Knowles D M
Department of Pathology, Cornell University Medical College, New York, New York, USA.
Mod Pathol. 1999 Feb;12(2):200-17.
The incidence of lymphoproliferative disease is significantly higher in individuals who have congenital, acquired, or iatrogenically induced immunodeficiency. The immunodeficiency-associated lymphoproliferative disorders are clinically and pathologically heterogeneous, are of variable clonal composition, and vary according to the immunodeficiency syndrome. Nonetheless, they share several features, including frequent origination in or involvement of extranodal sites, diffuse aggressive histology, B-cell lineage derivation, association with the Epstein-Barr virus (EBV), and, often, rapid clinical progression. Reactive and atypical lymphoid hyperplasias and malignant lymphomas occur in association with congenital (primary) immunodeficiency. Post-transplantation lymphoproliferative disorders are often comprised of a polymorphic cell population, making it difficult to identify their benign or malignant nature by histopathologic criteria alone. Recent studies suggest that they are divisible into plasmacytic hyperplasias, polymorphic lymphoproliferative disorders, and malignant lymphomas. The plasmacytic hyperplasias are polyclonal and generally regress spontaneously following withdrawal of immunosuppression. The malignant lymphomas are monoclonal, possess a variety of genetic alterations, and generally progress despite aggressive therapy. The polymorphic lymphoproliferative disorders are also monoclonal but display variable clinical behavior, their progression apparently correlating with bcl-6 gene mutation. Non-Hodgkin's lymphoma (NHL) is the second most common AIDS-related neoplasm and an AIDS-defining illness. AIDS-related NHLs are divisible by anatomic site of origin into systemic (nodal/extra nodal), primary central nervous system, and body cavity-based (primary effusion) lymphomas; and by histopathology into Burkitt's and Burkitt's-like lymphoma, large cell lymphoma, and large cell immunoblastic (plasmacytoid) lymphoma More than 90% are monoclonal B-cell neoplasms. The primary effusion lymphomas contain the Kaposi's sarcoma-associated herpesvirus. Multiple molecular pathways appear to operate in AIDS lymphomagenesis and some may be preferentially associated with specific histopathologic categories or anatomic sites of origin. In conclusion, the immunodeficiency-associated lymphoproliferative disorders often represent a significant diagnostic problem requiring correlative analysis of the clinical behavior of the patient with the histopathology, immunophenotype, clonal composition, viral content, and genetic alterations of the lymphoproliferative disorder. They also represent an important biological model for studying the development and progression of lymphoid neoplasia
在患有先天性、获得性或医源性免疫缺陷的个体中，淋巴增殖性疾病的发病率显著更高。免疫缺陷相关的淋巴增殖性疾病在临床和病理上具有异质性，克隆组成各异，并因免疫缺陷综合征的不同而有所差异。尽管如此，它们具有一些共同特征，包括常起源于结外部位或累及结外部位、弥漫性侵袭性组织学、B细胞谱系来源、与爱泼斯坦-巴尔病毒（EBV）相关，且通常临床进展迅速。反应性和非典型淋巴组织增生以及恶性淋巴瘤与先天性（原发性）免疫缺陷相关。移植后淋巴增殖性疾病通常由多形性细胞群体组成，仅通过组织病理学标准很难确定其良性或恶性性质。最近的研究表明，它们可分为浆细胞增生、多形性淋巴增殖性疾病和恶性淋巴瘤。浆细胞增生是多克隆性的，在停用免疫抑制后通常会自发消退。恶性淋巴瘤是单克隆性的，具有多种基因改变，尽管进行积极治疗通常仍会进展。多形性淋巴增殖性疾病也是单克隆性的，但表现出不同的临床行为，其进展显然与bcl-6基因突变相关。非霍奇金淋巴瘤（NHL）是第二常见的与艾滋病相关的肿瘤，也是一种艾滋病定义疾病。与艾滋病相关的NHL可根据起源的解剖部位分为全身性（淋巴结/结外）、原发性中枢神经系统和体腔性（原发性渗出性）淋巴瘤；根据组织病理学分为伯基特淋巴瘤和伯基特样淋巴瘤、大细胞淋巴瘤以及大细胞免疫母细胞（浆细胞样）淋巴瘤。超过90%是单克隆B细胞肿瘤。原发性渗出性淋巴瘤含有卡波西肉瘤相关疱疹病毒。多种分子途径似乎在艾滋病淋巴瘤发生过程中起作用，其中一些可能与特定的组织病理学类别或起源的解剖部位优先相关。总之，免疫缺陷相关的淋巴增殖性疾病常常代表一个重大的诊断难题，需要对患者的临床行为与淋巴增殖性疾病的组织病理学、免疫表型、克隆组成、病毒含量和基因改变进行相关分析。它们也是研究淋巴肿瘤发生发展和进展的重要生物学模型。
