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Review
. 2025 Apr 15;64(8):1267-1274.
doi: 10.2169/internalmedicine.3817-24. Epub 2024 Sep 4.

Cognitive Dysfunction as an Initial Manifestation of Rheumatoid Arthritis-associated Intravascular Large B-cell Lymphoma

Junya Kitai  1   2 , Ryuichi Minoda Sada  1   3   4 , Satoko Yamaguchi  5 , Akiyo Shinde  5 , Wataru Maruyama  6
Affiliations
Review

Cognitive Dysfunction as an Initial Manifestation of Rheumatoid Arthritis-associated Intravascular Large B-cell Lymphoma

Junya Kitai et al. Intern Med. .

Abstract

A 58-year-old Japanese woman with rheumatoid arthritis (RA) presented with the sudden onset of cognitive dysfunction. A random skin biopsy revealed intravascular large B-cell lymphoma (IVLBCL), which resolved spontaneously with methotrexate withdrawal. However, four months later, the disease relapsed with liver injury. After completion of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy, both RA and IVLBCL remained in remission for two years. Among the pathological subtypes of RA-associated lymphoproliferative diseases, reports on IVLBCL are limited, and little is known about its clinical course. Our literature review summarizes the clinical course and mortality of 11 patients with RA-IVLBCL.

Keywords: cognitive dysfunction; intravascular large B-cell lymphoma; lymphoproliferative disorder; methotrexate; rheumatoid arthritis.

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Conflict of interest statement

The authors state that they have no Conflict of Interest (COI).

Figures

Figure 1.
Figure 1.
Initial MRI findings. a) Diffuse high-signal areas in the bilateral cerebral hemispheres on diffusion-weighted and FLAIR images. b) Subcortical high signal and linear high signal around the lateral ventricles on post-contrast T2-weighted images. c) Contrast effects with subarachnoid pattern on post-contrast FLAIR images. Arrowheads indicate high-intensity lesions. CE-FLAIR: contrast-enhanced fluid-attenuated inversion recovery, DWI: diffusion-weighted imaging, L: left, R: right
Figure 2.
Figure 2.
Biopsy findings. a) A skin biopsy shows large, atypical cells in the small vessels. Hematoxylin and Eosin (H&E) staining ×400. b) Positive immunostaining for CD20. H&E staining ×200.
Figure 3.
Figure 3.
MRI findings after MTX withdrawal. a) The subcortical high signal and periventricular linear high signal in the lateral ventricles seen on post-contrast T2-weighted MRI are improved. b) The subarachnoid pattern seen on post-contrast FLAIR MRI is improved. L: left, MRI: magnetic resonance imaging, MTX: methotrexate, R: right, FLAIR: fluid attenuated inversion recovery
Figure 4.
Figure 4.
Clinical course of the patient. LDH: lactate dehydrogenase, MTX: methotrexate, R-CHOP: rituximab, doxorubicin, cyclophosphamide, vincristine, prednisolone
See this image and copyright information in PMC

References

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    1. Honda S, Sakai R, Inoue E, et al. Association of methotrexate use and lymphoproliferative disorder in patients with rheumatoid arthritis: results from a Japanese multi-institutional retrospective study. Mod Rheumatol 32: 16-23, 2022. - PubMed
    1. Banko A, Miljanovic D, Lazarevic I, et al. New evidence of significant association between EBV presence and lymphoproliferative disorders susceptibility in patients with rheumatoid arthritis: a systematic review with meta-analysis. Viruses 14: 115, 2022. - PMC - PubMed
    1. Gaulard P, Swerdlow SH, Harris NL, Sundstrom C, Jaffe ES. Other iatrogenic immunodeficiency-associated lymphoproliferative disorders. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th ed. Swerdlow SH, Campo E, Harris NLet al. , Eds. IARC Press, Lyon, 2017: 462-464.
    1. Tokuhira M, Tamaru JI, Kizaki M. Clinical management for other iatrogenic immunodeficiency-associated lymphoproliferative disorders. J Clin Exp Hematop 59: 72-92, 2019. - PMC - PubMed

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