Background: Primary gastrointestinal Epstein-Barr virus (EBV)-associated NK/T-cell lymphoproliferative disorder (LPD) (PIEBV+NK/T-LPD) is quite rare. Moreover, it has strong heterogeneity in clinical manifestation and course progression among individuals. In most cases, this disorder mimics the corresponding presentation of inflammatory bowel disease (IBD). It has become a clinical challenge to confirm its diagnosis on time. We summarize and analyze the clinicopathological features and differential diagnosis of 11 Chinese PIEBV+NK/T-LPD in order to raise knowledge about it.
Methods: Patients, who were diagnosed with PIEBV+NK/T-LPD in West China Hospital between 2014 and 2016, were included in this study. The clinical, endoscopic, surgical and histopathological characters were reviewed and the differential diagnosis was analyzed for these patients.
Results: In total 11 cases with confirmed PIEBV+NK/T-LPD were enrolled. The ratio of male to female was five to six, the median age of diagnosis was 37.3 years and the mean disease course was 2.7 years before a definite diagnosis was confirmed. Initial symptoms mainly included occasional fever (10/11), abdominal pain (8/11), hematochezia (7/11), diarrhea (3/11). At its advanced stage, complications in gut mainly comprised perforation (5/11), hemorrhage (2/11), obstruction (2/11). Endoscopy commonly revealed segmental ulcers or extensive inflammation of mucosa. Terminal ileum and colon were most likely involved.
At early stage, this disorder could present a mild to moderate infiltration of small or medium-sized lymphoid cells in lamina propria. Its main immunophenotypes included positivity for CD3, TIA-1 and Granzyme B and deletion of CD5. In situ hybridization was positive for EBER 1/2 in all cases, whereas peripheral blood EBV-DNA and EBV-capsid antigen-IgA were positive in 9/11 and 2/8 cases, respectively. Nine patients had ever been misdiagnosed with ulcerative colitis (UC) (4/9), Crohn's disease (CD) (3/9), or tuberculosis (TB) (2/9) because of mimicking histopathological performance. Moreover, two case who had ever been misdiagnosed as UC was further misdiagnosed as CD. The median endoscopic examination before confirmation of diagnosis was 3.5 times, and even four cases were confirmed until surgical specimens were examined after failure to multiple endoscopies.
Conclusions: PIEBV+NK/T-LPD could be challenging in diagnosis due to its resemblance to IBD endoscopically and pathologically. Thus EBV test and immunophenotype assessment together with repeated endoscopy or even reasonable surgery are essential to make an accurate diagnosis