Isolated Nervous System Histiocytic Neoplasms: Clinical Manifestations, Treatment, and Outcomes
Nabeela Nathoo1, Joon Uhm1, Alyx Porter3, Julie Hammack4, Kurt Jaeckle4, Maciej Mrugala3, Brian Crum1, Eoin Flanagan1, Sean Pittock1, Gauruv Goyal5, Jason Young4, Matthew Koster2, Robert Vassallo2, Jay Ryu2, Caroline Davidge-Pitts2, Corrie Bach2, Aishwarya Ravindran5, Julio Sartori Valinotti2, N. Nora Bennani2, Jithma Abeykoon2, Mithun Shah2, Christopher Hook2, Karen Rech2, Ronald Go2, W. Tobin1
1Neurology, Mayo Clinic Rochester, 2Mayo Clinic Rochester, 3Mayo Clinic Arizona, 4Mayo Clinic Jacksonville, 5University of Alabama at Birmingham
Objective:
To describe the frequency, clinical manifestations, imaging findings, and treatment response in individuals with isolated nervous system histiocytic neoplasms at initial presentation, and to determine the frequency at which those individuals later develop systemic manifestations.
Background:
Nervous system involvement of histiocytic neoplasms, including Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman disease (RDD) has been described in those with systemic manifestations. However, longitudinal studies in those with isolated nervous system involvement at initial presentation are more limited, and thus it is unknown whether those with initially only nervous system involvement differ in their treatment response, and whether treatment may help prevent future systemic involvement.
Design/Methods:
This retrospective cohort study of adult patients with histiocytic neoplasms took place at a tertiary care referral center. Inclusion criteria were: 1) diagnosis of a histiocytic neoplasm based on nervous system biopsy and appropriate clinical phenotype; 2) lack of systemic involvement based on initial body PET or CT of the chest, abdomen, and pelvis and nuclear bone scam, if available; and 3) sufficient medical records for review.
Results:
Isolated nervous system involvement at initial presentation was seen in 19/377 (5%) of histiocytic neoplasms: 3% (6/228) with LCH, 7% (7/103) with ECD, and 13% (6/46) with RDD. The most common neurological symptoms and signs were headache (11/19, 58%), weakness (8/19, 42%), and diabetes insipidus (7/19, 37%). Three patients later developed systemic involvement, including 1 with LCH (6 years later), and 2 with ECD (each <12 months later). BRAF V600E mutation was present in 29% (4/14 tested). Treatments were individualized with 50% showing clinical response and 67% showing radiological response ≥3 months after treatment.
Conclusions:
Isolated nervous system involvement of histiocytic neoplasms at initial presentation is uncommon. Surveillance systemic imaging should be undertaken even after initially being negative, as systemic manifestations can occur later.