RESUMO
A 66-year-old woman with rheumatoid arthritis (RA) who had been receiving methotrexate (MTX) for 2 years presented with tarry stools. Contrast-enhanced computed tomography (CT) of the abdomen revealed irregular wall thickening in the ileocecal region and multiple low-contrast masses in both lobes of the liver. Lower gastrointestinal endoscopy revealed a type 2 tumor in the ileocecal region with a semi-peripheral ulcer. Histological examination of liver and colon biopsies showed other iatrogenic immunodeficiency-associated lymphoproliferative disorder (Oi-LPD), diffuse large B-cell lymphoma type, with positivity for Epstein-Barr virus DNA. After withdrawal of MTX, the LPD lesions disappeared and the patient achieved remission. We considered this to be a sporadic case of Oi-LPD, diffuse large B-cell lymphoma type, in the liver and colon due to treatment with MTX. There has been no previous report of this condition with simultaneous hepatic and colonic lesions, and the present case is thought to be highly informative in relation to the pathogenesis.
Assuntos
Antirreumáticos , Artrite Reumatoide , Linfoma Difuso de Grandes Células B , Metotrexato , Humanos , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Idoso , Feminino , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Tomografia Computadorizada por Raios X , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/patologiaRESUMO
We herein report a case of methotrexate-associated lymphoproliferative disorder (MTX-LPD) showing fibrin-associated large B-cell lymphoma-like heart valve lesions, and Epstein-Barr virus (EBV)-positive mucocutaneous ulcer-like cutaneous and oral mucosal lesions. MTX-LPD is a critical complication that can occur in RA patients who are treated with MTX. EBV also plays a defining or important role in LPDs. Among the sites of MTX-LPD, 40-50% occur in extranodal sites, including the gastrointestinal tract, skin, liver, lung, and kidney. There are few reports of MTX-LPDs involving the heart valves, and to the best of our knowledge, this is the first case to be reported in the English literature. The possibility of EBV-positive LPD should be considered in RA patients, even in patients with an atypical site, as in this case.
Assuntos
Valva Aórtica , Artrite Reumatoide , Linfoma Difuso de Grandes Células B , Transtornos Linfoproliferativos , Metotrexato , Valva Mitral , Humanos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/induzido quimicamente , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Valva Mitral/patologia , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Valva Aórtica/patologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Fibrina/metabolismo , Feminino , Idoso , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , MasculinoRESUMO
BACKGROUND AND OBJECTIVE: Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are rare but well-known diseases that manifest during or after methotrexate (MTX) administration. Limited information is available on the clinical characteristics of OIIA-LPD of the lung because only a few cases have been reported. Thus, we aimed to assess the incidence and prognosis of patients with OIIA-LPD of the lung. METHODS: Patients with OIIA-LPD of the lung treated at our institution between January 2008 and July 2020 were retrospectively analysed. RESULTS: Among the 51 patients with OIIA-LPD, 16 (31.3%, 7 men, 9 women) had OIIA-LPD of the lung (median age, 69 [range, 63-82] years). Peripheral lesions were observed in 10 (62.5%), central lesions in two (12.5%), and both lesions in four (25.0%) patients. Nine of the 16 patients underwent bronchoscopic biopsy, seven were diagnosed (diagnostic yield, 77.8%) and, re-biopsy was performed in 2 patients. Eight (50.0%) patients had LPD and six (37.5%) had diffuse large B-cell lymphoma. In the 14 patients with confirmed treatment efficacy, the overall response rate to MTX withdrawal was 71.4%. However, chemotherapy was required in case of larger lesions (three patients). Death related to OIIA-LPD occurred in only one patient, and 11 of the 14 patients were alive during the study period (median follow-up time, 53.7 [range, 4.3-84.2] months). CONCLUSION: The incidence of OIIA-LPD of the lung is 31.3% and higher than that reported previously. The treatment effect of MTX withdrawal seems to be sufficient; however, in some cases, chemotherapy may be required from the beginning.
Assuntos
Doença Iatrogênica , Transtornos Linfoproliferativos , Metotrexato , Humanos , Metotrexato/efeitos adversos , Metotrexato/administração & dosagem , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Idoso , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/epidemiologia , Incidência , Prognóstico , Idoso de 80 Anos ou mais , Doença Iatrogênica/epidemiologia , Pneumopatias/induzido quimicamente , Pneumopatias/epidemiologia , Síndromes de Imunodeficiência/induzido quimicamente , Síndromes de Imunodeficiência/epidemiologia , Pulmão/patologia , Pulmão/efeitos dos fármacosRESUMO
This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD.
Assuntos
Artrite Reumatoide , Transtornos Linfoproliferativos , Humanos , Metotrexato/efeitos adversos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/diagnóstico , NecroseRESUMO
OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.
Assuntos
Antirreumáticos , Artrite Reumatoide , Transtornos Linfoproliferativos , Metotrexato , Inibidores do Fator de Necrose Tumoral , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Transtornos Linfoproliferativos/induzido quimicamente , Masculino , Feminino , Pessoa de Meia-Idade , Metotrexato/uso terapêutico , Idoso , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Japão , Tacrolimo/uso terapêutico , Tacrolimo/efeitos adversos , Quimioterapia Combinada , Infecções por Vírus Epstein-Barr/complicações , AdultoRESUMO
Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary.
Assuntos
Artrite Reumatoide , Infecções por Vírus Epstein-Barr , Doença de Hodgkin , Linfoma Difuso de Grandes Células B , Transtornos Linfoproliferativos , Humanos , Adulto , Metotrexato/efeitos adversos , Receptor Notch1/genética , Infecções por Vírus Epstein-Barr/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Herpesvirus Humano 4 , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/complicações , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/genética , Doença de Hodgkin/induzido quimicamenteAssuntos
Linfoma Anaplásico de Células Grandes , Linfoma Anaplásico Cutâneo Primário de Células Grandes , Transtornos Linfoproliferativos , Dermatopatias , Neoplasias Cutâneas , Humanos , Metotrexato/efeitos adversos , Linfoma Anaplásico Cutâneo Primário de Células Grandes/induzido quimicamente , Linfoma Anaplásico Cutâneo Primário de Células Grandes/diagnóstico , Linfoma Anaplásico Cutâneo Primário de Células Grandes/tratamento farmacológico , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/induzido quimicamente , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/patologiaRESUMO
An 80-year-old Caucasian female with a history of rheumatoid arthritis presented with a 6-month history of progressive right upper eyelid ptosis, edema, erythema, and pain. MRI demonstrated a superior orbital mass. An incisional biopsy was performed, and pathologic analysis revealed an atypical lymphoid infiltrate, co-expressing both B and T-cell markers, with a low proliferation rate. Flow cytometry and IgH rearrangement study did not demonstrate any B- or T-cell monoclonal proliferation. Based on these findings, she was diagnosed with an iatrogenic immunodeficiency-associated lymphoproliferative disorder. Discontinuation of methotrexate resulted in the complete resolution of her symptoms, and she remains in remission 18 months later. Given the increased risk of lymphoproliferative disease in patients with rheumatoid arthritis, careful evaluation and close monitoring upon immunosuppressive medication withdrawal is necessary to confirm the diagnosis.
Assuntos
Artrite Reumatoide , Transtornos Linfoproliferativos , Humanos , Feminino , Idoso de 80 Anos ou mais , Metotrexato/efeitos adversos , Órbita/patologia , Imunossupressores/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnósticoRESUMO
INTRODUCTION: Methotrexate induces lymphoproliferative disorders on rare occasions; however, its pathogenesis remains unknown. A clinical diagnosis based on imaging studies alone is often difficult. CASE PRESENTATION: A 57-year-old Japanese woman was referred to our department for the evaluation of multiple lung and hepatic nodules that developed during methotrexate treatment for rheumatoid arthritis. Since she had a history of nephrectomy for localized renal cell carcinoma, multiple lung and hepatic metastases were initially considered. However, pathological diagnosis of the lung nodules (needle biopsy) revealed methotrexate-associated polymorphic-type lymphoproliferative disorders. After methotrexate discontinuation, continuous smooth shrinkage of the lung and liver lymphoproliferative disorders was observed. CONCLUSION: Methotrexate-associated lymphoproliferative disorders should be considered in the event of newly appearing neoplastic lesions, even during follow-up for renal cell carcinoma, if methotrexate is being administered.
Assuntos
Antirreumáticos , Carcinoma de Células Renais , Infecções por Vírus Epstein-Barr , Neoplasias Renais , Transtornos Linfoproliferativos , Feminino , Humanos , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/complicações , Seguimentos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/complicações , Fígado/patologia , Pulmão/patologia , Transtornos Linfoproliferativos/induzido quimicamente , Metotrexato/efeitos adversosRESUMO
BACKGROUND: Methotrexate is an immunosuppressant commonly used to treat inflammatory conditions, such as rheumatoid arthritis. However, albeit exceedingly rare, it can have serious adverse effects within the central nervous system (CNS), such as methotrexate-associated lymphoproliferative disorder (MTX-LPD). Literature describing the natural history, treatment options, and clinical outcomes of patients with CNS MTX-LPD remains sparse. METHODS: We present a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a case illustration of CNS MTX-LPD. RESULTS: A systematic review of the literature revealed 12 published cases of CNS MTX-LPD, plus the case presented herein, for a total of 13 included cases. The most common indication for MTX was rheumatoid arthritis. The most common treatment for the LPD was MTX cessation (12, 92.3%), adjunct chemotherapy (2, 15.4%), total tumor resection (3, 23.1%), or steroid therapy (1, 7.7%). Treatment usually led to improvement of neurological symptoms (9, 69.2%) along with regression of the lesions (3, 23.1%) with no recurrence (6, 46.2%). Death was reported in four cases (30.8%) with a mean time from onset of 11 months. CONCLUSIONS: CNS MTX-LPD should be considered in the differential diagnosis for patients who are taking MTX presenting with neurologic symptoms, as immediate withdrawal of MTX has demonstrated good prognosis.
Assuntos
Artrite Reumatoide , Doenças do Sistema Nervoso Central , Transtornos Linfoproliferativos , Humanos , Metotrexato/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Imunossupressores/efeitos adversos , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/tratamento farmacológico , Doenças do Sistema Nervoso Central/complicações , Sistema Nervoso CentralAssuntos
Antirreumáticos , Artrite Reumatoide , Transtornos Linfoproliferativos , Humanos , Metotrexato/efeitos adversos , Glândula Tireoide/diagnóstico por imagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico por imagem , Transtornos Linfoproliferativos/complicaçõesRESUMO
ABSTRACT: Immunodeficiency-associated lymphoproliferative disorders (IA-LPDs) constitute a diverse range of conditions including posttransplant lymphoproliferative disorders, other iatrogenic IA-LPDs, and lymphoproliferative disorders associated with an underlying primary immune disorder or HIV infection. IA-LPDs are clinically and pathologically heterogeneous, and there is a lack of standardization of diagnostic terminology. They can represent a potential serious diagnostic pitfall because the histological features of clinically indolent proliferations may mimic those of high-grade lymphoma. However, correct identification of these entities is essential given that complete remission may occur upon reversal of the underlying cause of immunosuppression without the need for systemic therapy. IA-LPDs presenting in the skin are rare but well documented. One form of iatrogenic IA-LPD, methotrexate-associated lymphoproliferative disorder (MTX-LPD), can present with cutaneous nodules, plaques, or ulcers. Predominantly, MTX-LPD develops in the context of long-term treatment of autoimmune conditions, such as rheumatoid arthritis, dermatomyositis, and Sjögren syndrome, and may be associated with underlying Epstein-Barr virus (EBV) infection. We present 4 cases of cutaneous EBV-positive B-cell MTX-LPD and describe their clinical and morphological findings. Comparison of our histological findings to the diagnostic criteria for EBV-positive mucocutaneous ulcer (EBVMCU) revealed significant overlap, highlighting the intersection between MTX-LPD and EBVMCU. Withdrawal of methotrexate resulted in healing of all lesions at a mean time of 2 months. In summary, close clinicopathological correlation is vital to identify MTX-LPD presenting as cutaneous EBVMCU given that the initial treatment strategy is that of withdrawal of methotrexate without the need for immediate systemic therapy.
Assuntos
Infecções por Vírus Epstein-Barr , Infecções por HIV , Síndromes de Imunodeficiência , Linfoma de Células B , Transtornos Linfoproliferativos , Lesões Pré-Cancerosas , Humanos , Metotrexato/efeitos adversos , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4 , Úlcera/patologia , Infecções por HIV/complicações , Linfoma de Células B/tratamento farmacológico , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico , Lesões Pré-Cancerosas/tratamento farmacológico , Doença IatrogênicaRESUMO
Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a troublesome problem in patients receiving MTX for rheumatoid arthritis (RA). However, its incidence, prognosis, and risk factors remain unclear. In this retrospective study, we evaluated the actual incidence, prognostic impact, and risk factors of MTX-LPD. Of the 986 patients with RA treated with MTX, 90 patients experienced 95 new malignancies (NMs), with LPD as the most frequent in 26 patients. The cumulative LPD incidences were 1.3% and 4.7% at 5 and 10 years after MTX initiation, respectively. Among the 24 patients who discontinued MTX after developing LPD, 15 showed sustained regression, without difference in overall survival between patients with LPD and without NM. Inflammatory markers and absolute lymphocyte counts were not useful for early LPD development detection, but most of the patients with LPD had persistently elevated erythrocyte sedimentation ratios. Regarding concomitant drugs, tacrolimus increased the risk only if patients were not receiving biological disease-modifying antirheumatic drugs (bDMARDs). bDMARDs did not increase the risk for any of the drugs or the number of classes used. The number of LPD cases was lower in patients with IL-6A even after a long period after MTX, although with no statistically significant difference. Thus, approximately 1 in 20 patients with RA developed MTX-LPD over the 10 years of MTX treatment, but it did not affect the survival of patients with RA. Tacrolimus increased the risk of developing LPD for certain patients and should be used with caution.
Assuntos
Antirreumáticos , Artrite Reumatoide , Transtornos Linfoproliferativos , Humanos , Metotrexato/efeitos adversos , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/complicações , Antirreumáticos/efeitos adversos , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/epidemiologiaRESUMO
INTRODUCTION: MTX-LPD is a complication that occurs during MTX treatment. Skin lesions in MTX-LPD are often subcutaneous nodules with occasional necrosis and ulceration. Although MTX-LPD regression is frequently observed upon discontinuation of oral MTX treatment, delayed diagnosis of MTX-LPD with associated ulceration may lead to ulcer enlargement and the need for surgical procedures such as skin grafts. CASE REPORT: A 74-year-old female was diagnosed with RA and administered MTX for 3 years and 8 months. The patient presented with a 2-month-old ulcer on the dorsum of the hand. The ulcer size was 6.5 cm × 5 cm, and it was surrounded by an embankment tumor measuring 7 cm × 6 cm. Although a definitive diagnosis could not be made based on the biopsy specimen, excision of the ulcer-containing mass confirmed MTX-LPD diagnosis. MTX was discontinued, and free-flap reconstruction was performed 3 weeks after the first surgery. The postoperative period was uneventful, and MTX-LPD recurrence was not observed 10 months after the second surgery. CONCLUSION: Although MTX-LPD with ulceration is rare, it should be considered in cases of refractory ulcers in patients with RA. The discontinuation of MTX based on early MTX-LPD diagnosis is critical to avoid surgical procedures such as skin grafts and flap reconstruction.
Assuntos
Artrite Reumatoide , Transtornos Linfoproliferativos , Feminino , Humanos , Idoso , Lactente , Metotrexato/efeitos adversos , Úlcera/induzido quimicamente , Úlcera/diagnóstico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Mãos/patologia , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/complicaçõesRESUMO
BACKGROUND: Lymphoproliferative disorder represents a heterogeneous clinicopathological spectrum characterized by uncontrolled proliferation of lymphocytes. Immunodeficiency is a major trigger of its development. While induction of immunodeficiency is a well-known adverse effect of temozolomide therapy, development of lymphoproliferative disorder following temozolomide therapy has not previously been described. CASE PRESENTATION: A patient with brainstem glioma developed constitutional symptoms, pancytopenia, splenomegaly and generalized lymphadenopathy during the 2nd cycle of maintenance therapy following induction therapy with temozolomide. Epstein-Barr virus-infected lymphocytes were observed histopathologically and "other iatrogenic immunodeficiency-associated lymphoproliferative disorder" (OIIA-LPD) was diagnosed. Although discontinuation of temozolomide led to rapid remission, relapse was observed 4 months later. CHOP chemotherapy was induced, resulting in secondary remission. Vigilant follow-up for another 14 months showed radiologically stable brainstem glioma and no further recurrence of OIIA-LPD. CONCLUSIONS: This is the first report documenting OIIA-LPD during temozolomide administration. Timely diagnosis of the disease and discontinuation of the causative agent were considered to be the management of choice. Close monitoring for relapse should be continued. Finding a balance between glioma management and controlling the remission of OIIA-LPD remains to be clarified.
Assuntos
Infecções por Vírus Epstein-Barr , Síndromes de Imunodeficiência , Transtornos Linfoproliferativos , Humanos , Temozolomida/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Recidiva Local de Neoplasia , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/tratamento farmacológico , Síndromes de Imunodeficiência/complicaçõesRESUMO
A 56-year-old woman was treated for rheumatoid arthritis for 17 years with methotrexate (MTX). Night sweats, fever and weight loss made her visit our hospital. Although levofloxacin failed to resolve her fever, she was suspected of having sepsis because of pancytopenia, elevated procalcitonin and a nodular lesion in the lung. After urgent hospitalization, she was diagnosed finally with the methotrexate-related lymphoproliferative disorder (MTX-LPD) associated with macrophage activation syndrome (MAS). Her general condition was improved with MTX withdrawal and 5-day high-dose glucocorticoid administration. Thus, even when the patient was critically ill with MAS, no cytotoxic agents were required to control MTX-LPD.
Assuntos
Artrite Reumatoide , Transtornos Linfoproliferativos , Síndrome de Ativação Macrofágica , Humanos , Feminino , Pessoa de Meia-Idade , Metotrexato/efeitos adversos , Síndrome de Ativação Macrofágica/induzido quimicamente , Síndrome de Ativação Macrofágica/diagnóstico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/tratamento farmacológicoRESUMO
ABSTRACT: A 60-year-old man on methotrexate for treatment of adult-onset Still disease presented with acute onset of fever, pancytopenia, and deranged liver function. Besides FDG-avid lesions in spleen and skeleton, his 18 F-FDG PET/CT study showed diffuse and intense uptake in the liver with significantly suppressed heart and brain activity (reminiscent of a hepatic superscan). Subsequent biopsy confirmed the diagnosis of methotrexate-associated lymphoproliferative disorder.
Assuntos
Transtornos Linfoproliferativos , Metotrexato , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Metotrexato/efeitos adversos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Fígado/diagnóstico por imagem , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico por imagemRESUMO
A 55-year old female patient was treated with methotrexate (MTX) and infliximab (IFX) for rheumatoid arthritis (RA). She experienced unknown fever, generalized lymphadenopathy, and liver tumors. Histological examination of the inguinal lymph node and a liver tumor resulted in the pathological diagnosis of classic Hodgkin lymphoma, with many Reed-Sternberg cells with the positivity of Epstein-Barr virus (EBV). She was diagnosed with MTX-related lymphoproliferative disorders (MTX-LPDs). She received chemotherapy after the cessation of MTX and IFX and achieved complete remission. RA showed recurrence after a while, and she was treated with steroids or other drugs. Six years after the chemotherapy, she experienced low-grade fever and anorexia. Whole computed tomography images showed an appendix tumor and enlargement of the surrounding lymph nodes. Appendectomy with the radical lymph nodes dissection was performed. The pathological diagnosis was diffuse large B-cell lymphoma, resulting in the clinical diagnosis of the relapse of MTX-LPD. EBV was negative at this point. The pathological findings of MTX-LPD may change at relapse; thus, biopsy should be considered when the relapse of MTX-LPD is suggested.
Assuntos
Artrite Reumatoide , Infecções por Vírus Epstein-Barr , Transtornos Linfoproliferativos , Feminino , Humanos , Pessoa de Meia-Idade , Metotrexato/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4 , Recidiva Local de Neoplasia/tratamento farmacológico , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/diagnósticoRESUMO
OBJECTIVES: To determine the magnetic resonance imaging (MRI) features of methotrexate-related lymphoproliferative disorder (MTX-LPD) in the oral cavity of a patient with a chief complaint of oral symptoms. METHODS: We included six patients who visited our hospital between November 2014 and November 2019, histopathologically diagnosed with MTX-LPD. All images were examined using 3 T MRI and reviewed by two radiologists. RESULTS: Masses were detected in five cases; all masses demonstrated signal hypointensity and homogeneous signal hyperintensity on T1- and T2-weighted images with fat suppression. Homogeneous enhancement with fat suppression was evident on post-contrast T1-weighted imaging. We performed dynamic contrast-enhanced MRI in three cases and observed early enhancement with a low washout ratio pattern in all cases. Four patients underwent diffusion-weighted MRI and revealed low mean apparent diffusion coefficient (ADC) of 0.57 (range 0.5-0.65) × 10-3 mm2/s. CONCLUSIONS: We reported on the imaging characteristics of six rare cases of MTX-LPD in the oral cavity. Homogeneous hyperintensity on fat-suppressed T2-weighted images and low ADC values are possible features of MTX-LPD. Moreover, MTX-LPD can be differentiated from other carcinomas in the oral cavity.
Assuntos
Artrite Reumatoide , Transtornos Linfoproliferativos , Humanos , Metotrexato/efeitos adversos , Artrite Reumatoide/patologia , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico por imagemRESUMO
Methotrexate-associated lymphoproliferative disorders (MTX-LPDs) with diffuse large B-cell lymphoma (DLBCL) pathology present with high rates of spontaneous regression after methotrexate (MTX) termination, especially in Epstein-Barr virus-encoded RNA (EBER)-positive cases. DLBCL with adrenal involvement is known for an extremely dismal prognosis. However, the prognosis of adrenal DLBCL in the context of MTX-LPD is unknown. We herein report two EBER-positive adrenal DLBCL MTX-LPD patients who achieved long-term remissions of 22 and 40 months with MTX termination alone. Both patients are doing well with no relapse at the time of reporting. Unlike adrenal DLBCL in general, adrenal involvement may not be a poor prognostic factor when restricted to DLBCL MTX-LPDs.