title: Double-hit lymphomas: clinical, morphological, immunohistochemical and cytogenetic study in a series of Brazilian patients with high-grade non-Hodgkin lymphoma.
abstract: BACKGROUND
  Double-hit lymphomas (DHL) are rare high-grade neoplasms characterized by two translocations: one involving the gene MYC and another involving genes BCL2 or BCL6, whose diagnosis depends on cytogenetic examination. This research studied DHL and morphological and/or immunophenotypic factors associated with the detection of these translocations in a group of high-grade non-Hodgkin lymphoma cases.
  
  
  METHODS
  Clinical and morphological reviews of 120 cases diagnosed with diffuse large B-cell lymphoma and Burkitt lymphoma were conducted. Immunohistochemistry (CD20, CD79a, PAX5, CD10, Bcl6, Bcl2, MUM1, TDT and Myc) and fluorescence in situ hybridization for detection of MYC, BCL2 and BCL6 gene translocations were performed in a tissue microarray platform.
  
  
  RESULTS
  Three cases of DHL were detected: two with translocations of MYC and BCL2 and one with translocations of MYC and BCL6, all leading to death in less than six months. Among 90 cytogenetically evaluable biopsies, associations were determined between immunohistochemistry and fluorescence in situ hybridization for MYC (p = 0.036) and BCL2 (p = 0.001). However, these showed only regular agreement, indicated by Kappa values of 0.23 [0.0;0.49] and 0.35 [0.13;0.56], respectively. "Starry sky" morphology was strongly associated with MYC positivity (p = 0.01). The detection of three cases of DHL, all resulting in death, confirms the rarity and aggressiveness of this neoplasm.
  
  
  CONCLUSIONS
  The "starry sky" morphological pattern and immunohistochemical expression of Myc and Bcl2 represent possible selection factors for additional cytogenetic diagnostic testing.
authors.affiliation: Department of Pathology, Botucatu School of Medicine, São Paulo State University (FMB UNESP), Botucatu, São Paulo, Brazil. cristiano_c_oliveira@hotmail.com.|Departamento de Patologia, Faculdade de Medicina de Botucatu (FMB), Universidade Estadual Paulista (UNESP), Distrito de Rubião Junior, s/n°, Botucatu, SP, Zip code: 18618-000, Brazil. cristiano_c_oliveira@hotmail.com.
authors.forename: Cristiano Claudino
authors.initials: CC
authors.lastname: Oliveira
authors.affiliation: Botucatu School of Medicine, São Paulo State University (FMB UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Helena
authors.initials: H
authors.lastname: Maciel-Guerra
authors.affiliation: Botucatu School of Medicine, São Paulo State University (FMB UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Luan
authors.initials: L
authors.lastname: Kucko
authors.affiliation: Botucatu School of Medicine, São Paulo State University (FMB UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Eric Jun
authors.initials: EJ
authors.lastname: Hirama
authors.affiliation: Department of Pathology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Américo Delgado
authors.initials: AD
authors.lastname: Brilhante
authors.affiliation: Department of Pathology, Amaral Carvalho Hospital, Jaú, São Paulo, Brazil.
authors.forename: Francisco Carlos
authors.initials: FC
authors.lastname: Quevedo
authors.affiliation: Department of Pathology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Isabela Werneck
authors.initials: IW
authors.lastname: da Cunha
authors.affiliation: Department of Pathology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Department of Internal Medicine, Botucatu School of Medicine, São Paulo State University (FMB UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Ligia
authors.initials: L
authors.lastname: Niero-Melo
authors.affiliation: Botucatu School of Medicine, São Paulo State University (FMB UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Patrícia Pintor
authors.initials: PP
authors.lastname: Dos Reis
authors.affiliation: Department of Pathology, Botucatu School of Medicine, São Paulo State University (FMB UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Maria Aparecida Custodio
authors.initials: MA
authors.lastname: Domingues
mesh_terms: D000328:Adult; D000368:Aged; D001938:Brazil; D005260:Female; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D046888:Tissue Array Analysis; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: C000595707:BCL2 protein, human; C084103:BCL6 protein, human; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc
keywords: Cytogenetics; Immunohistochemistry; In situ hybridization fluorescence; Lymphoma; Lymphoma, non-Hodgkin