Radiation Exposure As a Link to Primary Ocular Diffuse Large B Cell Lymphoma (PODLBCL) - a Possible Cluster Related to the Chernobyl Explosion

Background: PODLBCL, a rare form of diffuse large B cell lymphoma (DLBCL), arises primarily from the retina and urea. It is estimated to occur in 100 patients/3 years in the United States. Its etiology is unknown although chronic inflammation is thought to play a significant role. It is observed most commonly in immunocompetent patients. EB virus has not been associated with the form of lymphoma. The disease is frequently bilateral (80%) and 56-85% of patients will develop intracerebral metastases. There is a slight male predominance. The peak of incidence is between the fifth and seventh decade.

Methods: We have recently had an opportunity to evaluate six patients at the MS/BICCC from 2010-2013. All received initial therapy at MS/BICC. We have analyzed disease presentation, various demographic factors, possible exposure information, treatment and outcome. In addition, epidemiologic studies of the Chernobyl (Ukraine) nuclear power plant explosion (April 26, 1986) were reviewed. The most contaminated regions included Belarus and the Ukraine, with volatile fission products traveling at greater distances (Bard D, Verger P, Hubert P. Chernobyl, 10 Years After: Health Consequences Epidemiologic Reviews 1997:19 (2):187-201). The main health effect continues to be that of thyroid cancers. With respect to ocular findings, liquidators were found to develop senile cataracts, premature myopia and arteriosclerosis of the fundic vessels. The ten-year follow-up demonstrated a slight increase in subcapsular lens changes in children. At the 20 year follow-up (Cardis E, Howe G, Ron E, et al.) Cancer Consequences of the Chernobyl Accident: 20 Years On. J. Radiol Prot 2006; 26:127-140) there has been no conclusive reported increase in childhood or adult leukemia of lymphoma. In the most recent update (Pflugbeil S, Claussen A, Schmitz-Feuerhake. Health Effects of Chernobyl 25 Years After the Reactor Catastrophe. 2011: Gesellschaft fur Strahlenschutz) there is still no definitive evidence of an increase in lymphoma. Results: In our series the most common complaint was cloudiness of vision and the most common findings were anterior chamber inflammation, sheets of cells within the vitreous, uveitis and subretinal and retinal infiltrates. The presentation was bilateral in all patients. The mean age at presentation was 76 years (62-84), including five women and one man (the female predominance is unusual). At the time of exposure, four of the patients were living in the Ukraine; one in Moldova and one is southern Poland. The mean time possible exposure to appearance of PODLBCL was 26 years. The diagnosis was made by vitreous FNA (2), vitreous biopsy (4), clinical presentation (1). Initial treatments included chemotherapy (high dose methotrexate) in two patients, and radiation therapy in four patients. Of the six there was one synchronous presentation with brain lymphoma. Two patients developed spread to the brain, one of whom expired and one of whom is considered NED after whole brain irradiation and temazolomide. Five patients remain NED, but at short follow-up.

Conclusions: Conceptionally, lymphomas are thought to develop because of an inherent sensitivity of lymphoid cells to genetic instability, immune stimulation, inherited genetic disorders, toxins, infections agents as well as radiation injury. For almost all etiologies it is accepted that a long prodromal period between exposure and subsequent appearance of neoplasia occurs and these case reports may be an illustration of this phenomena. It is estimated that several million Europeans were exposed to radiation as a result of this explosion. As the ocular globe would appear to be one of the most exposed organs, more patients with this unusual malignancy may be seen and an appreciation of this possibility would seem warranted.