Exploring the spectrum: adult orbital xanthogranulomatous disease – insights into pathogenesis, clinical variability and treatment
Author: Sanne Detiger
Base Hospital / Institution: The Rotterdam Eye Hospital
Rapid fire oral presentation
Abstract ID: 24-151
Purpose
Adult orbital xanthogranulomatous disease (AOXGD) is a spectrum of rare histiocytoses. Four subtypes are identified: adult-onset xanthogranuloma (AOX), adult-onset asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX) and Erdheim-Chester disease (ECD). Mutations in genes of the mitogen-activated protein kinase (MAPK) pathway have been detected in various histiocytoses. Therapy options vary and little is known about the long-term effect of treatment. This presentation analyses the long-term outcome and activation of the MAPK pathway in patients with AOXGD.
Methods
Outcomes of 28 patients with AOXGD are presented, treated between 1989 and 2021 in the Rotterdam Eye Hospital and Erasmus MC University Medical Center. Standard next-generation sequencing (NGS) and/or formalin-fixed paraffin-embedded-targeted locus capture NGS were used to analyse for somatic mutations of the MAPK pathway. Immunohistochemical staining for phosphorylated ERK (pERK) and cyclin D1 was performed to verify constitutive MAPK pathway activation.
Results
7/11 patients with AOX were treated with surgery alone, 3/11 received surgery with additional therapy and 1/11 was treated with systemic therapy alone. Recurrence was seen in 4. 5/5 patients with AAPOX required systemic therapy, with recurrence in 3. 2/6 patients with NBX were treated with surgery alone, with recurrence in 1. 4/6 patients required additional therapy with recurrence in 2. 4/4 patients with ECD required systemic therapy.
MAPK pathway gene mutations were detected in 7/28 patients. Positive staining for either pERK or cyclin D1 was found in 17/27 of whom 12/17 did not harbour a known MAPK pathway-activating mutation.
Conclusion
Recognition of AOXGD is important, in particular because of the potential severe systemic locations in the different subtypes. Surgical excision might be a sufficient for patients with AOX. Patients with AAPOX, NBX and ECD warrant systemic therapy. Activation of the MAPK pathway is observed across all subtypes of AOXGD, even when no genomic mutations are found.
Additional Authors
| First name | Last name | Base Hospital / Institution |
|---|---|---|
| Dion | Paridaens | The Rotterdam Eye Hospital |
| Jan | van Laar | Erasmus MC University Medical Center Rotterdam |
| Martin | van Hagen | Erasmus MC University Medical Center Rotterdam |
| Astrid | van Halteren | Erasmus MC University Medical Center Rotterdam |
| Paul | Kemps | Leiden University Medical Center |
| Rob | Verdijk | Erasmus MC University Medical Center Rotterdam |
