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Cytology of a vitreous specimen from a patient with PVRL showing large lymphoma cells with large irregular nuclei, prominent nucleoli and scanty basophilic cytoplasm. (Giemsa stain, original magnification x400).
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Primary vitreoretinal lymphoma (PVRL), previously called primary intraocular lymphoma (PIOL), is a rare and fatal ocular malignancy. PVRL is a subset of primary central nervous system lymphoma (PCNSL), mostly a diffuse large B-cell lymphoma. The diagnosis of PVRL is often challenging as it often masquerades as chronic uveitis. PVRL requires invasiv...
Context in source publication
Context 1
... PVRL cells rapidly die once they leave the eye, it is critical to process the specimen promptly (Chan, 2003). Routine cytology and histopathology are used to identify PVRL cells, which are characterized with large irregular nuclei, prominent nucleoli, and scanty basophilic cytoplasm (Figure 3). Mitoses are variable. ...
Similar publications
Primary vitreoretinal lymphoma (PVRL) is a rare ocular lymphoid malignancy, which consists a subset of primary central system lymphoma (PCNSL) and the most common type of intraocular lymphoma. The involvement of eyes is estimated to be approximately 20% of PCNSL, but the brain involvement may be up to 80% of PVRL. Typically, PVRL is a high grade B-...
Primary intraocular lymphoma (PIOL) is an ocular malignancy that is a subset of primary central system lymphoma (PCNSL). Approximately a third of PIOL patients will have concurrent PCNSL at presentation, and 42% to 92% will develop PCNSL within a mean of 8 to 29 months. Although rare, the incidence has been rising in both immunocompromised and immu...
Citations
... Prof. Xiaoxin Li of China, her two colleagues: Lyu-Zhen Huang, Peng Zhou, and myself co-authored a Chapter entitled Genetics and pathology of inflammatory components on AMD in Volume I [6] . One of my most favorite research subjects that demonstrated fruitful global collaboration was vitreoretinal lymphoma (VRL)-the most common intraocular lymphoma, formally known as primary vitreoretinal lymphoma, primary intraocular lymphoma, and reticular cell sarcoma [7][8][9] . There were two international VRL meetings in which I participated and coauthored two articles [7,10] . ...
... There were two international VRL meetings in which I participated and coauthored two articles [7,10] . VRL is a non-Hodgkin lymphoma of the central nervous system (CNS) involving the eye initially or secondarily [7][8][9][10] . Most of the VRL are large B-cell lymphoma; T-cell lymphoma is exceptionally rare [11] . ...
... Timely and accurate diagnosis of VRL improves patient outcome. Clinical history and examination, cytology and pathology are essential and the gold standard for the diagnosis of VRL [7][8]13] . Monoclonality is detected in VRL cells by immunohistochemistry, flow cytometry, and/or molecular analysis. ...
... 67 Similarly, primary vitreoretinal lymphoma requires aggressive chemotherapy and radiotherapy, although it typically responds well to initial treatment, the prognosis is generally poor due to a high recurrence rate. 68 3.4.2. Targeted chemotherapy 3.4.2.1. ...
... While the diagnosis of vitreoretinal lymphoma may be made via histologic and immunochemical confirmation via a vitreous sample obtained through diagnostic vitretomy [9], the low sensitivity may confound the diagnosis leading to delays in the diagnosis and treatment [10][11][12]. ...
... Vitreous biopsy with cytology is frequently utilized to establish a diagnosis of intraocular lymphoma [9]; however, a significant portion of the patients may have false negative results further delaying the diagnosis and treatment [10][11][12]. Moreover, the fragility and paucity of the vitreous lymphoma cells present another challenge in preserving the tissue for cytologic analysis [15]. ...
Purpose
To report a case of primary vitreoretinal lymphoma masquerading as infectious retinitis that was diagnosed via a retinal biopsy.
Observations
A 72-year-old female patient was referred to our ophthalmology clinic for evaluation of retinitis and vasculitis in the right eye (OD). On examination, best-corrected visual acuities (BCVAs) were hand motions OD and 20/20 in the left eye (OS). Fundus examination revealed optic disc edema and diffuse retinal whitening superior to the superotemporal arcade OD. Given the high suspicion of infectious retinitis, the patient was treated with intravitreal foscarnet, systemic acyclovir, and oral prednisone and underwent a comprehensive uveitis workup, which was unremarkable for viral and autoimmune entities. Given the patient’s history of diffuse large B cell lymphoma with cutaneous involvement, vitreoretinal lymphoma was suspected, prompting pars plana vitrectomy with a retinal biopsy. Biopsy and immunohistochemistry results were consistent with B-cell lymphoma, and the patient was treated with high-dose methotrexate and rituximab. At 5-month follow-up, BCVAs were hand motions OD and 20/30 OS, and fundus examination demonstrated disc edema with resolution of retinal whitening OD. She responded well to the treatment with regression of vitreoretinal lymphoma on examination and is being monitored closely for lymphoma recurrence.
Conclusions and importance
Although uncommon, patients with vitreoretinal lymphoma may masquerade as infectious retinitis, and vitreoretinal lymphoma should be suspected when refractory to antiviral therapy and in the setting of a negative workup for viral etiologies. Vitrectomy with retinal biopsy may be considered to aid the diagnosis of vitreoretinal lymphoma although careful consideration of the risks and benefits is warranted.
... When ocular lesions are the initial manifestation, central nervous system (CNS) infiltration that directly impacts the prognosis occurs frequently, occurring in approximately 56% to 90% of the cases within a few years of onset. 4,6 On the other hand, cases of primary CNS lymphoma infiltrating the eye represent approximately 10% to 20% of VRL. Additionally, reports indicate that 16% to 34% of cases presenting with ocular lesions at the onset of VRL already have CNS lesions. 2 The frequency of involvement of primary organs other than CNS, known as secondary (metastatic) cases, is approximately 12.4%. ...
Purpose:
Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL.
Methods:
Comprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort.
Results:
In total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations.
Conclusions:
This study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.
... Although not generally diagnostic in isolation, ancillary tests are therefore used to support the diagnosis. These tests include flow cytometry, detection of interleukins 6 (IL-6) and 10 (IL-10) and their ratio IL10:IL6, clonality analyses through immunoglobulin heavy (IgH) chain rearrangements, and MYD88 mutation analysis [5][6][7]. The diagnostic laboratory tools for VRL ideally are tests with high positive predictive value, thereby being able to detect as many cases of VRL as possible while carefully distributing the small sample. ...
Citation: Gozzi, F.; Bertolini, M.; Gentile, P.; Verzellesi, L.; Trojani, V.; De Simone, L.; Bolletta, E.; Mastrofilippo, V.; Farnetti, E.; Nicoli, D.; et al. Artificial Intelligence-Assisted Processing of Abstract: Anterior segment optical coherence tomography (AS-OCT) allows the explore not only the anterior chamber but also the front part of the vitreous cavity. Our cross-sectional single-centre study investigated whether AS-OCT can distinguish between vitreous involvement due to vitreoretinal lymphoma (VRL) and vitritis in uveitis. We studied AS-OCT images from 28 patients (11 with biopsy-proven VRL and 17 with differential diagnosis uveitis) using publicly available radiomics software written in MATLAB. Patients were divided into two balanced groups: training and testing. Overall, 3260/3705 (88%) AS-OCT images met our defined quality criteria, making them eligible for analysis. We studied five different sets of grey-level samplings (16, 32, 64, 128, and 256 levels), finding that 128 grey levels performed the best. We selected the five most effective radiomic features ranked by the ability to predict the class (VRL or uveitis). We built a classification model using the xgboost python function; through our model, 87% of eyes were correctly diagnosed as VRL or uveitis, regardless of exam technique or lens status. Areas under the receiver operating characteristic curves (AUC) in the 128 grey-level model were 0.95 [CI 0.94, 0.96] and 0.84 for training and testing datasets, respectively. This preliminary retrospective study highlights how AS-OCT can support ophthalmologists when there is clinical suspicion of VRL.
... When clinically suspected, a confirmative diagnostic test should be conducted. In the past years, the gold standard for diagnosis was the detection of malignant lymphoid cells in vitreous samples 14,15 . Immunohistochemistry, cytokine concentration analysis (IL-10/IL-6 ratio), flow cytometry, and polymerase chain reaction tests to detect immunoglobulin heavy chains or T-cell receptor gene rearrangement, respectively, may also support the diagnosis of VRL 15,16 . ...
... In the past years, the gold standard for diagnosis was the detection of malignant lymphoid cells in vitreous samples 14,15 . Immunohistochemistry, cytokine concentration analysis (IL-10/IL-6 ratio), flow cytometry, and polymerase chain reaction tests to detect immunoglobulin heavy chains or T-cell receptor gene rearrangement, respectively, may also support the diagnosis of VRL 15,16 . In our study, cytological analysis of vitreous specimens (56.6%) and cytokine analysis (36.3%) were the most commonly used methods to confirm the diagnosis of VRL. ...
To clarify the long-term visual prognosis and prognostic factors for vision loss in patients with vitreoretinal lymphoma (VRL). This retrospective longitudinal study included 64 consecutive patients with VRL. We analyzed the best-corrected visual acuity (BCVA), optical coherence tomography findings, and clinical features at every visit. Significant vision loss was defined as a final BCVA ≥ 0.5 logMAR. Predictors of significant vision loss following treatment were evaluated using univariate and multivariate linear regression analyses. We included 113 eyes of 64 patients (mean age, 64.2 ± 10.9 years), and 49 patients (76.6%) showed bilateral ocular involvement. The mean follow-up duration was 35.4 ± 25.8 months. At diagnosis, 36 (56.3%), 17 (26.6%), and 11 (17.2%) patients had primary, secondary, and concurrent VRL, respectively. All eyes received intraocular methotrexate injections (mean, 17.1 ± 5.5 injections). The mean BCVA improved from 0.44 ± 0.28 at diagnosis to 0.33 ± 0.29 1 month after treatment initiation. Vision improved significantly after treatment (final mean BCVA, 0.24 ± 0.21). Univariate and multivariate analyses showed that baseline BCVA and retinal/subretinal infiltration were significantly correlated with vision loss. In this study, a good visual outcome was maintained for > 35 months in patients with VRL. Baseline BCVA and retinal/subretinal infiltration were significant predictors of vision loss after treatment for VRL.
... Vitreoretinal lymphoma (VRL) is a rare ocular malignancy with an incidence of under 3% among intraocular tumors [44]. It is considered to be a subtype of central nervous system (CNS) lymphomas that predominantly affects the vitreous and/or retina, and usually resembles chronic intermediate or posterior uveitis [45,46]. [16,17]. ...
Preretinal deposits (PDs) are a rare condition among fundus diseases. We found that preretinal deposits have some features in common that can provide clinical information. This review affords an overview of PDs in different but related ocular diseases and events, and summarizes the clinical features and possible origin of PDs in related conditions, providing diagnostic clues for ophthalmologists when facing PDs. A literature search was performed using three major electronic databases (PubMed, EMBASE, and Google Scholar) to identify potentially relevant articles published on or before June 4, 2022. Most of the cases in the enrolled articles had optical coherence tomography (OCT) images to confirm the preretinal location of the deposits. Thirty-two publications reported PD-related conditions, including ocular toxoplasmosis (OT), syphilitic uveitis, vitreoretinal lymphoma, human T-cell lymphotropic virus type 1 (HTLV-I) associated uveitis or HTLV-I carriers, acute retinal necrosis, endogenous fungal endophthalmitis, idiopathic uveitis, and exogenous materials. Based on our review, OT is the most frequent infectious disease to exhibit PDs, and silicone oil tamponade is the most common exogenous cause of preretinal deposits. PDs in inflammatory diseases are highly suggestive of active infectious disease and are preferentially accompanied by a retinitis area. However, PDs will largely resolve after etiological treatment in either inflammatory or exogenous conditions.
... Primary vitreoretinal lymphoma (PVRL) is a rare extranodal non-Hodgkin lymphoma of the retina, vitreous, and optic nerve. Most PVRL patients are of the B-cell lineage; approximately 80% develop intracranial progression eventually, while 15%-20% of patients with primary central nervous system lymphoma (PCNSL) have intraocular involvement at diagnosis (1)(2)(3)(4). Thus, PVRL is also considered a subset of PCNSL. ...
... In brief, pathology is the gold standard for VRL diagnosis. Meanwhile, patients who fulfilled the following criteria of 1 + 2 and two of 3/4/5 were diagnosed with VRL, B-cell type: (1) clinical manifestations including typical vitreous opacities, subretinal lesions, or both; (2) aqueous humor or vitreous fluid IL-10/IL-6 >1; (3) vitreous pathology showing neoplastic lymphoma cells; (4) positive vitreous cell immunoglobulin gene rearrangement (IgH, Igk, or Igl); and (5) vitreous flow cytometry positive for lymphoma biomarkers. VRL patients with no evidence of CNS or systemic lymphoma were considered PVRL. ...
Primary vitreoretinal lymphoma (PVRL) is a rare variant of primary central nervous system lymphoma (PCNSL) that presents diagnostic challenges. Here, we focused on circulating cell-free DNA (cfDNA) and interleukin-10 (IL-10) isolated from cerebrospinal fluid. Twenty-three VRL patients (17 PVRL, 2 PCNSL/O, and 4 relapsed VRL, from 10/2018 to 12/2021) and 8 uveitis patients were included in this study. CSF samples from 19 vitreoretinal lymphoma patients had sufficient cfDNA for next-generation sequencing. Of these patients, 73.7% (14/19) had at least one meaningful non-Hodgkin lymphoma-related mutation. The characteristic MYD88 L265P mutation was detected in the CSF of 12 VRL patients, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 63.2%, 100%, 100%, and 46.2%, respectively. No meaningful lymphoma related mutations were found in CSF samples from uveitis controls with typical intraocular lesions. Meanwhile, CSF IL-10 levels were elevated in 95.7% of the VRL patients, with a sensitivity, specificity, PPV, and NPV of 95.7%, 100%, 100% and 88.9%, respectively. Key somatic mutations like MYD88 L265P and CD79B detected from CSF cfDNA and elevated CSF IL-10 levels can be promising adjuncts for primary vitreoretinal lymphoma diagnosis.
... In the past years, the gold standard for diagnosis was the detection of malignant lymphoid cells in vitreous samples. 8, 19 Immunohistochemistry, cytokine concentration analysis (IL-10/IL-6 ratio), ow cytometry, and polymerase chain reaction tests to detect immunoglobulin heavy chains or T-cell receptor gene rearrangement, respectively, may also support the diagnosis of VRL. 19,20 In our study, cytological analysis of vitreous specimens (60.3%) and cytokine analysis (31.3%) were the most commonly used methods to con rm the diagnosis of VRL. ...
... 8, 19 Immunohistochemistry, cytokine concentration analysis (IL-10/IL-6 ratio), ow cytometry, and polymerase chain reaction tests to detect immunoglobulin heavy chains or T-cell receptor gene rearrangement, respectively, may also support the diagnosis of VRL. 19,20 In our study, cytological analysis of vitreous specimens (60.3%) and cytokine analysis (31.3%) were the most commonly used methods to con rm the diagnosis of VRL. ...
Purpose: To clarify the long-term visual prognosis and prognostic factors for vision loss in patients with vitreoretinal lymphoma (VRL).
Methods: This retrospective longitudinal study included 64 consecutive patients with VRL. We analyzed the best-corrected visual acuity (BCVA), optical coherence tomography findings, and clinical features at every visit. Significant vision loss was defined as a final BCVA ≥0.5 logMAR. Predictors of significant vision loss following treatment were evaluated using univariate and multivariate linear regression analyses.
Results: We included 64 eyes of 64 patients (mean age, 64.2±10.9 years), and 49 patients (76.6%) showed bilateral ocular involvement. The mean follow-up duration was 35.4±25.8 months. At diagnosis, 36 (56.3%), 17 (26.6%), and 11 (17.2%) patients had primary, secondary, and concurrent VRL, respectively. All patients received intraocular methotrexate injections (mean, 16.3±5.9 injections).
The mean BCVA improved from 0.46±0.33 at diagnosis to 0.39±0.32 1 month after treatment initiation. Vision improved significantly after treatment (final mean BCVA, 0.29±0.29). Univariate and multivariate analyses showed that baseline BCVA and retinal/subretinal infiltration were significantly correlated with vision loss.
Conclusion: In this study, a good visual outcome was maintained for >35 months in patients with VRL. Baseline BCVA and retinal/subretinal infiltration were significant predictors of vision loss after treatment for VRL.
... Over 50% of patients with PVRL eventually develop brain lymphoma and 15% to 20% of patients with PCNSL present with intraocular lymphoma. [4] PVRL is difficult to diagnose early in clinical practice. The reasons for this are as follows. ...
Rationale:
Primary vitreoretinal lymphoma is a great masquerader and provides a diagnostic challenge.It is most frequently misdiagnosed as a chronic uveitis. Steroid treatment for presumed uveitis can interfere with the correct diagnosis of vitreoretinal lymphoma. Herein, we present a case of primary vitreoretinal lymphoma in which the correct diagnosis was delayed by short-term steroids until 2 years later.
Patient concerns:
A 45-year-old woman presented with floaters and blurred vision in her right eye for 3 months. An ocular examination revealed dense vitreous cells. Three months later, she developed headache and suicidal ideation after taking a 3-week medication of oral steroid medication from another eye clinic. Brain magnetic resonance imaging revealed a tumor involving the corpus callosum and periventricular region.
Interventions:
Vitreous biopsy and repeated brain biopsies were carried out for the patient.
Diagnosis:
A brain biopsy was performed for the first time, and a vitreous biopsy was performed when steroid medication was suspended for 20 and 41 days, respectively. Both biopsies were negative for the presence of malignant cells. Follow-up magnetic resonance imaging revealed complete remission of the brain tumor. Two years later, the tumor recurred in the optic chiasm. Diffuse large B-cell lymphoma was confirmed by a second brain biopsy.
Outcome:
The patient had complete tumor remission after receiving brain radiation therapy and chemotherapy.
Lessons:
Vitreoretinal lymphoma is difficult to diagnose owing to its rarity, masquerading presentation, and steroid-induced apoptosis of lymphoma cells. Physicians should consider vitreoretinal lymphoma as an important differential diagnosis in patients presenting with chronic uveitis and use steroids cautiously before making a definitive diagnosis.
