Diagnosing Vitreoretinal Lymphomas—An Analysis of the Sensitivity of Existing Tools

SIMPLE SUMMARY: Diagnostics of vitreoretinal lymphoma is very challenging, as the possibility of receiving false negative results is common. We retrospectively analyzed the sensitivity of the most commonly used diagnostic methods including ancillary immunohistochemistry, Myeloid Differentiation Factor 88 (MyD88) L256P mutation analysis, polymerase chain reaction (PCR) for monoclonal rearrangements of immunoglobulin heavy chain (IgH) and T-cell Receptor (TCR) genes, flow cytometry, and IL10 and IL6 analysis, to diagnose vitreoretinal lymphomas from published data in the literature. MyD88 mutation analysis caused by a hotspot mutation in MyD88 was the most sensitive and had the lowest coefficient of variation. ABSTRACT: Vitreoretinal lymphoma (VRL) is a rare ocular pathology that is notorious for mimicking chronic uveitis, which is a seemingly benign condition in comparison. The most common form of VRL is the diffuse large B-cell type, and there has been a high mortality rate. This dismal prognosis can be improved significantly if the disease is diagnosed early, but until now there is no consensus on an appropriate diagnostic algorithm. We conducted a retrospective search of PubMed Central(®) and analyzed results from thirty-three studies that were published between 2011–2021. The chosen studies incorporated some popular testing tools for VRL, and our analyses focused on comparing the average sensitivity of five diagnostic methods. The methods included cytology including ancillary immunohistochemistry, Myeloid Differentiation Factor 88 (MyD88) mutation analysis, polymerase chain reaction (PCR) for monoclonal rearrangements of immunoglobulin heavy chain (IgH) and T-cell Receptor (TCR) genes, flow cytometry, and IL10 and IL6 analysis. Across the varied diagnostic methods employed in thirty-three studies explored in this analysis, MyD88 mutation assay emerged as a strong contender given its sensitivity and low coefficient of variation. There is an imminent need for the introduction of newer assays that can further improve the sensitivity of identifying MyD88 mutation in cancer cells seen in the vitreous.