坦桑尼亚恶性淋巴瘤：WHO 分类、表现、倍性、增殖与 HIV/EBV 相关性。
Tanzanian malignant lymphomas: WHO classification, presentation, ploidy, proliferation and HIV/EBV association.
机构信息
Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska University Hospital Solna/Karolinska Institute, Stockholm, Sweden.
出版信息
BMC Cancer. 2010 Jul 1;10:344. doi: 10.1186/1471-2407-10-344.
BACKGROUND
In Tanzania, the International Working Formulation [WF] rather than the WHO Classification is still being used in diagnosing malignant lymphomas (ML) and the biological characterization including the HIV/EBV association is sketchy, thus restraining comparison, prognostication and application of established therapeutic protocols.
METHODS
Archival, diagnostic ML biopsies (N = 336), available sera (N = 35) screened by ELISA for HIV antibodies and corresponding clinical/histological reports at Muhimbili National Hospital (MNH) in Tanzania between 1996 and 2006 were retrieved and evaluated. A fraction (N = 174) were analyzed by histopathology and immunohistochemistry (IHC). Selected biopsies were characterized by flow-cytometry (FC) for DNA ploidy (N = 60) and some by in-situ hybridization (ISH) for EBV-encoded RNA (EBER, N = 37).
RESULTS
A third (38.8%, 109/281) of the ML patients with available clinical information had extranodal disease presentation. A total of 158 out of 174 biopsies selected for immunophenotyping were confirmed to be ML which were mostly (84. 8%, 134/158) non-Hodgkin lymphoma (NHL). Most (83.6%, 112/134) of NHL were B-cell lymphomas (BCL) (CD20+), of which 50.9%, (57/112) were diffuse large B-cell (DLBCL). Out of the 158 confirmed MLs, 22 (13.9%) were T-cell [CD3+] lymphomas (TCL) and 24 (15.2%) were Hodgkin lymphomas (HL) [CD30+]. Furthermore, out of the 60 FC analyzed ML cases, 27 (M:F ratio 2:1) were DLBCL, a slight majority (55.6%, 15/27) with activated B-cell like (ABC) and 45% (12/27) with germinal center B-cell like (GCB) immunophenotype. Overall, 40% (24/60) ML were aneuploid mostly (63.0%, 17/27) the DLBCL and TCL (54.5%, 6/11). DNA index (DI) of FC-analyzed ML ranged from 1.103-2.407 (median = 1.51) and most (75.0%) aneuploid cases showed high (>40%) cell proliferation by Ki-67 reactivity. The majority (51.4%, 19/37) of EBER ISH analyzed lymphoma biopsies were positive. Of the serologically tested MLs, 40.0% (14/35) were HIV positive, mostly with high (> or =40.0%) Ki-67 reactivity.
CONCLUSIONS
According to the 2001 WHO Classification, most subtypes are represented in Tanzanian ML. Extranodal presentation was common among MNH lymphoma patients who also showed high aneuploidy, tumor proliferation (KI-67) and EBER positivity. DLBCL was frequent and phenotype heterogeneity appeared similar to observations in Western countries suggesting applicability of established intervention approaches. HIV was apparently associated with high ML cell proliferation but extended studies are needed to clarify this.
背景
在坦桑尼亚，国际工作分类（WF）而非世界卫生组织（WHO）分类仍用于诊断恶性淋巴瘤（ML），且生物学特征，包括 HIV/EBV 关联，尚不完善，从而限制了比较、预后判断和既定治疗方案的应用。
方法
检索并评估了 1996 年至 2006 年期间坦桑尼亚姆万扎国家医院（MNH）存档的 ML 活检标本（N=336）、可获得的血清（N=35），这些标本通过 ELISA 检测 HIV 抗体，并附有相应的临床/组织学报告。其中一部分（N=174）通过组织病理学和免疫组织化学（IHC）进行分析。选择部分活检标本进行流式细胞术（FC）检测 DNA 倍体（N=60），部分进行原位杂交（ISH）检测 EBV 编码 RNA（EBER，N=37）。
结果
在有临床资料的 ML 患者中，三分之一（38.8%，109/281）存在结外疾病表现。为免疫表型选择的 174 个活检标本中，有 158 个被确认为 ML，其中绝大多数（84.8%，134/158）为非霍奇金淋巴瘤（NHL）。大多数 NHL（83.6%，112/134）为 B 细胞淋巴瘤（BCL）（CD20+），其中 50.9%（57/112）为弥漫性大 B 细胞（DLBCL）。在 158 例确诊的 ML 中，22 例（13.9%）为 T 细胞[CD3+]淋巴瘤（TCL），24 例（15.2%）为霍奇金淋巴瘤（HL）[CD30+]。此外，在 60 例进行 FC 分析的 ML 病例中，27 例（男女比例为 2:1）为 DLBCL，略占多数（55.6%，15/27）为激活 B 细胞样（ABC），45%（12/27）为生发中心 B 细胞样（GCB）免疫表型。总体而言，40%（24/60）的 ML 为非整倍体，主要是 DLBCL 和 TCL（63.0%，17/27）和 54.5%（6/11）的 TCL。FC 分析的 ML 的 DNA 指数（DI）范围为 1.103-2.407（中位数=1.51），大多数（75.0%）非整倍体病例通过 Ki-67 反应显示出高（>40%）细胞增殖。进行 EBER ISH 分析的淋巴瘤活检标本中，大多数（51.4%，19/37）为阳性。在血清学检测的 ML 中，40.0%（14/35）为 HIV 阳性，大多数 Ki-67 反应性较高（>或=40.0%）。
结论
根据 2001 年 WHO 分类，坦桑尼亚的大多数 ML 亚型都有代表。MNH 淋巴瘤患者有结外表现，且存在高非整倍体、肿瘤增殖（KI-67）和 EBER 阳性，较为常见。DLBCL 较为常见，表型异质性与西方国家的观察结果相似，提示可以应用既定的干预方法。HIV 似乎与 ML 细胞的高增殖有关，但需要进一步研究来阐明这一点。
Zotero 插件