Radioresistant but Alectinib-Responsive Isolated Intramedullary ALK-Positive Histiocytosis

A 56-year-old woman with a history of C4-C5 myelomeningocele repair as a newborn and cervical syringomyelia presented with one week of rapidly worsening bilateral lower extremity weakness and numbness, saddle anesthesia, and bladder incontinence. MRI of the entire spine revealed a 1.5 × 0.5 cm homogenously enhancing intramedullary lesion at T7-T8 with associated cord edema and rostral syrinx formation. MRI of the brain and FDG PET-CT scan were unremarkable. She was taken to the operating room for a T6-T8 laminectomy and biopsy. H&E staining revealed a relatively dense mononuclear-cell infiltrate, which comprised numerous medium-sized cells with round, irregular, or reniform nuclei, slightly dispersed chromatin, and relatively abundant eosinophilic, and occasionally, somewhat vacuolated cytoplasm. Immunohistochemical staining was strongly positive for CD163, PU.1, CD68, and ALK. FISH studies demonstrated ALK rearrangement in 70% of nuclei. Next-generation sequencing including both DNA and RNA testing on a formalin-fixed, paraffin-embedded tissue sample detected a KIF5B/ALK gene fusion. She received radiotherapy with 2000 cGY in 200 cGy fractions to T6-T9 with no change in lesional size or enhancement. She was started on the ALK inhibitor alectinib. Subsequent MRI showed a complete response. She has had no evidence of disease recurrence on alectinib for 18 months. ALK-positive histiocytosis is a recently described distinct clinicopathologic entity. Our case is notable for older age at diagnosis, isolated intramedullary involvement, and radioresistance but later marked targeted-therapy response, thus furthering the understanding of the spectrum of ALK-positive histiocytosis biology.