Diagnostic Utility of Peripheral Blood MYD88 L265P Testing in Vitreoretinal Lymphoma

Vitreoretinal lymphoma (VRL) is a rare form of non-Hodgkin lymphoma. Molecular analysis of MYD88 mutations in intraocular fluids (aqueous or vitreous humor) has emerged as a valuable diagnostic tool in VRL. The purpose of this study was to evaluate the diagnostic utility of peripheral blood MYD88 L265P testing in VRL and its relationship with central nervous system (CNS) involvement.

Patients presenting with suspected VRL between 03/2021 and 03/2024 were included. Aqueous humor samples were collected from all patients during the initial office visit. Peripheral blood samples were obtained from all patients before treatment. All patients were evaluated for the presence of the MYD88 (NM_002468.4) c.794T>C (p.L265P) mutation in their aqueous humor and peripheral blood samples by using an allele-specific, real-time polymerase chain reaction assay. VRL diagnosis was established clinically and confirmed by vitreous cytopathology. Vitreous humor was also tested for MYD88 L265P mutation when vitrectomy was done at our institution.

Twelve patients (eight males, four females) with VRL were included. Seven patients had CNS involvement, and four were on systemic chemotherapy at the time of sampling. Aqueous humor-derived MYD88 L265P mutation was identified in 9/12 patients (75.0%), and vitreous humor-derived MYD88 L265P mutation was identified in 8/9 patients tested (88.9%). The mutation was not identified in any of the blood samples.

While aqueous and vitreous humor samples demonstrated high detection rates for the MYD88 L265P mutation in VRL, allele-specific real-time PCR analysis of predominantly leukocyte-derived DNA extracted from the whole blood did not detect the MYD88 L265P mutation. This finding supports the concept that VRL, including cases with CNS involvement, appears to be mainly confined to immune-privileged sites with no detectable circulating lymphoma cells for useful peripheral blood DNA analysis.