Typically, patients diagnosed with LG (medium age 58 years) have been asymptomatic at presentation with their disease being detected during GI tract examinations done for other reasons. Three of twenty patients diagnosed with LG complained of pain or discomfort in the upper abdominal region. Symptomatic individuals with either disease generally have a long history of persistent or intermittent symptoms. Pathophysiology
NK cells normally occupy the GI tract where they contribute to innate immunity by becoming active in killing pathogen-infected and cancerous cells. The proliferating lymphocytes in NKCE and LG express CD56 and CD7 proteins on their cell surface membrane, CD3γ protein in their cytoplasm, and granzyme B, perforin, and T-cell intracellular antigen-1 cytotoxic proteins within their cytoplasmic granules. This pattern of protein expression identifies these cells as NK cells that, because of their expression of the cytotoxic granule-bound proteins, have been activated. However, the cause(s) for the activation of these cells as wells as for their rapid proliferation to produce NKCE and LG is unknown. To date, no evidence of NK cell clonality (i.e. cells developing from a single precursor) or for these cells to bear gene mutations or chromosome abnormalities have been reported in NKCE or LG. These findings help distinguish LB and NKCE from many lymphomas and support the conclusion that neither disease is malignant. The NK cells in LG and NKCE are not infected with the Epstein-Barr virus (EBV), as evidenced by their failure to express this viruss latency proteins and latency ncRNAs.
In contrast to NKCE and LG, extranodal NK/T cell 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 cells that have numerous gene mutations and chromosome abnormalities and that center around and destroy blood vessels. Monomorphic epitheliotropic intestinal T cell 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 cells that may have mutations or other genetic abnormalities in their STAT5B, JAK3, TP53, SETD2, BRAF, KRAS, GNA12, CREBBP, and/or Myc genes. Indolent T cell 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.