To characterize spinal cord and root involvement in Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LH), and Rosai-Dorfman disease (RDD), and to compare patterns of involvement and outcomes across these disorders.

Histiocytic neoplasms are multisystem diseases that can involve the nervous system. Although cerebral and brainstem lesions are well described, spinal cord and root involvement are less characterized and may be underdiagnosed due to dominant cerebral/brainstem symptoms and the infrequent use of spinal MRI.

We conducted a retrospective observational cohort study at a single center, including all patients with ECD, LH, or RDD identified between 01/01/2016 and 12/31/2024. Baseline characteristics and outcomes were summarized descriptively; group comparisons were performed using standard tests for categorical and continuous variables.

We assessed 415 patients with definitive histiocytic neoplasms (183 ECD [44.1%], 144 LH [34.7%], 88 RDD [21.2%]). Nervous system involvement occurred in 107/183 ECD (58.5%), 43/144 LH (29.9%), and 21/88 RDD (23.9%). Spinal cord involvement was found in 26 ECD (14.2%; 12 infiltration, 8 compression, 5 both, 1 meningeal; multifocal in 15/17 [88.2%]), 4 LH (2.8%; 2 infiltration, 1 compression, 1 meningeal), and 7 RDD (8.0%; 5 compression, 1 infiltration, 1 both). Isolated root involvement occurred in 1 ECD (0.5%) and 4 RDD (4.5%). Most cases were symptomatic (36/42, 85.7%), presenting as the first medical manifestation in 19/36 (52.8%) and first neurological symptom in 26/36 (72.2%). At peak, median EDSS was 4.0 (range 0–9), with 18/42 (42.9%) requiring ambulatory aid, without intergroup differences (p = 0.749). At last follow-up, 22/36 (61.1%) symptomatic patients improved after treatment—less often in ECD (10/22, 45.5%) than LH (2/3, 66.7%) or RDD (10/11, 90.9%).

Spinal cord involvement occurs in a significant proportion of patients with histiocytic neoplasms, whereas isolated root involvement is rare. It typically presents early, is symptomatic, and has a notable impact on disability.