MYD88 L265P mutation in intraocular lymphoma: A potential diagnostic marker

Narasimhan, Sandhya; Joshi, M.M.; Parameswaran, Sowmya; Rishi, Pukhraj; Khetan, Vikas; Ganesan, Suganeswari; Biswas, Jyotirmay; Natarajan, Sundaram; Sreenivasan, Janani; Verma, Sonali; Krishnamurthy, Vanitha; Krishnakumar, Subramanian

doi:10.4103/ijo.ijo_1712_19

Cited by 17 publications

(5 citation statements)

References 23 publications

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“…While the authors acknowledged the diagnostic predictive power of any single clinical or multimodal imaging feature, they emphasized the importance of the combined presence of multiple suggestive features, such as abnormal sheets or veils or vitreous cells, subretinal infiltration, and a leopard spot pattern of RPE disruption -particularly in older, at-risk patients. Their work confirmed the utility of MYD88 mutation testing, [29][30][31][32][33][34][35][36][37] including the use of minimally invasive paracentesis -as reported recently by Hiemcke-Jiwa et al 38 and Miserocchi et al 39 Wang et al 15 evaluated six distinct fixatives for processing VRL fluid specimens with regard to preservation of cellular morphology in histology/immunohistochemistry and DNA/ RNA integrity. All tests were run on B-cell-like diffuse large B-cell lymphoma Pfeiffer cells.…”

supporting

confidence: 66%

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Intraocular Lymphoma

Cunningham

Miserocchi²,

Smith

et al. 2021

Ocular Immunology and Inflammation

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supporting

confidence: 66%

“…The L265P mutation was identified in 20 of 29 vitreous samples (69.0%). The authors acknowledged comparably high rates of this specific MYD88 mutation in other diverse cohorts, [29][30][31][32][33][34][35][36][37] and concluded that ddPCR may offer a rapid, sensitive, and specific approach to diagnosing VRL.…”

mentioning

confidence: 99%

Intraocular Lymphoma

Cunningham

Miserocchi²,

Smith

et al. 2021

Ocular Immunology and Inflammation

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“…Both cases had complete CDKN2A deletions, an alteration we have observed to be highly recurrent in VRL patients and which is a promising genomic biomarker with potential clinical utility that warrants further investigation [ 42 ]. MYD88 , a gene encoding for an NF-kB pathway component, is also recurrent in B-cell lymphomas [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ] and was found here as a truncal activating mutation in Case 2. Interestingly, Case 1 harbored a MYD88 p.A221T mutation with a highly subclonal status in the brain tissue sample (8% variant fraction).…”

Section: Discussionmentioning

confidence: 85%

Comparative Molecular Analysis of Primary Central Nervous System Lymphomas and Matched Vitreoretinal Lymphomas by Vitreous Liquid Biopsy

Balikov

Liu

et al. 2021

IJMS

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Primary Central Nervous System Lymphoma (PCNSL) is a lymphoid malignancy of the brain that occurs in ~1500 patients per year in the US. PCNSL can spread to the vitreous and retina, where it is known as vitreoretinal lymphoma (VRL). While confirmatory testing for diagnosis is dependent on invasive brain tissue or cerebrospinal fluid sampling, the ability to access the vitreous as a proximal biofluid for liquid biopsy to diagnose PCNSL is an attractive prospect given ease of access and minimization of risks and complications from other biopsy strategies. However, the extent to which VRL, previously considered genetically identical to PCNSL, resembles PCNSL in the same individual with respect to genetic alterations, diagnostic strategies, and precision-medicine based approaches has hitherto not been explored. Furthermore, the degree of intra-patient tumor genomic heterogeneity between the brain and vitreous sites has not been studied. In this work, we report on targeted DNA next-generation sequencing (NGS) of matched brain and vitreous samples in two patients who each harbored VRL and PCSNL. Our strategy showed enhanced sensitivity for molecular diagnosis confirmation over current clinically used vitreous liquid biopsy methods. We observed a clonal relationship between the eye and brain samples in both patients, which carried clonal CDKN2A deep deletions, a highly recurrent alteration in VRL patients, as well as MYD88 p.L265P activating mutation in one patient. Several subclonal alterations, however, in the genes SETD2, BRCA2, TERT, and broad chromosomal regions showed heterogeneity between the brain and the eyes, between the two eyes, and among different regions of the PCNSL brain lesion. Taken together, our data show that NGS of vitreous liquid biopsies in PCNSL patients with VRL highlights shared and distinct genetic alterations that suggest a common origin for these lymphomas, but with additional site-specific alterations. Liquid biopsy of VRL accurately replicates the findings for PCNSL truncal (tumor-initiating) genomic alterations; it can also nominate precision medicine interventions and shows intra-patient heterogeneity in subclonal alterations. To the best of our knowledge, this study represents the first interrogation of genetic underpinnings of PCNSL with matched VRL samples. Our findings support continued investigation into the utility of vitreous liquid biopsy in precision diagnosis and treatment of PCNSL/VRL.

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“…23,55 According to recent mutational analyses of DLBCL and VRL specimens, MYD88 l265P mutation has been reported in a large percentage of examined samples. 56 Additionally, Yonese et al showed that 35% of VRL vitreous samples presented CD79b mutations. 57 The MYD88 l265P mutation has also been identified as a potential diagnostic target using aqueous tap.…”

Section: Diagnosismentioning

confidence: 99%

A comprehensive overview of diagnosis, imaging and treatment of vitreoretinal lymphoma

Menean,

Giuffrè,

Cicinelli

et al. 2023

European Journal of Ophthalmology

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Vitreoretinal lymphoma (VRL) is a rare B-cell intraocular neoplasia characterized by poor long-term prognosis and lack of effective therapies. It mainly involves the vitreous humor, the retina, and the retinal pigment epithelium (RPE), although anterior segment involvement can occur. VRL is classified as a lymphoma of immune privileged sites, along with testis lymphoma and primary central nervous system lymphoma (PCNSL). VRL and PCNSL are strictly connected indeed: 80% of VRL develop PCNSL, while 20% of patients with PCNSL present VRL during natural history of lymphoma. Due to the lack of worldwide consensus about diagnosis, therapy, and follow-up timing, VRL represents one of the most challenging ocular affections. VRL commonly masquerades as a posterior uveitis, and misdiagnosis often occurs because of partial response to topical steroids. Gold standard for diagnosis is cytological analysis of vitreous humor. However, this technique lacks sensitivity and supplemental molecular analyses can improve the diagnostic process. Multimodal imaging allows ophthalmologists to empower their clinical suspicion and a comprehensive examination can highlight typical features of VRL and justify further invasive procedures. There is no consensus about VRL therapy, and none of the therapeutical scheme has demonstrated to prevent cerebral involvement and improve patient's overall survival. Intravitreal injections of chemotherapeutics drugs, ocular radiation therapy and systemic chemotherapy can be considered in the treatment of VRL. Once cerebral involvement occurs, systemic chemotherapy must be included in the treatment as a life-saving therapy. Further multicentric studies are required to find out the best treatment of patients with VRL.

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MYD88 L265P mutation in intraocular lymphoma: A potential diagnostic marker

Cited by 17 publications

References 23 publications

Intraocular Lymphoma

Intraocular Lymphoma

Comparative Molecular Analysis of Primary Central Nervous System Lymphomas and Matched Vitreoretinal Lymphomas by Vitreous Liquid Biopsy

A comprehensive overview of diagnosis, imaging and treatment of vitreoretinal lymphoma

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