Double amplifications of CDK4 and MDM2 in a gastric inflammatory myofibroblastic tumor mimicking cancer with local invasion of the spleen and diaphragm

Abstract

Inflammatory myofibroblastic tumor (IMT) is currently recognized as an intermediate mesenchymal neoplasm. It can arise anywhere in the body, but it is particularly common in the lungs. Gastric IMT is very rare in adults. In this study, we report a case of a 68-year-old woman with IMT in the gastric cardia, with invasion into the spleen and diaphragm. Because of its location and aggressive clinical features, it was first mistaken for gastric cancer. However, pathology and immunohistochemistry were used to finally confirm the diagnosis of IMT after total resection of the tumor and spleen and partial resection of the diaphragm. In order to provide better understanding of this rare tumor, targeted next-generation sequencing (NGS) and IHC were performed to assess genetic and protein abnormalities of the tumor. Both IHC and NGS were found to be negative for ALK or other gene fusions. However, double amplification of CDK4 and MDM2 were found by NGS, and IHC also found CDK4 and MDM2 to be positive. To the best of our knowledge, this is the first gastric IMT report to show double invasion of the spleen and the diaphragm, and double amplification of CDK4 and MDM2 in IMT are also reported for the first time. This genomic aberration with protein overexpression is the most likely tumorigenic driver of this rare and aggressive tumor. ARTICLE HISTORY

Amplification of CDK4 and MDM2: a detailed study of a high-risk neuroblastoma subgroup

“…The amplifications in the mentioned regions might promote clinical features related to metastatic homing and tumor invasion that mimic WT. The co-amplification of CDK4/MDM2 has also been noted to change the location and clinical features of rare cases of inflammatory myofibroblastic tumors, causing them to be mistaken for gastric cancer with local invasion of the spleen and diaphragm 55 . Predilection for lung metastasis have been confirmed in several malignancies such as melanoma, sarcoma, kidney- and breast cancer, in which the preferential site for metastasizing also is subtype dependent 56 .…”

Inflammatory Myofibroblastic Tumour: State of the Art

“…Although mouse double minute 2 ( MDM2 ) gene amplification has also been detected in 27% of IMT cases, no data are available at this moment regarding the efficacy of MDM2 inhibitors alone or in combination with CDK4 inhibition [ 49 , 50 ].…”

ALK-Negative Lung Inflammatory Myofibroblastic Tumor in a Young Adult: a Case Report and Literature Review of Molecular Alterations

“…They all bene ted from treatment with crizotinib (250 mg) with a signi cant reduction in tumor size. (31)(32)(33)(34) Jia He et al found for the rst time a double ampli cation of CDK4 and MDM2 with protein overexpression by NGS and IHC in a 68-year-old woman with a gastric IMT with local invasion of spleen and diaphragm (35). Furthermore, Antonescu et al found correlations between the genotypes and certain clinic-pathologic characteristics of the IMT .…”