title: 'Inflammatory myofibroblastic tumour'-like dedifferentiation of anaplastic lymphoma kinase-rearranged lung adenocarcinoma.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Emily F
authors.initials: EF
authors.lastname: Mason
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Christopher D M
authors.initials: CD
authors.lastname: Fletcher
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Sholl
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016726:Plasma Cell Granuloma, Pulmonary / Q000235:genetics* / Q000473:pathology*
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion
keywords: EML4-ALK; inflammatory myofibroblastic tumour; lung adenocarcinoma