Al-Ibraheemi Alyaa, Zhou Yan, Rullo Emma, Alaggio Rita
Department of Pathology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55455, USA.
Virchows Arch. 2025 Jan;486(1):127-141. doi: 10.1007/s00428-024-03964-9. Epub 2024 Nov 5.
Fibroblastic and myofibroblastic neoplasms represent about 12% of pediatric soft tissue tumors. Most of these neoplasms in children are either benign or locally aggressive with rare metastasis, while malignant cases are uncommon. Diagnosing these tumors is challenging due to overlapping morphologies and the limited utility of immunohistochemistry. Advances in molecular techniques, especially RNA sequencing, have improved our understanding of the molecular drivers of these tumors, leading to better classification. Key molecular alterations, such as RTK and MAPK activation, are central in the development of tumors like infantile fibrosarcoma (IFS) and inflammatory myofibroblastic tumors (IMT). The identification of alternative fusions in IFS and IMT underscores the importance of an integrated diagnostic approach. Furthermore, new RTK-driven lesions, now included in the WHO's "NTRK-rearranged mesenchymal neoplasms", have been identified. This review provides an update on recent findings in RTK-driven myofibroblastic tumors and highlights novel entities still in need of classification.
纤维母细胞性和肌纤维母细胞性肿瘤约占儿童软组织肿瘤的12%。儿童中的这些肿瘤大多为良性或局部侵袭性，很少发生转移，而恶性病例并不常见。由于形态学重叠以及免疫组织化学的效用有限，诊断这些肿瘤具有挑战性。分子技术的进步，尤其是RNA测序，提高了我们对这些肿瘤分子驱动因素的理解，从而实现了更好的分类。关键的分子改变，如RTK和MAPK激活，在婴儿纤维肉瘤（IFS）和炎性肌纤维母细胞肿瘤（IMT）等肿瘤的发生发展中起着核心作用。IFS和IMT中替代融合的鉴定强调了综合诊断方法的重要性。此外，现已确定了新的由RTK驱动的病变，目前已被纳入世界卫生组织的“NTRK重排间叶性肿瘤”。本综述提供了关于RTK驱动的肌纤维母细胞性肿瘤最新发现的最新信息，并强调了仍需分类的新实体。
