Purpose: To investigate whether MYD88 L265P mutation, which is frequently present in vitreoretinal lymphoma, can be detected in aqueous humor, a specimen that can be obtained in a clinic setting, potentially mitigating the need for more invasive vitrectomy procedures, and whether this approach can be used to monitor treatment response.

Design: Observational case series.

Subjects: Patients who were diagnosed with biopsy-confirmed or clinically diagnosed vitreoretinal lymphoma or biopsy-confirmed vitritis.

Methods: We evaluated aqueous humor-derived (AHD) MYD88 L265P mutation during vitreous biopsy or at the initial presentation in the clinic if vitreous biopsy was not feasible. Demographic or clinical features of patients were retrospectively reviewed. Aqueous humor-derived MYD88 L265P mutation was re-evaluated after patients completed a course of intravitreal methotrexate and rituximab injection therapy. The NM_002468.4: c.794T>C (p.L265P) mutation in the MYD88 gene was evaluated in AHD cellular and cell-free DNA using allele-specific polymerase chain reaction.

Main Outcome Measures: Detection of AHD MYD88 L265P mutation at the initial diagnosis and to monitor the treatment response.

Results: Aqueous humor from 18 eyes of 14 patients with biopsy-confirmed or clinically diagnosed vitreoretinal lymphoma and 3 eyes of 3 patients with biopsy-confirmed vitritis were evaluated. Aqueous humor-derived MYD88 L265P mutation was detected in cell-based and cell-free DNA from 15 (83%) of 18 eyes with biopsy-confirmed or clinically diagnosed vitreoretinal lymphoma but not identified in any of the 3 eyes with vitritis. The mutation was less readily detectable in cellular DNA (10 of 18) compared with cell-free DNA (15 of 18). Furthermore, aqueous sampling after intravitreal methotrexate and rituximab injection therapy revealed absence of this mutation after complete response in 7 eyes. The mutation was detected in 1 eye that developed recurrence in a posttreatment window of 6 months. After a mean of follow-up of 9 months, there was no clinical evidence of vitreoretinal lymphoma recurrence in the 7 eyes with no detectable AHD MYD88 L265P mutation.

Conclusions: This investigational study suggests that AHD MYD88 L265P can be detected in eyes with lymphoma and may thus serve as a surrogate, less invasive biopsy in the diagnosis and follow-up of vitreoretinal lymphoma, particularly when cell-free DNA is evaluated.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oret.2022.08.005DOI Listing

Publication Analysis

Top Keywords

myd88 l265p
32
vitreoretinal lymphoma
28
l265p mutation
24
aqueous humor-derived
16
ahd myd88
16
cell-free dna
16
humor-derived myd88
12
biopsy-confirmed clinically
12
clinically diagnosed
12
diagnosed vitreoretinal
12

Similar Publications

There has been remarkable progress over the past 80 years since Jan Waldenstrom first described patients with a hyperviscosity syndrome related to IgM paraprotein in 1944. The definition of Waldenstrom macroglobulinemia (WM) has evolved from a clinical syndrome to a distinct clinicopathologic entity with characteristic morphology, immunophenotype and molecular features. The landmark discovery of MYD88 mutation among most WM cases in 2012 marked the dawning of an era of molecular genomic exploration that led to a paradigm shift in clinical practice.

View Article and Find Full Text PDF

CD5 expression is seen in 5%-10% of de novo diffuse large B-cell lymphomas (DLBCLs). Primary large B-cell lymphoma of the central nervous system (PCNS-LBCL) also exhibits CD5 expression in a minority of cases, however, clinicopathological and molecular features remain largely unclarified. Here we present the clinical, molecular, and pathological features of 11 CD5-positive () PCNS-LBCL cases, occupying 6.

View Article and Find Full Text PDF
Article Synopsis
  • The MYD88 L265P mutation, linked to increased cancer cell activity, is prevalent in Waldenstrom macroglobulinemia and non-germinal center diffuse large B-cell lymphoma (DLBCL) but its occurrence in the Pakistani population is not well-documented.
  • A study at the Armed Forces Institute of Pathology analyzed 82 DLBCL cases, finding the mutation in 3.6% of germinal center B-cell (GCB) subtype and 22.2% of non-GCB subtype cases.
  • The significant association (P = 0.024) suggests that targeting this mutation could improve treatment outcomes for DLBCL patients, especially those with the non-GCB subtype.
View Article and Find Full Text PDF

This multicentre phase II study Fondazione Italiana Linfomi (FIL)-bortezomib plus rituximab plus bendamustine (BRB) tested a combination of bendamustine (90 mg/m on days 1-2), rituximab (375 mg/m intravenously on day 1) and bortezomib (1.3 mg/m sc on days 1, 8, 15, 22) every 28 days for six cycles in 38 symptomatic patients with relapsed/refractory Waldenstrom macroglobulinaemia (RR-WM). Moreover, MYD88 and CXCR4 mutations were tested by droplet digital polymerase chain reaction (ddPCR) both at baseline and at the end of treatment in 21 patients.

View Article and Find Full Text PDF
Article Synopsis
  • * A needle biopsy of an enlarged left axillary lymph node revealed a different type of diffuse large B-cell lymphoma, indicating a complex lymphoma situation rather than a simple case of fluid overload.
  • * Both lymphomas displayed different levels of CD10 expression but were found to be clonally related with a shared MYD88 L265P mutation, demonstrating a conflict between traditional criteria for classification and genetic analysis results.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!