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1.
Autops. Case Rep ; 9(4): e2019117, Oct.-Dec. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1024240

RESUMO

Sporadic Burkitt lymphoma (SBL) is a variant of Burkitt lymphoma that occurs worldwide, affecting mainly children and young adults. Association with Epstein-Barr virus (EBV) can be identified in approximately 20-30% of cases. Herein we described a case of a 63-year-old male presenting intraoral bilateral mandibular swelling, subjacent to fixed dental prosthesis, with one month of duration. Incisional biopsies were performed, and after two days, the patient was hospitalized due to malaise and breathing difficulty, and died after a week when an abdominal tumor was detected. The mandibular biopsies revealed a diffuse proliferation of medium-sized monomorphic atypical lymphoid cells exhibiting numerous mitoses and areas of "starry-sky" pattern. The tumor showed immunohistochemical positivity for CD20, CD10, Bcl-6, and Ki-67 (≈ 100%); it was negative for CD3, Bcl-2, Vs38c, and MUM-1. Positivity for EBV was found by in situ hybridization. The final diagnosis was intraoral SBL positive for EBV. Clinical, morphological and molecular criteria are necessary for the correct diagnosis of aggressive B-cell neoplasms positive for EBV in elderly patients.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Linfoma de Burkitt/patologia , Herpesvirus Humano 4 , Linfoma não Hodgkin/patologia
2.
Anticancer Res ; 39(11): 6413-6416, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704875

RESUMO

BACKGROUND/AIM: The aim of this study was to present the clinical characteristics, natural history and survival outcomes of primary gastrointestinal non-Hodgkin lymphomas (PGINHL) in the pediatric population. PATIENTS AND METHODS: Surveillance, Epidemiology, and End Results (SEER) database was queried for patients aged 0 to 19 years with PGINHL between 1973 and 2014. RESULTS: A total of 452 cases were identified [mean age 11.0 (±5.1)] years, whites 84.1%, males (76.5%). The majority of tumors were noted in the small bowel (SB) (47.6%), followed by large bowel (LB) (28.5%) and the stomach (10.0%). Overall, the most common histological subtype was Burkitt lymphoma (51.8%), followed by diffuse large B-cell lymphoma (DLBCL) (26.1%). Mean overall survival (OS) of the entire cohort was 33,33 years with a 5-yr, 10-yr and 30-yr survival rate of 86%, 86% and 79%, respectively. Large bowel tumors had the best long-term survival rates whereas; gastric tumors had the worst with 30-yr survival rate 84% and 74%, respectively. Overall, 328 (72.6%) patients received surgery. No significant survival difference was noted between patients who underwent surgery and those who did not. CONCLUSION: This study presents the largest dataset of pediatric PGINHL and describes the clinical features and outcomes of these patients in addition to summarizing the literature.


Assuntos
Neoplasias Gastrointestinais , Linfoma não Hodgkin , Adolescente , Linfoma de Burkitt/mortalidade , Linfoma de Burkitt/patologia , Linfoma de Burkitt/cirurgia , Neoplasias do Ceco/mortalidade , Neoplasias do Ceco/patologia , Neoplasias do Ceco/cirurgia , Criança , Pré-Escolar , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Humanos , Neoplasias do Íleo/mortalidade , Neoplasias do Íleo/patologia , Neoplasias do Íleo/cirurgia , Lactente , Recém-Nascido , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/cirurgia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/cirurgia , Masculino , Programa de SEER , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Adulto Jovem
3.
Ann Hematol ; 98(11): 2561-2567, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31515574

RESUMO

Overt central nervous system (CNS) involvement in aggressive non-Hodgkin's lymphoma (NHL) is rare at diagnosis. Much effort is put to identify risk factors for occult CNS involvement, and the risk assessment of CNS relapse. Prophylactic treatment carries risk of adverse events and its efficacy is not clear. Detection of cerebrospinal fluid molecular gene rearrangement (GRR) as a method to detect occult disease has been studied in acute leukemia and primary CNS lymphoma. To date, the capacity of a positive GRR in newly diagnosed NHL patients to predict CNS relapse has not been addressed. We retrospectively studied the prognostic value of GRR in cerebrospinal fluid samples of 148 newly diagnosed patients with high grade NHL. We demonstrate that positive GRR at diagnosis does not affect PFS or OS and did not predict CNS relapse. However, although numbers were small, repeated positive samples (≥ 2) correlated with a higher risk for CNS relapse (p = 0.048), possibly stressing the need for an aggressive preventive approach.


Assuntos
Neoplasias do Sistema Nervoso Central , Rearranjo Gênico , Linfoma não Hodgkin , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Medicine (Baltimore) ; 98(35): e16841, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464910

RESUMO

RATIONALE: Multiple primary central nervous system lymphoma (MPCNSL) is a rare disease with differential diagnosis and treatment. As the underlying pathogenesis is not yet clarified, the early-stage clinical manifestations are occult and atypical. Also, the imaging manifestations are not specific, which is challenging for the clinical diagnosis and treatment. Therefore, additional clinical research is essential to understand the etiology of the disease. PATIENT CONCERNS: A 63-year-old male patient suffered from MPCNSLs but without typical clinical manifestations. The findings of the imaging examination were as follows. Magnetic resonance imaging (MRI) showed long T1 and T2 signal shadows in the right frontal lobe, right hippocampus, right cerebellar hemisphere, and the left occipital lobe. In addition, patchy T1-enhanced signal shadows were observed in the right frontal lobe and around the midline. Frontal lesions were detected in the magnetic resonance spectroscopy (MRS), Cho peak increased, and N-acetylaspartate (NAA) peak decreased. On the other hand, in the diffusion weighted imaging (DWI), apparent dispersion coefficient (ADC) showed low-value changes and high signal changes. The positron emission tomography-computed tomography (PET-CT) displayed radioactive accumulation in the right frontal lobe. DIAGNOSIS: Multiple primary central nervous system lymphoma. INTERVENTIONS: The patient received some conservative medical treatment, but his condition continued to worsen. Finally, he received a pathological biopsy, and refused further treatment after the result was reported. OUTCOMES: The patient died 1 week after biopsy, and the course of disease was about 100 days. LESSONS: PCNSL is a primary intracranial malignancy with low incidence and a high degree of malignancy and specificity in clinical manifestations. To facilitate early clinical treatment and improve the long-term survival of patients, it is necessary to master the imaging diagnostic methods and its features. The comprehensive application of multiple imaging examinations, such as CT, MRI, PET/CT, and PET/MRI, as well as, cerebrospinal fluid cytology can greatly improve the diagnosis of PCNSL.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Linfoma não Hodgkin/diagnóstico por imagem , Imagem Multimodal/métodos , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Imagem de Difusão por Ressonância Magnética , Evolução Fatal , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/patologia , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
5.
Hematol Oncol ; 37(4): 368-374, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325190

RESUMO

In 2009, the four laboratories of the Fondazione Italiana Linfomi (FIL) minimal residual disease (MRD) Network started a collaborative effort to harmonize and standardize their methodologies at the national level, performing quality control (QC) rounds for follicular lymphoma (FL) and mantle cell lymphoma (MCL) MRD assessment. In 16 QC rounds between 2010 and 2017, the four laboratories received 208 bone marrow (BM) samples (126 FL; 82 MCL); 187 were analyzed, according to the EuroMRD Consortium guidelines, by both nested (NEST) polymerase chain reaction (PCR) and real-time quantitative (RQ) PCR for BCL2/IGH MBR or IGHV rearrangements. Here, we aimed at analyzing the samples that challenged the interlaboratory reproducibility and data interpretation. Overall, 156/187 BM samples (83%) were concordantly classified as NEST+/RQ+ or NEST-/RQ- by all the four laboratories. The remaining 31 samples (17%) resulted alternatively positive and negative in the interlaboratory evaluations, independently of the method and the type of rearrangement, and were defined "borderline" (brd) samples: 12 proved NEST brd/RQ brd, 7 NEST-/RQ brd, 10 NEST brd/RQ positive not quantifiable (PNQ), and 2 NEST brd/RQ-. Results did not change even increasing the number of replicates/sample. In 6/31 brd samples, droplet digital PCR (ddPCR) was tested and showed no interlaboratory discordance. Despite the high interlaboratory reproducibility in the MRD analysis obtained and maintained by the QC round strategy, samples with the lowest MRD levels can still represent a challenge: 17% (31/187) of our samples showed discordant results in interlaboratory assessments, with 6.4% (12/187) remained brd even applying the two methods. Thus, although representing a minority, brd samples are still problematic, especially when a clinically oriented interpretation of MRD results is required. Alternative, novel methods such as ddPCR and next-generation sequencing have the potential to overcome the current limitations.


Assuntos
Exame de Medula Óssea , Medula Óssea/patologia , Ensaio de Proficiência Laboratorial , Linfoma não Hodgkin/patologia , Reação em Cadeia da Polimerase , Exame de Medula Óssea/normas , Células Clonais , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Genes de Imunoglobulinas , Genes bcl-2 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Itália/epidemiologia , Linfoma não Hodgkin/genética , Neoplasia Residual , Proteínas de Fusão Oncogênica/análise , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/normas , Proteínas Proto-Oncogênicas c-bcl-2/genética , Garantia da Qualidade dos Cuidados de Saúde , Reprodutibilidade dos Testes , Translocação Genética
6.
Medicine (Baltimore) ; 98(26): e16129, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261533

RESUMO

Individuals infected with human immunodeficiency virus (HIV) have higher morbidity and mortality due to cancer, which is the third most common cause of death in this group, despite the high effectiveness of antiretroviral therapy (ART). We describe the clinical and laboratory characteristics, initial staging and outcome of HIV-related lymphoma.We included 18 patients in the study, of whom 61.1% were male, mean age 41 years. Nine of the 18 patients (50%) had a diagnosis of HIV infection concurrent with the diagnosis of lymphoma.The most common histological types were diffuse non-Hodgkin B-cell lymphoma, 8 patients (44.4%); and Burkitt lymphoma, 5 (27.8%) cases. The Cotswold revision of the Ann Arbor staging classification in 14 patients (77.7%) was between III and IV. B Symptoms were present in 11 patients (61.1%), bulky mass was observed in 11 cases (61.1%) and had extra-nodal involvement in 8 patients (44.4%).Of the 18 cases analyzed, 8 followed on to second-line treatment, wherein the CODOX-M/IVAC scheme (cyclophosphamide, adriamycin, vincristine, methotrexate/ifosfamide, etoposide, and cytosine arabinoside) was used in 3 of the cases. The second most common scheme was etoposide, doxorubicin, vincristine and cyclophosphamide (EPOCH), used in 2 cases (25%), while in single cases (12.5% each) cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP), ifosfamide, etoposide, and carboplatin (ICE) and dexamethasone, cisplatin, and cytarabine (DHAP) were used.In this series, we observed very high mortality, equivalent to 44.4%, and a complete response in only 11.1%, much lower than that observed by other authors.We found that patients diagnosed with lymphoma associated with HIV had an advanced early clinical staging, and evolved with low response rates to chemotherapy.


Assuntos
Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/terapia , Adulto , Antineoplásicos/uso terapêutico , Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/patologia , Linfoma de Burkitt/terapia , Feminino , Humanos , Linfoma Relacionado a AIDS/patologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos
7.
Eur J Med Chem ; 179: 84-99, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247375

RESUMO

The DNA alkylating prodrug cyclophosphamide (CPA), alone or in combination with other agents, is one of the most commonly used anti-cancer agents. As a prodrug, CPA is activated by cytochrome P450 2B6 (CYP2B6), which is transcriptionally regulated by the human constitutive androstane receptor (hCAR). Therefore, hCAR agonists represent novel sensitizers for CPA-based therapies. Among known hCAR agonists, compound 6-(4-chlorophenyl)imidazo-[2,1-b]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO) is the most potent and broadly utilized in biological studies. Through structural modification of CITCO, we have developed a novel compound DL5016 (32), which has an EC50 value of 0.66 µM and EMAX value of 4.9 when activating hCAR. DL5016 robustly induced the expression of hCAR target gene CYP2B6, at both the mRNA and protein levels, and caused translocation of hCAR from the cytoplasm to the nucleus in human primary hepatocytes. The effects of DL5016 were highlighted by dramatically enhancing the efficacy of CPA-based cytotoxicity to non-Hodgkin lymphoma cells.


Assuntos
Antineoplásicos/farmacologia , Ciclofosfamida/farmacologia , Linfoma não Hodgkin/tratamento farmacológico , Pró-Fármacos/farmacologia , Receptores Citoplasmáticos e Nucleares/agonistas , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclofosfamida/síntese química , Ciclofosfamida/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Estrutura Molecular , Pró-Fármacos/síntese química , Pró-Fármacos/química , Receptores Citoplasmáticos e Nucleares/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
8.
Ann Hematol ; 98(8): 1981-1987, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177299

RESUMO

Infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric malignant lymphoma. The chronic inflammation of gastric mucosa by H. pylori infection induces lymphomagenesis. Although this chronic mucosal inflammation also results in atrophic gastritis, evidence supporting the possible significance of atrophic gastritis in gastric lymphomagenesis is scarce. Here, to evaluate the association between gastric mucosal atrophy and the risk of gastric lymphoma, we conducted a matched case-control study at Aichi Cancer Center focusing on the attribution of H. pylori infection status and pepsinogen (PG) serum levels. In total, 86 patients with gastric lymphoma (including 49 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and 24 cases of diffuse large B cell lymphoma (DLBCL)) and 1720 non-cancer controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results failed to show a statistically significant association between atrophic gastritis and the risk of gastric lymphoma. The adjusted ORs of positive atrophic gastritis relative to negative for overall gastric lymphoma, MALT lymphoma, DLBCL, and other lymphomas were 0.77 (95% CI 0.45-1.33), 0.65 (0.30-1.39), 1.03 (0.38-2.79), and 0.84 (0.22-3.29), respectively. In contrast, a positive association between overall gastric lymphoma and H. pylori infection was observed (OR = 2.14, 95% CI 1.30-3.54). A consistent association was observed for MALT lymphoma, DLBCL, and other lymphomas with ORs of 1.96 (1.00-3.86), 1.92 (0.74-4.95), and 5.80 (1.12-30.12), respectively. These findings suggest that H. pylori infection triggers gastric lymphoma but that epithelial changes due to atrophic gastritis do not inherently affect the development of gastric lymphoma.


Assuntos
Infecções por Helicobacter/diagnóstico , Helicobacter pylori/patogenicidade , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Carcinogênese/patologia , Estudos de Casos e Controles , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/complicações , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/fisiologia , Humanos , Japão , Modelos Logísticos , Linfoma de Zona Marginal Tipo Células B/etiologia , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/microbiologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/microbiologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pepsinogênio A/sangue , Fatores de Risco , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
9.
J Surg Oncol ; 120(3): 431-437, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31187517

RESUMO

BACKGROUND AND OBJECTIVES: Primary colonic lymphoma (PCL) is rare, heterogeneous, and presents a therapeutic challenge for surgeons. Optimal treatment strategies are difficult to standardize, leading to variation in therapy. Our objective was to describe the patient characteristics, short-term outcomes, and five-year survival of patients undergoing nonpalliative surgery for PCL. METHODS: We performed a retrospective cohort analysis in the National Cancer Database. Included patients underwent surgery for PCL between 2004 to 2014. Patients with metastases and palliative operations were excluded. Univariate predictors of overall survival were analyzed using multivariable Cox proportional hazard analysis. RESULTS: We identified 2153 patients. Median patient age was 68. Diffuse large B-cell lymphoma accounted for 57% of tumors. 30- and 90-Day mortality were high (5.6% and 11.1%, respectively). Thirty-nine percent of patients received adjuvant chemotherapy. For patients surviving 90 days, 5-year survival was 71.8%. Chemotherapy improved survival (surgery+chemo, 75.4% vs surgery, 68.6%; P = .01). Adjuvant chemotherapy was associated with overall survival after controlling for age, comorbidity, and lymphoma subtype (HR 1.27; 95% CI, 1.07-1.51; P = .01). CONCLUSIONS: Patients undergoing surgery for PCL have high rates of margin positivity and high short-term mortality. Chemotherapy improves survival, but <50% receive it. These data suggest the opportunity for improvement of care in patients with PCL.


Assuntos
Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Linfoma/mortalidade , Linfoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Big Data , Quimioterapia Adjuvante , Estudos de Coortes , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma/tratamento farmacológico , Linfoma/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/cirurgia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Radioterapia Adjuvante , Estudos Retrospectivos
10.
Virchows Arch ; 475(3): 365-372, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31044268

RESUMO

Incidental detection of lymphoma in lymph node (LN) dissection for carcinoma is extremely rare. The occurrence and clinicopathological features of this rare condition have not been characterised. The medical records of 11,889 consecutive patients who underwent LN dissection for carcinoma in the abdominopelvic cavity were retrospectively reviewed. Among these patients, 11 had lymphomas detected in LN dissections and 7 had no previous history of lymphoma, representing an incidental detection rate of 0.06% (7/11889). The patients had a median age of 63 years (range, 48-69 years), and the male-to-female ratio was 1:2.5. The sites and histological types of the carcinoma were as follows: adenocarcinoma of the sigmoid colon (2 cases), endometrioid adenocarcinoma of the endometrium (2 cases), squamous carcinoma of the uterine cervix (1 case), adenocarcinoma of the stomach (1 case), and adenocarcinoma of the rectum (1 case). All incidental lymphoma cases (100%, 7/7) were low-grade B cell non-Hodgkin lymphoma (B-NHL), including 5 cases of follicular lymphoma (grades 1-2) and 2 cases of small lymphocytic lymphoma. The median follow-up interval was 39 months (5-65 months). All the patients were alive at the end of the follow-up period. Low-grade B-NHL can be incidentally detected during LN dissection for carcinoma in the abdominopelvic cavity. The subtype of incidental lymphoma is likely related to the epidemiology of lymphoma classes in the corresponding area. We should be aware of simultaneous occurrence of incidental lymphoma during lymphadenectomy for carcinoma.


Assuntos
Cavidade Abdominal/patologia , Linfonodos/patologia , Neoplasias Pélvicas/patologia , Adenocarcinoma/patologia , Idoso , Carcinoma Endometrioide/patologia , Carcinoma de Células Escamosas/patologia , China , Feminino , Humanos , Achados Incidentais , Excisão de Linfonodo/métodos , Metástase Linfática/patologia , Linfoma/patologia , Linfoma Folicular/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Ann Hematol ; 98(8): 1953-1959, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31025161

RESUMO

The change in the incidence of lymphomas in function of the presence or absence of sustained virological response after anti-hepatitis C therapy in a cohort of human immunodeficiency (HIV)-hepatitis C (HCV) viruses coinfected patients was analyzed. A prospective cohort of 755 HIV-HCV coinfected patients who received their first anti-HCV therapy, based on interferon + ribavirin schemas, was evaluated. Incidence and histologic types of lymphomas were analyzed in two periods: (1) before administration of anti-HCV therapy and (2) after anti-HCV therapy. The association between lymphoma incidence and demographic, HIV- (minimum CD4+ cell count and CD4+ cell count at diagnosis of lymphoma, antiretroviral therapy, maximal HIV load and HIV load at diagnosis of lymphoma) and HCV-related variables (HCV load, genotype, sustained viral response to anti-HCV therapy) were analyzed. A total of 13 lymphomas [incidence rate (95% confidence interval), 0.72 (0.33-1.11) × 1000 person-years, time from HIV diagnosis to lymphoma diagnosis (median, interquartile range), 15 (11-19) years] were diagnosed. Nine of them were non-Hodgkin and four Hodgkin lymphomas. The median CD4+ T cell count at diagnosis of lymphoma was 457/mm3, with only two cases with values lower than 200/mm3. The incidence rate of non-Hodgkin lymphomas was similar pre- and post-anti HCV therapy [0.33 (0.00-0.65) vs 0.68 (0.08-1.26) × 1000 person-years, respectively, p > 0.05]. Patients with sustained virologic HCV response showed similar incidence rate of lymphomas than that of those without anti-HCV response. In conclusion, anti-HCV therapy does not modify the incidence rate of lymphomas in HIV-HCV coinfected patients.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Doença de Hodgkin/tratamento farmacológico , Interferon alfa-2/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Ribavirina/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Coinfecção , Combinação de Medicamentos , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , Infecções por HIV/complicações , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Doença de Hodgkin/complicações , Doença de Hodgkin/patologia , Doença de Hodgkin/virologia , Humanos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Carga Viral/efeitos dos fármacos
12.
Lancet Haematol ; 6(5): e254-e265, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30935953

RESUMO

BACKGROUND: Antibody-drug conjugates (ADCs) polatuzumab vedotin (pola) and pinatuzumab vedotin (pina) showed clinical activity and tolerability in phase 1 trials. The aim of this multicentre, open-label, phase 2 study was to compare rituximab plus pola (R-pola) or pina (R-pina) in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. METHODS: In this phase 2 randomised study at 39 investigational sites in six countries, patients were randomly assigned (1:1), by use of a dynamic hierarchical randomisation scheme, to receive R-pola or R-pina (375 mg/m2 rituximab plus 2·4 mg/kg ADCs) every 21 days until disease progression or unacceptable toxicity up to 1 year. Treatment allocations were not masked to the investigator, patients or sponsor after the patients were enrolled and randomly assigned. The primary objectives were safety and tolerability, and antitumour response. The study is registered with ClinicalTrials.gov, number NCT01691898, and is closed to accrual. FINDINGS: 81 patients with diffuse large B-cell lymphoma and 42 with follicular lymphoma were recruited between Sept 27, 2012, and Oct 10, 2013, and were assigned to treatment. 81 patients with diffuse large B-cell lymphoma and 41 patients with follicular lymphoma were eligible for analysis. Of the 42 patients with diffuse large B-cell lymphoma who received R-pina, 25 (60%, 95% CI 43-74) achieved an objective response and 11 (26%, 95% CI 14-42) achieved a complete response. Of the 39 patients in this cohort who received R-pola, 21 (54%, 95% CI 37-70) achieved an objective response, and eight (21%, 95% CI 9-36) achieved a complete response. Of the 21 patients in the follicular lymphoma cohort who received R-pina, 13 (62%, 95% CI 38-82) achieved an objective response, and one (5%, 95% CI 0·1-24) achieved a complete response. Of the 20 patients in this cohort who received R-pola, 14 (70%, 95% CI 46-88) achieved an objective response, and nine (45%, 95% CI 23-68) achieved a complete response. In the diffuse large B-cell lymphoma cohort, grade 3-5 adverse events occurred in 33 (79%) of 42 patients receiving R-pina (most common were neutropenia [29%] and hyperglycaemia [10%]; nine [21%] grade 5 adverse events, five of which were infection-related), and in 30 (77%) of 39 patients receiving R-pola (most common were neutropenia [23%], anaemia [8%] and diarrhoea [8%]; no grade 5 adverse events). In the follicular lymphoma cohort, grade 3-5 adverse events occurred in 13 (62%) of 21 patients receiving R-pina (most common were neutropenia [29%] and hyperglycaemia [14%]; no grade 5 adverse events) and in ten (50%) of 20 patients receiving R-pola (most common were neutropenia [15%] and diarrhoea [10%]; one grade 5 adverse event). INTERPRETATION: R-pina and R-pola are potential treatment options in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Pola was selected by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response than pina, and an overall benefit-risk favouring R-pola. FUNDING: F Hoffmann-La Roche.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoconjugados/administração & dosagem , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Rituximab/administração & dosagem , Resultado do Tratamento
13.
Biomed Res Int ; 2019: 1065652, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016181

RESUMO

Background: Accurate classification for different non-Hodgkin lymphomas (NHL) is one of the main challenges in clinical pathological diagnosis due to its intrinsic complexity. Therefore, this paper proposes an effective classification model for three types of NHL pathological images, including mantle cell lymphoma (MCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). Methods: There are three main parts with respect to our model. First, NHL pathological images stained by hematoxylin and eosin (H&E) are transferred into blue ratio (BR) and Lab spaces, respectively. Then specific patch-level textural and statistical features are extracted from BR images and color features are obtained from Lab images both using a hierarchical way, yielding a set of hand-crafted representations corresponding to different image spaces. A random forest classifier is subsequently trained for patch-level classification. Second, H&E images are cropped and fed into a pretrained google inception net (GoogLeNet) for learning high-level representations and a softmax classifier is used for patch-level classification. Finally, three image-level classification strategies based on patch-level results are discussed including a novel method for calculating the weighted sum of patch results. Different classification results are fused at both feature 1 and image levels to obtain a more satisfactory result. Results: The proposed model is evaluated on a public IICBU Malignant Lymphoma Dataset and achieves an improved overall accuracy of 0.991 and area under the receiver operating characteristic curve of 0.998. Conclusion: The experimentations demonstrate the significantly increased classification performance of the proposed model, indicating that it is a suitable classification approach for NHL pathological images.


Assuntos
Linfoma não Hodgkin/patologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma/patologia , Curva ROC
14.
Eur J Radiol ; 113: 110-115, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30927934

RESUMO

OBJECTIVE: To investigate the MDCT features of primary adrenal lymphoma (PAL) and correlate the results with clinicopathological findings. MATERIALS AND METHODS: Twenty eight patients (17 men, 11 women; median age, 61.5years) with pathologically confirmed PAL were included in this study. MDCT features of the lesions were retrospectively reviewed and correlated with clinicopathological findings. RESULTS: All of the 28 cases were non-Hodgkin's lymphoma (NHL), in which 25 cases were diffuse large B-cell lymphoma and 3 cases T-cell lymphoma. 21 (75%) patients had bilateral tumors with maximum diameter of 3.9-17.7 cm (median, 9.18 cm), and 7 (25%) patients had unilateral tumors with maximum diameter of 4.3-14.9 cm (median, 8.6 cm). The sign of infiltrating adjacent organs and encasing adjacent vessels were appeared in 10 and 15 patients respectively, in which 9 patients had both signs. 20 (71.4%) patients had the appearance of adeniform, and 3 (10.7%) patients showed infiltrating and embedding the adrenal gland. Among all the patients, 27 (96.4%) and 26 (92.9%) patients had mild enhancement on arterial and parenchymal phase, respectively; and 12 (42.8%) were homogenous, 14 (50%) slightly inhomogeneous and 2 (7.1%) heterogeneous on both phase. In addition, adrenal insufficiency was found in 33.3% (7/21) of the patients with bilateral lesions, and none in unilateral lesions. CONCLUSION: Large adrenal soft tissue mass with maintenance of adreniform shape, encasing vessels, homogenous or slightly inhomogeneous density with no calcification, and mild enhancement on both arterial and parenchymal phase could be seen as the main MDCT features of PAL. In addition, infiltrating and embedding the adrenal gland may be specific imaging characteristics of PAL.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Linfoma não Hodgkin/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcinose/diagnóstico por imagem , Calcinose/patologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Estudos Retrospectivos
15.
Int J Clin Oncol ; 24(9): 1020-1029, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30993483

RESUMO

BACKGROUND: Methotrexate (MTX) is used in first-line treatment of primary central nervous system lymphoma (PCNSL), but most cases result in relapse-acquired resistance to MTX. However, only few studies have reported on internal changes and chemotherapies in PCNSL. METHODS: In this study, we generated two MTX-resistant PCNSL cell lines, designated MTX-HKBML and MTX-TK, in addition to a MTX-resistant Burkitt lymphoma cell line, designated MTX-RAJI. We examined gene expression changes and drug sensitivity to a proteasome inhibitor, bortezomib, in these cells. RESULTS: Cytotoxic tests revealed that the 50% inhibitory concentration for MTX in MTX-HKBML is markedly higher than that in the other two cell lines. Expression of the genes in MTX and folate metabolisms, including gamma-glutamyl hydrolase and dihydrofolate reductase, are upregulated in both MTX-HKBML and MTX-TK, whereas the gene expression of folylpolyglutamate synthetase, thymidylate synthase, and methylenetetrahydrofolate dehydrogenase 1 were upregulated and downregulated in MTX-HKBML and MTX-TK, respectively, on the other hand, bortezomib sensitivity was observed in MTX-TK, as compared with control TK, but not in MTX-HKBML. CONCLUSION: These results indicate the cell-type-specific changes downstream of metabolic pathways for MTX and folate, bortezomib sensitivity, and purine and pyrimidine syntheses, in each PCNSL cell line. The MTX-resistant lymphoma cell lines established may be useful for in vitro relapse models for MTX and development of salvage chemotherapy and drug discovery.


Assuntos
Bortezomib/farmacologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma/tratamento farmacológico , Metotrexato/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bortezomib/administração & dosagem , Linhagem Celular Tumoral , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Ácido Fólico/genética , Ácido Fólico/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfoma/genética , Linfoma/patologia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Metotrexato/administração & dosagem , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Antígenos de Histocompatibilidade Menor/genética , Terapia de Alvo Molecular , Peptídeo Sintases/genética , Timidilato Sintase/genética
16.
Ann Biol Clin (Paris) ; 77(2): 191-195, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30907360

RESUMO

We report the case of an 83-year-old woman admitted to the accident and emergency unit for pneumopathy. The blood cell count on the DXH automaton (Coulter® ™ UniCel® DxH) found a normochromic and normocytic anemia, anormal platelet count and subnormal leukocyte formula. The only alarm raised by the automaton was the presence of a basocytosis. A control of the leucocyte count by flow cytometry and blood smear has been done. It revealed there was no basocytosis, but showed the presence of an atypical monomorphic lymphocytes B population (T/B < 1 ratio in flow cytometry), around which platelets aggregated. The lymphocytic immunophenotyping allowed us to highlight the presence of a CD5+ B clonal subpopulation.


Assuntos
Plaquetas/patologia , Linfócitos/patologia , Linfoma de Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Diagnóstico Diferencial , Feminino , Humanos , Imunofenotipagem , Linfoma de Células B/sangue , Linfoma de Células B/patologia , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/patologia
17.
EBioMedicine ; 41: 167-174, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30827933

RESUMO

BACKGROUND: This study aimed to investigate the association of pre-treatment inflammatory status with survival time and to develop a prognostic nomogram incorporating inflammatory cytokines in non-Hodgkin's lymphoma. METHODS: A total of 228 patients with diffuse large B-cell lymphoma (DLBCL) received R-CHOP-based regimens from a prospective randomized study (NCT01852435) were included as a training cohort. Other cohorts of 886 lymphoma patients were served as validation cohorts. Lymphocyte-monocyte ratio (LMR), serum levels of soluble interleukin s(IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α), were assessed before treatment. Least absolute shrinkage and selection operator (LASSO) regression were used to select variables for nomogram of overall survival (OS). The predictive accuracy of the nomogram was determined by concordance index (C-index). FINDINGS: The nomogram included lactate dehydrogenase (LDH), sIL-2R, TNF-α and decreased LMR. The C-index of the nomogram for OS prediction were range from 0.61 to 0.86 for training cohort of DLBCL and validation cohorts of DLBCL, PTCL, NKTCL and ASCT, which were superior to the predictive power of International Prognostic Index (IPI, 0.67 to 0.84) or NCCN-IPI (0.59 to 0.78), but not in those of indolent lymphoma like FL and MALT. INTERPRETATIONS: The nomogram incorporating inflammatory cytokines provides a useful tool for risk stratification in aggressive non-Hodgkin's lymphomas. FUND: National Natural Science Foundation of China, the Shanghai Commission of Science and Technology, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of SHDC, and Chang Jiang Scholars Program.


Assuntos
Biomarcadores Tumorais/sangue , Citocinas/sangue , Linfoma não Hodgkin/sangue , Nomogramas , Feminino , Humanos , Linfoma não Hodgkin/patologia , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
18.
Medicine (Baltimore) ; 98(10): e14802, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30855498

RESUMO

RATIONALE: Primary renal lymphoma (PRL) is a rare malignancy due to the absence of lymphatic tissues in the kidney, and patients with PRL have been reported to have a poor prognosis due to its rapid invasiveness and limited treatment strategies. Colon cancer is the third most common cancer, and has a high mortality rate. Both malignant diseases predominantly affected elderly men; however, a case with concomitant occurrence of the 2 cancers is extremely rare. PATIENT CONCERNS: A 78-year-old male patient with abdominal pain came to our hospital. Computed tomography (CT) indicated malignant masses in the left kidney, left adrenal gland, and the lower part of the descending colon. DIAGNOSES: PRL and colon cancer were diagnosed based on pathological examinations. INTERVENTIONS: The patient was treated with laparoscopic radical nephrectomy and laparoscopic radical resection of colon cancer. OUTCOMES: The patient was then transferred to the intensive care unit (ICU) because of poor condition after surgery. He died 3 months after discharge without receiving any other treatment. LESSONS: It is worth thinking about whether surgery was reasonable for elderly patients with double malignancies, or palliative treatment to improve the quality of life was more meaningful. This case also contributes to the understanding of the 2 malignancies and highlights the need to pay more attention to patients with multiple primary malignant neoplasms (MPMNs), explore genetic features, and investigate treatments with more survival benefits.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias do Colo/diagnóstico , Neoplasias Renais/diagnóstico , Linfoma não Hodgkin/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Neoplasias do Colo/complicações , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Cuidados Críticos , Diagnóstico Diferencial , Evolução Fatal , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/cirurgia , Masculino , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia
19.
Crit Rev Oncol Hematol ; 135: 8-19, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30819450

RESUMO

Primary extranodal non-Hodgkin's lymphomas (EN-NHL) are a heterogeneous group of malignancies that involve numerous entities with significant difference in terms of tumor site locations, prognostic factors, biology expression, and therapeutic options. In the literature, many EN-NHL types were reported from limited series which only allowed narrow views for elucidating prognostic factors and defining the role of loco-regional therapies in the era of new systemic and biologically targeted therapies. The Rare Cancer Network (RCN), an international multidisciplinary consortium, has published a number of reports on several EN-NHL sites which included many gland locations. In this review, we will focus on the recent literature for a selected number of EN-NHL types in both exocrine and endocrine gland locations. We aim to provide renewed and clear messages for the best practice in 2019 for diagnosis, histopathology, treatments, and also their prognostic implications. We believe that better understanding of molecular and genetic characteristics of these particular diseases is crucial for an appropriate management in the era of personalized treatment developments.


Assuntos
Linfoma não Hodgkin , Adulto , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino
20.
BMJ Case Rep ; 12(3)2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30846458

RESUMO

Neurolymphomatosis (NL) is the infiltration of lymphocytes into the peripheral nervous system in a haematological malignancy. We describe the imaging features of NL in a patient with relapsed Burkitt-like non-Hodgkin's lymphoma on positron emission tomography (PET) and ultrasound. Imaging features on ultrasound are infrequently described and provide useful information in helping to establish an imaging diagnosis of NL. Features of NL in our patient included intense linear fluorodeoxyglucose-18 (18FDG) uptake on PET along the affected median nerve. B-mode ultrasound demonstrated concentric tubular thickening and loss of fascicular architecture. Perineural and intraneural vascularity was present on colour Doppler ultrasound. It is important to be able to correlate ultrasound findings to features observed on 18FDG-PET as this aids in diagnosis and in guiding potential surgical biopsy.


Assuntos
Braço/inervação , Linfoma Difuso de Grandes Células B/patologia , Nervo Mediano/patologia , Neurolinfomatose/diagnóstico por imagem , Idoso , Braço/diagnóstico por imagem , Braço/patologia , Evolução Fatal , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Linfoma não Hodgkin/patologia , Neurolinfomatose/patologia , Neurolinfomatose/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Radioterapia/métodos , Ultrassonografia/métodos , Ultrassonografia Doppler Dupla/métodos
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