The symptoms of MEITL are generally non-specific. The diagnosis depends on endoscopic findings in the GI tract, histological findings on biopsied specimens from involved areas of the GI tract, evidence of disease involvement outside of the GI tract, and the differentiation of MEITL from other GI tract lymphomas and benign lymphoproliferative diseases. Endoscopy typically shows multiple raised and/or ulcerated lesions involving the jejunum or ileum, and less commonly, the duodenum, stomach, or colon. These lesions may occur at multiple sites or spread throughout large areas of the GI tract. Biopsied tissues show abnormally broad<unk>  villi caused by the infiltration of sheets of uniformly-sized lymphocytes. These lymphocytes may also infiltrate and disrupt the architecture of nearby<unk>  crypts and the epithelial lining. Unlike celiac disease-associated EATL, the lesions usually have little evidence of inflammatory cells (particularly lymphoplasmacytoid cells, i.e. cells showing a mixture of B cell and plasma cell morphological features) or of infiltration of the epithelium lining by the types of lymphocytes seen in celiac disease. The lymphocytes in these lesions are T cells expressing the marker molecules and genetic abnormalities given in the above Pathophysiology section. CT scans commonly reveal involvement of mesenteric lymph nodes. Advanced cases have involvement of the bone marrow and/or dissemination into other organs. Differential diagnosis MEITL must be differentiated from the following GI tract disorders with which it shares some common features. * Enteropathy-associated T cell lymphoma (EATL): By definition, MEITL differs from EATL in that EATL specifically occurs in patients with celiac disease. In cases where the presence of celiac disease is not obvious, EATL is differentiated from MEITL by: its occurrence primarily in individuals of Northern European descent, the presence of inflammatory plasmacytoid cells in its lesions, by the tendency of its lesions to consist of γδ rather than αβ T-cell receptor-expressing lymphocytes, by its T cells that express CD30 but not CD56 or megakaryocyte-associated tyrosine kinase. and by most (95%) individuals with EATL being of either the HLA-DQ2 or HLA-DQ8 rather than other HLA-DQ haplotypes. * Extranodal NK/T cell lymphoma, nasal type (ENKTCL-NT): ENKTCL-NT is a lymphoma that usually involves nasal and oropharyngeal airways but may involve lower areas of the GI tract with lesions that mimic MEITL. Unlike MEITL, it is more commonly due to the proliferation of NK rather than T cell lymphocytes, in all cases is caused by lymphocytes that are infected with the Epstein-Barr virus and therefore express this virus's products, and in almost all cases is caused by lymphocytes that do not express CD3 and have not rearranged their T cell receptors. * Anaplastic large cell lymphoma, ALK positive (ALCL,ALK+): ALCL,ALK+ is a subtype of anaplastic large cell lymphoma. It commonly involves the malignant proliferation of T cells in tissues outside of the GI tract but in some cases the disease involves primarily the GI tract. Unlike MEITL, ALCL,ALK+ occurs most commonly in young individuals and individuals from Western Countries and most often involves tissue infiltrates of large, anaplastic-appearing T cells which express a fusion gene involving the ALK gene (which encodes Anaplastic lymphoma kinase), but do not express CD3, CD8, or CD56. * Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS): PTCL-NOS is a heterogenous group of T cell lymphomas that involves lymph nodes, bone marrow, liver, spleen, and/or GI tract. Rarely this lymphoma may present in the GI tract without overt evidence of involvement of other tissues. Unlike MEITL, the T cells in this disease exhibit genetic abnormalities in TET2, IDH2, DNMT3A, RHOA, CD28, and VAV1 genes but in general do not have the genetic abnormalities or express the molecular markers found in MEITL. * Natural killer cell enteropathy (NKCE): NKCE is a benign disease of the GI tract which has GI tract lesions and symptoms that mimic MEITL. Unlike MEITL, NKCE involves the proliferation of non-clonal NK cell lymphocytes which exhibit activation markers (e.g. granzyme B, perforin, and T-cell intracellular antigen-1) but no genetic abnormalities. * Indolent T cell lymphoproliferative disorder of the gastrointestinal tract (ITCLD-GT): ITCLD-GT is a generally benign disease of the GI tract that has in some cases progressed to an aggressive lymphoma. It presents with clinical signs and GI tract lesions which may mimic MEITL. These lesions involve infiltrations of T-cells that unlike the T cells in MEITL proliferate slowly, are homogenously small-sized, CD56-negative, may express CD4, and usually do not express CD8.
Monomorphic epitheliotropic intestinal T cell lymphoma
Enteropathy-associated T-cell lymphoma
Duodenal-type follicular lymphoma
Hepatosplenic T-cell lymphoma
Splenic lymphoma with villous lymphocytes
Diffuse large B-cell lymphoma associated with chronic inflammation
Hereditary progressive mucinous histiocytosis
MALT lymphoma