The diagnosis of<unk>  is based on endoscopic findings of: 1) flattened duodenal folds and small intestinal fissures and ulcers; 2) biopsy findings of small intestinal inflammation, increased IEL, villous atrophy, and crypt hyperplasia; 3) HLA-DG serology typing and/or gene allele analyses showing results compatible with coeliac disease (see above section on genetics); and 4) positive serology tests for IgA antitissue translutamase antibodies, IgA antibodies to deamidated gliadin peptides, IgG antibodies to deamidated gliadin peptides, and/or IgA antibodies to antitissue translutamase. About 35% of<unk>  cases will be found to have spread of the disease to extra-intestinal sites with lesions in the mesenteric lymph nodes (~35% of cases), bone marrow (<10% of cases), and, uncommonly, blood that contain IEL with the same genetic abnormalities and<unk>  markers as those found in the IEL of their intestinal lesions. Intestinal biopsy specimens of<unk>  lesions also commonly show the presence of mucosal inflammatory<unk> s (particularly eosinophils and histiocytes); a greatly expanded population of medium- to large-sized or anaplastic IEL expressing iCD3 as well as cytotoxic and<unk>  activation markers (e.g. granzyme B and usually TIA1 and perforin); and, frequently CD30. In most cases these IEL also show genetic abnormalities, particularly activating mutations in JAK1 and/or STAT3 and to lesser extents those cited in the above section on<unk> . The malignant IEL in<unk>  do not express CD56. Rarely, patients present with<unk>  who have no gastrointestinal symptoms of celiac disease but rather with extra-intestinal manifestations that are<unk>  with the disease such as dermatitis herpetiformis, psoriasis, other chronic skin conditions, dental enamel defects, gluten-induced cerebellar ataxia, arthritis, and arthralgias. Differential diagnosis Other gastrointestinal T-cell lymphomas can resemble, and therefore need to be differentiated from,<unk> . These include: * Monomorphic epitheliotropic intestinal T<unk>  lymphoma is distinguished from<unk>  in that it is not<unk>  with coeliac disease; is more common in Asians than Northern Europeans; and their small intestine lesions show little or no inflammatory<unk> s plus numerous small- to medium-sized, normal appearing IEL that express CD56 but may not express CD30. The genetic abnormalities found in Monomorphic epitheliotropic intestinal T<unk>  lymphoma are similar to those in<unk> . * Small intestinal adenocarcinoma, while rare, is far more frequent in coeliac disease than in the general population. Unlike<unk> , it often occurs in celiac disease patients who, while otherwise well-maintained on a gluten-free diet, have vague gastrointestinal symptoms such as fatigue, malaise, and weight loss. However, it can cause severe symptoms such as bowel obstruction and intestinal bleeding. Also unlike<unk> , the adenocarcinoma often occurs in women and younger (<50 years old) individuals; is more likely to begin as a non-maligant adenoma; and has the histology typical of an adenocarcinoma. * Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) and anaplastic large<unk>  lymphoma (ALCL) are heterogeneous sets of aggressive T<unk>  lymphomas that exhibit variable morphologies. Unlike<unk> , they are not<unk>  with coeliac disease and rarely present as an intestinal lymphoma without involvement of extra-intestinal tissues. PTCL-NOS's genetic abnormalities differ from those in<unk> : its malignant<unk> s have recurrent mutations in TET2, IDH2, DNMT3A, RHOA, VAV1, and/or CD28 genes, rearrangements of the ITK gene with the SYK, FER, and ERBB4 genes, and/or rearrangements of the TP63 gene. ALCL likewise exhibits different mutations than those occurring in<unk> ; its malignant<unk> s, similar to those in PTCL-NOS, have recurrent mutations in VAV1, rearrangements of the ITK gene with the SYK, FER, and ERBB genes, and/or rearrangements of the TP63 gene. However, ALCL also has distinctive genetic abnormalities: malignant<unk> s in the ALK+ form of ALCL have a translocation between the NPM1 and ALK genes to form a gene encoding the chimeric protein, NPM-ALK while the malignant<unk> s in the ALK- form of ALCL have translocations of either the DUSP22 or TP63 genes. * Epstein-Barr virus-associated lymphoproliferative diseases are a large group of benign, pre-malignant and malignant lymphoproliferative diseases that are<unk>  with the infection of lymphocytes by the Epstein-Barr virus. One of these diseases, Extranodal NK/T<unk>  lymphoma, nasal type may develop primarily in the small intestine but unlike<unk>  often involves lesions in the nasal cavity, pharynx, lung, skin, or other tissues. Furthermore, the malignant T<unk> s in this disease express readily detectable products encoded by the Epstein-Barr virus's genes whereas those of<unk>  are not infected with this virus and therefore do not express these viral products. * Indolent T<unk>  lymphoproliferative disorder of the gastrointestinal tract (ITCLD-GT)) is a rare, slowly progressive, and potentially premalignant disorder of the GI tract that may be mistaken of<unk> , particularly with respect to the severity of its symptoms, the gross pathology of its intestinal lesions, and the presence in its intestinal lesions of T<unk> s that have monoclonal rearrangements of their TCR as well as genetic abnormalities in the JAK/STAT signaling pathway. Unlike<unk> , ITCLD-GT is not<unk>  with coeliac disease; often involves symptomatic lesions of the upper GI tract (i.e. stomach, esophagus, and pharynx); and has GI tract lesions populated by T<unk> s that express CD3 (rather than iCD3), do not express CD56, and, in many cases, express an abnormal STAT3-JAK2 fusion gene.
Enteropathy-associated T-cell lymphoma
Monomorphic epitheliotropic intestinal T cell lymphoma
Hereditary progressive mucinous histiocytosis
MALT lymphoma
Natural killer cell enteropathy
Duodenal-type follicular lymphoma
Gastric lymphoma
AIDS-related lymphoma