Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mod Pathol. 2012 Jan;25(1):145-56. doi: 10.1038/modpathol.2011.147. Epub 2011 Oct 14.
B-cell lymphomas with MYC/8q24 rearrangement and IGH@BCL2/t(14;18)(q32;q21), also known as double-hit or MYC/BCL2 B-cell lymphomas, are uncommon neoplasms. We report our experience with 60 cases: 52 MYC/BCL2 B-cell lymphomas and 8 tumors with extra MYC signals plus IGH@BCL2 or MYC rearrangement plus extra BCL2 signals/copies. There were 38 men and 22 women with a median age of 55 years. In all, 10 patients had antecedent/concurrent follicular lymphoma. Using the 2008 World Health Organization classification, there were 33 B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (henceforth referred to as unclassifiable, aggressive B-cell lymphoma), 23 diffuse large B-cell lymphoma, 1 follicular lymphoma grade 3B, 1 follicular lymphoma plus diffuse large B-cell lymphoma, 1 B-lymphoblastic lymphoma, and 1 composite diffuse large B-cell lymphoma with B-lymphoblastic lymphoma. Using older classification systems, the 33 unclassifiable, aggressive B-cell lymphomas most closely resembled Burkitt-like lymphoma (n=24) or atypical Burkitt lymphoma with BCL2 expression (n=9). Of 48 cases assessed, 47 (98%) had a germinal center B-cell immunophenotype. Patients were treated with standard (n=23) or more aggressive chemotherapy regimens (n=34). Adequate follow-up was available for 57 patients: 26 died and 31 were alive. For the 52 patients with MYC/BCL2 lymphoma, the median overall survival was 18.6 months. Patients with antecedent/concurrent follicular lymphoma had median overall survival of 7.8 months. Elevated serum lactate dehydrogenase level, ≥2 extranodal sites, bone marrow or central nervous system involvement, and International Prognostic Index >2 were associated with worse overall survival (P<0.05). Morphological features did not correlate with prognosis. Patients with neoplasms characterized by extra MYC signals plus IGH@BCL2 (n=6) or MYC rearrangement with extra BCL2 signals (n=2) had overall survival ranging from 1.7 to 49 months, similar to patients with MYC/BCL2 lymphomas. We conclude that MYC/BCL2 lymphomas are clinically aggressive, irrespective of their morphological appearance, with a germinal center B-cell immunophenotype. Tumors with extra MYC signals plus IGH@BCL2 or MYC rearrangement plus extra BCL2 signals, respectively, appear to behave as poorly as MYC/BCL2 lymphomas, possibly expanding the disease spectrum.
B 细胞淋巴瘤伴 MYC/8q24 重排和 IGH@BCL2/t(14;18)(q32;q21)，也称为双打击或 MYC/BCL2 B 细胞淋巴瘤，是不常见的肿瘤。我们报告了 60 例病例的经验：52 例 MYC/BCL2 B 细胞淋巴瘤和 8 例肿瘤有额外的 MYC 信号加上 IGH@BCL2 或 MYC 重排加上额外的 BCL2 信号/拷贝。其中 38 例为男性，22 例为女性，中位年龄为 55 岁。共有 10 例患者有前驱/并发滤泡性淋巴瘤。根据 2008 年世界卫生组织分类，有 33 例 B 细胞淋巴瘤，分类不明，弥漫性大 B 细胞淋巴瘤和伯基特淋巴瘤之间具有特征（因此称为分类不明，侵袭性 B 细胞淋巴瘤），23 例弥漫性大 B 细胞淋巴瘤，1 例滤泡性淋巴瘤 3B 级，1 例滤泡性淋巴瘤合并弥漫性大 B 细胞淋巴瘤，1 例 B 淋巴母细胞淋巴瘤和 1 例复合弥漫性大 B 细胞淋巴瘤伴 B 淋巴母细胞淋巴瘤。使用旧的分类系统，33 例分类不明的侵袭性 B 细胞淋巴瘤最类似于伯基特样淋巴瘤（n=24）或伴有 BCL2 表达的非典型伯基特淋巴瘤（n=9）。在评估的 48 例病例中，47 例（98%）具有生发中心 B 细胞免疫表型。患者接受标准（n=23）或更具侵袭性的化疗方案（n=34）治疗。57 例患者获得充分随访：26 例死亡，31 例存活。对于 52 例 MYC/BCL2 淋巴瘤患者，中位总生存期为 18.6 个月。有前驱/并发滤泡性淋巴瘤的患者中位总生存期为 7.8 个月。血清乳酸脱氢酶水平升高、≥2 个结外部位、骨髓或中枢神经系统受累以及国际预后指数>2 与总生存期较差相关（P<0.05）。形态学特征与预后无关。有额外 MYC 信号加上 IGH@BCL2 的肿瘤（n=6）或 MYC 重排伴有额外 BCL2 信号的肿瘤（n=2）的患者总生存期为 1.7 至 49 个月，与 MYC/BCL2 淋巴瘤患者相似。我们得出结论，MYC/BCL2 淋巴瘤具有临床侵袭性，不论其形态如何，均具有生发中心 B 细胞免疫表型。有额外 MYC 信号加上 IGH@BCL2 或 MYC 重排加上额外 BCL2 信号的肿瘤，其行为似乎与 MYC/BCL2 淋巴瘤一样差，可能扩大了疾病谱。
