Davis Jessica L, Al-Ibraheemi Alyaa, Rudzinski Erin R, Surrey Lea F
Department of Pathology, Oregon Health & Science University, Portland, Oregon, USA.
Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.
Histopathology. 2022 Jan;80(1):4-18. doi: 10.1111/his.14443.
Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.
激酶改变越来越被认为是间充质肿瘤的致癌驱动因素。婴儿纤维肉瘤及相关肾肿瘤——先天性中胚层肾瘤，是最早被证明含有复发性酪氨酸激酶融合的实体瘤之一，20多年前就已鉴定出典型的ETV6::NTRK3融合。尽管靶向检测长期以来一直用于诊断，但更强大的测序技术的出现推动了一系列间充质肿瘤中激酶改变的发现。随着我们识别这些基因改变能力的提高，我们对含有这些改变的肿瘤的认识和理解也有所提高。具体而言，本研究将聚焦于含有NTRK或其他激酶改变的间充质肿瘤，包括具有婴儿纤维肉瘤样外观的肿瘤、类似脂肪纤维瘤病或周围神经鞘瘤的梭形细胞肿瘤以及成人中出现的具有纤维肉瘤样外观的肿瘤。随着描述这些肿瘤组织学的出版物增多，报道的激酶改变种类也在增加，现在包括NTRK1/2/3、RET、MET、RAF1、BRAF、ALK、EGFR和ABL1融合或改变。迄今为止，这些肿瘤表现为局部侵袭性，很少发生转移，组织学分级中使用的传统特征（如有丝分裂活性、坏死）与预后之间没有明确联系。然而，这些肿瘤大多适合新的靶向治疗，这使得对它们的识别具有诊断和治疗意义。本研究的目的是回顾具有NTRK和其他酪氨酸激酶改变的肿瘤的临床病理特征，讨论最常见的鉴别诊断，并为分子确认及相关治疗建议提供推荐。
