Han Qianqian, He Xin, Cui Lijuan, Qiu Yan, Li Yuli, Chen Huijiao, Zhang Hongying
Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Department of Pathology, Suining Central Hospital, Suining, China.
Front Med (Lausanne). 2022 Feb 24;9:826705. doi: 10.3389/fmed.2022.826705. eCollection 2022.
Inflammatory myofibroblastic tumor (IMT) is a distinctive neoplasm that frequently arises in the lung and accounts for ~1% of lung tumors. Distant metastatic IMT is extremely rare and has been poorly investigated. This analysis was specifically performed to explore the clinicopathological and genetic features of early distant metastatic IMT. Two typical patients with distant metastatic IMTs were selected, which accounted for 1.13% of all diagnosed IMTs in the last 5 years. One patient was a 55 year-old male, and the other patient was a 56 year-old female. Both primary tumors arose from the lung, and the initial clinical symptoms of the two patients involved coughing. Both of the imaging examinations showed low-density nodular shadows in the lungs with enhancement around the mass. Microscopically, dense arranged tumor cells, prominent cellular atypia, and high mitotic activity with atypical form were more prominent in the metastatic lesions than in the primary lesions. All of the primary and metastatic tumors in both cases showed positive anaplastic lymphoma kinase () immunostaining and rearrangement fluorescence hybridization. The (exon 6) (exon 20) fusion variant (v3a/b) was identified by using next-generation sequencing (NGS) and was verified by using reverse transcription polymerase chain reaction (RT-PCR). Furthermore, intronic variants of and synonymous variants of were also detected NGS in one IMT for the first time and were verified in all of the primary and metastatic lesions PCR. Distant metastasis occurred during a short period of time (1 and 2 months) after the first surgery. One patient presented with multiple metastases to the subcutaneous tissue and bone that responded to inhibitor alectinib therapy, and the tumor was observed to regress 10 months after the initial inhibitor therapy. In contrast, the other patient presented with subcutaneous neck metastasis without inhibitor treatment and succumbed to the disease within 3 months after the surgery. This study demonstrated the possible role of -v3a/b in the malignant progression of IMT and proposed certain therapeutic effects of inhibitors on multiple metastatic IMTs.
炎性肌纤维母细胞瘤（IMT）是一种独特的肿瘤，常发生于肺部，约占肺肿瘤的1%。远处转移性IMT极为罕见，相关研究较少。本分析旨在探讨早期远处转移性IMT的临床病理及基因特征。选取了2例典型的远处转移性IMT患者，占过去5年所有确诊IMT的1.13%。1例患者为55岁男性，另1例为56岁女性。原发肿瘤均起源于肺，2例患者的初始临床症状均为咳嗽。影像学检查均显示肺部有低密度结节影，肿块周围有强化。显微镜下，转移灶中密集排列的肿瘤细胞、明显的细胞异型性以及非典型形式的高有丝分裂活性比原发灶更明显。2例患者的所有原发肿瘤和转移肿瘤均显示间变性淋巴瘤激酶（ALK）免疫染色阳性和ALK重排荧光原位杂交阳性。通过二代测序（NGS）鉴定出ALK（外显子6）-ALK（外显子20）融合变异体（v3a/b），并通过逆转录聚合酶链反应（RT-PCR）进行验证。此外，首次在1例IMT中通过NGS检测到ALK的内含子变异体和TP53的同义变异体，并在所有原发灶和转移灶中通过PCR进行验证。首次手术后短时间内（1个月和2个月）即发生远处转移。1例患者出现皮下组织和骨的多发转移，对ALK抑制剂阿来替尼治疗有反应，初始ALK抑制剂治疗10个月后肿瘤缩小。相比之下，另1例患者出现颈部皮下转移，未接受ALK抑制剂治疗，术后3个月内死于该病。本研究证明了ALK-v3a/b在IMT恶性进展中的可能作用，并提出了ALK抑制剂对多发转移性IMT的一定治疗效果。
