脾淋巴造血组织肿瘤的临床病理学特征

Tumors of lymphoid and hematopoietic tissue of spleen： a clinicopathologic analysis of 53 cases

目的 探讨脾淋巴造血组织肿瘤（TLTS）的临床病理学特征、诊断及鉴别诊断.方法收集2002年4月至2017年4月北京大学人民医院病理科诊断的TLTS 53例,按2008版WHO淋巴造血组织肿瘤分类和2016分类更新,应用光镜观察、免疫组织化学染色、EB 病毒编码的小 RNA （EBER）原位杂交,结合骨髓穿刺及临床相关检查进行临床病理学分析.结果 53例TLTS中,男女比为3.4：1.0,年龄范围21~76岁,平均年龄55.4岁,所有患者均有不同程度的脾肿大.实验室检查：22例外周血淋巴细胞百分比升高;24例乳酸脱氢酶水平升高;26例术前有血象异常,22例术后完全或部分好转（84.6%,22/26）;17例伴有腹腔内或其他淋巴结肿大.骨髓检查30例,19例可见肿瘤累及（63.3%）.53例中有43例符合原发性脾淋巴瘤（PSL）的诊断,其余10例为继发性 TLTS.Ann Arbor临床分期,Ⅰ、Ⅱ期14例,6例为Ⅲ期,28例为Ⅳ期.组织学类型,43例PSL依次为脾边缘区B细胞淋巴瘤（SMZL;48.8%,21/43）、弥漫性大B细胞淋巴瘤（DLBCL;23.3%,10/43）、脾弥漫性红髓小B细胞淋巴瘤（11.6%,5/43）、套细胞淋巴瘤（9.3%,4/43）、滤泡性淋巴瘤（4.7%,2/43）、复合性淋巴瘤（2.3%,1/43）.其余10例为慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（4例）、毛细胞白血病（1例）、肝脾T细胞淋巴瘤（HSTL,5例）,诊断时同时伴有其他部位病变.53例TLTS中,B细胞肿瘤为47例（88.7%,47/53）,T细胞肿瘤均为HSTL,共5例（9.4%,5/53）,1例为DLBCL与经典型霍奇金淋巴瘤复合性淋巴瘤.11例TLTS EBER均为阴性.48例获得随访资料,随访时间1-96个月,生存期中位数17.0个月.SMZL 和 DLBCL 的生存期平均为25.7和18.6个月.死亡13例（27.1%, 13/48）,乳酸脱氢酶水平升高、临床分期高、出现B症状、年龄〉60岁者明显预后差,DLBCL比SMZL预后差,但未表明以上因素与预后之间有统计学意义（均P〉0.05）.结论 TLTS多表现为脾肿大及血象异常,脾切除可使血象完全或部分缓解.病理类型以SMZL、DLBCL最为多见,结合临床表现、组织学特点、免疫表型、遗传学、骨髓及相关实验室检查,可对TLTS做出明确诊断.

Objective To study the clinicopathologic features, diagnosis and differential diagnosis of the tumors of lymphoidand hematopoietic tissue of the spleen（TLTS）. Methods Fifty-three cases of TLTS were selected from the pathologic files from Peking University People′s Hospital from April 2002 to April 2017. According to WHO classification of tumors of hematopoietic and lymphoid tissues（2008）and its updated classification（2016）,the cases were studied by microscopy, immunohistochemistry and in situ hybridization,combined with the bone marrow biopsy and clinical examination. Results In 53 cases of TLTS,the male to female ratio was 3.4：1.0;the mean age was 55.4 years（range 21-76 years）, and all patients presented with variable degree of splenomegaly. Laboratory examination showed increased percentage of lymphocyte in peripheral blood in 22 cases,and elevated serum LDH level in 24 cases. Abnormal blood counts were seen in 26 cases pre-operatively, in which 22 cases showed complete or partial correction of these abnormalities post-operatively（84.6%, 22/26）. The clinical symptoms included abdominal pain or distension, fatigue, fever, and weight loss, etc. Seventeen cases presented with lymphadenopathy of abdomen or other sites. Bone marrow biopsy was performed in 30 cases, and 19 cases were involved by tumor（63.3%）. Of all 53 cases, 43 were diagnosed as primary splenic lymphoma（PSL）, and the remaining 10 cases as secondary TLTS. According to Ann Arbor staging, 14 cases were stages Ⅰ or Ⅱ, 6 were stageⅢand 28 were stageⅣ. By histopathologic classification,43 cases of PSL were splenic B-cell marginal zone lymphoma（SMZL;48.8%,21/43）, diffuse large B cell lymphoma（DLBCL;23.3%, 10/43）,splenic diffuse red pulp small B-cell lymphoma（11.6%,5/43）, mantle cell lymphoma（9.3%, 4/43）,follicular lymphoma（4.7%,2/43）, and composite lymphoma（CL,DLBCL and classical Hodgkin lymphoma;2.3%,1/43）. The remaining 10 cases were chronic lymphocytic leukaemia/small lymphocytic lymphoma（4 cases）,hairy cell leukaemia（1 case）,hepatosplenic T-cell lymphoma（HSTL;5 cases）,with lesions in other sites. Of the 53 cases of TLTS,47 were B cell neoplasm（88.7%,47/53）, and the T cell neoplasms were all HSTL（5 cases, 9.4%,5/53）,1 case was composite lymphoma. In 11 cases of TLTS, EBER in situ hybridization was performed and all cases were negative. Forty eight cases had follow-up data, and the median survival period was 17.0 months（range：1-96 months）. The survival of patients with SMZL and DLBCL were 25.7 and 18.6 months respectively. Thirteen patients died（27.1%,13/48）.The prognosis of those with elevated LDH level,high clinical stage,B symptoms and older than 60 years of age was worse. And the prognosis of DLBCL was worse than that of SMZL. There was no statistically significant difference between these factors and prognosis（P＆gt;0.05）. Conclusions Most TLTS cases present with splenomegaly and abnormal blood counts, and complete or partial remission of blood counts isseen after splenectomy. The most common pathologic types of TLTS are SMZL and DLBCL. Definite diagnosis of TLTS could be made by combining clinical features, histopathology, immunophenotype, genetics, bone marrow biopsy and laboratory examination.