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[Immunoglobulin heavy chain gene rearrangement study in difficult cases of B-cell lymphoproliferative disorder].

OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.