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B. Harold Lee, MD; Jose S. Pulido, MD, MS; Helmut Buettner, MD; Diva Salomão, MD; Clive S. Zent, MD; Thomas P. Link, BA

Arch Ophthalmol. 2006;124:1357-1359.

Intravascular large B-cell lymphoma is a rare form of extranodal lymphoma characterized by the presence of large lymphoma cells in the lumen of small blood vessels, involving multiple organs. The diagnosis is usually made at the time of autopsy. We report a patient with intravascular large B-cell lymphoma who had vision loss from choroidal involvement, which improved with systemic therapy.

Report of a Case
A 44-year-old white man was initially seen with bilateral blurred vision, Coombs-negative hemolytic anemia, and a maculopapular skin rash on both upper arms. The patient's best-corrected visual acuity (Snellen) was OD 20/40 –2 and OS 20/50. There were bilateral serous detachments involving the macula (Figure 1A). A small, superficial intraretinal hemorrhage was noted along the inferotemporal vascular arcade in the right eye, and peripheral flame-shaped intraretinal hemorrhages were present in both eyes. Fluorescein and indocyanine green angiography demonstrated irregular filling of the choroid early with bilateral pinpoint areas of fluorescence later (1 day) (Figure 1C). B-scan ultrasonography showed thickening of the choroid bilaterally (Figure 1B).

View larger version (141K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 1. A, Color fundus photograph of the right eye revealing serous detachments and intraretinal heme along the inferotemporal arcade. B, B-scan ultrasound of the right globe at initial examination. There is marked choroidal thickening and elevation of the serous detachments. C, Late-frame fluorescein angiogram (1 day) of the right eye revealing punctate hyperfluorescence surrounding the localized serous detachments, which accumulate fluorescein dye. D, Indocyanine green angiogram of the right eye revealing punctate hyperfluorescent lesions of the choroid. E and F, Late frames of the right eye (1 week after treatment) demonstrating resolution of previously noted abnormalities.

The patient had a normocytic anemia with an increased reticulocyte count, lactate dehydrogenase level, and bilirubin concentration. A computed tomographic scan of his chest and abdomen showed hazy ground-glass infiltrates throughout the lungs (Figure 2A), splenomegaly, and diffuse edema within the subcutaneous tissues of the thorax and abdomen. A biopsy specimen of his skin lesions showed nonspecific inflammatory cell infiltration of the dermis. A bone marrow biopsy specimen revealed hypercellularity with trilineage hyperplasia consistent with a peripheral destructive process. The blood smear demonstrated several atypical lymphocytes with convoluted nuclei. Cerebrospinal fluid examination re sults were normal, while a lung biopsy specimen revealed large, atypical CD20-positive and CD3-negative lymphocytes filling the lumen of the capillaries in the alveolar septae (Figure 2B and C). These findings were diagnostic of malignant intravascular lymphoma of B-cell phenotype (intravascular lymphomatosis).

View larger version (77K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 2. A, Granular, ground-glass appearance of patient's computed tomographic scan of the chest. B, Hematoxylin-eosin stain of lung biopsy specimen (original magnification x 40) demonstrating large lymphoid cells within the vasculature of individual alveoli. C, Immunohistochemical stain (original magnification x 40) of lung biopsy specimen showing a positive stain for the CD20 marker in brown.

A regimen of hyper-CVAD (cycle 1: cyclophosphamide, vincristine, doxorubicin, and dexamethasone) chemotherapy, intrathecal methotrexate and cytarabine, and methylprednisolone was initiated 10 days after initial examination. A week later, there was a marked improvement in visual acuity (20/20 OU) and resolution of serous detachments and choroidal thickening, shown by repeat fluorescein angiography and indocyanine green angiography (Figure 1E and F). The patient continued to do well 2 months after starting therapy.

Comment
Intravascular large B-cell lymphoma is a rare form of extranodal malignant lymphoma in which the lymphoid cells are principally found within small vessels without extensive involvement of bone marrow or lymphoid tissue.¹ Aberrant expression or deletion of certain cell adhesion molecules critical for lymphocyte trafficking and transvascular migration (CD29 and CD54) contributes to the tumor's intravascular and disseminated pattern of distribution.² The tumor expresses CD20 and other B-cell markers and does not express the T-cell marker CD3.³ At diagnosis, the lymphoma typically involves various organs, including the central nervous system, skin, lung, kidneys, spleen, and adrenal glands.⁴ Other types of lymphoma may separately coexist with intravascular large B-cell lymphoma in the same patient.² Hematologic abnormalities, like microangiopathic and autoimmune hemolytic anemia, as in our case, are often associated with this disease process.¹ The prognosis is generally very poor because of the usually delayed diagnosis. Intravascular large B-cell lymphoma can also involve the small vessels of the choroid. The case presented herein adds the eye as another end organ involved by this rare malignancy.

AUTHOR INFORMATION
Correspondence: Dr Pulido, Mayo Clinic, Department of Ophthalmology, 200 First St SW, Rochester, MN 55901-0001 (pulido.jose{at}mayo.edu).

Author Contributions: Dr Pulido, principal investigator, had full access to all 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 project was funded by an unrestricted grant from Research to Prevent Blindness, New York, NY.

REFERENCES
1. Gattner KC, Warnke RA. Intravascular large B-cell lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer (IARC). Lyon, France: IARC Press; 2001:177-178. 2. Ponzoni M, Arrigoni G, Gould VE, et al. Lack of CD29 (beta integrin) and CD 54 (ICAM-1) adhesion molecules in intravascular lymphomatosis. Hum Pathol. 2000;31:220-226. FULL TEXT | ISI | PUBMED 3. Imai H, Kajimoto K, Taniwaki M, et al. Intravascular large B-cell lymphoma presenting with mass lesions in the central nervous system: a report of five cases. Pathol Int. 2004;54:231-236. FULL TEXT | ISI | PUBMED 4. Sugimoto KJ, Mori KL, Oshimi K. Intravascular large B-cell lymphoma. Am J Hematol. 2004;76:291-292. FULL TEXT | ISI | PUBMED

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