Diagnosing Vitreoretinal Lymphomas-An Analysis of the Sensitivity of Existing Tools.

Anahita Sehgal,Gabor Gy Deák,Tatyana Milman,Arman Mashayekhi,Jose S. Pulido

doi:10.3390/cancers14030598

Anahita Sehgal, Gabor Gy Deák + Show 3 more

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https://doi.org/10.3390/cancers14030598

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Abstract

Simple SummaryDiagnostics 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.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.

Highlights

Vitreoretinal Lymphoma presents a difficult challenge for clinicians and pathologists alike
Myeloid Differentiation Factor 88 (MyD88) mutation analysis has emerged as a powerful ancillary study in diagnosis of Vitreoretinal lymphoma (VRL), with a sensitivity of 69–88%, based on prior studies
Detection of MyD88 mutation supports the diagnosis of a B cell lymphoma, regardless of whether this is primary vitreoretinal lymphoma (PVRL)/central nervous system (CNS) Diffuse large B-cell lymphoma (DLBCL) or any other B cell lymphoma, and the presence of mutation essentially rules out uveitis [21]

Summary

Introduction

Vitreoretinal Lymphoma presents a difficult challenge for clinicians and pathologists alike. Diffuse large B-cell lymphoma (DLBCL) is the most commonly seen vitreoretinal lymphoma and is often confused for chronic uveitis (ocular inflammation) [1]. There is a need to shorten the time between onset of symptoms and the appropriate diagnosis. Various laboratory-based methods have been described to improve the diagnostic accuracy of this notorious masquerader [3,4,5,6,7]. We performed a review of the literature to better determine which of the commonly used methods has the highest sensitivity, and can function as a reliable tool in making the correct diagnosis

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