The diagnoses of NKCE and LG depends on clinical and pathological findings indicating that the two diseases: a) are indolent and non-malignant; b) usually manifested by mild, vague, or no symptoms; c) localize to the GI tract without involvement of the head, neck, or organs such as the liver and spleen; d) consist of one or more lesions localized primarily to the lamina propria of the esophagus, stomach, small intestine, and/or large intestine (for NKCE} or to the stomach (for LG); and e) involve lesions which contain medium-to large-sized, atypical, and non-clonal lymphocytes that are activated NK<unk> s (see Pathophysiology section) which proliferate at moderately rapid rates (as gauged by, e.g. analysis of their Ki-67 protein levels), lack evidence of Epstein-Barr virus infection, gene mutations, or chromosome abnormalities, and show little evidence of centering around, and destroying, blood vessels. Differential diagnosis In early studies, aggressive chemotherapy with or without bone marrow translanton and gastric resections were used to treat NKCE and LG, respectively, based on the assumptions that these diseases were malignant. Since there was no evidence that these treatments influenced the underlying disease and since NKCE and LG are essentially benign disorders, they must be distinguished from the malignant diseases which they mimic. Three malignant or potentially premalignant diseases which can closely resemble NKCE and LG along with some clinical and laboratory findings which differentiate them from NKCE and LT are: * Extranodal NK/T<unk>  lymphoma, nasal type: This disease can closely mimic NKCE and, to a lesser extent, LG. In contrast to NKCE and LG, extranodal NK/T<unk>  lymphoma, nasal type: is malignant and often aggressive; causes serious, persistent, and often progressive GI tract and other symptoms; commonly involves the head and neck areas and/or multiple organs outside of the GI tract; is deeply invasive, extending beyond the lamina propia of the GI tract; and consists of lesions which contain malignant Epstein-Barr virus-infected NK<unk> s that have numerous gene mutations and chromosome abnormalities and that center around and destroy blood vessels. * Monomorphic epitheliotropic intestinal T<unk>  lymphoma (MEITL): MEITL is a malignant and extremely aggressive GI tract disease. It is manifested by serious, sometimes life-threatening GI tract symptoms such as GI tract obstructions and perforations; is usually localized to the small intestine but may involve other areas of the GI tact; is invasive, e.g. spreads to the submucosa; commonly metastasizes to GI tract lymph nodes; and is composed of lesions which contain Epstein-Barr virus-negative homogenously appearing, medium-sized, malignant T<unk> s that may have mutations or other genetic abnormalities in their STAT5B, JAK3, TP53, SETD2, BRAF, KRAS, GNA12, CREBBP, and/or Myc genes. * Indolent T<unk>  lymphoproliferative disorder of the gastrointestinal tract: This recently described disease, while generally considered benign, has in rare cases been lethal with disease spreading to the bone marrow and blood. This disease is a potentially precancerous condition. Indolent T-cell lymphoproliferative disorder almost always presents with significant GI tract severe symptoms (chronic diarrhea, weight loss, abdominal pain, and/or GI bleeding); involves multiple lesions, most commonly located in the small intestine, colon, and, rarely, stomach, esophagus, and oral cavity; exhibits lesions that resemble those of NKCE and LG but involve infiltrations of T-cells that unlike the NK<unk> s of NKCE and LG, are slowly proliferating, homogenously small-sized, CD56-negative, usually express CD4 and CD8, are not infected by the Epstein-Barr virus, are clonal in nature based on their T-cell receptor rearrangements, and, while located primarily in the lamina propria, may infiltrate into nearby submucosal tissue. Other diseases which NKCE and LG may superficially resemble and require consideration as being in their differential diagnoses include: peripheral T-cell lymphoma not otherwise specified, T<unk>  lymphomas that consist of mature T<unk> s and occur in the GI tact, MALT lymphoma of the stomach, and other types of stomach lymphomas.
Natural killer cell enteropathy
Autoimmune enteropathy
Environmental enteropathy
Congenital tufting enteropathy
Food protein-induced enterocolitis syndrome
Tropical sprue
Coeliac disease
Schnitzler syndrome