Report Recommends Strategy to Identify CLL in Patient With Posterior Uveitis

It is rare for patients with chronic lymphocytic leukemia (CLL) to present with ocular involvement, but a mutational test could help clinicians identify patients more quickly.

Testing for myeloid differentiation factor 88 (MYD88) L265P mutation may be a useful tool in identifying chronic lymphocytic leukemia (CLL) in patients experiencing posterior uveitis, according to a new report.

The findings are based on a series of 4 cases in which patients with CLL tested negative for the MYD88 L265P mutation. The report was published in the journal Ocular Oncology and Pathology.1

Study authors explained that it is rare to have patients present with ocular involvement in CLL.

“Even more, there is a notable lack of any pattern of preferential CLL targeting to a particular ocular tissue in that the invasion of ocular tissue does not appear to correlate with the stage of CLL,” they wrote.

Yet, the authors noted that a review published in 2020 identified 86 articles describing 123 patients with CLL with ophthalmic involvement.2 The authors of that report said they believed cases of intraocular involvement in CLL might be underreported.

genetic mutation testing | Image Credit:

Ocular involvement is rare in cases of chronic lymphocytic leukemia, with the present authors concluding testing for the MYD88 L265P mutation may be a useful tool to add in this space | Image Credit:

The present authors said it is important to find ways to quickly and efficiently diagnose intraocular-involving CLL, in part because ocular symptoms might be the first or only signs that a patient previously in remission might be experiencing disease progression.

In their report, they described 4 cases in which patients were believed to be in remission for CLL and experienced posterior uveitis/vitritis. The patients were given liquid biopsies from aqueous and vitreous humor testing for MYD88 L265P to differentiate between CLL and other cancers, such as vitreoretinal lymphoma (VRL). Mutations of MYD88 L265P have been linked with VRL and primary central nervous system (CNS) lymphoma, the investigators noted. All 4 patients in the series were negative for the mutation, leading physicians to suspect intraocular CLL.

The investigators said that finding was important, because on average 74% of VRL tumors are positive for the mutation from tumor cell DNA, according to an unpublished meta-analysis.

“Hence, with high clinical suspicion for CLL and liquid biopsies without definitive cytopathological and flow cytometry metrics indicative of CLL (including samples that yield a paucity of cells for analysis), negative MYD88 L265P can help rule out [diffuse large B-cell lymphoma],” they wrote.

They noted that none of the 4 patients in the case reports were restaged by their oncologists, which the authors said might be due to the fact that the cancer appeared isolated to the intraocular space. All the patients in the series were initiated on systemic therapy and had improvement in their disease burden, the investigators said.

The authors reported a pair of limitations to their study. First, they noted that it is based on a small number of cases, which they said was tied largely to the relative rarity of intraocular CLL.

“We are not suggesting that negative MYD88 L265P molecular testing should replace gold-standard cytopathology or flow cytometry, but the aforementioned described cases provide a useful context of how negative MYD88 L265P testing can help clinicians provide excellent management of patients with challenging presentations of CLL, including initiation of potentially life-saving treatment,” they wrote.

In addition, they noted that 3 of the 4 patients in the case series were taking ibrutinib (Imbruvica; Pharmacyclics/Johnson & Johnson), although the investigators said they did not believe the drug affected the MYD88 L265P testing.

The authors concluded that the test appears to be a useful tool in cases where diagnosis proves challenging.

“In the context of nebulous or unequivocal gold-standard cytopathology and/or flow cytometry testing, molecular [polymerase chain reaction] testing for MYD88 L265P can be a useful adjuvant test for diagnosing ocular-involving CLL,” they said. “We anticipate that with any future specific biomarker associated with CLL [we] will utilize MYD88 L265P testing as a pertinent negative molecular test on liquid vitreous and aqueous biopsies.”


1. Balikov DA, Brown NA, Elner VM, Wubben TJ, Rao RC, Demirci H. Posterior uveitis in ocular-involving chronic lymphocytic leukemia and the utility of negative MYD88 L265P testing in the diagnosis. Ocul Oncol Pathol. 2024;10(2):103-113. doi:10.1159/000535951

2. Delestre F, Blanche P, Bouayed E, et al. Ophthalmic involvement of chronic lymphocytic leukemia: A systematic review of 123 cases. Surv Ophthalmol. 2021;66(1):124-131. doi:10.1016/j.survophthal.2020.05.001

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