'Inflammatory myofibroblastic tumour'-like dedifferentiation of anaplastic lymphoma kinase-rearranged lung adenocarcinoma

Aims: Anaplastic lymphoma kinase (ALK) functions as an oncogenic driver in a subset of haematopoietic, epithelial and mesenchymal neoplasms. Activation of ALK most commonly occurs through gene fusion events, the presence of which predicts response to ALK-targeted inhibitors in some tumour types. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions represent the majority of ALK rearrangements in lung adenocarcinomas and were, until recently, thought to be exclusive to that tumour type. However, recent work has identified EML4-ALK fusions in ~20% of inflammatory myofibroblastic tumours (IMTs), particularly in those arising in the lung. Here, we present a patient with an ALK-rearranged poorly differentiated lung adenocarcinoma with a predominant sarcomatoid component that was morphologically indistinguishable from IMT.

Methods and results: Targeted next-generation sequencing revealed EML4-ALK rearrangements in both components, with identical fusion sequences. Copy number analysis demonstrated focal gain of the MYC gene in the IMT-like component. The findings support a diagnosis of ALK-rearranged lung adenocarcinoma with IMT-like dedifferentiation.

Conclusions: Our findings suggest that ALK-driven epithelial and mesenchymal neoplasms exist on a morphological spectrum, and emphasize the need to consider translocation testing in pulmonary tumours with unusual sarcomatoid morphology.