Tanaka Mio, Kohashi Kenichi, Kushitani Kei, Yoshida Misa, Kurihara Sho, Kawashima Masumi, Ueda Yuka, Souzaki Ryota, Kinoshita Yoshiaki, Oda Yoshinao, Takeshima Yukio, Hiyama Eiso, Taguchi Tomoaki, Tanaka Yukichi
Department of Pathology, Kanagawa Children's Medical Center, Yokohama 232-8555, Japan.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Hum Pathol. 2017 Aug;66:177-182. doi: 10.1016/j.humpath.2017.06.013. Epub 2017 Jul 11.
We report 2 infantile cases of pulmonary tumor carrying a chimeric A2M-ALK gene. A2M-ALK is a newly identified anaplastic lymphoma kinase (ALK)-related chimeric gene from a tumor diagnosed as fetal lung interstitial tumor (FLIT). FLIT is a recently recognized infantile pulmonary lesion defined as a mass-like lesion that morphologically resembles the fetal lung. Grossly, FLIT characteristically appears as a well-circumscribed spongy mass, whereas the tumors in these patients were solid and firm. Histologically, the tumors showed intrapulmonary lesions composed of densely proliferating polygonal or spindle-shaped mesenchymal cells with diffuse and dense infiltrations of inflammatory cells forming microcystic or micropapillary structures lined by thyroid transcription factor 1-positive pneumocytes, favoring inflammatory myofibroblastic tumor rather than FLIT. The proliferating cells were immunoreactive for ALK, and A2M-ALK was identified in both tumors with reverse-transcription polymerase chain reaction. The dense infiltration of inflammatory cells, immunoreactivity for ALK, and identification of an ALK-related chimeric gene suggested a diagnosis of inflammatory myofibroblastic tumor. Histologically, most reported FLITs show sparse inflammatory infiltrates and a relatively low density of interstitial cells in the septa, although prominent infiltration of inflammatory cells and high cellularity of interstitial cells are seen in some FLITs. The present cases suggest that ALK rearrangements, including the chimeric A2M-ALK gene, may be present in these infantile pulmonary lesions, especially those with inflammatory cell infiltration. We propose that these infantile pulmonary lesions containing a chimeric A2M-ALK gene be categorized as a specific type of inflammatory myofibroblastic tumor that develops exclusively in neonates and infants.
我们报告了2例携带嵌合型A2M-ALK基因的婴儿肺部肿瘤病例。A2M-ALK是一种新发现的与间变性淋巴瘤激酶（ALK）相关的嵌合基因，来自一例被诊断为胎儿肺间质瘤（FLIT）的肿瘤。FLIT是一种最近才被认识的婴儿肺部病变，定义为形态上类似于胎儿肺的肿块样病变。大体上，FLIT特征性地表现为边界清楚的海绵状肿块，而这些患者的肿瘤是实性且质地坚硬的。组织学上，肿瘤显示为肺内病变，由密集增殖的多边形或梭形间充质细胞组成，伴有炎症细胞的弥漫性和密集浸润，形成由甲状腺转录因子1阳性肺细胞衬覆的微囊状或微乳头状结构，更倾向于炎症性肌纤维母细胞瘤而非FLIT。增殖细胞对ALK呈免疫反应性，通过逆转录聚合酶链反应在两个肿瘤中均鉴定出A2M-ALK。炎症细胞的密集浸润、对ALK的免疫反应性以及ALK相关嵌合基因的鉴定提示诊断为炎症性肌纤维母细胞瘤。组织学上，大多数报道的FLIT显示炎症浸润稀疏，间隔中间质细胞密度相对较低，尽管在一些FLIT中可见炎症细胞的显著浸润和间质细胞的高细胞密度。目前的病例表明，包括嵌合型A2M-ALK基因在内的ALK重排可能存在于这些婴儿肺部病变中，尤其是那些伴有炎症细胞浸润的病变。我们建议将这些含有嵌合型A2M-ALK基因的婴儿肺部病变归类为一种仅在新生儿和婴儿中发生的特定类型的炎症性肌纤维母细胞瘤。
