ArticleThe American journal of case reports2026
Single-Site ALK-Positive Histiocytosis With TFG-ALK Fusion: Expanding the Clinical Spectrum of This Rare Entity.
Article in The American journal of case reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare and recently described histiocytic neoplasm characterized by ALK gene rearrangements. Several ALK fusion partners have been reported, particularly in patients with multisystem disease. We report the first case of single-site ALK-positive histiocytosis involving a TFG-ALK fusion, a rearrangement previously linked to disseminated disease. CASE REPORT A man in his 50s with obesity, obstructive sleep apnea, diabetes mellitus, hypertension, coronary artery disease, and a 40-pack-year smoking history underwent computed tomography for lung cancer screening; the results showed a solitary 1.6-cm left lower lobe pulmonary nodule. Positron emission tomography demonstrated hypermetabolic activity confined to the lesion. He subsequently underwent video-assisted thoracoscopic wedge resection with mediastinal lymphadenectomy. Histopathologic evaluation revealed a well-circumscribed spindle cell neoplasm expressing histiocytic markers CD4, CD68, and CD163, with cytoplasmic ALK positivity. A TFG-ALK gene fusion was detected using Archer FusionPlex Pan Solid Tumor panel testing with anchored multiplex polymerase chain reaction via Illumina NextSeq 500. Immunohistochemical and flow cytometric studies excluded alternative ALK-rearranged neoplasms, including inflammatory myofibroblastic tumor, anaplastic large cell lymphoma, and ALK-positive diffuse large B-cell lymphoma. The patient received no systemic therapy and remains disease-free on radiographic surveillance. CONCLUSIONS To our knowledge, this case represents the first reported instance of single-site ALK-positive histiocytosis with a TFG-ALK fusion. It expands the molecular and clinical spectrum of this rare entity, suggesting that certain ALK fusion partners are associated with localized disease and an indolent clinical course. Recognition of such presentations is essential to avoid unnecessary systemic therapy.
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