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恶性淋巴瘤中的浆液性积液:综述

Serous effusions in malignant lymphomas: a review.

作者信息

Das Dilip K

机构信息

Department of Pathology, Faculty of Medicine, Kuwait University, Kuwait.

出版信息

Diagn Cytopathol. 2006 May;34(5):335-47. doi: 10.1002/dc.20432.

Abstract

Serous effusions are a common complication of lymphomas. Although the frequency of pleural effusion is 20-30% in non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD), the involvement of peritoneal and pericardial cavities is uncommon. Among lymphoma subtypes, T-cell neoplasms, especially the lymphoblastic lymphomas, more frequently involve the serous fluids. The thoracic duct obstruction and impaired lymphatic drainage appear to be the primary mechanism for pathogenesis of pleural effusion in HD and direct pleural infiltration is the predominant cause in NHL. There is wide variation in rate of positive cytologic findings of NHL in pleural effusion (22.2-94.1%). Cytologic features of specific lymphoma subtypes such as lymphoblastic lymphoma, follicular center cell lymphoma, including Burkitt-type lymphoma, marginal zone lymphoma, MALT lymphoma, and anaplastic large-cell lymphoma, etc., have been described in the literature. The differential diagnostic problems of lymphomas in serous effusions include reactive lymphocytoses, early involvement by lymphomatous process, small round-cell tumors (SRCT), and presence of look-alike of Reed-Sternberg cells. To overcome these difficulties, various ancillary studies, including immunocytochemistry (ICC), morphometry, flow cytometry (FCM), and cytogenetics/molecular genetics (PCR, in-situ hybridization, and Southern blotting), have been performed on effusion specimens. ICC not only distinguishes lymphomas from reactive lymphocytoses and SRCTs, it significantly modifies the morphologic diagnosis to achieve a better classification of lymphomas. Combined morphology and immunophenotyping by FCM, has a sensitivity as well as specificity of 100%. Morphometry also distinguishes reactive lymphocytoses from malignant lymphoma with a high degree of sensitivity (>85%) and specificity (>95%). Limitations of individual ancillary techniques can be overcome by using multiple parameters. Although lymphomas rarely present as serous effusions without the involvement of other thoracic and extrathoracic sites, a small group of lymphomas called primary effusion lymphomas (PEL) exhibit exclusive or dominant involvement of serous cavities, without a detectable solid tumor mass. This body cavity based lymphoma (BCBL) is a distinct clinicopathologic entity and is found predominantly in AIDS patients with preexisting Kaposi sarcoma. In the absence of obstructive or infiltrative tumor mass, its pathogenesis has been attributed to stimulation by vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF), leading to vascular leakage. Cytomorphologically, PEL is usually a large-cell lymphoma, which appears to bridge features of large-cell immunoblastic and anaplastic large-cell lymphoma (ALCL). Most of these cases comprise a unique subgroup of B-cell lymphoma, with features of both high-grade anaplastic and B-immunoblastic lymphoma, but T-cell and/or natural killer cell immunophenotypes are described. Its association with various viral DNAs has been studied in detail by molecular techniques. Pleural effusion due to lymphomas, either primary or otherwise, is considered as one of the factors adversely influencing overall survival. The presence of pleural effusion at the time of presentation is not only associated with extremely poor outcome of lymphomas, it is also a predictor of disease relapse after chemotherapy and decreased survival. When the patients of lymphomatous pleural effusions with and without mediastinal mass present in respiratory distress, thoracocentesis is the initial diagnostic and therapeutic choice in these patients. In such situations, cytology along with ancillary studies not only gives a quick diagnosis of lymphoma, but also offers prognostically significant information such as classification of lymphomas, its grade and immunophenotype, and presence/absence of viral DNAs and tumor lysis syndrome.

摘要

浆液性积液是淋巴瘤常见的并发症。虽然在非霍奇金淋巴瘤(NHL)和霍奇金病(HD)中胸腔积液的发生率为20%-30%,但腹腔和心包腔受累并不常见。在淋巴瘤亚型中,T细胞肿瘤,尤其是淋巴母细胞淋巴瘤,更常累及浆液。胸导管阻塞和淋巴引流受损似乎是HD中胸腔积液发病的主要机制,而直接胸膜浸润是NHL中的主要原因。NHL胸腔积液的细胞学阳性率差异很大(22.2%-94.1%)。文献中已描述了特定淋巴瘤亚型的细胞学特征,如淋巴母细胞淋巴瘤、滤泡中心细胞淋巴瘤(包括伯基特型淋巴瘤)、边缘区淋巴瘤、黏膜相关淋巴组织淋巴瘤和间变性大细胞淋巴瘤等。浆液性积液中淋巴瘤的鉴别诊断问题包括反应性淋巴细胞增多、淋巴瘤早期累及、小圆形细胞肿瘤(SRCT)以及里德-施特恩贝格细胞样细胞的存在。为克服这些困难,已对积液标本进行了各种辅助研究,包括免疫细胞化学(ICC)、形态计量学、流式细胞术(FCM)以及细胞遗传学/分子遗传学(PCR、原位杂交和Southern印迹法)。ICC不仅能将淋巴瘤与反应性淋巴细胞增多和SRCT区分开来,还能显著改进形态学诊断以更好地对淋巴瘤进行分类。结合形态学和FCM免疫表型分析的敏感性和特异性均为100%。形态计量学也能以高度的敏感性(>85%)和特异性(>95%)区分反应性淋巴细胞增多和恶性淋巴瘤。通过使用多个参数可克服个别辅助技术的局限性。虽然淋巴瘤很少仅以浆液性积液形式出现而无其他胸内和胸外部位受累,但一小群称为原发性渗出性淋巴瘤(PEL)的淋巴瘤表现为浆液腔的单独或主要受累,而无可检测到的实体瘤块。这种基于体腔的淋巴瘤(BCBL)是一种独特的临床病理实体,主要见于患有卡波西肉瘤的艾滋病患者。在无阻塞性或浸润性肿瘤块的情况下,其发病机制归因于血管内皮生长因子(VEGF)/血管通透性因子(VPF)的刺激,导致血管渗漏。细胞形态学上,PEL通常是大细胞淋巴瘤,似乎兼具大细胞免疫母细胞淋巴瘤和间变性大细胞淋巴瘤(ALCL)的特征。这些病例大多构成B细胞淋巴瘤的一个独特亚组,具有高级别间变性和B免疫母细胞淋巴瘤的特征,但也有T细胞和/或自然杀伤细胞免疫表型的描述。已通过分子技术详细研究了其与各种病毒DNA的关联。淋巴瘤引起的胸腔积液,无论是原发性还是其他情况,都被认为是对总体生存产生不利影响的因素之一。就诊时出现胸腔积液不仅与淋巴瘤的极差预后相关,也是化疗后疾病复发和生存降低的预测指标。当有或无纵隔肿块的淋巴瘤性胸腔积液患者出现呼吸窘迫时,胸腔穿刺术是这些患者的初始诊断和治疗选择。在这种情况下,细胞学检查及辅助研究不仅能快速诊断淋巴瘤,还能提供具有预后意义的信息,如淋巴瘤的分类、分级和免疫表型,以及病毒DNA和肿瘤溶解综合征的有无。

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