Natural killer cell enteropathy, also termed NK cell enteropathy (NKCE), and a closely related disorder, lymphomatoid gastropathy (LG), are non-malignant diseases in which one type of lymphocyte, the natural killer cell (i.e. NK cell), proliferates excessively in the gastrointestinal tract (GI tract). This proliferation causes red, sore-like spots, raised lesions, erosions, and ulcers in the mucosal layer surrounding the GI tract lumen. Both disorders cause either no or only vague symptoms of GI tract disturbances such as nausea, vomiting, and bleeding.
In 2006, a persistent but apparently benign disease that involved the proliferation of NK cells at multiple sites throughout the intestines was described. This disorder appeared similar to and easily mistaken for a highly malignant disease, extranodal NK/T-cell lymphoma, nasal type. In 2010, a similarly non-malignant disorder that involved the proliferation of NK cells in the stomach was described. The disease mimicked gastrointestinal lymphomas. Since these first descriptions, several case series and case reports have been published on these enteropathies.
The two NK cell proliferation diseases have been termed NK cell enteropathy and lymphomatoid gastropathy with NKCE being seen mostly in the United States and Korea and LG being seen mostly in Japan. Besides this geographical difference, the only other critical difference between the two diseases is that the lesions in NKCE occur in the small intestine, colon, stomach, and/or esophagus while those of LG are limited to the stomach. 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. 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.
