Oliveira Cristiano Claudino, Maciel-Guerra Helena, Kucko Luan, Hirama Eric Jun, Brilhante Américo Delgado, Quevedo Francisco Carlos, da Cunha Isabela Werneck, Soares Fernando Augusto, Niero-Melo Ligia, Dos Reis Patrícia Pintor, Domingues Maria Aparecida Custodio
Department of Pathology, Botucatu School of Medicine, São Paulo State University (FMB UNESP), Botucatu, São Paulo, Brazil.
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.
Diagn Pathol. 2017 Jan 7;12(1):3. doi: 10.1186/s13000-016-0593-0.
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.
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.
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.
The "starry sky" morphological pattern and immunohistochemical expression of Myc and Bcl2 represent possible selection factors for additional cytogenetic diagnostic testing.
双打击淋巴瘤（DHL）是罕见的高级别肿瘤，其特征为两种易位：一种涉及MYC基因，另一种涉及BCL2或BCL6基因，其诊断依赖于细胞遗传学检查。本研究在一组高级别非霍奇金淋巴瘤病例中研究了DHL以及与这些易位检测相关的形态学和/或免疫表型因素。
对120例诊断为弥漫性大B细胞淋巴瘤和伯基特淋巴瘤的病例进行临床和形态学回顾。在组织微阵列平台上进行免疫组织化学（CD20、CD79a、PAX5、CD10、Bcl6、Bcl2、MUM1、TDT和Myc）以及用于检测MYC、BCL2和BCL6基因易位的荧光原位杂交。
检测到3例DHL病例：2例为MYC和BCL2易位，1例为MYC和BCL6易位，所有病例均在不到6个月内死亡。在90例可进行细胞遗传学评估的活检标本中，确定了免疫组织化学与MYC（p = 0.03）和BCL2（p = 0.001）荧光原位杂交之间的相关性。然而，这些仅显示出一般一致性，Kappa值分别为0.23 [0.0;0.49]和0.35 [0.13;0.56]。“星空”形态与MYC阳性密切相关（p = 0.01）。3例DHL病例的检测结果均导致死亡，证实了该肿瘤的罕见性和侵袭性。
“星空”形态模式以及Myc和Bcl2的免疫组织化学表达代表了进行额外细胞遗传学诊断检测的可能选择因素。
