Double-hit lymphomas: clinical, morphological, immunohistochemical and cytogenetic study in a series of Brazilian patien
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RESEARCH
Open Access
Double-hit lymphomas: clinical, morphological, immunohistochemical and cytogenetic study in a series of Brazilian patients with high-grade non-Hodgkin lymphoma Cristiano Claudino Oliveira1,6*, Helena Maciel-Guerra2, Luan Kucko2, Eric Jun Hirama2, Américo Delgado Brilhante3, Francisco Carlos Quevedo4, Isabela Werneck da Cunha3, Fernando Augusto Soares3, Ligia Niero-Melo5, Patrícia Pintor dos Reis2 and Maria Aparecida Custodio Domingues1
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. Method: 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. Keywords: Lymphoma, Lymphoma, non-Hodgkin, Cytogenetics, In situ hybridization fluorescence, Immunohistochemistry
* Correspondence: [email protected] 1 Department of Pathology, Botucatu School of Medicine, São Paulo State University (FMB UNESP), Botucatu, São Paulo, Brazil 6 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 Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if chan
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