Duodenal follicular lymphoma lacks AID but expresses BACH2 and has memory B-cell characteristics.
We have reported previously that duodenal follicular lymphoma (FL) is distinct from nodal FL and showed more resemblance to mucosa-associated lymphoid tissue lymphoma, and that FL frequently involved the duodenal second portion. In the present study, we examined duodenal FLs and gastric/colonic FLs to clarify the clinicopathological and immunological differences between the tumor types. We analyzed 8 samples of gastric FL, 17 of duodenal ones, and 5 of colonic/rectal ones, and characterized them by immunohistochemistry, immunogenotyping, and histology. Gastric and colonic FLs presented in submucosal to subserosal areas, whereas duodenal ones presented in the mucosal to submucosal layers. Immunohistochemical analysis revealed that duodenal FLs exhibited the following phenotypes: CD10 (+), B-cell lymphoma 2 (BCL-2) (+), BCL-6 (+), activation-induced cytidine deaminase (AID) (-), BACH2 (+), CD27 (+), MUM-1 (-), Blimp-1 (-), and loose CD21 network (duodenal pattern). Gastric/colonic FLs exhibited the following phenotypes: CD10 (+), BCL-2 (+), BCL-6 (+), AID (+), BACH2 (+), CD27 (-), MUM-1 (-), Blimp-1 (-), and a dense CD21 network (nodal pattern). Expression of AID and CD27 in lymphoma cells and the CD21 network pattern were considerably different between duodenal FLs and gastric/colonic ones. Moreover, in situ hybridization revealed that, in the duodenal FLs, BACH2 was expressed at the periphery of the tumor follicle and tumor villi. The number of immunoglobulin heavy-chain variable domains VH4 and VH5 were higher in duodenal follicular lymphomoas than in gastric FLs. The lymphoma cells of duodenal FLs are different from those of gastric/colonic FLs, and duodenal FL is distinct even within the gastrointestinal tract. Somatic hypermutation in immunoglobulin genes and CD27 expression are hallmarks of memory B cells. We suggest that duodenal FL cells are in the memory B-cell stage, and require BACH2 instead of AID for ongoing mutation.
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Katsuyoshi
K
Takata
Yasuharu
Y
Sato
Naoya
N
Nakamura
Mami
M
Tokunaka
Yukari
Y
Miki
Yara
Y
Yukie Kikuti
Kazuhiko
K
Igarashi
Etsuro
E
Ito
Hideo
H
Harigae
Seiichi
S
Kato
Eiko
E
Hayashi
Takashi
T
Oka
Yoshinobu
Y
Hoshii
Akira
A
Tari
Hiroyuki
H
Okada
Lamia Abd
LA
Al-Kader
Abd Alkader Lamia
AA
Mohamad
Yoshinobu
Y
Maeda
Mitsune
M
Tanimoto
Tomohiro
T
Kinoshita
Tadashi
T
Yoshino
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D050976:Basic-Leucine Zipper Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D003564:Cytidine Deaminase / Q000032:analysis / Q000096:biosynthesis*; D004379:Duodenal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008224:Lymphoma, Follicular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
C491123:BACH2 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase