Inflammatory myofibroblastic tumors of the skin and mucosal sites: A clinicopathological and molecular analysis of 3 cases with emphasis on differential diagnosis.

This study presents three molecularly confirmed cases of ALK-rearranged inflammatory myofibroblastic tumors (IMTs) occurring in superficial locations, demonstrating their rarity, clinicopathologic heterogeneity and diagnostic complexity. The series comprised tumors involving oropharyngeal mucosa, dermal/subcutaneous tissue of the forearm, and tongue mucosa. Histopathological evaluation revealed characteristic proliferations of spindle-to-ovoid cells arranged in fascicular patterns within variably collagenous to myxoid stroma, accompanied by chronic inflammatory infiltrates. Notable morphologic variations included: (1) rhabdomyoblastic differentiation evidenced by rhabdoid morphology and desmin, MyoD1 and myogenin co-expression in one case, histologically overlapping with inflammatory rhabdomyoblastic tumor; and (2) histiocytoid morphology featuring microvesicular cytoplasm in another case, resembling non-neural granular cell tumor. All cases exhibited strong diffuse cytoplasmic ALK immunoreactivity. Molecular profiling identified DCTN1(exon26)::ALK(exon20) fusions in two cases and TIMP3(exon1)::ALK(exon19) fusion in the lingual lesion, the latter corroborating established associations between TIMP3::ALK fusions and head/neck mucosal sites. With follow-up periods of 4-30 months post complete resection, all patients remained disease-free. These findings expand the recognized morphologic spectrum of cutaneous and superficial mucosal ALK-rearranged IMTs while underscoring the indispensable role of integrated histopathologic and molecular pathologic evaluation in differentiating these neoplasms from their histologic mimics, such as inflammatory rhabdomyoblastic tumor, non-neural granular cell tumor, and epithelioid fibrous histiocytoma/superficial ALK-rearranged myxoid spindle cell neoplasm.