ALK rearranged malignant mesenchymal neoplasms of thorax: therapeutically targetable 'ALKomas' beyond the spectrum of non-small cell lung carcinomas and thoracic inflammatory myofibroblastic tumors.

The Anaplastic Lymphoma Kinase (ALK) protein, a receptor tyrosine kinase, is known to induce oncogenic transformation by point mutations, deletions, and gene rearrangements. Mesenchymal tumors like inflammatory myofibroblastic tumors (IMT) and epithelioid fibrous histiocytoma harbor ALK fusions, but other ALK-rearranged mesenchymal tumors are emerging. Herein, we present three such primary thoracic cases diagnosed by histopathology and ancillary techniques. The patients were young, non-smokers with a median age of 29 years (25-33 years) including two males and one female. Two of them presented with metastatic disease. Biopsies showed relatively monomorphic spindled to epithelioid tumor cells with necrosis and mitotic activity. All three cases were negative for pan-cytokeratin and smooth muscle actin with diffuse cytoplasmic ALK protein expression. Only one among the three cases was S100 positive while all three were CD34 negative. One patient showed response to crizotinib, while another patient died within a week of diagnosis. ALK-rearranged malignant mesenchymal tumors (non-IMT) of the thorax are rare, with only a few cases in literature. They lack distinct morphology and often face delayed diagnosis as ALK immunohistochemistry (IHC) is rarely included in initial panels. Given their potential response to ALK inhibitors, it is imperative to perform ALK immunohistochemistry when evaluating a cytokeratin-negative spindle cell neoplasm of the thorax in a young and non-smoking patient.