Intraocular Lymphoma: Update on Diagnosis and Management
Background: Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system lymphoma (PCNSL) in which lymphoma cells initially invade the retina, vitreous, or optic nerve head, with or without concomitant CNS involvement. The incidence of this previously rare condition has increased dramatically. Given its nonspecific presentation and aggressive course, PIOL provides a diagnostic and therapeutic challenge.
Methods: We review the current strategies for diagnosis and treatment of PIOL and present our own experience with PIOL.
Results: Recent developments in the diagnosis of PIOL include immunohistochemistry, flow cytometry, cytokine evaluation, and molecular analysis. However, definitive diagnosis still requires harvesting of tissue for histopathology. Optimal treatment for PIOL remains unclear. Initial therapeutic regimens should include methotrexate-based chemotherapy and radiotherapy to the brain and eye. In addition, promising results have been seen with intravitreal methotrexate and autologous stem cell transplantation for recurrent and refractory disease.
Conclusions: Efforts to further determine the immunophenotype and molecular characteristics of PIOL will continue to assist in the diagnosis of PIOL. Future studies are required to determine the role of radiotherapy and optimal local and systemic chemotherapeutic regimens.
Primary central nervous system lymphoma (PCNSL) is usually a diffuse large B-cell non-Hodgkin's lymphoma that originates in the brain, spinal cord, leptomeninges, or eyes. PCNSL accounts for 4% to 6% of primary brain tumors and 1% to 2% of extranodal lymphomas. Primary intraocular lymphoma (PIOL) is a subset of PCNSL in which malignant lymphoid cells involve the retina, vitreous, or optic nerve head, with or without concomitant CNS involvement. This disease entity has also been referred to ocular reticulum cell sarcoma in older literature. In rare cases, PCNSL and PIOL may be T-cell lymphomas. Because PIOL remains confined to neural structures, it is distinguished from primary orbital lymphoma and systemic non-Hodgkin's lymphomas that either involve or metastasize via the circulation to the uvea and ocular adnexa of the orbit, lacrimal gland, and conjunctiva.
While PIOL is a rare disease, its incidence over the past 15 years has risen, most likely due to the concomitant rise in PCNSL. The incidence of PCNSL has increased in both immunocompetent and immunocompromised people from 0.027/100,000 in 1973 to 1/100,000 in the early 1990s. While much of this rise can be accounted for by the increasing number of patients with immunodeficiencies, this does not completely account for the increase. The cause for the increased incidence in immunocompetent patients is unknown.
The median age of onset of PCNSL/PIOL in immunocompetent patients is the late 50s and 60s, with a reported range of 15 to 85 years of age for PIOL. The male-female ratio is 1.2-1.7:1. Half of the patient population with PCNSL has multifocal disease at the time of initial presentation, with ocular involvement found in 15% to 25%. On the other hand, 60% to 80% of patients in whom PIOL is initially diagnosed develop CNS disease within a mean of 29 months. Ocular disease is bilateral in 80% of cases. This literature review provides an update of current diagnostic and treatment options for PIOL.
Background: Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system lymphoma (PCNSL) in which lymphoma cells initially invade the retina, vitreous, or optic nerve head, with or without concomitant CNS involvement. The incidence of this previously rare condition has increased dramatically. Given its nonspecific presentation and aggressive course, PIOL provides a diagnostic and therapeutic challenge.
Methods: We review the current strategies for diagnosis and treatment of PIOL and present our own experience with PIOL.
Results: Recent developments in the diagnosis of PIOL include immunohistochemistry, flow cytometry, cytokine evaluation, and molecular analysis. However, definitive diagnosis still requires harvesting of tissue for histopathology. Optimal treatment for PIOL remains unclear. Initial therapeutic regimens should include methotrexate-based chemotherapy and radiotherapy to the brain and eye. In addition, promising results have been seen with intravitreal methotrexate and autologous stem cell transplantation for recurrent and refractory disease.
Conclusions: Efforts to further determine the immunophenotype and molecular characteristics of PIOL will continue to assist in the diagnosis of PIOL. Future studies are required to determine the role of radiotherapy and optimal local and systemic chemotherapeutic regimens.
Primary central nervous system lymphoma (PCNSL) is usually a diffuse large B-cell non-Hodgkin's lymphoma that originates in the brain, spinal cord, leptomeninges, or eyes. PCNSL accounts for 4% to 6% of primary brain tumors and 1% to 2% of extranodal lymphomas. Primary intraocular lymphoma (PIOL) is a subset of PCNSL in which malignant lymphoid cells involve the retina, vitreous, or optic nerve head, with or without concomitant CNS involvement. This disease entity has also been referred to ocular reticulum cell sarcoma in older literature. In rare cases, PCNSL and PIOL may be T-cell lymphomas. Because PIOL remains confined to neural structures, it is distinguished from primary orbital lymphoma and systemic non-Hodgkin's lymphomas that either involve or metastasize via the circulation to the uvea and ocular adnexa of the orbit, lacrimal gland, and conjunctiva.
While PIOL is a rare disease, its incidence over the past 15 years has risen, most likely due to the concomitant rise in PCNSL. The incidence of PCNSL has increased in both immunocompetent and immunocompromised people from 0.027/100,000 in 1973 to 1/100,000 in the early 1990s. While much of this rise can be accounted for by the increasing number of patients with immunodeficiencies, this does not completely account for the increase. The cause for the increased incidence in immunocompetent patients is unknown.
The median age of onset of PCNSL/PIOL in immunocompetent patients is the late 50s and 60s, with a reported range of 15 to 85 years of age for PIOL. The male-female ratio is 1.2-1.7:1. Half of the patient population with PCNSL has multifocal disease at the time of initial presentation, with ocular involvement found in 15% to 25%. On the other hand, 60% to 80% of patients in whom PIOL is initially diagnosed develop CNS disease within a mean of 29 months. Ocular disease is bilateral in 80% of cases. This literature review provides an update of current diagnostic and treatment options for PIOL.