The Role of IGH and IGK Clonality Testing in Diagnostic Work-Up of Suspected Gastric Mucosa Associated Lymphoid Tissue (MALT) Lymphomas.
Bella Graber, Howard Ratech, Qiulu Pan, Juan Du, Shanxiang Shen, Yungtai Lo, Christine McMahon. Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
Background: Distinguishing gastric MALT lymphomas from severe chronic gastritis can be challenging. Molecular testing for clonal immunoglobulin heavy chain (IGH) gene rearrangements by PCR is a widely used adjunct to morphologic evaluation in establishing a diagnosis of MALT lymphoma. Sensitivity can be improved by testing for kappa immunoglobulin light chain (IGK) clonality in addition to IGH. However this could affect specificity.
Design: We identified 88 gastric biopsies with suspected MALT lymphomas that had undergone IGH clonality testing. Slides from these cases were reevaluated by 2 pathologists blinded to the clonality results. Presence or absence of MALT lymphoma-associated features were tabulated for each case, as was the overall histopathologic impression of whether or not the cases showed MALT lymphoma. Residual DNA samples were analyzed for IGK clonality. Both IGH and IGK PCR assays were performed using BIOMED-2 protocols. The results of IGH and IGK analysis were correlated with the individual morphologic features.
Results: 31 of 88 cases (35%) were found to have clonal gene rearrangements. 11 cases had clones detected in both IGH and IGK assays; 7 had only IGH clones detected and 13 had only IGK clones detected. IGH clonality correlated significantly with IGK clonality, despite the 20 discordant cases (p=0.001, Fisher's exact test). The following morphologic features correlated significantly with the detection of a B-cell clone (either IGH, IGK, or both): destructive lymphoepithelial lesions (LEL) (p=0.013) and overall histopathologic impression (p=<0.0001). Foveolar expansion (sheets of CD20+ B-cells reaching the tips of the foveolae) had a trend towards significance (p=0.1183). The following features did not correlate with B-cell clonality detection: follicular colonization, non-destructive LEL, acute inflammation, and presence of microorganisms consistent with H. pylori.
IGH, IGK, and IGH+IGK clonality results defined distinct groups of cases, the features of which are summarized as follows:
|% monocytoid lymphocytes||Foveolar expansion by B-cells||Destuctive LEL|
|(average)||# cases (%)||# cases (%)|
|Polyclonal (n=57)||43||24 (42)||17(30)|
|IGH only (n=7)||51||4 (57)||3 (43)|
|IGK only (n=13)||46||7 (54)||6 (46)|
|IGH + IGK (n=11)||75||8 (73)||10 (91)|