RESUMO
Aggressive B-cell lymphomas incorporate a wide spectrum of lymphomas that pose challenges in diagnosis as well as treatment. We evaluated the clinicopathological features of 44 patients with aggressive B-cell lymphomas which were classified into 3 groups based on the World Health Organization 2008 classification as follows: including 30 cases of diffuse large B-cell lymphoma (DLBCL), 8 cases of Burkitt lymphoma (BL) and 6 cases of B-cell lymphoma, unclassifiable, with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (BCLU). Male predominance was observed in BL and BCLU groups and the mean age varied from 29 years in BL, 61 years in DLBCL and 70 years in BCLU. Patients with BCLU presented at more advanced stages and had a higher international prognostic index. By immunohistochemistry, they shared characteristics of both BL (including more frequent expression of SOX11) and DLBCL. FISH analyses showed three cases with more than one rearrangement: one MYC/BCL2 and two BCL2/BCL6, in addition to which one case with BCL2/IGH translocation and another with MYC rearrangement were also detected. The mean follow-up survival time of BCLU was 6.6 months, which was significantly shorter in comparison to DLBCL (31 months) and BL (30 months), respectively. The importance of recognizing this BCLU group relies on its different clinical course, poor prognosis and shorter survival than DLBCL and BL. An accurate diagnosis is critical for risk stratification and to improve therapeutic approaches and outcomes.
Assuntos
Linfoma de Burkitt/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Adulto , Idoso , Argentina/epidemiologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/mortalidade , Feminino , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Transcrição SOXC/metabolismo , Taxa de Sobrevida , Análise Serial de Tecidos , Translocação GenéticaRESUMO
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, is a diagnostic provisional category in the World Health Organization (WHO) 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typically, these cases share features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this study, we present 10 cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and have organized the criteria described by the WHO into four patterns along with detailed clinical, morphological and immunophenotypic characterization and outcome data. Our findings show a male preponderance, median age of 37 years and a mediastinal presentation in 80% of cases. All cases expressed at least two markers associated with B-cell lineage and good response to combination chemotherapy currently employed for non-Hodgkin lymphomas.
Assuntos
Doença de Hodgkin/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias do Mediastino/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Rearranjo Gênico do Linfócito B , Doença de Hodgkin/genética , Doença de Hodgkin/metabolismo , Doença de Hodgkin/terapia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/terapia , Masculino , Neoplasias do Mediastino/metabolismo , Neoplasias do Mediastino/terapia , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Radioterapia Adjuvante , Rituximab , Vincristina/uso terapêutico , Adulto JovemRESUMO
Diffuse large B-cell lymphoma can be subclassified into at least two molecular subgroups by gene expression profiling: germinal center B-cell like and activated B-cell like diffuse large B-cell lymphoma. Several immunohistological algorithms have been proposed as surrogates to gene expression profiling at the level of protein expression, but their reliability has been an issue of controversy. Furthermore, the proportion of misclassified cases of germinal center B-cell subgroup by immunohistochemistry, in all reported algorithms, is higher compared with germinal center B-cell cases defined by gene expression profiling. We analyzed 424 cases of nodal diffuse large B-cell lymphoma with the panel of markers included in the three previously described algorithms: Hans, Choi, and Tally. To test whether the sensitivity of detecting germinal center B-cell cases could be improved, the germinal center B-cell marker HGAL/GCET2 was also added to all three algorithms. Our results show that the inclusion of HGAL/GCET2 significantly increased the detection of germinal center B-cell cases in all three algorithms (P<0.001). The proportions of germinal center B-cell cases in the original algorithms were 27%, 34%, and 19% for Hans, Choi, and Tally, respectively. In the modified algorithms, with the inclusion of HGAL/GCET2, the frequencies of germinal center B-cell cases were increased to 38%, 48%, and 35%, respectively. Therefore, HGAL/GCET2 protein expression may function as a marker for germinal center B-cell type diffuse large B-cell lymphoma. Consideration should be given to the inclusion of HGAL/GCET2 analysis in algorithms to better predict the cell of origin. These findings bear further validation, from comparison to gene expression profiles and from clinical/therapeutic data.
Assuntos
Algoritmos , Biomarcadores Tumorais/análise , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/química , Proteínas de Neoplasias/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Criança , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Modelos Lineares , Linfoma Difuso de Grandes Células B/patologia , Masculino , Proteínas dos Microfilamentos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise Serial de Tecidos , Adulto JovemRESUMO
We described 2 cases of plasmacytoma presenting with a preponderant involvement of the pleural membranes simulating clinically, radiologically, and on gross pathologic inspection a primary mesothelioma. The patients were an 80-year-old man and a 45-year-old woman. In both cases, the clinical presentation was that of a serosal tumor, including effusions and pleural thickening. In the former, the serosal infiltration raised the suspicion of mesothelioma reinforced by history of occupational exposure to asbestos. Patient general condition deteriorated rapidly. Postmortem examination revealed unilateral encasing of the lung within a thick, irregular neoplastic rind. In addition, tumoral involvement was seen in the homolateral third rib and the clavicle. Histologic examination of pleural masses demonstrated diffuse infiltration by highly atypical, pleomorphic plasma cells with kappa chain restriction. In the second case, clinical presentation was also suspicious of mesothelioma. Nonetheless, a pleural biopsy specimen showed irregular sheets of plasma cells showing kappa light chain restriction. A bone marrow aspirate was also positive for abnormal plasma cell infiltrates. Despite chemotherapy, the patient died 4 months after presentation. Although rarely, it seems that plasmacytoma may present with an exclusive or preponderant pleural involvement; and it may therefore be added to the list of pseudomesotheliomatous tumors.
Assuntos
Mesotelioma/patologia , Mieloma Múltiplo/patologia , Pleura/patologia , Neoplasias Pleurais/patologia , Idoso de 80 Anos ou mais , Biópsia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Cadeias kappa de Imunoglobulina/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pleura/metabolismoRESUMO
A 10-year-old Caucasian boy was admitted to the hospital with a 3-month history of headache, vomiting, ataxia, and right amaurosis. A magnetic resonance imaging (MRI) showed a solid, expansive, parasagittal mass in the right parietal hemisphere that extended sagitally to include the optical chiasm. The lesion was considered unresectable. Histology and immunophenotyping of biopsy tissue revealed characteristics of peripheral T-cell lymphoma. No other anatomical region, including bone marrow, was compromised. Primary T-cell lymphomas of the central nervous system are rare, especially in childhood. Here, we describe the rapidly deteriorating and fatal clinical course of a boy with a primary T-cell lymphoma in the central nervous system.
Assuntos
Neoplasias Encefálicas/patologia , Linfoma de Células T Periférico/patologia , Biomarcadores Tumorais/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Criança , Evolução Fatal , Humanos , Linfoma de Células T Periférico/metabolismo , Imageamento por Ressonância Magnética , MasculinoRESUMO
We present a case of autoimmune lymphoproliferative syndrome (ALPS) caused by a previously undescribed minimal deletion in the death domain of the FAS gene. ALPS is an uncommon disease associated with an impaired Fas-mediated apoptosis. The patient presented with a history of splenomegaly since 4 months of age, associated with cervical lymphadenopathy, which improved with oral corticosteroid treatment. Relevant laboratory findings were the presence of anemia, thrombocytopenia, and positive direct and indirect Coombs tests. He was not an offspring of consanguineous parents. Two cervical lymph node biopsies were performed, at 4 years and at 6 years of age. In both lymph nodes, there was marked paracortical expansion by lymphocytes in variable stages of immunoblastic transformation and a very high cell proliferating index. Some clear cells were also present, raising the suspicion of malignant lymphoma. In one of the lymph nodes, there was also a focus rich in large histiocytes with round nuclei and emperipolesis, consistent with focal Rosai-Dorfman disease. Immunostaining showed numerous CD3+ cells, many of which were double-negative (CD4- CD8-) and expressed CD57, especially around the follicles. Molecular studies of the lymph node biopsy showed a point deletion (4-base pair deletion) in exon 9 of the FAS gene (930del TGCT), which results in 3 missense amino acids.
Assuntos
Doenças Autoimunes/genética , Proteína de Domínio de Morte Associada a Fas/genética , Transtornos Linfoproliferativos/genética , Deleção de Sequência , Criança , Humanos , Masculino , Receptor fas/metabolismoRESUMO
Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma, composed of a monomorphic population of medium-sized B cells with a high proliferation rate and a consistent MYC translocation. Epstein-Barr virus (EBV) has been associated with BL with different frequencies depending on the clinical variant. Kaposi sarcoma-associated herpesvirus, or human herpesvirus 8 (HHV-8), infects a wide range of normal cells, having a well-established role in the pathogenesis of various neoplasms, including Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease (MCD) and MCD-associated plasmablastic lymphoma. In secondary immunodeficiencies, such as HIV-1 infection and organ transplantation, HHV-8 is considered an opportunistic pathogen linked to the development of lymphomas in patients with AIDS and HIV + patients. We studied the association of EBV and HHV-8 by immunohistochemical analysis, in situ hybridization, and polymerase chain reaction in a large number of well-characterized BLs. EBV was present in 45.0% of all BL cases with higher incidence in the pediatric group; most cases were EBV type A. We found no association of BL with HHV-8 in EBV + BL or in EBV-cases, including the HIV + BL group.
Assuntos
Linfoma de Burkitt/virologia , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Breast involvement by non-Hodgkin lymphomas is rare. We studied the morphological, immunophenotypical, and clinical features of 53 cases of malignant lymphomas involving the breast in a population of Brazilian patients. Most of the cases were of B-cell phenotype. Four of the patients with primary breast lymphomas had T-cell lymphomas, 3 had CD30-positive anaplastic large cell lymphomas, and 1 had panniculitis-like T-cell lymphoma. Most patients presented with an incidental breast mass. Secondary breast lymphoma was seen in 19 patients and most commonly occurred as part of widespread nodal disease. Two patients presented with bilateral breast involvement. The most prevalent histological subtype was also diffuse large B-cell lymphoma, followed by follicular lymphoma. This study shows that the broad morphological and immunophenotypical spectrum of malignant lymphoma of the breast occurring in a large series of Brazilian patients has many similarities with that seen in Western countries, with a higher proportion of high-grade lymphomas in both primary and secondary cases.
Assuntos
Neoplasias da Mama Masculina/patologia , Neoplasias da Mama/patologia , Linfoma de Células B/patologia , Linfoma de Células T/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Linfoma de Células B/metabolismo , Linfoma de Células T/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: KLHL6 is a recently described BTB-Kelch protein with selective expression in lymphoid tissues and is most strongly expressed in germinal center B cells. METHODS: Using gene expression profiling as well as immunohistochemistry with an anti-KLHL6 monoclonal antibody, we have characterized the expression of this molecule in normal and neoplastic tissues. Protein expression was evaluated in 1,058 hematopoietic neoplasms. RESULTS: Consistent with its discovery as a germinal center marker, KLHL6 was positive mainly in B-cell neoplasms of germinal center derivation, including 95% of follicular lymphomas (106/112). B-cell lymphomas of non-germinal center derivation were generally negative (0/33 chronic lymphocytic leukemias/small lymphocytic lymphomas, 3/49 marginal zone lymphomas, and 2/66 mantle cell lymphomas). CONCLUSIONS: In addition to other germinal center markers, including BCL6, CD10, HGAL, and LMO2, KLHL6 immunohistochemistry may prove a useful adjunct in the diagnosis and future classification of B-cell lymphomas.
Assuntos
Linfócitos B/metabolismo , Proteínas de Transporte/genética , Regulação Neoplásica da Expressão Gênica/genética , Centro Germinativo/metabolismo , Linfoma de Células B/genética , Linfócitos B/imunologia , Linfócitos B/patologia , Biomarcadores Tumorais/metabolismo , Perfilação da Expressão Gênica/métodos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Humanos , Imuno-Histoquímica/métodos , Linfoma de Células B/patologia , Linfoma Folicular/patologiaRESUMO
The relative contribution of heritable and nonheritable factors to disease expression in BRCA2 mutation carriers is largely unknown. This report describes a familial breast cancer syndrome in a pair of identical female twins. These twins showed an extremely high concordance in their clinical histories; both twins exhibited similar cancer-related risk factors, and developed breast cancer at the same age with the same disease stage and identical histological features. No differences were detected in hormone receptors status, p53, bcl-2, erbB-2 and LI Ki67 expression by immunohistochemistry. A BRCA2 exon 11 protein truncation test showed a lower molecular weight band than the one expected for a normal allele, in both twins. Sequence analysis of DNA showed a 6 bp insertion between nucleotides 4359-4360, which resulted in a premature stop codon at position 1378. The remarkable disease similarity observed in this identical twin pair is in accordance with an important role for heritable factors in disease expression among patients carrying BRCA germline mutations.
Assuntos
Neoplasias da Mama/genética , Doenças em Gêmeos/genética , Genes BRCA2 , Mutação em Linhagem Germinativa , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , LinhagemRESUMO
The diagnosis of marginal zone lymphomas (MZL) is challenged by the lack of specific markers that distinguish them from other low-grade non-Hodgkin B-cell lymphomas. Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein that labels myelomonocytic cells as well as B lymphocytes that localize to the marginal zone areas of splenic white pulp. We evaluated MNDA expression in a large series of B-cell lymphomas to assess the sensitivity and specificity of this antigen for the characterization of MZL. A total of 440 tissue sections containing extramedullary B-cell lymphomas and 216 bone marrow biopsies containing atypical or neoplastic lymphoid infiltrates were stained for MNDA by immunohistochemistry. Among the extramedullary lymphoma cases, approximately 67% of nodal MZL, 61% of extranodal MZL, and 24% of splenic MZL expressed MNDA. MNDA was also infrequently expressed in other B-cell neoplasms including mantle cell lymphoma (6%), chronic lymphocytic leukemia/small lymphocytic lymphoma (13%), follicular lymphoma (FL) (4%), lymphoplasmacytic lymphoma (25%), and diffuse large B-cell lymphoma (3%). In contrast, MNDA was only expressed in 2.3% of all bone marrow biopsies involved by lymphoid infiltrates, including 2 cases of FL and one case of MZL. Collectively, these data support the inclusion of MNDA in the diagnostic evaluation of extramedullary B-cell lymphomas, particularly those in which the differential diagnosis is between low-grade FL and MZL.
Assuntos
Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores Tumorais/metabolismo , Linfonodos/metabolismo , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma Folicular/diagnóstico , Fatores de Transcrição/metabolismo , Linfócitos B/metabolismo , Linfócitos B/patologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Linfonodos/patologia , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Folicular/metabolismo , Linfoma Folicular/patologiaRESUMO
PURPOSE: Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. PATIENTS AND METHODS: We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. RESULTS: The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). CONCLUSION: Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants.
Assuntos
Implantes de Mama/efeitos adversos , Neoplasias da Mama/etiologia , Linfoma Anaplásico de Células Grandes/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/efeitos dos fármacos , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Remoção de Dispositivo/estatística & dados numéricos , Intervalo Livre de Doença , Tratamento Farmacológico/métodos , Tratamento Farmacológico/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/terapia , Pessoa de Meia-Idade , Fatores de Tempo , Conduta Expectante/estatística & dados numéricosRESUMO
Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype.
Assuntos
Neoplasias Encefálicas/patologia , Infecções por Vírus Epstein-Barr/patologia , Linfoma Difuso de Grandes Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/virologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Centro Germinativo/patologia , Centro Germinativo/virologia , Herpesvirus Humano 4 , Humanos , Imuno-Histoquímica , Hibridização In Situ , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/virologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Primary Hodgkin's lymphoma (HL) of the stomach is an extremely rare entity. Most cases of gastric involvement by HL are observed in the setting of disseminated disease. The nonspecific nature of the symptoms and endoscopic findings, which include a large malignant-looking ulcer and mass or wall thickening, together with the considerable histological overlap between HLs and some non-HLs or undifferentiated carcinoma, make the surgical resection diagnosis extremely difficult. An accurate diagnosis is important as treatment and outcome differ significantly for these neoplasms. In small endoscopic gastric biopsies and even in postoperative specimens, the precise histological diagnosis of HL is particularly challenging. Here, the authors report 5 cases of 2 women and 3 men aged 22 to 68, with gastric involvement by classic HLs-3 primary gastric HLs and 2 as part of widespread disease. All 5 patients presented with digestive symptoms. At endoscopy, the lesions presented as ulcerated and elevated lesions, with or without mucosal thickening. Four patients were misdiagnosed in the preoperative biopsy or in the gastrectomy specimen. Association with Epstein-Barr virus (EBV) was detected in 4 cases, with a predominance of subtype A EBV. These cases illustrate the significant difficulties, both clinical and pathological, in achieving the diagnosis of HL involving the stomach in immunocompetent patients.
Assuntos
Herpesvirus Humano 4 , Doença de Hodgkin , Biópsia , Doença de Hodgkin/diagnóstico , Humanos , EstômagoRESUMO
Extranodal natural killer/T-cell lymphoma, nasal type (NK/TCL) is more prevalent in Asia and in some areas of South and Central America, but it is rarely seen in the United States and Europe. In this study, a series of 122 cases of NK/TCL from Brazil was analyzed with respect to clinicopathologic features. Clinical characteristics and geographic distribution were evaluated in 97 cases of nasal/nasopharyngeal region and 23 cases in extranasal sites including 6 nodal cases. Clinical staging and follow-up information was available in a subset of 21 patients. All cases harbored Epstein-Barr virus (EBV), 95% and 85% expressed cytoplasmic CD3 and CD56, respectively, and all cases were positive for at least 1 marker for cytotoxic granules. The global distribution of EBV subtypes showed predominance of strain subtype A, 89%, and subtype B, 11%. No dual infections were detected. TCR-γ TCR-gene rearrangement was observed in 7 cases; all of them extranodal. Three of TCR-γ(+) cases showed EBV subtype A. Two TCR-γ(+)/CD56(+) cases showed EBV subtype B. Geographic distribution of NK/TCL showed higher frequency in the southeast and northeast regions of Brazil. Striking differences among geographic regions were seen with the vast majority of EBV subtype B (86%) occurring in the south and southeast regions.
Assuntos
Herpesvirus Humano 4/classificação , Linfoma Extranodal de Células T-NK/virologia , Linfoma de Células T/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Distribuição de Qui-Quadrado , Criança , DNA Viral/isolamento & purificação , Feminino , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T , Genes Codificadores da Cadeia gama de Receptores de Linfócitos T , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Estimativa de Kaplan-Meier , Linfonodos/patologia , Linfonodos/virologia , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/patologia , Linfoma de Células T/genética , Linfoma de Células T/mortalidade , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Características de Residência , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Análise Serial de Tecidos , Adulto JovemRESUMO
MUM1/IRF4 protein is a member of the interferon regulatory factor (IRF) family of transcriptional factors initially described as downstream regulators of interferon signaling. The quantity of this factor varies within the hematopoietic system in a lineage and stage-specific way. It is considered to be a key regulator of several steps in lymphoid, myeloid, and dendritic cell differentiation and maturation. MUM1/IRF4 expression is observed in many lymphoid and myeloid malignancies, and may be a promising target for the treatment of some of these neoplasms. We reviewed the literature on MUM1/IRF4, with emphasis on the pathologic aspects of this marker in reactive and malignant hematologic and nonhematologic conditions.
Assuntos
Fatores Reguladores de Interferon , Biomarcadores Tumorais , Humanos , Imuno-Histoquímica , Fatores Reguladores de Interferon/genética , Linfoma de Células B/genética , Linfoma de Células B/patologia , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Oncogenes/genéticaRESUMO
The physiologic expression of the product of the proto-oncogene TCL1 (T-cell leukemia 1) is primarily restricted to early embryonic cells. In nonneoplastic B cells, the expression of TCL1 is determined by the differentiation step with silencing at the germinal center stage. TCL1 protein is overexpressed in a wide variety of human diseases. It has been shown that TCL1 is a powerful B-cell oncogene, which has been implicated in the pathogenesis of various types of mature B-cell lymphomas. There is no comparative information in the literature addressing the expression of TCL1 in pediatric and adult nodal diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma. We studied 55 cases of adult and pediatric diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma to analyze the phenotypic profile of these lymphomas, including TCL1 expression, and its relationship with clinical outcome in different age groups. The cases were analyzed by immunohistochemistry for the expression of TCL1, CD10, BCL-2, BCL-6, and MUM1. We also evaluated c-MYC translocation by fluorescence in situ hybridization. TCL1 was observed in 11 cases, 5 pediatric and 6 adult cases, all but one diffuse large B-cell lymphoma. Pediatric cases showed a significant association between TCL1 expression, high proliferative index, and presence of c-MYC translocation. TCL1 positivity was predominantly found in germinal center phenotype diffuse large B-cell lymphoma. Overall survival was worse in adult TCL1-positive cases than pediatric ones. Primary mediastinal large B-cell lymphomas infrequently expressed TCL1 in both age groups.
Assuntos
Infecções por Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/isolamento & purificação , Linfoma de Células B/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Neoplasias do Mediastino/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Criança , Infecções por Vírus Epstein-Barr/patologia , Feminino , Genes myc , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfonodos/metabolismo , Linfonodos/patologia , Linfoma de Células B/patologia , Linfoma de Células B/virologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Masculino , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/virologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Taxa de Sobrevida , Translocação Genética , Adulto JovemRESUMO
Mantle cell lymphoma (MCL) characteristically express CD20, CD5, and cyclin-D1, carries the translocation t(11;14) (q13;q32) and typically has no expression of germinal center cell markers. So-called aberrant phenotypes such as CD5 negative and cyclin-D1-negative MCL have been described. Also few cases with CD10 and/or BCL-6 protein expression have been reported. We analyzed 127 MCL looking for the frequency of aberrant immunophenotype, CD10, BCL-6, and MUM1 expression. All cases were CD20 and cyclin-D1 positive, 96% expressed CD5, and 98% showed the t(11;14). BCL-6 expression was observed in 12% of the cases and MUM1 in 35%. No one case showed CD10 positivity in 30% or more neoplastic cells. Only 3 cases showed 10% to 20% of tumoral cells positive for CD10. MUM1 expression was observed in 67% of the BCL-6 positive cases. Thirty-two percent of the cases showed a MUM1+/BCL-6-/CD10- phenotype and 56% had a triple-negative-pattern. Aberrant phenotype is infrequent but not rare, and does not rule out a diagnosis of MCL in an otherwise typical case.