Targeted therapy for ALK-positive histiocytosis masquerading as optic nerve tumor: a case report.

ALK-positive histiocytosis is a recently described histiocytic neoplasm characterized by ALK immunoreactivity in CD163-positive histiocytes and has been shown to respond favorably to ALK inhibitors. ALK-positive histiocytosis is a clonal neoplastic disorder that can manifest as single-system or multisystem disease, with frequent neurological involvement. Reported gene fusions include KIF5B-ALK, TPM3-ALK, and others, leading to constitutive activation of downstream signaling pathways such as MAPK and PI3K/AKT/mTOR. Although surgical resection and conventional chemotherapy have been used, ALK inhibitors offer a targeted and effective therapeutic option, particularly for intracranial disease. We report a case of a 17-month-old boy presenting with left eye deviation, ptosis, and visual loss. Magnetic resonance imaging revealed a lobulated, contrast-enhancing mass involving the orbital and canalicular segments of the left optic nerve, extending into the cavernous sinus, with additional enhancing foci in the left frontal and pineal regions. Given the atypical radiological features, surgical biopsy was performed and demonstrated ALK-positive histiocytosis with KIF5B-ALK gene fusion. Lorlatinib, a third-generation ALK tyrosine kinase inhibitor, was started which showed significant disease regression at 18-month follow-up. This report highlights the favorable response to targeted ALK inhibition in central nervous system ALK-positive histiocytosis.