Duodenal follicular lymphoma lacks AID but expresses BACH2 and has memory B-cell characteristics

Abstract

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:and loose CD21 network (duodenal pattern). Gastric/colonic FLs exhibited the following phenotypes:, 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.

Gastrointestinal follicular lymphoma: Current knowledge and future challenges

“…But it needs further study with a greater number of cases. Of note, GI‐FL without duodenal lesion (such as gastric or colonic FL) showed dense FDC meshwork as nodal FL …”

Recent advances in intestinal lymphomas

“…Neoplastic lymphoid cells with the same immunophenotype infiltrate the lamina propria between the follicles and the villi. CD21 and/or CD23 highlight the follicular dendritic cell (FDC) meshwork, often with a ‘hollowed‐out’ distribution at the periphery of the follicles . Most cases harbour a BCL2 gene rearrangement.…”

“…Most cases harbour a BCL2 gene rearrangement. By staging, the disease is confined to the intestinal wall (stage I) in approximately 60% of the cases, and bone marrow involvement is present in only 6% of the cases …”

“…Intestinal FL, similar to nodal FL, exhibits ongoing somatic hypermutations of the IGH‐V regions, but duodenal cases in particular do not express activation‐induced cytidine deaminase (AID) . Instead of AID, BACH2, a regulator of the germinal centre antibody response, is thought to drive that process . In addition to BCL2 translocation, intestinal FL harbours secondary genomic alterations, mostly not shared with those found in nodal cases.…”

Protocadherin γ A3 is expressed in follicular lymphoma irrespective of BCL2 status and is associated with tumor cell growth

“…no. sc47778; Santa Cruz Biotechnology, Inc., Dallas, TX, USA) served as a loading control, as previously described (12). The membrane was washed in PBS-T, and incubated with horseradish peroxidase-conjugated secondary antibody at room temperature for 1 h. The following secondary antibodies were used: Donkey anti-rabbit (1:50,000; cat.…”