Clinical features of primary vitreoretinal lymphoma developing extra‐central nervous system (CNS)/testicular lymphomas with or without CNS involvement: A single‐centre study of 13 cases

Vitreoretinal lymphoma (VRL) is a type of haematologic malignant neoplasm. Among VRLs, primary VRL (PVRL) is a subset of primary central nervous system (CNS) lymphoma (CNSL), which initially manifests in the eye with or without simultaneous CNS involvement. VRL is a rare malignancy typically classified as diffuse large Bcell lymphoma. PVRL most frequently affects older populations and usually develops in the retina, the vitreous chamber, and/or the optic nerve. In a previous report, 65% of patients presenting with PVRL developed CNSL, usually within 29 months, with poor survival outcome.1 PVRL has been reported to have a fiveyear survival rate of less than 30%.2 On the other hand, a multicentre study in Japan reported that the fiveyear survival rate of PVRL improved to 61.1% due to earlier diagnosis, new diagnostic tests, and refined diagnostic criteria.3 The reason for the high incidence of CNSL and testicular lymphoma in PVRL is that the eye, CNS, and testis are immuneprivileged sites, with similar immune mechanisms.4 On the other hand, extraCNS/testicular involvement after PVRL is rare. Although some cases have been reported,5– 11 there are no crosssectional or cohort studies. Among 105 patients diagnosed with VRL in our department, some of the patients diagnosed with PVRL subsequently developed lymphomas in organs other than the CNS and testis. In this study, we examined the demographic and clinical features as well as diagnostic findings of these cases. We retrospectively reviewed the medical records of all patients diagnosed with VRL at the Department of Ophthalmology of Tokyo Medical University Hospital. Institutional review board approval was obtained for this retrospective study. The diagnosis of VRL was based on clinical features and test results of diagnostic vitrectomy, comprising cytology, cytokine analysis and polymerase chain reaction analysis, as described previously.12 All patients with ocular lesions were examined by cranial magnetic resonance imaging (MRI) and/or computed tomography (CT) to detect CNSL during the followup period. Lymphomas in extraCNS/testicular organs were detected and diagnosed by biopsy and/or systemic workup such as systemic CT and/or scintigraphy gallium scintigraphy and/or positron emission tomography (PET)/ CT fusion scan. Primary measures in this study were the clinical features of PVRL with subsequent extraCNS/testicular involvement, including the presence or absence of CNS lesion, number of relapses, and disease duration. Statistical analyses were performed using JMP version 13 (Business Unit of SAS, Cary, NC, USA). Upon testing for normal distribution with the Shapiro– Wilk test, the data were found to be not normally distributed. Thus, nonparametric tests (chisquared test and Mann– Whitney test) were used to determine significant differences between two groups. The fiveyear survival rate was defined as the proportion of patients surviving five years or longer after the initial diagnosis of VRL. Survival curves were estimated by the Kaplan– Meier method and analysed using the logrank test. A p value less than 0.05 was considered statistically significant. A total of 163 eyes of 105 patients diagnosed with VRL during the study period were included in the study. Their demographic and clinical data are shown in Table S1. Thirtyone patients (29.5%) had PVRL only; 53 patients (50.5%) had both VRL and CNSL; and 21 patients (20.0%) had VRL and extraCNS/testicular lymphoma. Among 21 patients with VRL and extraCNS/testicular involvement, 13 (12.4% of all VRL patients) had PVRL and subsequent extraCNS/testicular involvement with/without CNSL; eight patients (7.6% of all VRL patients) had primary extraCNS/testicular lymphoma with subsequent development of VRL with/without CNSL during the observation period. The clinical features of VRL diagnosed in our institution are summarized in Figure 1 and Table S1. The 13 patients in the PVRL + extraCNS/testicular involvement group were the subjects of analysis in this study. Table S2 shows the detailed clinical features and relapses in these patients. The sites of involvement were lymph nodes (LN) in five cases; skin in two cases; bone marrow in two cases; and lung, heart, paranasal sinus, buccal region, spleen, ascites, and pleural and pericardial effusion in one case each (with overlap). The imaging findings of representative systemic lymphomas Received: 4 November 2022 | Accepted: 10 January 2023