A 35-year-old male presented with diarrhea and abdominal pain after eating seafood and drinking 5 months before admission. The abdominal pain could be relieved after defecation. Two weeks later, he began to have a fever, up to 39.8 C, accompanied by chills. He was admitted to the local hospital and broad spectrum antibacterial drugs were started empirically. Despite antibiotics, the fever continued to occur repeatedly, in peaks up to 41 C, and the diarrhea persisted. Then the patient was suggested to be transferred to our institution.
Laboratory tests showed leukocytosis (20.79 x 109/L), moderate anemia (69 g/L), increased percent of neutrophils (91.6%), increased C-reactive protein (CRP) (80.90 mg/L), procalcitonin (PCT) (5.87 ng/ml) and erythrocyte sedimentation rate (ESR) (106.0 mm/h) level, and mild hypoalbuminemia (31.0 g/L). Stool routine revealed Leukocyte ++++/HP, pus cell ++++/HP, stool blood was positive. Amoeba cysts were found after repeated stool examinations, but no trophozoites. Blood cultures, HBV, CMV-DNA, TORCH-IgM, G/GM, TB-IGRA, parasite antibody were negative. The plasma biochemistry of liver and kidney functions were normal. A total of three colonoscopes and biopsies were performed for the patient, and the results showed multiple irregular ulcers in the whole colon (Figure 1). Colonic biopsies diagnosed Epstein-barr virus-associated lymphoproliferative disorder, but the sample was inadequate for definitive diagnosis. Bone marrow examination showed the proliferation of hematopoietic cells were active, mainly granulocytes, and immature granulocytes increased. Findings of CT images of chest and neck were normal. Contrast-enhanced CT scan of the whole abdomen revealed multi-segmental intestinal wall thickening and enhancement (Figure 2A). 18F-FDG PET/CT demonstrated increased FDG uptake in the whole colon, bone marrow and spleen (Figure 3).
Treatment of the patient was provided with anti-infective (moxifloxacin, rifaximin, metronidazole and imipenem, vancomycin, and cefperazone-sulbactam, tigecycline were given successively). However, he still had diarrhea and recurrent fever, the body temperature fluctuated at 39-40 C. Blood cultures were still negative. No positive bacilli was found by acid fast staining and no DNA fragment of Mycobacterium tuberculosis was found by qPCR. During the hospitalization, the patient developed a fierce abdominal pain, CT indicated gastrointestinal perforation (Figure 2B). An emergency surgery was performed. During surgery, it was found that there were two 0.5 cm breaks in the ileocecal junction, a 3 cm break in the descending colon, three perforation holes of varying sizes were seen in the sigmoid colon with a diameter of about 0.5-1 cm, and three 0.5-4 cm breaks in the upper rectal segment 3 cm from the peritoneal reflection. The intestinal wall around the breaks was edematous and congestive. He underwent total colectomy and enterostomy. ENKTL was diagnosed for pathological diagnosis of surgical samples. Histologically, the tumor cells were medium in size with irregular nuclei (Figure 4B). There were mixed inflammatory infiltrated mainly including lymphocytes and plasmacytes. The tumor cells infiltrated the whole wall of the intestinal wall with ulcer, necrosis (Figure 4A). Immunohistochemical staining showed that CD3, CD2, CD43, granzyme B (GB), TIA-1 were positive, while CD20, CD5, CD7, CD4, CD8, CD56 were negative (Figures 4B-G). CD30 was focally positive. The Ki-67 labeling index was 60% (Figure 4I). EBV-encoded small RNA (EBER) analysis showed positive (Figure 4H). Gene rearrangement test found the low amplification peak of TR gene.
After recovering from surgery, the patient was treated with two courses of etoposide 50 mg and dexamethasone 5 mg (ED) regimen. Gemcitabine was added on the third day of the second course of therapy. Two weeks later, PD-1 monoclonal antibody 100 mg was used to replace ED regimen because his general condition and the expected chemotherapy tolerance were poor (A total of 3 times, each interval of 3 weeks). Fortunately, the patient was discharged the next day after the last treatment with PD-1 monoclonal antibody. By the time he was discharged from the hospital, his general condition improved significantly. PD-1 monoclonal antibody 100 mg was used on day 23, 56, 85 after discharged. To date, the patient has treated with a total of six courses of PD-1 monoclonal antibody. Eleven months follow-up was uneventful.