Rapid Diagnosis of Gastric Malignant Lymphoma from Biopsy Specimens: Detection of Immunoglobulin Heavy Chain Rearrangement by Polymerase Chain Reaction

Abstract

The endoscopic appearances of the gastrointestinal lymphomas differ widely, and it is often difficult to make the distinction between a benign lymphoproliferative disorder and a malignant lymphoma even with a histologic evaluation. Since almost all primary malignant lymphomas of the gastrointestinal tract are of B‐cell origin, the confirmation of monoclonality in immunoglobulin (Ig) is helpful for differential diagnosis. Rearrangements of the Ig heavy chain gene were examined by polymerase chain reaction (PCR) analysis in frozen biopsy specimens of human stomach. The sensitivity of the analysis was sufficient to detect even a 5% clonal B‐cell proliferation and results could be obtained within 17 h. In a clinical investigation, seven of eight cases (88%) of primary gastric malignant lymphoma showed a single band in polyacrylamide gel electrophoresis (PAGE) after PCR, suggesting a monoclonal proliferation of B‐cell lineage. By contrast, all seven cases of reactive lymphoreticnlar hyperplasias showed a broad smear pattern in PAGE, which is thought to reflect polyclonal proliferation. None of the lymphocytes infiltrating around gastritis (7 cases), gastric ulcers (12 cases) and gastric carcinomas (15 cases) showed a monoclonal proliferation pattern. These findings suggest that detection of monoclonality in Ig heavy gene rearrangement by PCR is useful for the differential diagnosis of B‐cell lymphoproliferative diseases in the gastrointestinal tract.

Analytical Detection of Immunoglobulin Heavy Chain Gene Rearrangements in Gastric Lymphoid Infiltrates by Peak Area Analysis of the Melting Curve in the LightCycler System

“…22,24 In our hands, we obtained 95.2% sensitivity and 100% specificity, which seem to be similar to other authors. 22,27 In addition, the use of a seminested protocol might explain our ability to detect as little as 1.56% of monoclonal IgH gene rearrangement from gastric MALT lymphoma in a chronic gastritis background. This range of detection is different from that reported by Xu et al, 18 who achieved 12.5% also using the same LightCycler instrument.…”

Primary gastric lymphoma

“…Pathologists can differentiate between pseudolymphomas and lymphomas based on several histological characteristics which indicate malignant 6 ISSN 1007-9327 CN 14-1219/ R World J Gastroenterol January 1, 2004 Volume 10 Number 1 changes, like prominent lymphoepithelial lesions (lymphoid infiltration of glands or crypts with partial destruction), Dutcher bodies and moderate cytologic atypia [35] . In cases which can not be diagnosed with histological differentiation, immunohistochemical marker studies or molecular biology utilizing polymerase chain reaction (PCR) may facilitate establishing an accurate diagnosis [36,37] . However, recent studies have indicated that the great majority of pseudolymphomas are in fact true lymphomas of low-grade malignancy using markers of clonality, and this term preferably has to be abandoned [37] .…”

High incidence of B-cell monoclonality in follicular gastritis: a possible association between follicular gastritis and MALT lymphoma

“…Analysis of IgH gene rearrangements was performed using seminested PCR according to the method of Ono et al with some modification [22]. Briefly, each 25-µl reaction mixture contained 1 X PCR buffer II for the J region, 5′-TGA′GGA′GAC′GGT′GAC′C-3′ (termed LJH); and 5′-GTG′ACC′AGG′GTN′CCT′TGG′CCC′CAG-3′ (termed VLJH).…”