Original Article

Modern Pathology (2009) 22, 940–949; doi:10.1038/modpathol.2009.51; published online 24 April 2009

Duodenal and nodal follicular lymphomas are distinct: the former lacks activation-induced cytidine deaminase and follicular dendritic cells despite ongoing somatic hypermutations

Katsuyoshi Takata1, Yasuharu Sato1, Naoya Nakamura2, Yara Yukie Kikuti2, Koichi Ichimura1, Takehiro Tanaka1, Toshiaki Morito1, Maiko Tamura1, Takashi Oka1, Eisaku Kondo1, Hiroyuki Okada3, Akira Tari4 and Tadashi Yoshino1

  1. 1Department of Pathology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan
  2. 2Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
  3. 3Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan
  4. 4Department of Internal Medicine, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan

Correspondence: Professor T Yoshino, MD, PhD, Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama city, Okayama, 700-8558, Japan. E-mail: yoshino@md.okayama-u.ac.jp

Received 25 January 2009; Revised 24 February 2009; Accepted 25 February 2009; Published online 24 April 2009.

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Abstract

Although most follicular lymphomas are believed to be of nodal origin, they sometimes originate from the duodenum. We have reported that the latter differ from nodal follicular lymphomas in having lower clinical stages and uniformly low histological grades, along with variable region of immunoglobulin heavy chain gene (VH) usage that is more similar to mucosa-associated lymphoid tissue (MALT) lymphomas. Little is known, however, about whether they possess other characteristics of nodal follicular lymphomas, particularly ongoing mutations with follicular dendritic cells. We examined 17 cases for which PCR identified the monoclonal bands of the immunoglobulin gene. The duodenal cases showed ongoing mutations, but they lacked activation-induced cytidine deaminase (AID) expression, a statistically significant difference from the nodal cases (P<0.001), and their follicular dendritic cell networks were disrupted. Moreover, not only were VH deviations observed but also they used very restricted VH genes. Although the mechanisms of ongoing mutation without AID and follicular dendritic cell were not clarified, restricted VH usage strongly suggested that antigen stimulation was involved, and that was similar to MALT lymphomas. In conclusion, duodenal follicular lymphomas were shown to be unique, in that they had ongoing hypermutations such as nodal cases, but the mechanisms involved in the hypermutation were quite different; furthermore, restricted VH usage suggested a strong similarity to the antigen-dependent origin of MALT lymphomas.

Keywords:

duodenal follicular lymphoma, AID, follicular dendritic cell

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