RESEARCH - Lymphoproliferative disorders in RA: clinicopathological analyisis of 76 cases in relation to MTX

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J Rheumatol. 2006 Nov 15; [Epub ahead of print]

Lymphoproliferative Disorders in Rheumatoid Arthritis: Clinicopathological

Analysis of 76 Cases in Relation to Methotrexate Medication.

Hoshida Y, Xu JX, Fujita S, Nakamichi I, Ikeda JI, Tomita Y, Nakatsuka SI,

Tamaru JI, Iizuka A, Takeuchi T, Aozasa K.

From the Department of Pathology, Osaka University Graduate School of

Medicine, Suita, Osaka; and the Department of Pathology and Second

Department of Internal Medicine, Saitama Medical Center, Saitama Medical

School, Saitama, Japan.

OBJECTIVE: Individuals with rheumatoid arthritis (RA) with or without

methotrexate (MTX) medication occasionally develop lymphoproliferative

disorders (MTX-LPD and non-MTX-LPD, respectively). The hyperimmune state of

RA itself or the immunosuppressive state induced by MTX administration might

contribute to development of LPD. Our objective was to characterize MTX-LPD

in comparison to non-MTX-LPD and sporadic LPD in patients with RA. METHODS:

We compared MTX-LPD to non-MTX-LPD and sporadic LPD by evaluating 48 cases

of MTX-LPD, 28 non-MTX-LPD, and 150 sporadic LPD. RESULTS: Later onset age

of LPD and female predominance were evident in patients with RA-LPD compared

to sporadic LPD. The interval between the diagnosis of RA and LPD in MTX-LPD

(median 132 mo) was significantly shorter than that in non-MTX-LPD (240 mo).

The frequency of diffuse large B cell lymphoma (DLBCL) and positive rate of

Epstein-Barr virus (EBV) in RA-LPD was significantly higher than in sporadic

LPD (57.9% vs 42.7%, 27.6% vs 9.9%, respectively). After withdrawal of MTX,

11 of the MTX-LPD cases showed a spontaneous regression of tumors. The

5-year survival rate in RA-LPD (59.2%) was significantly worse than that in

sporadic LPD (74.6%).

CONCLUSION: The majority of cases of RA-LPD show similar clinicopathological

characteristics irrespective of MTX medication, except for spontaneous

regression of LPD after withdrawal of MTX in MTX-LPD, and a shorter interval

between the diagnosis of RA and LPD in MTX-LPD than in non-MTX-LPD. RA-LPD

cases showed younger age of onset, female predominance, unfavorable

prognosis, and higher frequencies of DLBCL and EBV positivity compared to

sporadic LPD.

PMID: 17117491

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

7117491

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