Methtrexate-associated lymphoproliferative disorders. A clinicopathological study of 13 Japanese cases

Kojima, Masaru; Itoh, Hideaki; Hirabayashi, Kaoru; Igarashi, Seiji; Tamaki, Yasuhiro; Murayama, Kayoko; Ogura, Haruyuki; Saitoh, Ryuta; Kashiwabara, Kenji; Takimoto, Jyuro; Masawa, Nobuhide; Nakamura, Shigeo

doi:10.1016/j.prp.2006.05.007

Cited by 62 publications

(39 citation statements)

References 16 publications

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“…Among Japanese population, stomach cancer remains the most common type of malignancy, followed by lung cancer and colorectal cancer in men, and breast cancer became the most common type of malignancy followed by uterus cancer and stomach cancer in women. Lymphoma is far less common malignancy in the general Japanese population; however, it has been a well-known site-speciWc malignancy in Japanese RA patients [6,22,23]. Nonetheless, the degree of excess incidence of lymphoma and the incidence of overall or other site-speciWc malignancies in Japanese RA patients have not yet been investigated.…”

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confidence: 99%

Incidence of malignancy in Japanese patients with rheumatoid arthritis

et al. 2010

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To determine the incidence of malignancy and site-specific malignancies in Japanese patients with rheumatoid arthritis (RA). In a prospective large observational cohort study named IORRA, 7,566 patients with RA were enrolled from April 2001 to April 2005 and were followed up to October 2005. Occurrence of malignancy was originally collected by patient reports of IORRA survey biannually from April 2001 to October 2005, and was confirmed by medical records. Standardized incidence rate (SIR) of the observed-to-expected cancer incidence and 95% confidence intervals (95% CI) were then calculated. Factors obtained at first enrollment in IORRA were assessed for association with risk of malignancy using the Cox proportional hazards model. A total of 177 malignancies in 173 patients (58 in men, 115 in women) were identified during the observation period of 25,567 person-years. The age- and sex-standardized incidence rate of malignancy was 437.1 (men, 706.8; women, 366.1) per 100,000 person-years. The SIR of malignancy was slightly excess (SIR 1.18, [95% CI 1.02-1.37]) in all patients, but 1.29 (95% CI 0.99-1.67) in men, and 1.13 (95% CI 0.94-1.36) in women. A significant excess of lymphoma (SIR 6.07, [95% CI 3.71-9.37]) and lung cancer (SIR 2.29, [95% CI 1.57-3.21]), whereas decreased incidence of colorectal cancer (SIR 0.49, [95% CI 0.26-0.83]), were found. Male gender and older age were identified as risk factors for malignancy. A slight excess in the incidence of overall malignancy and highly excess of lymphoma in Japanese RA patients was demonstrated.

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Section: Introductionmentioning

confidence: 99%

Incidence of malignancy in Japanese patients with rheumatoid arthritis

et al. 2010

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“…Overall, approximately 40% of reported cases have involved extranodal sites, including the gastrointestinal tract, skin, lung, kidney, and soft tissues [3,5]. However, to our knowledge, the English literature includes only five case reports as a MTX-associated LPD (MTX-LPD) in the oral cavity [6][7][8][9]. Observation studies germane to the relationship between LPD and immunosuppression in the oral cavity are listed in Table 1.…”

Section: Introductionmentioning

confidence: 99%

Methotrexate-Related Epstein-Barr Virus (EBV)-Associated Lymphoproliferative Disorder—So-Called “Hodgkin-Like Lesion”—of the Oral Cavity in a Patient with Rheumatoid Arthritis

Kikuchi

Miyazaki

Tanaka

et al. 2010

Head and Neck Pathol

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Patients affected by autoimmune diseases (rheumatoid arthritis, psoriasis, dermatomyositis) who are treated with methotrexate (MTX) sometimes develop lymphoproliferative disorders (LPDs). In approximately 40% of reported cases, the affected sites have been extranodal, and have included the gastrointestinal tract, skin, lung, kidney, and soft tissues. However, MTX-associated LPD (MTX-LPD) is extremely rare in the oral cavity. Here we report a 69-year-old Japanese woman with rheumatoid arthritis (RA) who developed MTX-LPD resembling Hodgkin's disease--so-called "Hodgkin-like lesion"--in the left upper jaw. Histopathologically, large atypical lymphoid cells including Hodgkin or Reed-Sternberg-like cells were found to have infiltrated into granulation tissue in the ulcerative oral mucosa. Immunohistochemistry showed that the large atypical cells were positive for CD20, CD30 and Epstein-Barr virus (EBV)-latent infection membrane protein-1 (LMP-1) and negative for CD15. EBV was detected by in situ hybridization (ISH) with EBV-encoded small RNA (EBER), and polymerase chain reaction (PCR) for LMP-1 and EBNA-2 in material taken from the formalin-fixed, paraffin-embedded specimen. To our knowledge, this is the first reported case of MTX-related EBV-associated LPD (MTX-EBVLPD), "Hodgkin-like lesion", of the oral cavity in a patient with RA.

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“…[25][26][27][28] A proportion of MTX-induced LPD exhibited atypical lymphoplasmacytic infiltrations showing histological findings similar to those in our cases including the presence of (i) an expanded paracortical area consisting of a mixed cell population, including small-and medium-sized lymphocytes, plasmacytoid lymphocytes, and immunoblasts, and (ii) immunoblasts including Hodgkin-like cells usually showing a B-cell phenotype, and a proportion of these cells were CD30-positive but CD15-negative. 27,28 However, there was no history of MTX therapy in the present 9 cases.…”

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Atypical Lymphoplasmacytic and Immunoblastic Proliferation of Autoimmune Disease : Clinicopathologic and Immunohistochemical Study of 9 Cases

Kojima

Nakamura

Tsukamoto

et al. 2010

J Clin Exp Hematopathol

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Atypical lymphoplasmacytic immunoblastic proliferation (ALPIB) is a rare lymphoproliferative disorder (LPD) associated with autoimmune disease (AID). To further clarify the clinicopathologic, immunohistological, and genotypic findings of ALPIB in lymph nodes associated with well-documented AIDs, 9 cases are presented. These 9 patients consisted of 4 patients with systemic lupus erythematosus, 3 patients with rheumatoid arthritis, and one case each with Sjögren's syndrome and dermatomyositis. All 9 patients were females aged from 25 to 71 years with a median age of 49 years. Four cases presented with lymphadenopathy as the initial manifestation. In 4 patients, immunosuppressive drugs were administered before the onset of lymph node lesion. However, none of the 9 patients received methotrexate therapy. The present 9 cases were characterized by : (i) prominent lymphoplasmacytic and B-immunoblastic infiltration ; (ii) absence of pronounced arborizing vascular proliferation ; (iii) absence of CD10 + "clear cells" ; (iv) presence of hyperplastic germinal center in 7 cases ; (v) immunohistochemistry, flow cytometry, and polymerase chain reaction demonstrated a reactive nature of the T-and B-lymphocytes ; and (vi) on in situ hybridization, there were no Epstein-Barr virus -infected lymphoid cells in any of the 9 cases. Overall 5-year survival of our patients was 83%. The combination of clinical, immunophenotypic, and genotypic findings indicated that the present 9 cases can be regarded as having an essentially benign reactive process. Finally, we emphasized that ALPIB should be added to the differential diagnostic problems of atypical LPDs, particularly lymph node lesions of IgG4-related diseases. 〔J Clin Exp Hematopathol 50(2) : 113-119, 2010〕

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Methtrexate-associated lymphoproliferative disorders. A clinicopathological study of 13 Japanese cases

Cited by 62 publications

References 16 publications

Incidence of malignancy in Japanese patients with rheumatoid arthritis

Incidence of malignancy in Japanese patients with rheumatoid arthritis

Methotrexate-Related Epstein-Barr Virus (EBV)-Associated Lymphoproliferative Disorder—So-Called “Hodgkin-Like Lesion”—of the Oral Cavity in a Patient with Rheumatoid Arthritis

Atypical Lymphoplasmacytic and Immunoblastic Proliferation of Autoimmune Disease : Clinicopathologic and Immunohistochemical Study of 9 Cases

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