Case Report: Early Distant Metastatic Inflammatory Myofibroblastic Tumor Harboring EML4-ALK Fusion Gene: Study of Two Typical Cases and Review of Literature

Abstract

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 (ALK) immunostaining and ALK rearrangement via fluorescence in situ hybridization. The EML4 (exon 6)-ALK (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 NOTCH1 and synonymous variants of ARAF were also detected via NGS in one IMT for the first time and were verified in all of the primary and metastatic lesions via 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 ALK inhibitor alectinib therapy, and the tumor was observed to regress 10 months after the initial ALK inhibitor therapy. In contrast, the other patient presented with subcutaneous neck metastasis without ALK inhibitor treatment and succumbed to the disease within 3 months after the surgery. This study demonstrated the possible role of EML4-ALKv3a/b in the malignant progression of IMT and proposed certain therapeutic effects of ALK inhibitors on multiple metastatic IMTs.

A case of inflammatory myofibroblastic tumor harboring EML4‐ALK fusion with a brain metastasis responding to alectinib

“…Qianqian et al reported the rate to be 1.13% at their own institution. 4 The most commonly reported metastatic organs of IMT are lung, brain, and bone; brain metastases were found in six of 50 metastatic IMT cases. 4 Previous reports have shown that 50% of surgically resected IMT cases are positive for ALK rearrangement.…”

“…4 The most commonly reported metastatic organs of IMT are lung, brain, and bone; brain metastases were found in six of 50 metastatic IMT cases. 4 Previous reports have shown that 50% of surgically resected IMT cases are positive for ALK rearrangement. 5 Considering the fact that 19 of 37 patients with metastatic IMT were ALK-positive, 4 there seems no difference in the frequency of ALK rearrangement positivity between metastatic and nonmetastatic IMT.…”

“…IMT with metastases, like this case is considered to be very rare. Qianqian et al reported the rate to be 1.13% at their own institution 4 . The most commonly reported metastatic organs of IMT are lung, brain, and bone; brain metastases were found in six of 50 metastatic IMT cases 4 …”

Epithelioid Fibrous Histiocytoma with CARS-ALK Fusion: First Case Report

“…These morphological features are reminiscent of the spindle cell variant of epithelioid cell histiocytofibroma [ 7 ], which has been reported to present ALK fusions with DCTN1 , TMP3 and EML4 genes [ 8 ]. Furthermore, these fusions have also been identified in IMT [ 9 , 10 , 11 ]. IMT and EFH can both show cytoplasmic expression of ALK and factor XIIIa, but, unlike IMT and some classical benign fibrous histiocytomas, EFH does not express smooth muscle actin [ 12 ].…”

An extremely rare case of malignant jejunal mesenteric inflammatory myofibroblastic tumor in a 61-year-old male patient: A case report and literature review

“…Currently, the World Health Organization states its nature as an intermediate malignant neoplasm with mesenchymal origin ( 2 ). IMT has been reported in almost all body and soft tissue visceral organs ( 3 , 4 ). Most recorded cases were in the lung, followed by the mesentery and the omentum ( 5 , 6 ).…”