Nodal Diffuse Large B-cell Lymphomas in Children and Adolescents: Immunohistochemical Expression Patterns and c-MYC Translocation in Relation to Clinical Outcome

Consultoria em Patologia, Botucatu, Sao Paulo, Brazil.
The American journal of surgical pathology (Impact Factor: 5.15). 10/2009; 33(12):1815-22. DOI: 10.1097/PAS.0b013e3181bb9a18
Source: PubMed


Diffuse large B-cell lymphoma (DLBCL) is a very infrequent neoplasm in the pediatric age group; therefore there are very few studies on the immunophenotype or genetics of these cases. We studied a series of 16 patients with nodal DLBCL occurring in patients between 10 and 18 years of age. The cases were classified according to the 2008 World Health Organization classification criteria, with application of immunohistochemistry for the detection of CD10, BCL-6, and MUM1 proteins to divide the lymphomas into germinal center and nongerminal center types. In addition, TCL1, BCL-2 expression, and the Ki-67 proliferation index were evaluated by immunohistochemistry, and c-MYC and BCL2 translocations were evaluated by fluorescence in situ hybridization. All these parameters were correlated with clinical features and outcome. Our study revealed that centroblastic morphology and the germinal center type of DLBCL are more prevalent in these young patients (63%), with 37% containing a c-MYC translocation. Only 1 case showed a BCL2 translocation, reflecting a double-hit case with features intermediate between DLBCL and Burkitt lymphoma. We found a higher frequency of BCL-2 expression than previously reported, with no direct influence on the outcome of the disease in univariate or multivariate analysis. The expression of TCL1 has not been specifically studied in nodal pediatric DLBCL before; we found a 31% incidence of TCL1 expression. MUM1 expression was observed in 44% of the cases and these positive cases showed a significant negative impact on clinical outcome. TCL1 is directly and significantly associated with the presence of c-MYC and a high proliferative index. The germinal center and nongerminal center subtypes showed significant differences for both overall survival and disease-free interval. c-MYC translocation was found in 37% of patients, and had a favorable impact on clinical outcome. We conclude that nodal pediatric and adolescent DLBCL are mainly of the germinal center type, with a generally good outcome despite the frequent expression of BCL-2 and the presence of c-MYC translocation. TCL1 expression seems to be associated with a good clinical outcome, whereas MUM1 expression predicts a poor clinical outcome.

9 Reads
  • Source
    • "Nine cases of DLBCL were diagnosed as histiocytic/T‐cell rich B‐cell lymphomas. It is worth noting that this type is infrequently reported in children.32,45–49 "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. A retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. We believe that it represents the largest series of pediatric lymphomas presented from Brazil. Non-Hodgkin lymphomas represented 68% of the cases, including those of precursor (36%) and mature (64%) cell origin. Mature cell lymphomas comprised 81% of the B-cell phenotype and 19% of the T-cell phenotype. Hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. The geographic distribution showed 38.4% of the cases in the Southeast region, 28.7% in the Northeast, 16.1% in the South, 8.8% in the North, and 8% in the Central-west region. The distribution by age groups was 15-18 years old, 33%; 11-14 years old, 26%; 6-10 years old, 24%; and 6 years old or younger, 17%. Among mature B-cell lymphomas, most of the cases were Burkitt lymphomas (65%), followed by diffuse large B-cell lymphomas (24%). In the mature T-cell group, anaplastic large cell lymphoma, ALK-positive was the most prevalent (57%), followed by peripheral T-cell lymphoma, then not otherwise specified (25%). In the group of classic Hodgkin lymphomas, the main histological subtype was nodular sclerosis (76%). Nodular lymphocyte predominance occurred more frequently than in other series. Some of the results found in this study may reflect the heterogeneous socioeconomical status and environmental factors of the Brazilian population in different regions.
    Clinics (São Paulo, Brazil) 12/2010; 65(12):1267-77. DOI:10.1590/S1807-59322010001200008 · 1.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 02/2010; 18(4):301-10. DOI:10.1097/PAI.0b013e3181cf1126 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Human pathology 04/2010; 41(9):1238-44. DOI:10.1016/j.humpath.2010.01.015 · 2.77 Impact Factor
Show more


9 Reads
Available from