发于惰性B细胞恶性肿瘤的侵袭性淋巴造血系统肿瘤：两例罕见病例.ppt

CD68+CD163+ * * According to the previous concept, only committed B-cell precursors or mature B-cells would have IG gene rearranged. Clonal rearrangement of IGH gene detected may suggest a clonal relationship between follicular lymphoma and histiocytic sarcoma. Frame work 1 primer * The answer is NO! In this article, 9 out of 23 cases are positive for clonal rearrangement of IGH/K gene. Then how are we going to confirm the clonal relationship in this case? * Sequential occurring (Primary versus secondary) or concurrent tumors * * * * * 23例中9例具有同源的免疫球蛋白基因重组。我们该如何去进一步确认该病例中两种恶性肿瘤的同源关系？ 确认两种相继或同时出现的肿瘤间的同源关系 细胞遗传学（包括FISH）： 滤泡淋巴瘤中t(14;18), IGH/BCL2; 套细胞淋巴瘤中t(11;14), CCND1/IGH PCR分析：了解转位情况，如t(14;18), t(11;14); IGH/K, TCRG/D基因 PCR/测序明确断裂点特征 IGH/BCL2的FISH结果（黄色信号） FISH for IGH/BCL2 (yellow signal) Wang et al. Am J Surg Pathol 2011;35:457-463 Hematopoiesis Google Images 8例滤泡淋巴瘤并发或继发H/Dc肉瘤 通过检测IGH/K基因重组来分析两种形态学和免疫表型明显不同的肿瘤的克隆关系，PCR、FISH检测IGH/BCL2 体外和鼠模型提示转录因子，如PAX5发生改变，证实成熟B细胞肿瘤具有细胞系可塑性 三个可能机制: 共同的祖细胞 区分好 转移性分化 两种成熟细胞淋巴造血系统肿瘤间可能的细胞分化路径 Transdifferentiation Dedifferentiation Dedifferentiation Common progenitor Follicular lymphoma Histiocytic sarcoma ↓PAX5 Table from archive of pathology 文献报道的由B细胞淋巴瘤转化来的组织细胞肉瘤及基因型分析 患者随访 患者接受R-CHOP治疗和局部放疗，反应良好。然而一年半后确诊组织细胞肉瘤并治疗，发现腹膜后淋巴肿大。CT引导穿刺活检，形态学如下所示： Biopsy of retroperitoneal lymph node Wang et al. Am J Surg Pathol 2011;35:457-463腹膜后淋巴结活检 CD20 BCL6 BCL2 CD10 弥漫大B细胞淋巴瘤， 可能由滤泡淋巴瘤转化 腹膜后淋巴结活检诊断 IGH基因重组检测 IGH gene Rearrangement Studies Wang et al. Am J Surg Pathol 2011;35:457-463 DLBCL 组织细胞肉瘤 IGH/BCL2 融合的FISH结果 组织细胞肉瘤 DLBCL ? 1st biopsy 2nd biopsy* 3rd biopsy Diagnosis FL HS DLBCL Biopsy sites Left inguinal LN Supraclavicular LN Retroperitoneal LN Age/interval (years) 44/0 61/17 62/18.5 Histology Follicular pattern with small centrocyte-like cells Diffuse pattern with histiocytoid cells Diffuse pattern with medium/large lymphoid cells Immunophenotype ? ? ? CD45 ND W+ ND CD20 ND - + CD4 ND W+ ND CD10 ND - W+ BCL6 ND W/M+ + CD