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Non-Hodgkin Lymphoma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Piers Blombery, David C. Linch
Intestinal T-cell lymphoma—this group of rare lymphomas can be divided into two main entities: (i) enteropathy-associated T-cell lymphoma (EATL) and (ii) monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). EATL has a clear association with celiac disease;113 however, there is sometimes little clinical evidence of this before the lymphoma diagnosis. The pathogenesis of EATL is incompletely understood; however, it is postulated that chronic antigenic stimulation by gliadin in the context of the susceptible HLA-DQA1*0501, HLA-DQB1*0201 haplotype (seen in most patients with celiac disease) leads to the development of T-cell clones that predispose to lymphoma following additional genetic mutations.114–117 Specifically, mutations in the JAK3/STAT5B signaling pathway are common drivers in this group of disorders.118 Patients often have a poor performance status at presentation. Malnutrition and intestinal perforation are common, and the outcome following conventional chemotherapy is poor, with long-term remissions only achieved in 10%–30% treated with CHOP-type chemotherapy.119–121 Superior outcomes can possibly be obtained with more intensified upfront chemotherapy and ASCT in those able to tolerate it.122
Gene Rearrangement in Leukemias and Lymphomas
Published in John T. Kemshead, Pediatric Tumors: Immunological and Molecular Markers, 2020
The determination of T cell clonality by immunological and genetic methods in malignant histiocytosis of the intestine (MHI) has shown that it is of T cell rather than of histiocytic origin.88 Consequently, it has been suggested that the term “enteropathy-associated T cell lymphoma” is a more accurate description of this condition.89 The existence of neoplasms in which the cell of origin is histiocytic has been questioned by some authors following the molecular study of MHI and “histiocytic” malignancies.90 In one study, 5/6 cases which were judged to be histiocytic by morphological criteria were found to have either rearranged Ig or Cβ genes.90 However, only 1/5 cases of large cell lymphoma which expressed macrophage antigens possessed nongermline configurations of TCR Cβ genes; all had germline configurations of Ig genes.83
Celiac disease
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
The histological lesion in active celiac disease is strikingly different from that of other T-cell–mediated enteropathies, such as graft-versus-host disease and autoimmune enteropathy. In celiac disease, the crypts are intact and regenerative, but the surface epithelium is profoundly altered. Furthermore, a major infiltration of lymphocytes in the epithelium can develop into enteropathy-associated T-cell lymphoma in rare cases. In contrast, crypt destruction is common in other enteropathies, and intraepithelial lymphocytosis is minor or appears late in the disease. Enteropathy-associated T-cell lymphoma has not been reported in intestinal inflammatory disorders other than celiac disease. These histological differences suggest that the surface epithelium is preferentially targeted, and IELs are abnormally activated in celiac disease.
Diagnostic and therapeutic challenge of unclassifiable enteropathies with increased intraepithelial CD103+ CD8+ T lymphocytes: a single center case series
Published in Scandinavian Journal of Gastroenterology, 2021
Christina Hartl, Jürgen Finke, Peter Hasselblatt, Wolfgang Kreisel, Annette Schmitt-Graeff
Persistent intraepithelial lymphocytosis in refractory CD is considered a precursor lesion of enteropathy-associated T-cell lymphoma (EATL) and may also harbor an increased risk for intestinal lymphoma in AIE [13–15]. We therefore performed repeated TCR-γ gene rearrangement studies on intestinal biopsies from 6/9 patients within our cohort. While the biopsies of 4 patients exhibited polyclonal T-cell populations consistent with inflammatory or reactive changes, clonal TCR-γ gene rearrangements were detected in 2 patients (#1, #9). In #1, an identical rearrangement pattern was present in duodenal, ileal and gastric biopsies and peripheral blood for 8 years without any clinical or pathologic evidence for progression to lymphoma. A more aggressive clinical course was observed in #9, in whom a clonal TCR-γ gene rearrangement favored the diagnosis of a purely intraepithelial CD8+ T-cell LPD evolving from chronic IEL (see below).
An updated overview on celiac disease: from immuno-pathogenesis and immuno-genetics to therapeutic implications
Published in Expert Review of Clinical Immunology, 2021
Paolo D’Avino, Gloria Serena, Victoria Kenyon, Alessio Fasano
RCDI is characterized by intestinal villous atrophy and increased number of IEL. RCDII, instead, is characterized by clonal expansion of abnormal IEL that lack expression of surface markers such as CD3, CD8, and TCR but with a preserved expression of intracellular CD3 [147,148]. Symptoms differ between the two types of RCDs. While RCDI patients present mild symptoms associated with protein-losing enteropathy, subjects affected by RCDII are characterized by severe malnutrition with a poor prognosis (5 years survival rate between 44 and 58%) [149]. Between 33–52% of RCDII patients develops enteropathy-associated T cell lymphoma (EATL) within 5 years after diagnosis. This kind of lymphoma is rarer in RCDI patients[148]. EATL might develop not only in the intestine but also in the cutaneous lesions of RCDII and it is characterized by expression of integrin CD103[150].
Update on the classification of T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms
Published in Expert Review of Hematology, 2019
Akira Satou, N. Nora Bennani, Andrew L. Feldman
Enteropathy-associated T-cell lymphoma (EATL), previously designated type I EATL, is a highly aggressive lymphoma of the gastrointestinal (GI) tract. EATL is associated with celiac disease, typically in northern European populations, and involves intraepithelial T cells characterized by varying degrees of cellular pleomorphism [55]. Most cases show a TCRαβ phenotype. Patients usually carry human leukocyte antigen (HLA)-DQ2 or DQ8 [56], and the tumors frequently demonstrate chromosomal gains of 1q and 5q [57,58]. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as type II EATL, is not associated with celiac disease and is characterized by monomorphic small- to medium-sized tumor cells that express CD8, CD56, and MATK [59]. Most MEITLs show a TCRγδ phenotype [60]. Mutations in STAT5B and gains of the 8q24 locus involving MYC are frequently recurring abnormalities [61,62]. Recent whole-exome sequencing of 41 EATLs and 23 MEITLs revealed highly overlapping genetic alterations suggesting shared mechanisms underlying their pathogenesis [63]. The most commonly mutated gene was SETD2; frequent mutations in genes associated with the JAK-STAT pathway, including STAT5B, JAK1, JAK3, STAT3, and SOCS1, also were identified. Mutzbauer et al. have reported that spleen tyrosine kinase (SYK) expression was a distinctive feature of MEITL (95%) but not of EATL (0%), and suggested that SYK immunohistochemistry might be used as diagnostic marker [64].