Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA.
Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Histopathology. 2022 Mar;80(4):698-707. doi: 10.1111/his.14603. Epub 2022 Jan 2.
Recurrent alterations in receptor tyrosine kinase (RTK) and downstream effectors are described in infantile fibrosarcoma (IFS)/cellular congenital mesoblastic nephroma (cCMN) and a subset of spindle cell sarcomas, provisionally designated 'NTRK-rearranged' spindle cell neoplasms. These two groups of tumours demonstrate overlapping morphologies and harbour alterations in NTRK1/2/3, RET, MET, ABL1, ROS1, RAF1 and BRAF, although their relationship is not fully elucidated. We describe herein a cohort of paediatric tumours with clinicopathological features not typical for inflammatory myofibroblastic tumour, but rather with similarities to cCMN/IFS harbouring ALK fusions.
Clinicopathological features were assessed and partner agnostic targeted RNA sequencing on clinically validated platforms were performed. Tumours occurred in patients aged from 2 to 10 years (median age 2 years) with a 2:2 male to female ratio and an average size of 8.4 cm. Two tumours arose in soft tissues and two in the kidney. Morphological features included spindle to ovoid cells arranged in long fascicles or haphazardly within a myxoid to collagenised stroma; a subset of cases had either dilated, ectatic vessels or focal perivascular hyalinosis. By immunohistochemistry, all cases tested showed cytoplasmic expression of anaplastic lymphoma kinase (ALK) and one case demonstrated co-expression of CD34 and S100.
This series of ALK-rearranged IFS-like tumours expands the spectrum of targetable kinases altered in these tumours and reinforces the potential overlap between IFS/cCMN-like tumours and the provisional entity of 'NTRK-rearranged' spindle cell neoplasms.
受体酪氨酸激酶（RTK）及其下游效应物的反复改变在婴儿纤维肉瘤（IFS）/细胞先天性中胚层肾瘤（cCMN）和一部分梭形细胞肉瘤中被描述，这些肿瘤暂被命名为“NTRK 重排”梭形细胞肿瘤。这两组肿瘤具有重叠的形态学特征，并存在 NTRK1/2/3、RET、MET、ABL1、ROS1、RAF1 和 BRAF 的改变，尽管它们之间的关系尚未完全阐明。我们在此描述了一组儿科肿瘤，其临床病理特征与炎症性肌纤维母细胞瘤不典型，但与具有 ALK 融合的 cCMN/IFS 相似。
评估了临床病理特征，并在经过临床验证的平台上进行了无伴侣靶向 RNA 测序。肿瘤患者年龄为 2 至 10 岁（中位年龄 2 岁），男女比例为 2:2，平均大小为 8.4cm。两个肿瘤发生在软组织，两个发生在肾脏。形态学特征包括长束状或杂乱排列的梭形至卵圆形细胞，位于黏液样至胶原化基质中；一部分病例有扩张的、扩张的血管或局灶性血管周围玻璃样变性。通过免疫组织化学染色，所有检测的病例均显示细胞质表达间变性淋巴瘤激酶（ALK），一个病例显示 CD34 和 S100 的共表达。
这一系列 ALK 重排的 IFS 样肿瘤扩大了这些肿瘤中改变的靶向激酶谱，并强调了 IFS/cCMN 样肿瘤和“NTRK 重排”梭形细胞肿瘤这一暂定实体之间的潜在重叠。
