Daruish Maged, Ambrogio Francesca, Colagrande Anna, Marzullo Andrea, Alaggio Rita, Trilli Irma, Ingravallo Giuseppe, Cazzato Gerardo
Dorset County Hospital NHS Foundation Trust, Dorchester DT1 2JY, UK.
Section of Dermatology and Venereology, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari "Aldo Moro", 70124 Bari, Italy.
Dermatopathology (Basel). 2024 Feb 14;11(1):112-123. doi: 10.3390/dermatopathology11010010.
In recent years, particular interest has developed in molecular biology applied to the field of dermatopathology, with a focus on nevi of the Spitz spectrum. From 2014 onwards, an increasing number of papers have been published to classify, stratify, and correctly frame molecular alterations, including kinase fusions. In this paper, we try to synthesize the knowledge gained in this area so far. In December 2023, we searched Medline and Scopus for case reports and case series, narrative and systematic reviews, meta-analyses, observational studies-either longitudinal or historical, case series, and case reports published in English in the last 15 years using the keywords spitzoid neoplasms, kinase fusions, ALK, ROS1, NTRK (1-2-3), MET, RET, MAP3K8, and RAF1. ALK-rearranged Spitz tumors and ROS-1-rearranged tumors are among the most studied and characterized entities in the literature, in an attempt (although not always successful) to correlate histopathological features with the probable molecular driver alteration. NTRK-, RET-, and MET-rearranged Spitz tumors present another studied and characterized entity, with several rearrangements described but as of yet incomplete information about their prognostic significance. Furthermore, although rarer, rearrangements of serine-threonine kinases such as BRAF, RAF1, and MAP3K8 have also been described, but more cases with more detailed information about possible histopathological alterations, mechanisms of etiopathogenesis, and also prognosis are needed. The knowledge of molecular drivers is of great interest in the field of melanocytic diagnostics, and it is important to consider that in addition to immunohistochemistry, molecular techniques such as FISH, PCR, and/or NGS are essential to confirm and classify the different patterns of mutation. Future studies with large case series and molecular sequencing techniques are needed to allow for a more complete and comprehensive understanding of the role of fusion kinases in the spitzoid tumor family.
近年来，分子生物学在皮肤病理学领域的应用引发了特别的关注，重点是斯皮茨谱系痣。从2014年起，越来越多的论文发表，旨在对包括激酶融合在内的分子改变进行分类、分层并正确界定。在本文中，我们试图总结到目前为止在该领域所获得的知识。2023年12月，我们在Medline和Scopus数据库中检索了过去15年以英文发表的病例报告和病例系列、叙述性和系统性综述、荟萃分析、观察性研究（纵向或历史性）、病例系列和病例报告，使用的关键词有梭形细胞肿瘤、激酶融合、ALK、ROS1、NTRK（1 - 2 - 3）、MET、RET、MAP3K8和RAF1。ALK重排的斯皮茨肿瘤和ROS - 1重排的肿瘤是文献中研究和特征描述最多的实体之一，试图（尽管并非总是成功）将组织病理学特征与可能的分子驱动改变相关联。NTRK、RET和MET重排的斯皮茨肿瘤是另一个经过研究和特征描述的实体，已描述了多种重排，但关于其预后意义的信息尚不完整。此外，虽然较为罕见，但也已描述了丝氨酸 - 苏氨酸激酶如BRAF、RAF1和MAP3K8的重排，但还需要更多病例以及关于可能的组织病理学改变、病因发病机制和预后的更详细信息。分子驱动因素的知识在黑素细胞诊断领域非常重要，并且需要考虑到除免疫组化外，诸如FISH、PCR和/或NGS等分子技术对于确认和分类不同的突变模式至关重要。需要开展有大量病例系列和分子测序技术的未来研究，以便更全面、深入地了解融合激酶在梭形细胞肿瘤家族中的作用。
