Diffuse large B‐cell lymphoma of the ocular adnexal region: A nation‐based study

Purpose: To characterize the clinicopathological features of diffuse large B‐cell lymphoma (DLBCL) of the ocular adnexal region. Methods: The present series of orbital and adnexal DLBCLs were found by searching the Danish Registry of Pathology between 1980 and 2009. Histological specimens were re‐evaluated using a panel of monoclonal antibodies. Clinical files from all patients with confirmed DLBCL were collected. Results: A total of 34 patients with DLBCL of the ocular adnexal region were identified. Eighteen of the patients were men. The patients had a median age of 78 years (range 35–97 years). Ninety‐seven per cent of the patients had unilateral ocular adnexal region involvement, and the orbit (76%) was the most frequently affected site. Nineteen patients (56%) presented with Stage I lymphoma. Of these, 18 were diagnosed with primary lymphoma. Four patients (12%) had Stage II, one patient (3%) had Stage III and ten patients (29%) presented with Stage IV lymphoma. The 5‐year overall survival (OS) rate for the whole study group was 20%. The patients with Stage I lymphoma had a significantly better 5‐year OS rate (28%) than patients in Stage II‐IV (5‐year OS rate, 9%). In Cox regression analysis, concordant bone marrow involvement and the International Prognostic Index (IPI) score were prognostic factors for OS. Conclusions: Diffuse large B‐cell lymphoma of the ocular adnexal region is mainly prevalent in elderly patients. Most patients had unilateral orbital involvement. The overall prognosis is poor. Concordant bone marrow involvement and the IPI score were independent prognostic factors for mortality.     

Relationship between vitreoretinal lymphoma and the site of lymphoma development in the central nervous system

Japanese Journal of Ophthalmology - To investigate diffuse large B-cell lymphoma lesions with central nervous system (CNS) involvement in patients with vitreoretinal lymphoma (VRL) during long-term...     

B-scan ultrasound and cytology of the vitreous in primary central nervous system lymphoma with vitreoretinal involvement

AIM: To evaluate the diagnostic value of B-scan ultrasound and explore the cytological characteristics of patients with vitreoretinal lymphoma (VRL) and primary central nervous system lymphoma (PCNSL). METHODS: The clinical data and pathologic specimens from patients with VRL diagnosed at the North Huashan Hospital from 2016 to 2017 were retrospectively reviewed. The patients were diagnosed by slit lamp ophthalmoscopy, B-scan ultrasound, cytology of the vitreous, which was obtained by vitrectomy, and cytokine measurements of interleukin (IL)-10 and IL-6. RESULTS: Twenty-six eyes (19.4%) out of 134 eyes of 67 patients (47 men and 20 women) with PCNSL were diagnosed with VRL by B-scan ultrasound, and 14 eyes (10.4%) were diagnosed by slit lamp ophthalmoscopy. Twenty-four eyes (17.9%) of 17 patients were confirmed as having VRL with cytology. No difference in the association between intracranial lesion location and ocular involvement was found. VRL patients had higher levels of vitreous IL-10 and IL-10/IL-6 when compared with macular hole cases, but the difference was not statistically significant. CONCLUSION: A total of 25.4% of the PCNSL patients had VRL, B-scan ultrasound examination had characteristic features and is recommended over slit lamp ophthalmoscopy for the screening diagnosis of PCNSL with intraocular involvement. Moreover, the cytological and immunohistochemical analyses performed after 25-gauge diagnostic vitrectomy were accurate diagnostic techniques.     

Association between ocular findings and preventive therapy with onset of central nervous system involvement in patients with primary vitreoretinal lymphoma

Purpose

To investigate if the site of ocular lesions and prophylactic treatment in patients with primary vitreoretinal lymphoma (PVRL) are associated with the time to onset of central nervous system (CNS) involvement.

Methods

We retrospectively studied 26 patients (seven men, 19 women; mean age, 67.0?±?11.1 years) with a diagnosis of PVRL at our hospital between January 2001 and October 2011 and a minimum 2-year follow-up after treatment. We classified the PVRL lesions as: (1) the vitreous opacity type, vitreous opacity of 2+ or higher without retinal lesions, (2) the retina type, vitreous opacity of 1+ or less with retinal lesions only, or (3) the concomitant type, with both. We also evaluated whether prophylactic treatment of systemic chemotherapy such as high-dose methotrexate (HD-MTX) and intrathecal MTX (IT-MTX), or topical ocular treatments such as intravitreal injections of MTX and rituximab, inhibited the onset of CNS involvement in patients with PVRL without cerebral involvement.

Results

During a mean follow-up of 44.0?±?18.7 months, CNS involvement began in 14 patients (53.8 %), i.e., three (60 %) of five patients with retina-type lesions, five (41.7 %) of 12 patients with vitreous opacity-type lesions, and six (66.7 %) of nine patients with concomitant-type lesions. There was no significant (P?=?0.496) association between the site of the ocular lesions and the onset of brain lesions. In addition, CNS involvement occurred in eight of 11 patients receiving CNS prophylactic chemotherapy and six of 15 patients receiving no prophylaxis; the difference between the two did not reach significance (P?=?0.131). The time to onset of cerebral involvement in the CNS prophylactic chemotherapy group (42.8?±?13.8 months) was significantly (P?=?0.0005) longer than in the group that did not receive prophylaxis (10.2?±?2.0 months). Preventive systemic chemotherapy, especially HD-MTX, significantly prolonged the time to the onset of brain lesions compared to IT-MTX and local ocular therapy.

Conclusions

While prophylactic systemic chemotherapy did not inhibit the onset of CNS involvement in most of patients with PVRL, it significantly prolonged the time to cerebral involvement.     

Malignant lymphoma of the central nervous system and eye

Intraocular lymphoma was encountered in 11.4% of the 79 examined patients with malignant lymphoma of the central nervous system. In most cases it had occurred long on an average of 26 months before the development of neurological manifestations and the diagnosis of cerebral lymphoma. Biomicroscopy showed intraocular lymphoma to manifest itself as corneal endothelial precipitation of translucent corpuscles, opacity of the vitreous body, and its posterior detachment. Isolated intraocular lymphoma has been misinterpreted as uveitis of unclear etiology. In this connection, resistance to steroidal and antibacterial therapy should be an indication for diagnostic vitrectomy, followed by an immunohistochemical study of a biopsy specimen. The intraarterial administration of methotrexate, by breaking the blood-brain barrier, caused regression of cerebral lymphoma, but did not result in that of intraocular lymphoma, on this basis the authors consider the intravitreal injection of the agent to be indicated.     

Intraocular and central nervous system lymphoma in a cardiac transplant recipient.

BACKGROUND: Although B-cell lymphomas are the most frequent cancers that evolve in transplant patients, histopathologic verification of intraocular lymphoma as a result of cyclosporine immunosuppression has not been previously recognized. METHODS: A complete autopsy was performed on a 67-year-old woman who died 33 months after orthotopic heart transplantation. FINDINGS: Large cell lymphoma extensively involved the anterior segment of the left eye, as well as the vitreous, retina, subretinal pigment epithelial zone, and optic nerve. Tumor also was found in the ipsilateral orbitofrontal cortex and hypothalamic areas. No systemic lymphoma was present. CONCLUSION: Ocular and central nervous system lymphoma developed in a heart transplant patient. In addition to opportunistic infections, ophthalmologists should be aware that opportunistic lymphoproliferative disorders involving the eye and brain can occur in these immunosuppressed individuals. Epstein-Barr virus infection has been implicated as playing a major role.     

Intraocular-central nervous system lymphoma: clinical features, diagnosis, and outcomes.

OBJECTIVE: To analyze the clinical features, laboratory investigations, and diagnosis of intraocular-central nervous system (CNS) lymphoma in a cohort of patients who underwent diagnostic vitrectomy. DESIGN: Retrospective case series. METHOD AND STUDY MATERIALS: Thirty-four vitreous biopsy specimens obtained from 26 patients with treatment-resistant or unusual uveitis were re-evaluated in a masked fashion. The specimens were classified into three groups: "negative," "suspicious of malignancy," and "positive" based on the cytologic features, immunomarkers, and flow cytometry. The medical records of the patients were reviewed retrospectively. MAIN OUTCOME MEASURES: The reliability of vitreous cytology in diagnosing intraocular-CNS lymphoma and the differences in clinical features of patients with intraocular-CNS lymphoma and uveitis. RESULTS: The two ocular pathologists concurred in their criteria for interpretation of all specimens. There was 100% concordance between the cytologic reports read independently by the two ocular pathologists over the 5-year period and the read-out done in a masked fashion at the time of the study. Ten patients were diagnosed with intraocular-CNS lymphoma based on the vitreous cytology and clinical features. The time interval between the initial presentation and vitreous biopsy was 1 week to 2 years, with 80% of the patients diagnosed within the first year. Retinal involvement in the form of lymphomatous subretinal pigment epithelial infiltrates, vasculitis, and apparent retinochoroiditis was present in six cases. Initial neuroimaging studies revealed concomitant CNS involvement in three patients, and an additional three developed CNS lymphoma following diagnosis by vitreous biopsy. Patients were treated with radiotherapy, chemotherapy, or both. Two of the four patients with a follow-up of greater than 12 months died due to CNS involvement. CONCLUSIONS: Vitreous cytology is a sensitive, reliable, and reproducible method of diagnosing intraocular-CNS lymphoma. A high index of suspicion based on the clinical findings and course of the uveitis is critically important in decision-making for diagnostic vitrectomy. Central nervous system involvement is frequent and associated with a high mortality rate. Ophthalmology 1999;106:1805-1810     

Maculopathy as a complication of blood-brain barrier disruption in patients with central nervous system lymphoma

PURPOSE: To report on the development of visually significant maculopathy associated with blood-brain barrier disruption (BBBD) therapy for the treatment of central nervous system (CNS) lymphoma. DESIGN: Retrospective case series. METHODS: Chart review of 20 patients undergoing BBBD therapy for treatment of CNS lymphoma at the Cleveland Clinic. Patients with documented maculopathy were included in analysis. RESULTS: Seven (54%) of 13 patients were identified with new macular retinal pigment epithelium (RPE) changes after BBBD treatment. The RPE changes consisted of fine clumps of hyperpigmentation in the foveal region associated with variable degrees of RPE loss. These changes were bilateral but often asymmetric. Two patients had decreased visual acuity resulting from maculopathy. One patient had documented progression of maculopathy after completion of treatment. CONCLUSIONS: Maculopathy is a frequent finding after BBBD therapy for CNS lymphoma.     

Bilateral ophthalmic artery occlusion in a patient with acquired immunodeficiency syndrome and central nervous system lymphoma

PURPOSE: Clinical course and autopsy findings in a patient with human immunodeficiency virus-1 immunodeficiency, central nervous system lymphoma, and bilateral, simultaneous ophthalmic artery occlusions. DESIGN: Observational case report. METHODS: Clinical examination, fundus photography, gross and microscopic pathologic study. RESULTS: Fundus photographs disclosed stasis in retinal arterioles, the absence of a cherry-red spot; internal carotid arteriography disclosed bilateral ophthalmic artery occlusions; postmortem histopathologic examination disclosed bilateral ophthalmic artery atherosclerosis, retinal ischemic necrosis, ischemic optic neuropathy, diffuse large-cell lymphoma of multiple areas of the central nervous system, cytomegalovirus encephalitis, atherosclerosis, and bronchopneumonia. CONCLUSIONS: A 47-year-old male with acquired immunodeficiency syndrome, profound immunodeficiency, systemic hypertension, and central nervous system lymphoma, developed deep vein thrombosis, bilateral ophthalmic artery occlusions, and died of pneumonia 7 weeks after the onset of blindness. Postmortem study revealed bilateral ophthalmic artery hemorrhagic atherosclerosis, ischemic optic neuropathy, ischemic retinal necrosis, diffuse large-cell central nervous system lymphoma, cytomegalovirus encephalitis, pneumonitis, and systemic atherosclerosis.