Posterior Uveitis in Ocular-Involving Chronic Lymphocytic Leukemia and the Utility of Negative MYD88 L265P Testing in the Diagnosis

Daniel A Balikov; Noah A Brown; Victor M Elner; Thomas J Wubben; Rajesh C Rao; Hakan Demirci

doi:10.1159/000535951

Posterior Uveitis in Ocular-Involving Chronic Lymphocytic Leukemia and the Utility of Negative MYD88 L265P Testing in the Diagnosis

Ocul Oncol Pathol. 2024 Jun;10(2):103-113. doi: 10.1159/000535951. Epub 2024 Mar 23.

Authors

Daniel A Balikov¹, Noah A Brown², Victor M Elner^{1

2}, Thomas J Wubben¹, Rajesh C Rao^{1

2

3

4

5

6

7}, Hakan Demirci¹

Affiliations

¹ Department of Ophthalmology and Visual Science, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI, USA.
² Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
³ Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
⁴ Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
⁵ Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI, USA.
⁶ A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, MI, USA.
⁷ Division of Ophthalmology, Surgical ServiceVeterans Administration Ann Arbor Healthcare System, Ann Arbor, MI, USA.

Abstract

Introduction: The aim of this study was to investigate if a negative test result for MYD88 L265P mutation, associated with vitreoretinal lymphoma (VRL) and primary CNS lymphoma, in liquid biopsies from intraocular fluids can be a useful adjuvant test to diagnose chronic lymphocytic leukemia in clinically challenging cases.

Case presentations: We selected patients with a past medical history or examinations findings suspicious for intraocular lymphoma. We evaluated both vitreous and aqueous humor-derived (AHD) MYD88 L265P mutation from patients that had suspected intraocular lymphoma that warranted a liquid biopsy procedure. Gold-standard cytopathology, flow cytometry, and gene rearrangement studies were also performed. All 4 patients had negative AHD MYD88 L265P mutation testing. Gold-standard testing (cytology) either showed paucicellular specimens (1/4) or specimens with high background inflammation (3/4). One case showed a rare B-cell clonal population (CD5⁺, Kappa-restricted by flow cytometry), but this was not sufficient to make any definitive diagnosis. All patients were subsequently initiated on systemic therapy and had improvement in their disease burden.

Conclusions: Negative AHD MYD88 L265P mutation testing can serve as an adjuvant molecular test to diagnose difficult cases of intraocular CLL.

Keywords: Adult ocular oncology; Eye and systemic disease; Intraocular tumors; Lymphoma.

Publication types

Case Reports

Grants and funding

H.D. was supported by the Richard N. and Marilyn K. Witham Professorship of Ophthalmology and Visual Sciences. R.C.R. was supported by the National Eye Institute (NEI) (R01EY030989), Research to Prevent Blindness (RPB), A. Alfred Taubman Medical Research Institute, the Beatrice and Reymont Paul Foundation, March Hoops to Beat Blindness, and Leonard G. Miller Endowed Professorship and Ophthalmic Research Fund at the Kellogg Eye Center. Additional support for this research was provided by Grossman, Elaine Sandman, Marek and Maria Spatz (endowed fund), Greenspon, Dunn, Avers, Boustikakis, Sweiden, and Terauchi research funds.