Wang Qian, Li Xiao-qiu, Zhu Xiong-zeng, Zhu Xiao-li, Lu Hong-fen, Zhang Tai-ming, Zhou Xiao-yan
Department of Pathology, Cancer Hospital, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Zhonghua Bing Li Xue Za Zhi. 2010 May;39(5):296-301.
To evaluate the ancillary diagnostic value of IgH gene rearrangements in those B-cell lymphoproliferative disorder cases whom are difficult in making a final diagnosis.
IgH gene clonal rearrangements were retrospectively analyzed in a total of 77 diagnostically difficult B-cell lympho-proliferative patients. Standardized BIOMED-2 system IgH gene clonality assay kit targeting FR1, FR2, FR3 was used, followed by heteroduplex-polyacrylamide gel electrophoresis (PAGE) and silver nitrate staining.
The final diagnoses of the 77 cases were: 12 cases of reactive lymphoid hyperplasia, 20 cases of atypical lymphoid hyperplasia or suspicious lymphoma, and 45 cases of B-cell lymphoma. Detection rates of at least one positive reaction were 2/12, 11/20 (55%), 36/45 (80%) in the three groups, respectively. In B-cell lymphomas, the clonality detection rate of FR1, FR2 and FR3 was 60% (27/45), 60% (27/45) and 56% (25/45), respectively. The type distribution were: 20 marginal zone lymphomas, including 18 extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, 7 diffuse large B-cell lymphomas, 7 follicular lymphomas, 1 mantle-cell lymphoma, 1 Burkitt's lymphoma, 4 plasma cell neoplasms and 5 unclassified B-cell lymphomas. Rearrangements of FR1, FR2 or FR3 were not detected in 9 (20%) of the B cell lymphoma cases, nevertheless, one of them had developed liver lesion later, and was confirmed finally to be B cell lymphoma. Fourteen patients of reactive lymphoid hyperplasia with positive IgH gene clonal rearrangements, and atypical lymphoid hyperplasia had follow-up history available. Four of them were diagnosed as lymphoid malignancies upon further biopsy, and in three of them, clonal IgH gene rearrangements were detected.
B-cell lymphoproliferative disorder requiring a detection of clonal IgH gene rearrangement for making a final diagnosis. Combined detections of three IgH FR1, FR2 and FR3 rearrangements provide important ancillary diagnostic value in confirming suspected B-cell lympho-proliferative disorders. It is important to take an additional biopsy or to follow-up those patients who that have a detectable IgH gene clonal rearrangement but without apparent morphological evidence of lymphoma. For cases with a negative IgH gene rearrangements, it might be necessary to perform clonality analysis for other forms of gene rearrangements including IgH or IgK and IgL in order to further improve the detection sensitivity.
评估IgH基因重排在那些难以做出最终诊断的B细胞淋巴增殖性疾病病例中的辅助诊断价值。
对77例诊断困难的B细胞淋巴增殖性疾病患者进行IgH基因克隆重排的回顾性分析。使用靶向FR1、FR2、FR3的标准化BIOMED-2系统IgH基因克隆性检测试剂盒，随后进行异源双链-聚丙烯酰胺凝胶电泳（PAGE）和硝酸银染色。
77例患者的最终诊断为：反应性淋巴组织增生12例，非典型淋巴组织增生或可疑淋巴瘤20例，B细胞淋巴瘤45例。三组中至少有一次阳性反应的检测率分别为2/12、11/20（55%）、36/45（80%）。在B细胞淋巴瘤中，FR1、FR2和FR3的克隆性检测率分别为60%（27/45）、60%（27/45）和56%（25/45）。类型分布为：边缘区淋巴瘤20例，其中黏膜相关淋巴组织结外边缘区B细胞淋巴瘤18例，弥漫性大B细胞淋巴瘤7例，滤泡性淋巴瘤7例，套细胞淋巴瘤1例，伯基特淋巴瘤1例，浆细胞肿瘤4例，未分类B细胞淋巴瘤5例。9例（20%）B细胞淋巴瘤病例未检测到FR1、FR2或FR3重排，不过其中1例后来出现肝脏病变，最终确诊为B细胞淋巴瘤。14例IgH基因克隆重排阳性的反应性淋巴组织增生和非典型淋巴组织增生患者有随访记录。其中4例经进一步活检诊断为淋巴恶性肿瘤，3例检测到克隆性IgH基因重排。
B细胞淋巴增殖性疾病需要检测克隆性IgH基因重排以做出最终诊断。联合检测IgH的FR1、FR2和FR3三种重排在确诊可疑B细胞淋巴增殖性疾病中具有重要的辅助诊断价值。对那些有可检测到的IgH基因克隆重排但无明显淋巴瘤形态学证据的患者进行再次活检或随访很重要。对于IgH基因重排阴性的病例，可能有必要对包括IgH或IgK和IgL在内的其他形式的基因重排进行克隆性分析，以进一步提高检测灵敏度。
