高度浸润性生长，并表达 S100 和 CD34 免疫标记物。与激酶融合相关的其他新兴形态表型包括婴儿/成人纤维肉瘤和恶性外周神经鞘瘤样模式。在这项研究中，对包括 44 例先前发表的病例在内的 73 例各种激酶融合阳性的 STT 进行了研究，以确定是否存在 LPFNT 表型，从而更好地定义这种独特形态模式的发生率及其与各种基因融合的关系。令人惊讶的是，一半（36/73）具有激酶融合的 STT 至少具有一个焦点 LPFNT 成分，定义为>10%。大多数肿瘤发生在四肢（n=25）和躯干（n=9）的儿童或年轻成年人（<30 岁）的皮下组织中，男女均有。这些病例中有三分之二（24/36）表现出混合形态，交替存在 LPFNT 和同质梭形至卵圆形肿瘤细胞的实性区域，具有束状或随意排列，而三分之一（12/36）具有纯 LPFNT 形态。其他常见的组织学发现包括淋巴细胞浸润、鹿角状血管、血管周围或基质玻璃样变性，特别是在混合病例中。有丝分裂活性通常较低（<81%病例中每 10 个高倍视野<4 个），仅在少数病例中增加。CD34 免疫反应性（混合病例中 92%，纯病例中 89%）和 S100 免疫反应性（混合病例中 89%，纯病例中 64%）通常存在。最常见涉及的基因重排是 NTRK1（75%），其次是 RET（8%），较少涉及 NTRK2、NTRK3、ROS1、ALK 和 MET。
