Since the pathophysiological features of the two diseases are virtually identical, NKCE and LG are now commonly viewed as manifestations of the same disease.Only 36 patients with NKCE or LG have been reported as of January 2019. Nonetheless, these diseases are emerging as important clinical entities because they 1) are newly described and likely to be diagnosed more often as they become better known and 2) have been mistaken for, and treated as, various types of pre-malignant and malignant lymphomas of the GI tract. Given the radical differences in the prognoses and treatments of NKCE and LG compared to the lymphomas that they can mimic, the evaluation of many lymphocyte-proliferating disorders of the GI tract must consider and rule out the possibility that they are NKCE or LG rather than a pre-malignant disorder or malignant lymphoma. Presentation
Most cases of NKCE and LG have been reported in middle-aged or older individuals. Patients diagnosed with NKCE (medium age 46 years) have presented with vague abdominal pain, indigestion, vomiting, diarrhea, constipation, weight loss, anemia, and/or GI bleeding. Two patients complained of biliary colic (i.e. gallbladder pain) and were found to have typical lesions of NKCE in their cystic ducts. These two cases indicate that NKCE involvement is not totally limited to the alimentary canal. Three of 15 individuals diagnosed with NKCE disease reported no symptoms, their disease being found on endoscopy conducted for screening purposes.
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 cells 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 cell lymphomas that consist of mature T cells and occur in the GI tact, MALT lymphoma of the stomach, and other types of stomach lymphomas. Treatment
Patients with NKCE or LG should be treated for symptom relief but, as currently recommended, not for the underlying NK cell proliferative disease. Regular follow-ups that include repeated endoscopic analyses of their GI tracts and tests for the spreading of the disease to other organs are recommended to insure the original diagnosis is correct. Prognosis
NKCE and LG usually follow a persistent or regressing-relapsing coarse but uncommonly spontaneously relapses without a recurrence even in cases that have been mistreated with chemotherapy, bone marrow transplantation, or gastric resection. Patients with LG are less likely to have persistent or regressing-relapsing coarse.