RESUMO
DISEASE OVERVIEW: Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals. DIAGNOSIS: The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. RISK STRATIFICATION: Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival. MANAGEMENT: Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Plasmablástico , Humanos , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/terapia , Linfoma Plasmablástico/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medição de Risco , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Prednisona/uso terapêutico , Lenalidomida/uso terapêutico , Lenalidomida/administração & dosagem , Prognóstico , Bortezomib/uso terapêutico , Bortezomib/administração & dosagem , Diagnóstico Diferencial , Gerenciamento Clínico , Pessoa de Meia-Idade , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Anticorpos Monoclonais , EtoposídeoAssuntos
Anticorpos Biespecíficos , Antígeno de Maturação de Linfócitos B , Linfoma Plasmablástico , Humanos , Anticorpos Biespecíficos/uso terapêutico , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/patologia , Antígeno de Maturação de Linfócitos B/imunologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Antineoplásicos Imunológicos/uso terapêuticoRESUMO
ABSTRACT: Plasmablastic transformation of follicular lymphoma is very rare and has been reported in only 5 cases till date. We report a case of simultaneous identification of extranodal, soft tissue plasmablastic lymphoma in the ankle and bone marrow involvement by follicular lymphoma. This unusual case presentation is a challenge for the treating physician with the patient becoming resistant to chemotherapy and succumbing to the disease within a few months of diagnosis. These cases are known to have an aggressive clinical course with very poor prognosis and survival rate of less than 6 months. This report broadens the spectrum of morphological transformation of follicular lymphoma and it may represent a new category of high-grade transformation of follicular lymphoma.
Assuntos
Linfoma Folicular , Linfoma Plasmablástico , Humanos , Medula Óssea/patologia , Transformação Celular Neoplásica/patologia , Evolução Fatal , Imuno-Histoquímica , Linfoma Folicular/patologia , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamento farmacológico , Linfoma Plasmablástico/patologia , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/tratamento farmacológicoRESUMO
CONTEXT: Primary gastrointestinal plasmablastic lymphoma (GI-PBL) is a rare variant of diffuse B-cell lymphoma with an aggressive clinical course. PBL was initially reported among HIV-positive patients; however, subsequent studies have shown that it also occurs among HIV-negative patients. Its clinical characteristics remain poorly understood. This study aims to retrospectively analyze the clinicopathological findings of primary GI-PBLs in HIV-negative patients. DESIGN: Primary HIV-negative GI-PBL cases from 2008 to 2022 were reviewed. Clinicopathologic features and outcomes were analyzed. RESULTS: The cohort of 13 patients had a male-to-female ratio of 9:1 (3 patients' genders not available), with an average age of 61 (range, 30-92) years. The most involved location was the colon (n = 7 [53.8 %]), followed by the small bowel (n = 3 [23.1 %]), stomach (n = 2 [15.4 %]), rectum (n = 1 [7.7 %]), and anus (n = 1 [7.7 %]). Most patients (n = 10 [77 %]) showed isolated GI tract involvement. Eight patients had chronic inflammatory and/or immunocompromised status, including 4 with inflammatory bowel disease (all of whom underwent treatment), 3 with post-organ transplant status, and 1 with irritable bowel syndrome. All cases exhibited cytokeratin-/CD20-/PAX-5-/CD138+ and/or MUM1+ immunophenotype. Based on available data, 8 of 11 (72.7 %) patients had Epstein-Barr virus reactivation. Among 11 patients with follow-up data, the mean follow-up duration was 13.5 (range, 3-40) months; at the end of follow-up, 45.5 % of patients (5 of 11 patients) showed complete remission after chemotherapy. CONCLUSION: Primary HIV-negative GI-PBL occurs predominantly in the colon of relatively elderly males with immunosuppression. Its clinical course can be heterogenous, presenting a comorbidity with inflammatory bowel disease or post-organ transplantation status.
Assuntos
Infecções por Vírus Epstein-Barr , Infecções por HIV , Doenças Inflamatórias Intestinais , Linfoma Plasmablástico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Progressão da Doença , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Infecções por HIV/complicações , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/patologia , Estudos Retrospectivos , Estômago/patologia , Adulto , Idoso de 80 Anos ou maisAssuntos
Infecções por HIV , Linfoma Plasmablástico , Humanos , Linfoma Plasmablástico/complicações , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/tratamento farmacológico , Estômago/patologia , Biópsia , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Hemorragia Gastrointestinal/etiologiaRESUMO
A 53-year-old man who had a history of ulcerative colitis (UC) for 2 years underwent colonoscopy as regular follow-up. The results showed an elevated lesion in the descending colon, which was diagnosed as plasmablastic lymphoma (PBL) based on pathological findings. In situ hybridization for the Epstein-Barr virus-encoded RNA probe was positive. Fluorescence in situ hybridization revealed rearrangement of the MYC gene. He had been taking prednisolone, 5-aminosalicylic acid, azathiopurine, and ustekinumab at the diagnosis of PBL and had multiple prior therapies for UC including infliximab, tacrolimus, and tofacitinib due to steroid dependence. PBL is a rare aggressive B cell lymphoma initially described in the oral cavity of human immunodeficiency virus positive patients and it is suspected to have an association with immunocompromised status of patients. The number of cases of PBL in inflammatory bowel disease (IBD) patients is extremely rare. All these patients were administered immunosuppressive therapy including thiopurines or biologics. IBD patients with immunosuppressive therapy have a higher potential for developing lymphoproliferative disorders. Clinicians should be aware of the risk of lymphoma, including PBL.
Assuntos
Colite Ulcerativa , Infecções por Vírus Epstein-Barr , Linfoma Plasmablástico , Masculino , Humanos , Pessoa de Meia-Idade , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/patologia , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Infecções por Vírus Epstein-Barr/complicações , Hibridização in Situ Fluorescente , Herpesvirus Humano 4 , Terapia de ImunossupressãoRESUMO
Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B-cell lymphoma that is frequently associated with HIV infection or other immunodeficiencies. We present a case of HIV-negative primary testicular PBL with long-term complete remission (CR) and successful treatment with bortezomib in combination with EPOCH (V-EPOCH). Because of rapidly increasing right testicular swelling, an 86-year-old man without immunodeficiencies was admitted to our hospital. Following that, a right high orchiectomy was performed. Histopathological and immunohistochemical analyses revealed diffuse infiltration of plasmablastic lymphocytes, which were positive for CD38, CD138, CD56, MUM1, lambda, EBER, and MYC respectively, but negative for CD20. The MIB-1 index was 90%. FDG abnormal uptake was discovered on PET/CT at systemic lymph nodes. There was no abnormal cell infiltration in either the bone marrow or cerebral spinal fluid. He was diagnosed with PBL, clinical-stage IIIE-A, IPI high-intermediate risk. He achieved durable CR more than 30 months after the diagnosis after six courses of V-EPOCH, followed by intrathecal prophylaxis (IT) and adjuvant radiation therapy (total 30 Gy). Although PBL shows an aggressive clinical course and poor prognosis, adequate therapeutic approaches for PBL have not been established due to the rarity of this disease. According to our findings, V-EPOCH combined with IT and adjuvant radiotherapy appeared to be feasible and effective as a frontline treatment for elderly patients with primary testicular PBL.
Assuntos
Infecções por HIV , Linfoma Plasmablástico , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Bortezomib/uso terapêutico , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Indução de RemissãoRESUMO
Plasmablastic lymphoma (PBL) is an aggressive and rare subtype of non-Hodgkin lymphoma with no standard-of-care therapy. We reviewed all patients diagnosed with histologically confirmed PBL in British Columbia, Canada between 1997 and 2019. Overall, 42 patients were identified, including 15 (36%) positive for HIV and nine (21%) on chronic immunosuppression. Curative-intent treatment consisting primarily of cyclophosphamide, doxorubicin, vincristine and prednisone was administered to 31 patients, of which 74% achieved response, however 61% relapsed after a median of 7.5 months. At a median follow-up of eight years for the whole cohort, five-year progression-free survival (PFS) and overall survival (OS) were 18% [95% confidence interval (CI): 6%, 30%] and 22% (95% CI: 8%, 36%) with median eight and 15 months respectively. There were no differences in relapse rate (p = 0.962), PFS (p = 0.228) or OS (p = 0.340) according to immune status. For those treated with curative intent, five-year PFS and OS were 24% (95% CI: 8%, 40%) and 31% (95% CI: 13%, 49%) with median 18 and 27 months respectively. In this population-based cohort of PBL patients spanning 20 years, survival outcomes were poor. Ultimately, further research is needed to develop more effective treatment strategies and to improve survival for patients.
Assuntos
Linfoma Plasmablástico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colúmbia Britânica/epidemiologia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Recidiva Local de Neoplasia , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/tratamento farmacológico , Prednisona/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
Plasmablastic lymphoma is a rare subtype of large B-cell lymphoma characterised by an aggressive clinical course with frequent relapses and refractoriness to chemotherapy. It is usually associated with HIV, however, it can also be seen in immunocompetent patients. It has distinct pathological characteristics, such as plasmablastic morphology and lack of CD20 expression. These characteristics pose a clinical and pathological challenge. There is no standard of care established in this entity. In this case report, we described a novel bortezomib-based plasma cell targeted regimen in a HIV-negative patient refractory to chemotherapy.
Assuntos
Infecções por HIV , Linfoma Plasmablástico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Lenalidomida/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/patologiaAssuntos
Ifosfamida , Linfoma Plasmablástico , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina , Etoposídeo , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Linfoma Plasmablástico/tratamento farmacológico , Terapia de SalvaçãoRESUMO
OBJECTIVE: To describe the clinical profile and outcome of patients with HIV-associated plasmablastic lymphoma (PBL) treated with cyclophosphamide, doxorubicin, oncovin, prednisone (CHOP) chemotherapy in a tertiary hospital in KwaZulu-Natal, South Africa. METHODS: This 12-year retrospective clinical chart review, from 2006 to 2018, of patients with PBL treated with CHOP chemotherapy describes their clinical presentation, complete response (CR), progression-free survival (PFS) and disease-free survival (DFS). Response to salvage chemotherapy was also assessed, as was the overall survival (OS). RESULTS: Of 26 patients included in the study, PBL was the presenting manifestation of underlying HIV infection in 58% (n = 15). The median age was 35 years (range 13-49), and 62% (n = 16) were males. The median CD4 count was 285 cells/µL (range 45-863). All patients had extranodal disease, with 4% having bone marrow involvement (n = 1) and > 60% presenting with advanced stage and high-risk PBL. Central nervous system (CNS) involvement was present in 15% (n = 4). A CR was attained in 46% (n = 12). The median DFS was 23.5 months (range 5-91 months), with an overall 2-year survival of 42% (n = 11). CONCLUSIONS: Patients with PBL had a low CR with CHOP chemotherapy and poor OS. Use of alternative chemotherapy regimens needs to be investigated to optimally manage this aggressive lymphoma. The surprisingly low incidence of marrow involvement is the focus of ongoing local research.
Assuntos
Infecções por HIV , Linfoma Plasmablástico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Linfoma Plasmablástico/complicações , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/patologia , Prednisona/uso terapêutico , Estudos Retrospectivos , África do Sul/epidemiologia , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto JovemRESUMO
Plasmablastic lymphoma (PBL) is an uncommon and aggressive type of mature B cell lymphoma rarely involving gastrointestinal (GI) tract. Here, we describe a case of PBL involving the colon in HIV/Epstein-Barr virus negative immunocompetent patient who presented with anaemia and weight loss but no significant GI symptoms. It emphasises that even in the absence of classical risk factors, one should consider possibility of this condition as this is potentially curable. Also, we would like to highlight the diagnostic and treatment challenges of such an aggressive lymphoma in a frail elderly patient with multiple comorbidities.
Assuntos
Infecções por Vírus Epstein-Barr , Linfoma de Células B , Linfoma Plasmablástico , Idoso , Herpesvirus Humano 4 , Humanos , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/tratamento farmacológico , Fatores de RiscoAssuntos
Adenina/análogos & derivados , Antineoplásicos/uso terapêutico , Evolução Clonal , Piperidinas/uso terapêutico , Linfoma Plasmablástico/etiologia , Inibidores de Proteínas Quinases/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Adenina/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Bortezomib/uso terapêutico , Ciclofosfamida/administração & dosagem , Progressão da Doença , Doxorrubicina/administração & dosagem , Evolução Fatal , Feminino , Humanos , Imunoglobulina M/sangue , Cadeias kappa de Imunoglobulina/sangue , Linfonodos/patologia , Fator 88 de Diferenciação Mieloide/genética , Proteínas de Neoplasias/sangue , Linfoma Plasmablástico/sangue , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/patologia , Prednisona/administração & dosagem , Vincristina/administração & dosagem , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/patologiaAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/radioterapia , Idoso , Infecções por HIV/complicações , Herpesvirus Humano 4/isolamento & purificação , Humanos , Masculino , Linfoma Plasmablástico/complicações , Resultado do TratamentoRESUMO
Lymphomas remain a leading cause of morbidity and mortality for HIV-positive patients. The most common lymphomas include diffuse large B-cell lymphoma, Burkitt lymphoma, primary effusion lymphoma, plasmablastic lymphoma and Hodgkin lymphoma. Appropriate approach is determined by lymphoma stage, performans status, comorbidities, histological subtype, status of the HIV disease and immunosuppression. Treatment outcomes have improved due to chemotherapy modalities and effective antiretroviral therapy. This review summarizes epidemiology, pathogenesis, pathology, and current treatment landscape in HIV associated lymphoma.
Assuntos
Infecções por HIV/complicações , Linfoma Relacionado a AIDS/virologia , Fármacos Anti-HIV/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/patologia , Linfoma de Burkitt/virologia , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/virologia , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/complicações , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Doença de Hodgkin/virologia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Hospedeiro Imunocomprometido , Incidência , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Linfoma de Efusão Primária/tratamento farmacológico , Linfoma de Efusão Primária/patologia , Linfoma de Efusão Primária/virologia , Linfoma Plasmablástico/tratamento farmacológico , Linfoma Plasmablástico/patologia , Linfoma Plasmablástico/virologia , Prognóstico , RecidivaRESUMO
Plasmablastic lymphoma (PBL) is a rare and aggressive hematological malignancy. PBL commonly occurs in immune incompetent patients, such as those with human immunodeficiency virus (HIV), post-transplant status, or immunosenescence. Given its rarity, there is no specific standard treatment for PBL. However, small case series have shown that intensive chemotherapies combined with anti-myeloma agents such as bortezomib and lenalidomide were effective in treating PBL. Unfortunately, some fragile patients could not tolerate intensive chemotherapeutic regimens, especially the elderly patients. Here we presented a 76-year-old female PBL patient refractory to miniCHOP regimen combined with bortezomib but achieved complete remission when treated with tislelizumab combined with lenalidomide, indicating that immune therapy may be a potential treatment for PBL. To our knowledge, this is the first chemoresistant PBL patient that has been successfully treated with checkpoint inhibitor plus lenalidomide, thus providing new insight towards PBL management.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Lenalidomida/administração & dosagem , Linfoma Plasmablástico/tratamento farmacológico , Idoso , Feminino , HumanosRESUMO
Plasmablastic lymphoma (PBL) is a very rare disease and it is usually considered a human immunodeficiency virus (HIV)-related B-cell lymphoma that carries a poor prognosis. It mostly involves the oral cavity, lungs, nasal cavity, gastrointestinal tract, lymph node, and skin. Therapeutic regimens like dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (DA-EPOCH) have shown better results in these aggressive lymphomas. We report a rare case of PBL in an HIV-negative patient who presented to the clinic with a complaint of left testicular swelling for 3 months. Ultrasound showed an enlarged left testicle. He underwent a left orchiectomy and the pathology showed PBL with involvement of the spermatic cord margin. Positron emission tomography scan showed hypermetabolic mediastinal and hilar lymph nodes. He was started on DA-EPOCH but showed no response. Accordingly, salvage therapy with bortezomib in addition to ifosfamide carboplatin and etoposide (B-ICE) chemotherapy was initiated with remarkable response. Several other regimens can be used in the refractory setting; however, the evidence is mostly based on retrospective analysis.
Assuntos
Infecções por HIV , Linfoma Plasmablástico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Masculino , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/tratamento farmacológico , Estudos Retrospectivos , TestículoRESUMO
PURPOSE: Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell malignancy with a heterogenous clinical and prognostic spectrum, determined by multiple factors, including age, HIV- and MYC-status. While there exist several validated scoring systems for diffuse large B-cell lymphoma, which incorporate basic clinical features (age, lactate dehydrogenase, sites of (extranodal) involvement, stage and performance), none of these have been systematically assessed in PBL. METHODS: We determined the (age-adjusted; aa)-International Prognostic Index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI) in a comprehensive multi-center cohort (n = 78) of PBL patients. Further, all indices were comparatively investigated for model quality and concordance. RESULTS: Univariate analysis revealed significant prognostic capabilities for all indices, all of which identified a subgroup with favorable outcome. Discriminatory power between patients with less benign prognosis and especially refractory disease exhibited significant variability. Subsequently, stratified models for each risk score were compared employing corrected Akaike's information criterion (cAIC) and Harrel's concordance index (c-index). Here, the NCCN-IPI outperformed both IPI and R-IPI regarding c-index with ambiguous cAIC results, underlining its clinical utility and suggesting it for preferential use in clinical practice. CONCLUSION: Our current observations support the use of the IPI and its enhanced derivatives in PBL patients. There is, however, a distinct requirement for novel prognostic tools to better delineate subgroups at risk for early relapse or refractory disease as well as late relapse. A comprehensive molecular characterization of a clinically annotated cohort of PBL patients is therefore urgently warranted.