RESUMO
Hepatosplenic T-cell lymphoma (HSTCL) is an uncommon and highly aggressive subtype of peripheral T-cell lymphoma characterized by liver, spleen, and bone marrow involvement. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative treatment for HSTCL, but it carries a significant risk of relapse. Cytomegalovirus (CMV) reactivation is a frequent complication after alloHSCT, particularly in patients undergoing lymphocyte-toxic therapies. A 27-year-old man diagnosed with HSTCL underwent an alloHSCT with active disease after six lines of therapy. A CMV reactivation was successfully treated with foscarnet. A sudden reappearance of symptomatic lymphocytosis (15,550/µL) by day +20, prior to engraftment, raised suspicion of disease progression. A comprehensive diagnostic work-up revealed an oligoclonal expansion of donor lymphocytes along with complete donor chimerism, leading to an alternative diagnosis of a CMV-driven T-cell expansion. This was confirmed by an in vitro assay testing T-cell specificity against CMV. The patient achieved both complete response and complete donor chimerism despite persisting lymphocytosis, but ultimately relapsed. This case highlights the importance of diagnostic tools in understanding disease progression and guiding treatment decisions.
Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Linfocitose , Linfoma de Células T Periférico , Linfoma de Células T , Masculino , Humanos , Adulto , Citomegalovirus , Linfoma de Células T Periférico/etiologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Linfocitose/etiologia , Transplante Homólogo/efeitos adversos , Recidiva Local de Neoplasia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfoma de Células T/etiologia , Progressão da DoençaRESUMO
OBJECTIVES: The advanced extra-nodal NK/T-cell lymphoma (ENKTL) is highly aggressive and lacks effective treatment with a poor prognosis. This study aimed to investigate the effectiveness and safety of autologous hematopoietic stem cell transplantation (ASCT) in CR1. METHODS: Forty of 121 patients with advanced ENKTL from four Chinese hospitals between January 2006 to December 2021 who achieved first complete remission (CR1) and received at least 4 cycles chemotherapy, were enrolled for analysis. Twenty patients received ASCT as up-front consolidation therapy (Group A), and 20 patients only received chemotherapy (Group B). Clinical features, treatment and follow-up information were collected. RESULTS: With a median follow-up of 27 months (range, 4-188 months), the 2-year overall survival (OS) in Group A, 61% (95% CI 37%-85%), was better than that in Group B, 26% (95% CI 2%-50%), p = .018. The 2-year progression-free survival (PFS) was 56% (95% CI 32%-80%) in Group A, 26% (95% CI 2%-50%) in Group B, p = .026. III-IV grade hematological toxicity was the most common adverse event. No treatment-related deaths were observed in both groups. CONCLUSION: Up-front ASCT could improve survival of advanced ENKTL patients in first complete remission, but need be confirmed by a prospective clinical trial.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Extranodal de Células T-NK , Linfoma de Células T Periférico , Células T Matadoras Naturais , Humanos , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Prognóstico , Linfoma de Células T Periférico/etiologiaRESUMO
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous and often clinically aggressive group of neoplasms derived from mature post-thymic T-lymphocytes. These neoplasms are rare and usually diagnostically challenging. Our understanding of the pathogenesis of PTCL is increasing and this improved knowledge is leading us to better molecular characterization, more objective and accurate diagnostic criteria, more effective risk assessment, and potentially better treatments. The focus of this paper is to present a brief overview of the current pathology criteria and molecular and genetic features of nodal peripheral T-cell lymphomas focusing on distinct genetically and molecularly defined subgroups that are being recognized within each major nodal PTCL category. It is expected that the molecular stratification will improve the diagnosis and will provide novel therapeutic opportunities (biomarker-driven and targeted therapies) that might benefit and change the outcomes of patients with these neoplasms.
Assuntos
Linfoma de Células T Periférico , Biomarcadores , Humanos , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/genética , Linfócitos TRESUMO
T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. Herein we report a case of CD30-positive T-cell PTLD that was successfully treated with BV-CHP, suggesting the added value of the addition of BV to chemotherapy, contributing to our patient's long and ongoing progression-free survival. To our knowledge, this is the first documented case of successful treatment using BV-CHP for a CD30-positive, EBV-negative, late T-cell PTLD.
Assuntos
Linfoma de Células T Periférico , Transtornos Linfoproliferativos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Antígeno Ki-1/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/etiologia , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/etiologia , Prednisona/uso terapêuticoRESUMO
Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0-122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3-4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.
Assuntos
Linfoma Cutâneo de Células T/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia/epidemiologia , Terapia Combinada , Diagnóstico Diferencial , Gerenciamento Clínico , Feminino , Humanos , Incidência , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/etiologia , Linfoma Cutâneo de Células T/terapia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/epidemiologia , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vigilância em Saúde Pública , Sistema de Registros , Adulto JovemRESUMO
OPINION STATEMENT: Peripheral T cell lymphoma (PTCL) represents a heterogeneous group of rare lymphoproliferative disorders. Historically, there has been a lack of pathobiological understanding of PTCL. With the exception of ALK-positive anaplastic large cell lymphoma, patients with PTCL have less favorable outcomes, with most patients relapsing shortly after conventional anthracycline-containing multi-agent chemotherapy. The standard management approach for PTCL involves induction therapy followed by autologous stem cell transplantation. Patients with relapsed/refractory PTCL have dismal outcomes and limited treatment options despite the available novel agents, therefore remaining a critical unmet need. By virtue of advancement in cancer biology over the recent years, the treatment landscape of PTCL has gradually evolved from conventional chemotherapy based on solely morphological diagnosis toward more individualized therapies by integrating molecular attributes of PTCL to the traditional treatment paradigm. We are at the edge of witnessing a paradigm shift in PTCL management.
Assuntos
Linfoma de Células T Periférico/terapia , Algoritmos , Biomarcadores Tumorais , Tomada de Decisão Clínica , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Árvores de Decisões , Gerenciamento Clínico , Suscetibilidade a Doenças , Resistencia a Medicamentos Antineoplásicos , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/mortalidade , Gradação de Tumores , Estadiamento de Neoplasias , Medicina de Precisão , Prognóstico , Recidiva , Retratamento , Resultado do TratamentoRESUMO
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphomas that are frequently associated with a poor prognosis. For many decades, the standard-of-care has been CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based therapy, but it is well-recognized that survival outcomes are unsatisfactory, especially when compared with B-cell lymphomas. Major recent advances in cancer diagnosis and management have the potential to significantly improve PTCL outcomes. These include: (1) improved diagnostic techniques that incorporate molecular genetic data to further refine diagnosis and subtyping; (2) the development of novel agents; and (3) improved monitoring modalities, such as 18F-fluorodeoxyglucose positron emission tomography-computed tomography scans and circulating tumor DNA. In this review, we aim to explore these 3 advances in the context of frontline management of PTCL.
Assuntos
Linfoma de Células T Periférico/terapia , Biomarcadores Tumorais , Tomada de Decisão Clínica , Ensaios Clínicos como Assunto , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Diagnóstico Diferencial , Diagnóstico por Imagem/métodos , Gerenciamento Clínico , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/mortalidade , Técnicas de Diagnóstico Molecular , Monitorização Fisiológica , Vigilância da População , Prognóstico , Resultado do TratamentoRESUMO
INTRODUCTION: T cell lymphomas are a heterogeneous group, with varying incidences, geographic patterns, and risk factors. Although until recently approached in a manner similar to B cell lymphomas, the treatment outcomes are poor and this disease is characterized by high relapse rates. The treatment advances in PTCL have been slow compared to B cell lymphomas. The outcomes of patients who progress following stem cell transplantation are worse. AREAS COVERED: This review focuses on the novel targeted agents that are approved and/or are under investigation for patients with relapsed/refractory PTCL. We conducted an electronic literature search of the studies using PubMed, clincaltrials.gov, MEDLINE, using the key words 'PTCL,' 'second line therapy,' and 'targeted agents.' Studies published before January 2020 were included in the search criteria. EXPERT OPINION: Development of newer therapies such as HDAC inhibitors and kinases are promising new agents with activity in relapsed/refractory PTCL. Combination therapy using novel agents may be the future for treatment of PTCL. Therapies in the next few years may take a more personalized approach taking into consideration not just the histology, but also the epigenomic landscape.
Assuntos
Linfoma de Células T Periférico/terapia , Biomarcadores Tumorais , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Resistencia a Medicamentos Antineoplásicos , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/mortalidade , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Melhoria de Qualidade , Recidiva , Retratamento , Falha de Tratamento , Resultado do TratamentoRESUMO
Lymphomatoid papulosis (LyP) is a self-limiting cutaneous T-cell lymphoproliferative disorder that may progress into malignant lymphoma. Most of the previously reported associated lymphomas are primary cutaneous anaplastic large-cell lymphoma and mycosis fungoides with a low mortality rate. We report a case of primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), associated with LyP after long-term follow up. The patient was a 79-year old Japanese man followed up for 9 years. He suddenly developed a 3-cm ulcerated lesion on his forehead, which was diagnosed as an exacerbation of LyP. The lesion regressed after conservative treatment, but the patient soon developed multifocal pcPTCL-NOS. Thereafter, the patient developed pneumonia and cerebral infarction and died within a few months of the onset of malignant lymphoma. Aggressive cutaneous lymphoma may develop in LyP patients. The present case re-emphasizes the need for careful follow up of patients with persistent LyP.
Assuntos
Linfoma Cutâneo de Células T/diagnóstico , Linfoma de Células T Periférico/diagnóstico , Papulose Linfomatoide/diagnóstico , Neoplasias Cutâneas/diagnóstico , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Biópsia , Quimiorradioterapia/métodos , Progressão da Doença , Evolução Fatal , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Linfoma Cutâneo de Células T/etiologia , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/terapia , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/terapia , Papulose Linfomatoide/complicações , Papulose Linfomatoide/tratamento farmacológico , Papulose Linfomatoide/patologia , Masculino , Pele/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapiaRESUMO
OBJECTIVES: A treatment regimen consisting of bendamustine and brentuximab vedotin (BV) has been described as a highly potent salvage therapy and as an effective induction therapy leading to high response rates before autologous stem cell transplantation (ASCT) in patients with classical Hodgkin lymphoma (cHL). In this retrospective analysis, we aimed to assess this therapy's efficacy in unselected patients with cHL and CD30+ peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Data of 28 patients with cHL and five patients with PTCL treated with a combination of bendamustine and BV at three Austrian tertiary cancer centers were analyzed. RESULTS: In patients with cHL, the ORR was 100% (78.6% CR, 21.4% PR). After 17 months median follow-up, median survival times were not reached; 1-year PFS was 81.9%, and 1-year OS was 95.7%. Thirteen eligible patients (46.4%) successfully underwent planned ASCT after salvage therapy with bendamustine and BV and subsequent high-dose chemotherapy. Three of the five PTCL patients achieved CR, while two did not respond and died during or shortly after therapy. CONCLUSION: A combination of bendamustine and BV is an effective salvage and induction therapy before ASCT in patients with relapsed/refractory cHL. Further research is warranted to evaluate the use in patients with PTCL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Linfoma de Células T Periférico/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Brentuximab Vedotin/administração & dosagem , Criança , Terapia Combinada , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/etiologia , Humanos , Quimioterapia de Indução , Antígeno Ki-1/metabolismo , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Adulto JovemRESUMO
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of mature T-cell malignancies; approximately one-third of cases are designated as PTCL-not otherwise specified (PTCL-NOS). Using gene-expression profiling (GEP), we have previously defined 2 major molecular subtypes of PTCL-NOS, PTCL-GATA3 and PTCL-TBX21, which have distinct biological differences in oncogenic pathways and prognosis. In the current study, we generated an immunohistochemistry (IHC) algorithm to identify the 2 subtypes in paraffin tissue using antibodies to key transcriptional factors (GATA3 and TBX21) and their target proteins (CCR4 and CXCR3). In a training cohort of 49 cases of PTCL-NOS with corresponding GEP data, the 2 subtypes identified by the IHC algorithm matched the GEP results with high sensitivity (85%) and showed a significant difference in overall survival (OS) (P = .03). The IHC algorithm classification showed high interobserver reproducibility among pathologists and was validated in a second PTCL-NOS cohort (n = 124), where a significant difference in OS between the PTCL-GATA3 and PTCL-TBX21 subtypes was confirmed (P = .003). In multivariate analysis, a high International Prognostic Index score (3-5) and the PTCL-GATA3 subtype identified by IHC were independent adverse predictors of OS (P = .0015). Additionally, the 2 IHC-defined subtypes were significantly associated with distinct morphological features (P < .001), and there was a significant enrichment of an activated CD8+ cytotoxic phenotype in the PTCL-TBX21 subtype (P = .03). The IHC algorithm will aid in identifying the 2 subtypes in clinical practice, which will aid the future clinical management of patients and facilitate risk stratification in clinical trials.
Assuntos
Biomarcadores Tumorais , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/etiologia , Adulto , Idoso , Algoritmos , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Imunofenotipagem , Linfoma de Células T Periférico/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos TestesAssuntos
Aminopterina/análogos & derivados , Antagonistas do Ácido Fólico/uso terapêutico , Transplante de Coração/efeitos adversos , Linfoma de Células T Periférico/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Aminopterina/farmacologia , Aminopterina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Cardiomiopatias/cirurgia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Antagonistas do Ácido Fólico/farmacologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Insuficiência Cardíaca/cirurgia , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/patologia , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Período Periparto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are frequently expressed in T-cell lymphomas. This provides a rationale for exploration of immune checkpoint inhibitors in the management of T-cell lymphomas. PATIENTS AND METHODS: In this phase II single-arm multicenter trial, patients with relapsed or refractory systemic T-cell lymphoma were treated with 200 mg pembrolizumab intravenously every 21 days. The primary endpoint was progression-free survival (PFS). The secondary endpoints were response rate, overall survival, response duration, and safety. We assessed PD-L1, p-AKT expression, and peripheral blood immune cells as potential predictive biomarkers. RESULTS: Of 18 enrolled patients, 13 were evaluable for the primary endpoint. The trial was halted early after a preplanned interim futility analysis. The overall response rate was 33% (95% confidence interval [CI], 9%-55%); 4 patients achieved a complete response (27%; 95% CI, 5%-49%). The median PFS was 3.2 months (95% CI, 1.2-3.7 months), and the median overall survival was 10.6 months (95% CI, 3.2-100 months). The median duration of response was 2.9 months (95% CI, 0-10.1 months). Two of the 4 complete responders remain in remission > 15 months. Rash was the most common adverse event (17%; n = 3). The most common ≥ grade 3 treatment-emergent adverse events were rash and pneumonitis (11%; n = 2 each). Neither PD-L1 nor p-AKT expression were associated with outcomes. However, a higher relative frequency of CD4+ T lymphocytes pre-treatment was associated with improved PFS (hazard ratio, 0.15; 95% CI, 0.03-0.74). CONCLUSION: Pembrolizumab demonstrated modest single-agent activity in relapsed or refractory T-cell lymphoma.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Biomarcadores Tumorais , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Recidiva , Resultado do Tratamento , Adulto JovemRESUMO
Patients with angioimmunoblastic T-cell lymphoma (AITL), one of the most common types of peripheral T-cell lymphoma (PTCL), typically present with advanced disease, systemic symptoms, and immune deregulation. Treatment can be challenging owing to frequent relapses after initial and subsequent therapy. The front-line treatment approach currently mirrors the approach used for other nodal PTCLs with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy and consideration for autologous stem-cell transplant (SCT). In the relapsed and refractory settings, allogeneic SCT offers the chance for long-term remission. Choice of treatment of relapsed or refractory disease depends on whether an allogeneic SCT is planned. Agents with preferential activity in relapsed or refractory AITL include epigenetic modifiers such as histone deacetylase inhibitors and hypomethylating agents. Other targeted agents show promise in AITL, including brentuximab vedotin and phosphoinositide-3-kinase inhibitors. Ongoing studies are evaluating new potential targets for AITL, with particular focus on identifying markers of response and resistance. Additional studies are assessing incorporation of novel agents into the front-line treatment of AITL. These studies will lead to more individualized treatment approaches and, ultimately, improved outcomes for patients with AITL.
Assuntos
Linfoma de Células T Periférico/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Terapia Combinada , Gerenciamento Clínico , Feminino , Humanos , Imunofenotipagem , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/etiologia , Recidiva , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: Peripheral T-cell lymphomas (PTCLs) represent diverse and aggressive malignancies, with few recent therapeutic improvements. Recent high-throughput genomic studies have revealed the complex mutational landscape of these rare diseases. These novel findings provide the grounds to a more comprehensive classification of these diseases, reflected in the 2017 WHO classification. RECENT FINDINGS: Our review is focused on selected PTCL entities. Angioimmunoblastic T-cell lymphoma and other lymphomas derived from T follicular helper cells feature a rather homogeneous mutational landscape. These neoplasms recapitulate a multistep oncogenic process associating epigenetic deregulation, and second hit mutations affecting the T-cell receptor signaling pathway. This model inferred from comprehensive analyses of patients samples, was confirmed in mouse models. Among ALK-negative anaplastic large-cell lymphomas, translocation-associated subsets are found in both systemic and cutaneous types, and the newly described breast implant-associated type is usually indolent. Extranodal lymphomas of the innate immune system also harbor a combination of mutations affecting different classes of epigenetic modifiers, and mutation-induced activation of the Janus Kinase/signal transduction and activator of transcription pathway. SUMMARY: Understanding of PTCL pathogenesis has substantially improved, and oncogenic events have been identified. The current challenge is to mount efficient therapeutic strategies targeting these aberrations to improve patients' outcome.
Assuntos
Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/etiologia , Humanos , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patologia , Transdução de SinaisRESUMO
BACKGROUND: Epstein-Barr virus positive peripheral T cell lymphoma (EBV + PTCL) is a rare type of lymphoproliferative disorder which is always present in late adulthood. However, pediatric EBV + PTCL is extremely rare and always present with lymphadenopathy. Additionally, gene detection was not performed in all of these pediatric patients. CASE PRESENTATION: We report an EBV + PTCL in a 9-year-old child with initial symptom of subcutaneous masses without lymph node involvement. Histologically, the neoplastic cells were centroblastoid with round or oval nuclei, slightly condensed chromatin and median eosinophilic inconspicuous nucleoli. Immunohistochemically, all neoplastic cells were positive for CD8, GranzymeB and TIA-1. Two novel variants (S420Y and E623K) were detected in STAT5B. CONCLUSION: To the best of our knowledge, this is the first case of EBV + PTCL with STAT5B variants of a pediatric patient presented as extranodal lesions.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Variação Genética , Herpesvirus Humano 4 , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/etiologia , Fator de Transcrição STAT5/genética , Biomarcadores , Biópsia , Criança , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Imunofenotipagem , Linfoma de Células T Periférico/terapia , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Análise de Sequência de DNARESUMO
Posttransplant lymphoproliferative disorders are a spectrum of lymphoproliferative disorders seen in recipients of solid-organ, bone marrow, and stem cell allografts. They include polyclonal early lesions mimicking infectious mononucleosis and monoclonal proliferations of B and T cells, indistinguishable from lymphomas occurring in immunocompetent individuals. Although most posttransplant lymphoproliferative disorders are B-cell neoplasms, T-cell posttransplant lymphoproliferative disorders are very rare. Among solid-organ transplants, renal allografts have low risk for development of posttransplant lymphoproliferative disorders. We describe the case of an adult male who developed a T-cell posttransplant lympho?roliferative disorder involving the small intestine after renal transplant, which was diagnosed as peripheral T-cell lymphoma, not otherwise specified.
Assuntos
Neoplasias do Jejuno/etiologia , Transplante de Rim/efeitos adversos , Linfoma de Células T Periférico/etiologia , Biomarcadores Tumorais/análise , Biópsia , Humanos , Imuno-Histoquímica , Neoplasias do Jejuno/química , Neoplasias do Jejuno/patologia , Neoplasias do Jejuno/cirurgia , Linfoma de Células T Periférico/química , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/cirurgia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Mogamulizumab is a defucosylated humanized anti-CC chemokine receptor type 4 (CCR4) antibody that exerts an anti-tumor immune effect against various tumors through a suppressive effect on regulatory T-cells. We herein report a patient with peripheral T-cell lymphoma who developed Epstein-Barr virus (EBV)-related primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) after mogamulizumab therapy. Our experience should alert physicians to the possibility of the development of EBV-related CNS DLBCL in patients treated for primary lymphoma and suggests that the anti-tumor immune effect of mogamulizumab is ineffective for the prophylaxis of EBV-related lymphomas.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Doenças do Sistema Nervoso Central/etiologia , Herpesvirus Humano 4 , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma de Células T Periférico/etiologia , Idoso , Doenças do Sistema Nervoso Central/virologia , Feminino , Humanos , Linfoma de Células T Periférico/virologia , Masculino , Receptores CCR4/imunologia , Linfócitos T ReguladoresRESUMO
Reports of sequential occurrence of two or more types of lymphoma are rare, especially when they involve different cell lineages. Herein, we report a rare case of sequential development of peripheral t-cell lymphoma following treatment of diffuse large B cell lymphoma. In a 73-year-old Chinese male patient, diffuse large B-cell lymphoma (DLBCL) was diagnosed in September 2011 based on the result of a tongue biopsy. Afterwards, he received rituximab combined with chemotherapy and local radiotherapy. Though he achieved completed remission, he had a new symptom of one enlarged left inguinal lymph node in November of 2015. A new biopsy was then performed. Immunohistochemistry and polymerase chain reaction (PCR) for gene rearrangements proved monoclonal T-cell lymphoma. We didn't detect EBV infection in either of two biopsies, nor any evidence of immune dysfunction complications. Sequential development of B-cell and T-cell malignancy in this patient maybe an example of treatment-related secondary lymphoma.