Methotrexate-induced CD30+ T-cell lymphoproliferative disorder of the oral cavity

Saleh, Jamal Z.; Lee, Linda H.; Schieke, Stefan M.; Hosking, Paul; Hwang, Samuel T

doi:10.1016/j.jdcr.2016.02.002

Cited by 11 publications

(6 citation statements)

References 9 publications

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“…MTX has been linked with lymphoproliferative disorders [61]. A study found a link between MTX treatment and an increased risk of lymphoma [62]. Additional research has validated the conclusion of the previous studies that there are MTX-associated lymphoproliferative diseases [63].…”

Section: Mtx Increases Infection Riskmentioning

confidence: 52%

“…In addition, a study discovered a higher incidence of diarrhea in RA patients who receive oral MTX medication [79]. Some recent investigations, such as a study in 2016, have revealed that MTX usage can cause mucocutaneous ulcers in the mouth, specifically in a number of individuals who also tested positive for the Epstein-Barr virus [62]. The pathogenic pathway that causes gastrointestinal side effects involves several organs.…”

Section: Gastrointestinal Side Effects Of Mtxmentioning

confidence: 99%

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Overview of Methotrexate Toxicity: A Comprehensive Literature Review

Hamed¹,

Dighriri²,

Baomar³

et al. 2022

Cureus

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Methotrexate (MTX) is significantly more effective than and has a considerable advantage over placebo in patients with severe and persistent rheumatoid arthritis (RA). The drug is used to treat a variety of malignant disorders (leukemia and cancer of the lung, breast, and uterus) and ectopic pregnancy. As its side effects are outweighed by its effectiveness, MTX is a first-line antirheumatic drug in many countries. MTX is found in extracellular compartments, such as the synovium, as well as other organs, such as the kidney and liver. To improve treatment, increase adherence, and decrease mortality in MTX therapy, it is essential to reduce its toxicity and understand its side effects. Therefore, this comprehensive review was conducted to assist physicians and researchers in better understanding the toxicity of MTX and how to deal with this toxicity. MTX is eliminated via the kidneys, which are capable of excretion and reabsorption within the renal tubules. Although higher doses of MTX (known as high-dose MTX (HD-MTX), defined as doses of 500 mg/m 2 or greater) are often more beneficial, they can produce toxicity and side effects such as bone marrow suppression, pulmonary toxicity, nephrotoxicity, hematologic toxicity, and an increased risk of infections. Treatment of severe MTX toxicity has three main goals: clearance of MTX from the bloodstream, folinic acid therapy, and organ treatment. Leucovorin is highly beneficial in preventing myelosuppression, gastric toxicity, and neurotoxic effects after HD-MTX therapy. The preferred antidote for MTX poisoning is folinic acid. Glucarpidase has been licensed for the treatment of high plasma MTX levels of >1 μmol/L in patients with compromised renal function who have delayed MTX elimination. In patients with renal deficiency, a lower initial dose is considered with an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/minute. These patients need to be monitored, and a more gradual dosage increase and a lower weekly maximum should be considered regarding their general health situation. MTX is contraindicated in patients with RA if the eGFR is <30 mL/minute.

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Section: Mtx Increases Infection Riskmentioning

confidence: 52%

Section: Gastrointestinal Side Effects Of Mtxmentioning

confidence: 99%

Overview of Methotrexate Toxicity: A Comprehensive Literature Review

Hamed¹,

Dighriri²,

Baomar³

et al. 2022

Cureus

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“…According to the WHO classification and previous large studies, methotrexate-associated lymphoproliferative disorder is mainly a B-cell lymphoproliferative disorder or Hodgkin lymphoma type, whereas T-cell lymphoproliferative disorders are relatively rare (4-8%) [3,[7][8][9][10]. Only a small number of methotrexate-associated T-cell lymphoproliferative disorders have been detailed thus far: five cases of angioimmunoblastic T-cell lymphoma, four cases of Epstein-Barr virus + CD8 + T-cell lymphoproliferative disorders, one case of Epstein-Barr virus − CD8 + T-cell lymphoproliferative disorder, and one case of adult T-cell leukemia/lymphoma [7,[12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Methotrexate-associated lymphoproliferative disorders of T-cell phenotype: clinicopathological analysis of 28 cases

et al. 2019

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Methotrexate-associated lymphoproliferative disorders are categorized as "other immunodeficiency-associated lymphoproliferative disorders in the WHO classification. Methotrexate-associated lymphoproliferative disorder is mainly a B-cell lymphoproliferative disorders or Hodgkin lymphoma type, whereas T-cell lymphoproliferative disorders are relatively rare (4-8%). Only a small number of methotrexate-associated T-cell lymphoproliferative disorders have been detailed thus far. Because of the rarity, methotrexate-associated T-cell lymphoproliferative disorder has not been well studied and its clinicopathological characteristics are unknown. A total of 28 cases of methotrexate-associated T-cell lymphoproliferative disorders were retrospectively analyzed. Histologically and immunohistochemically, they were divided into three main types: angioimmunoblastic T-cell lymphoma (n = 19), peripheral T-cell lymphoma, NOS (n = 6), and CD8 + cytotoxic Tcell lymphoma (n = 3). Among the 28 cases, only one CD8 + cytotoxic T-cell lymphoma case was Epstein-Barr viruspositive. The other 27 cases were negative for Epstein-Barr virus on tumor cells, but scattered Epstein-Barr virus-infected Bcells were detected in 24 cases (89%), implying the reactivation of Epstein-Barr virus caused by immunodeficient status of the patients. After the diagnosis of methotrexate-associated T-cell lymphoproliferative disorder, methotrexate was immediately withdrawn in 26 cases. Twenty (77%) cases presented with spontaneous regression. Compared to methotrexateassociated B-cell lymphoproliferative disorder, patients with methotrexate-associated T-cell lymphoproliferative disorder had a significantly higher proportion of males (p = 0.035) and presence of B-symptoms (p = 0.036), and lower proportion of Epstein-Barr virus + tumor cells (p < 0.001). Although the difference was not significant, the methotrexate-associated T-cell lymphoproliferative disorder also had more frequent spontaneous regression (p = 0.061). In conclusion, methotrexateassociated T-cell lymphoproliferative disorder was divided into three main types: angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, NOS, and CD8 + cytotoxic T-cell lymphoma. Angioimmunoblastic T-cell lymphoma was the most common type. Methotrexate-associated T-cell lymphoproliferative disorder was characterized by a high rate of spontaneous regression after methotrexate cessation. Epstein-Barr virus positivity was relatively rare in methotrexateassociated T-cell lymphoproliferative disorder, significantly less frequent than methotrexate-associated B-cell lymphoproliferative disorder, suggesting different pathogenesis.

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“…Therefore, this suggestion does not appear readily applicable. As described in Table 1, while the tumor cells were positive for EBV in 8 (17%) of 48 patients, background cells were positive in 32 (82%) of 39 patients with available data (2,4,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). In relation to patients with AITL or those with AITLlike lymphomas, background cells were EBV-positive in 24 (96%) of 25 patients with available data.…”

Section: Discussionmentioning

confidence: 96%

Case Report: Composite Angioimmunoblastic T-Cell Lymphoma and Epstein-Barr Virus-Positive B-Cell Lymphoproliferative Disorder as Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders

et al. 2020

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Immunosuppressants are widely used to treat patients with rheumatoid arthritis (RA), and their adverse effects have been known to cause other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs). We report a patient with RA who had been treated with methotrexate (MTX) and tacrolimus (TAC) and who developed whole body lymphadenopathy. We simultaneously confirmed angioimmunoblastic T-cell lymphoma (AITL) through a right cervical lymph node biopsy and Epstein-Barr virus-positive B-cell lymphoproliferative disorder (EBV-positive B-LPD) through a bone marrow examination. After cessation of immunosuppressant therapy, both LPDs completely disappeared. Patients with AITL are occasionally reported to develop B-cell lymphoma through reactivation of the EBV, which leads to clonal expansion in the microenvironment. Immunohistochemistry results revealed that both LPD components were positive for EBV-encoded RNA. Moreover, in this patient, the plasma EBV DNA level was found to be high; therefore, EBV infection was a probable etiology. Synchronous coexistence of AITL and B-LPD as an OIIA-LPD has rarely been reported. This case report is the first to discuss the disappearance of both LPDs on withdrawal of immunosuppressants only. AITL occasionally accompany B-LPD; however, this composite lymphoma comprised AITL and B-LPD, and OIIA-LPDs should not be overlooked.

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Methotrexate-induced CD30+ T-cell lymphoproliferative disorder of the oral cavity

Cited by 11 publications

References 9 publications

Overview of Methotrexate Toxicity: A Comprehensive Literature Review

Overview of Methotrexate Toxicity: A Comprehensive Literature Review

Methotrexate-associated lymphoproliferative disorders of T-cell phenotype: clinicopathological analysis of 28 cases

Case Report: Composite Angioimmunoblastic T-Cell Lymphoma and Epstein-Barr Virus-Positive B-Cell Lymphoproliferative Disorder as Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders

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