Trejo Olga, Ramos-Casals Manuel, López-Guillermo Armando, García-Carrasco Mario, Yagüe Jordi, Cervera Ricard, Font Josep, Ingelmo Miguel
Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Spain.
Semin Arthritis Rheum. 2003 Aug;33(1):19-28. doi: 10.1053/sarh.2003.50020.
To determine the prevalence and clinical characteristics of hematologic malignancies occurring in a large series of patients diagnosed with cryoglobulinemia, and to study their association and overlap with autoimmune and/or chronic viral diseases.
We retrospectively analyzed the occurrence of hematologic malignancies in 607 patients diagnosed with cryoglobulinemia in a single institution. Clinical, histologic, and serologic characteristics of patients were recorded on a protocol form. Hematologic malignancies were diagnosed according to the Revised European-American Lymphoma/World Health Organization classification criteria.
Of the total cohort of 607 patients with cryoglobulinemia, we retrospectively identified 27 patients (5%) in whom a hematologic malignancy was diagnosed, including 24 (89%) lymphoproliferative and 3 (11%) myeloid malignancies. Fifteen (56%) were men and 12 (44%) women, with a median age at diagnosis of hematologic malignancy of 67 years (range, 44 to 88 years). The identified hematologic malignancies were non-Hodgkin lymphoma (n = 18), Hodgkin lymphoma (n = 2), chronic lymphocytic leukemia (n = 2), and 1 case each of multiple myeloma, Waldenström macroglobulinemia, Castleman disease, chronic myeloid leukemia and myelodysplastic syndrome. Of the 18 patients with non-Hodgkin lymphoma, there was a predilection for specific histologic types (diffuse large B-cell lymphoma in 8 cases and small lymphocytic lymphoma in 4) and a higher frequency of a primary extranodal origin in 6 (33%) cases. Conditions associated with hematologic malignancies were hepatitis C virus (HCV) infection in 14 patients (52%) and systemic autoimmune diseases in 13 (48%), with both HCV and systemic autoimmune disease in 6 cases (22%).
Hematologic neoplasia associated with cryoglobulinemia is defined by a clear predominance of lymphoproliferative disorders (mainly non-Hodgkin lymphoma), with substantial extranodal involvement and an elevated presence of immunologic markers. HCV infection is the main etiologic factor associated with hematologic malignancies in patients with cryoglobulinemia, followed by specific systemic autoimmune diseases such as Sjögren syndrome and systemic lupus erythematosus, highlighting the close relationship between lymphoproliferation, autoimmunity, and viruses.
确定大量诊断为冷球蛋白血症患者中血液系统恶性肿瘤的患病率及临床特征，并研究其与自身免疫性和/或慢性病毒性疾病的关联及重叠情况。
我们回顾性分析了在单一机构中诊断为冷球蛋白血症的607例患者中血液系统恶性肿瘤的发生情况。患者的临床、组织学和血清学特征记录在一份方案表格上。血液系统恶性肿瘤根据修订的欧美淋巴瘤/世界卫生组织分类标准进行诊断。
在607例冷球蛋白血症患者的整个队列中，我们回顾性鉴定出27例（5%）诊断为血液系统恶性肿瘤的患者，其中包括24例（89%）淋巴增殖性肿瘤和3例（11%）髓系恶性肿瘤。15例（56%）为男性，12例（44%）为女性，血液系统恶性肿瘤诊断时的中位年龄为67岁（范围44至88岁）。鉴定出的血液系统恶性肿瘤包括非霍奇金淋巴瘤（n = 18）、霍奇金淋巴瘤（n = 2）、慢性淋巴细胞白血病（n = 2），以及多发性骨髓瘤、华氏巨球蛋白血症、Castleman病、慢性髓性白血病和骨髓增生异常综合征各1例。在18例非霍奇金淋巴瘤患者中，特定组织学类型有偏好（8例为弥漫性大B细胞淋巴瘤，4例为小淋巴细胞淋巴瘤），6例（33%）患者原发结外起源的频率更高。与血液系统恶性肿瘤相关的情况包括14例（52%）患者丙型肝炎病毒（HCV）感染和13例（48%）患者系统性自身免疫性疾病，6例（约22%）患者同时存在HCV感染和系统性自身免疫性疾病。
与冷球蛋白血症相关的血液系统肿瘤以淋巴增殖性疾病（主要是非霍奇金淋巴瘤）明显占主导为特征，有大量结外受累且免疫标志物水平升高。HCV感染是冷球蛋白血症患者血液系统恶性肿瘤的主要病因，其次是特定的系统性自身免疫性疾病，如干燥综合征和系统性红斑狼疮，突出了淋巴增殖、自身免疫和病毒之间的密切关系。
