伴显著边缘带分化的滤泡性淋巴瘤的临床病理学特征及预后

Clinicopathologic features and prognosis of follicular lymphoma with marginal zone B-cell differentiation

目的:探讨一组形态学伴边缘带分化的滤泡性淋巴瘤(follicular lymphoma,FL)的临床特点、发病机制、诊断、鉴别诊断及预后。方法:收集北京友谊医院病理科2008年至2017年伴边缘带分化的FL患者12例,整理临床资料,观察形态学,进行免疫组织化学检测及分析,最后电话随访患者。结果:患者男5例,女7例,年龄30~77(中位年龄53)岁;11例临床表现为多发淋巴结病变,1例为多发淋巴结肿大伴脾脏多发结节;Ann Arbor分期Ⅰ~Ⅱ期及Ⅲ~Ⅳ期各6例。镜下12例均以滤泡增生为主,8例为低级别,4例为高级别(3a级);肿瘤性滤泡周围围绕明显的边缘带样细胞;边缘带样细胞胞质丰富淡染,细胞核小、不规则、扭曲,可见核皱褶,部分类似中心细胞的细胞核,可见散在中心母细胞。免疫组织化学:12例肿瘤细胞均表达B细胞抗原CD20,CD79α及Pax-5,不表达T细胞抗原CD3,CD5;生发中心细胞标志物(CD10及Bcl-6)在肿瘤性滤泡区(neoplasticfol licular region,NFR)及边缘带分化区(marginal zone differentiation region,MZDR)的表达不一致,表现为:NFR,12例均弥漫表达;MZDR,12例均可见表达,但阳性细胞数量不等,其中10例(83.3%)散在、1例(8.3%)部分及1例(8.3%))较多细胞阳性;Bcl-2,11例弥漫阳性,1例(WHO 3a级)NFR阴性、MZDR阳性。随访时间1~113个月(中位数24个月),7例疾病稳定,2例进展(1例转化为弥漫大B细胞淋巴瘤),3例失访。结论:伴边缘带分化的FL形态特殊,生发中心标志物(CD10及Bcl-6)在FL的MZDR总是可以见到阳性细胞,这在其鉴别诊断中具有重要价值,也提示边缘带样细胞可能是FL的肿瘤成分。伴边缘带分化的FL可以向弥漫大B细胞淋巴瘤转化。

Objective: To evaluate the clinical features, pathogenesis, differential diagnosis and prognosis of a series of Follicular lymphoma(FL) with marginal zone B-cell differentiation. Methods: Totally 12 cases of FL with marginal zone B-cell differentiation were collected from 2008 to 2017 in Beijing Friendship Hospital. The clinicopathological features, immunophenotype and follow-up data were analyzed. Results: There were 5 males and 7 females, ranged in age from 30 to 77 years(median, 53 years). All patients presented with multiple lymphadenopathies, except for 1 had additional splenic nodules, half of who were at Ⅰ–Ⅱ or Ⅲ–Ⅳ in Ann Arbor stage. Morphologically, all cases showed follicular growth pattern, including 8 cases of low grade and 4 cases of high grade(grade 3 a). The neoplastic follicles surrounded by marginal zone like-cells distinctly were seen in all cases. The marginal zone-like cells featured abundant pale cytoplasm and small, irregular, distorted or cleaved nuclei, partly resembling centrocyte-like cells, and immunoblasts were scattered. Ⅰmmunohistochemically, the tumor cells were positive for CD20, CD79α and Pax-5, and negative for CD3, CD5. The expression of the germinal center markers(CD10 and Bcl-6) in the neoplastic follicular region(NFR) cells were different from that in the marginal zone differentiation region(MZDR) cells: in NFR, all 12 cases expressed diffusely;Ⅰn MZDR, the distribution of the weakly positive(CD10)/positive(Bcl-6) cells varied featuring scattered(83.3%, n=10), focal(8.3%, n=1) and most(8.3%, n=1) staining. Bcl-2 was diffusely positive in all cases but 1(grade 3 a), in which cells were negative in NFR and positive in MZDR. The median follow-up time was 24 months(1–113 months). The follow-up was available in 9 out of 12 cases: 7 patients were stable, 2 progressed(1 case showed a transformation to diffuse large B cell lymphoma). Conclusion: FL with marginal zone differentiation is rare and distinct. Positive cells of germinal center markers(CD10, Bcl-6) are always found in MZDR of FL, which can contribute to the diagnosis and also indicates that marginal zone-like cells are not reactive but the neoplastic nature. FL with marginal zone B-cell differentiation can transform to diffuse large B cell lymphoma at times.