Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms

Abstract

Immunoproliferative small intestinal disease (IPSID) was recently added to the growing list of infectious pathogen-associated human lymphomas. Molecular and immunohistochemical studies demonstrated an association with Campylobacter jejuni. IPSID is a variant of the B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), which involves mainly the proximal small intestine resulting in malabsorption, diarrhea, and abdominal pain. Geographically, IPSID is most prevalent in the Middle East and Africa. IPSID lymphomas reveal excessive plasma cell differentiation and produce truncated alpha heavy chain proteins lacking the light chains as well as the first constant domain. The corresponding mRNA lacks the variable heavy chain (V(H)) and the constant heavy chain 1 (C(H)1) sequences and contains deletions as well as insertions of unknown origin. The encoding gene sequence reveals a deletion of V region and parts of C(H)1 domain. Cytogenetic studies demonstrated clonal rearrangements involving predominantly the heavy and light chain genes, including t(9;14) translocation involving the PAX5 gene. Early-stage IPSID responds to antibiotics (30%-70% complete remission). Most untreated IPSID patients progress to lymphoplasmacytic and immunoblastic lymphoma invading the intestinal wall and mesenteric lymph nodes, and may metastasize to a distant organ. IPSID lymphoma shares clinical, morphologic, and molecular features with MALT lymphoma, lymphoplasmacytic lymphoma, and plasma cell neoplasms.

Lymphoproliferative Disorders of the Gastrointestinal Tract: A Review and Pragmatic Guide to Diagnosis

“…63- 65 The discovery of benign-appearing follicles, together with lymphomatous cells that conform to the centrocyte-like cells of MALT, add credence to the classification of IPSID as a form of extranodal marginal cell lymphoma of MALT type developing in mucosaassociated lymphoid tissue of the small intestine. 37,[64][65][66] The exact antigenic stimulus to form reactive follicles in IPSID is unknown, but recent molecular and immunohistochemical studies demonstrate a proposed association with Campylobacter jejuni, although this relationship remains tenuous.…”

“…37,[64][65][66] The exact antigenic stimulus to form reactive follicles in IPSID is unknown, but recent molecular and immunohistochemical studies demonstrate a proposed association with Campylobacter jejuni, although this relationship remains tenuous. 65,67,68 Patients at an early stage of mucosal involvement frequently respond to antibiotics, whereas patients whose disease evolves to large cell lymphoma, specifically the immunoblastic variant, classically have a better median survival than Western patients with de novo large B-cell lymphoma of the intestine.…”

Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

“…In addition to H. pylori, various other infectious agents have been reported to be related to the development of MALT lymphoma, such as Borrelia burgdorferi in cutaneous (Roggero et al, 2000), Chlamydia psittaci in orbital (Ferreri et al, 2004), and Campylobacter jejuni in small intestinal lymphoma (Al-Saleem & Al-Mondhiry, 2005). However, few data are available on the pathogenesis of MALT lymphoma of organs other than the stomach.…”

Emerging Role of Infectious Etiologies in the Pathogenesis of Marginal Zone B-cell Lymphomas

“…Immunosuppressive small intestinal disease (IPSID), previously also known as a-heavy chain disease or Mediterranean lymphoma, is a special subtype of MALT lymphoma (6,84,85). Although it is endemic in the Middle East, especially in the Mediterranean area, IPSID can also be diagnosed in industrialized Western countries, usually among immigrants from the endemic area.…”