Images from a patient with Epstein-Barr virus–positive diffuse large B-cell lymphoma of the elderly. A and B, Before starting chemotherapy. C and D, After completion of chemotherapy. E, Positron emission tomography confirms marked left orbital uptake. There is also uptake in the spleen, mediastinum, and involved lymph nodes. F and G, Orbital magnetic resonance imaging shows a cystic mass in the left periorbital region that invades the orbit and anterior ethmoid sinus and is accompanied by eyelid ulceration. The mass shows heterogeneous low signal intensity on a T1-weighted axial image (F) and high signal intensity on a T2-weighted axial image (G).
Histological examination findings from the eyelid of a patient with Epstein-Barr virus–positive diffuse large B-cell lymphoma of the elderly. A, A diffuse lymphoid infiltrate with necrosis can be seen at low power (hematoxylin-eosin). B, At higher power, the infiltrate comprises large and pleomorphic tumor cells, including Hodgkinlike cells and Reed-Sternberg–like giant cells, with a background of smaller reactive inflammatory cells (hematoxylin-eosin). The tumor cells express B-cell markers CD20 (C) and Pax-5 (D), while CD30 (E) and latent membrane protein 1 (F) are also positive.
Tsuji H, Tamura M, Yokoyama M, Takeuchi K, Mimura T. Ocular Involvement by Epstein-Barr Virus–Positive Diffuse Large B-Cell Lymphoma of the Elderly: A New Disease Entity in the World Health Organization Classification. Arch Ophthalmol. 2010;128(2):258-259. doi:10.1001/archophthalmol.2009.381
The new World Health Organization classification of lymphoma places great emphasis on the definition of real biological disease entities in the category of diffuse large B-cell lymphoma (DLBCL). Epstein-Barr virus (EBV)–positive DLBCL of the elderly is a new subtype of DLBCL according to the 2008 World Health Organization classification. This is an extremely rare tumor, and no case of ocular EBV-positive DLBCL of the elderly has been reported to our knowledge. Here we describe the first case of EBV-positive DLBCL of the elderly with involvement of the eyelid and orbit.
An 83-year-old woman was referred with an eyelid tumor of her left eye. Serologically, human immunodeficiency virus antigen and anti–human T-cell lymphoma virus 1 antigen were both negative. The left upper and lower eyelids were affected by a hyperemic tumor with a rough surface and a small scab, which caused ectropion (Figure 1A and B). Physical examination revealed that her left submandibular, parotid, and cervical lymph nodes were enlarged. Staging examination showed that she had stage III B-cell malignant lymphoma according to the Ann Arbor classification. Orbital magnetic resonance imaging revealed a cystic mass in the left periorbital region, invading the orbit and the anterior ethmoid sinus (Figure 1F and G). Incisional biopsy of the left eyelid lesion was performed, revealing a tumor composed of pleomorphic large cells and marked by the presence of mononuclear Hodgkinlike cells and multinucleated Reed-Sternberg–like cells (Figure 2A and B). Immunohistochemistry revealed that the tumor cells expressed CD20 (Figure 2C), Pax-5 (Figure 2D), CD30 (Figure 2E), and multiple myeloma oncogene 1 protein (not shown). The tumor cells were also positive for latent membrane protein 1 (Figure 2F) but negative for EBV nuclear antigen 2 (not shown), indicating that the EBV infection pattern in this case was type 2 latency. Staining results for CD5, CD10, and the follicular B-cell lymphoma marker bcl-6 were negative (not shown). Based on these findings, a diagnosis of EBV-positive DLBCL of the elderly was made according to the new World Health Organization lymphoma classification. Cervical lymph node involvement was also confirmed by biopsy. Immediately after the biopsy, the patient received standard chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, followed by rituximab and etoposide. She achieved near complete remission after 4 months of chemotherapy. During the subsequent 4 months, there has been no evidence of local recurrence.
Epstein-Barr virus–associated B-cell lymphomas have been mainly reported in immunosuppressed patients such as those with human immunodeficiency virus infection, organ transplantation, or methotrexate therapy for rheumatoid arthritis.1 Epstein-Barr virus–positive DLBCL of the elderly is defined as a lymphoproliferative disorder arising in patients without predisposing immunodeficiency, including human immunodeficiency virus and human T-cell lymphoma virus 1 infection, a history of chemotherapy or radiotherapy, and autoimmune disease, and is thought to result from immunological deterioration associated with aging.2,3 According to the World Health Organization classification, EBV-positive DLBCL of the elderly is a rare DLBCL that accounts for 8% to 10% of DLBCL among patients without predisposing immunodeficiency in Asian countries.4 Interestingly, EBV-positive DLBCL of the elderly frequently involves extranodal sites.3,5 Most patients with extranodal disease also have nodal disease. In fact, 70% of patients have extranodal disease affecting sites such as the skin, lung, tonsils, or stomach, while 30% of patients have lymph node involvement alone.4 However, no case of ocular involvement, which is an extranodal site, has been reported. To our knowledge, our case is the first report of EBV-positive DLBCL of the elderly involving the eyelid and orbit.
Epstein-Barr virus–positive DLBCL of the elderly with ocular involvement is totally distinct, both clinically and pathologically, from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, an indolent tumor that is the most common form of lymphoma in the orbital region. Although relatively uncommon, EBV-positive DLBCL of the elderly should be considered in the differential diagnosis of ocular lymphoma since it needs to be treated appropriately as a highly aggressive lymphoma.
Correspondence: Dr Tsuji, Department of Ophthalmology, The Cancer Institute Hospital of JFCR, 3-10-6 Ariake, Kouto-ku, Tokyo 135-8550, Japan (email@example.com).
Author Contributions: Dr Tsuji had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Financial Disclosure: None reported.
Funding/Support: This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.