Detection of germinal center B-cell lymphoma in archival specimens: critical evaluation of Bcl-6 protein expression in diffuse large B-cell lymphoma of the tonsil.
Expression of Bcl-6 and CD10, markers for the tumor of the germinal center (GC) B-cell derivation, has been studied in primary diffuse large B-cell lymphomas (DLBCLs) of the lymph node, gastrointestinal tract, and mediastinum. In these studies, the coexpression rate of CD10 and Bcl-6 was relatively constant at 30% approximately 40%, but the frequency of Bcl-6+ tumors varied from 55% to 100%, raising doubts about the usefulness of Bcl-6 expression in identifying the tumor of GC B-cell derivation. Because the expression of Bcl-6 in tumors of non-GC B-cell origin has recently been reported, we critically evaluated the expression of Bcl-6 and CD10 in primary DLBCLs of the tonsil, a relatively common tumor in Japan and Korea. The cases (n = 51) represented a consecutive series for any recent 2-year period at several teaching hospitals in Korea and Japan. Formalin-fixed, paraffin-embedded specimens were used for immunostaining. Staining for Bcl-6 and CD10 was positive in 44 (86%) and 22 cases (45%), respectively. However, among those positive for Bcl-6 (>10% Bcl-6+ tumor cells), 2 basic patterns were recognized: uniform and nonuniform. The uniform pattern was characterized by a dense population (>75%) and a consistent density in any given area, resembling the staining pattern observed in GC or follicular lymphoma (FL) (the "GC/FL" pattern). In contrast, the nonuniform pattern exhibited a varying density from area to area, as well as a less-dense population (<75%). The uniform pattern was observed in 26 cases (51%). All but 1 (95%) of the CD10+ tumors coexpressed Bcl-6, with most (82%) displaying the uniform pattern. We conclude that tumors showing a uniform pattern of Bcl-6 expression should be distinguished from those showing a nonuniform pattern, because the former most likely represent tumors of GC B-cell derivation and the latter most likely represent tumors of non-GC derivation. GC B-cell lymphoma thus defined accounted for 51% of tonsillar DLBCL, a proportion comparable to that of the nodal DLBCL. CD10 expression correlated with the "GC/FL" pattern, but appeared to be not essential for the identification of GC B-cell lymphoma. This study suggests that a significant proportion of tonsillar DLBCLs in Asia is of GC B-cell origin rather than of mucosa-associated lymphoid tissue origin. This finding may have significance for clinical management of these lymphomas.
Ree
Howe J
HJ
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Ohsima
Koichi
K
Aozasa
Katsuyuki
K
Takeuchi
Kengo
K
Kim
Chul Woo
CW
Yang
Woo Ick
WI
Huh
Joor Yung
JY
Lee
Seung-Sook
SS
Ko
Yong-Hye
YH
Kwon
Mi Seon
MS
Cho
Eun Yoon
EY
Choi
Yoon-La
YL
Rhee
Jong Chul
JC
Kikuchi
Masahiro
M
Mori
Shigeo
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001109:Archives; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018858:Germinal Center / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D014067:Tonsillar Neoplasms / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D015260:Neprilysin