A previously healthy 43-years-old woman living in pasturing area, with no personal or family history of immunodeficiency, presented with a 2-months history of intermittent fever that was sometimes accompanied with chill, abdominal pain, diarrhea and hematochezia.
The woman reported to a local hospital initially, where she was diagnosed with inflammatory bowel disease and treated with clindamycin, resulting in some clinical improvement. When her previous symptoms deteriorated for 10 days, she was seen at the Gastroenterology Department at our hospital. An X-ray of patient's abdomen at out-patient department showed signs of "incomplete intestinal obstruction" and she was admitted for further evaluation. Her physical examination was unremarkable, except for low blood pressure (97/71 mmHg) and a pale appearance. There was no self-reported loss of weight/appetite or other significant clinical findings at initial presentation. The laboratory tests at this initial presentation are summarized in Table 1.
The patient was treated with anti-infective and symptomatic therapy initially. An enhanced-CT scan performed on day 2 in the hospital showed diffusible change in ascending, transverse and descending colon mimic ulcerous colitis. Multiple lymph nodes of mesenteric and posterior-peritoneum areas were visible (Figure 1). An emergency colonoscopy examination was suggested, which revealed multiple, discrete ulcers with irregular boundaries and clean base, scattered throughout the colon. The diameters of ulcers varied from 6 to 30 mm and errhysis could be seen around the erosion. Normal mucosa was also clearly visible amid the ulcers (Figure 2).
The specific clonoscopic presentation made a strong indication of inflammatory disease including Ulcerative colitis (UC) and Crohn Disease (CD). Specific infectious bowel disease, especially intestinal tuberculosis, was also suspected because of patient's persistent fever, and the intestinal lymphoma diagnosis also could not be excluded. Further laboratory tests were done, including, chronic inflammatory enteropathy combination, anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), rheumatism related factors (ASO+RF+ CRP), tumor markers of digestive tract, procalcitonin (PCT), blood culture, stool culture, amebic trophozoite detection, cytomegalovirus (CMV), anti-EBV antibodies, T-cell spot experiment and PPD test for Mycobacterium tuberculosis, Widal reaction, anti-Brucella antibodies, hepatitis virus indicators, Fungi D glucan detection, etc. Results for all of these tests were either negative or unremarkable, except for the high EBV-related antibody titers: anti-EBV viral capsid antigen (VCA)-IgG: (4.157 s/co), anti-EBV VCA-IgM (0.391 s/co), Epstein barr nuclear antigen (EBNA) IgG (0.865 s/co), EBEA IgG (1.933 s/co), and Epstein barr early antigen (EBEA) IgM (0.187 s/co).
Patient showed no signs of remission during hospitalization. On day 10, a color Doppler ultrasound of abdomen showed splenomegaly. Patient developed severe intestinal bleeding 14 days after admission and underwent an emergency total colectomy, terminal ileum ectomy, small intestine and rectum anastomosis and preventive ileostomy. She was discharged after stable condition and was treated with mesalazine for ulcerative colitis (UC), based on the post-surgery pathological diagnosis made by our hospital. Mesalazine was stopped after a few courses.
Capital Medical University-affiliated Beijing Friendship Hospital made a histological diagnosis of EBV T-cell LPD (II: Borderline) after histological examination of the resected tissue. Microscopic examination of resected colon slides revealed ulceration of intestinal mucosa and intestinal interstitial edema, which was accompanied by diffuse infiltration of small-to-medium-sized pleomorphic mild atypical lymphoid cells within mucosa and submucosa with a mixture of plasma cells and eosinophilic granulocyte and tissue cells. Some of the lymphoid cells had big nucleus and more obvious nucleoli. Lymphoid cells were observed to be distributed in muscular layer and serosa (Figure 3). We confirmed the diagnosis of EBV-associated T-cell LPD, based on the results from immunohistochemistry (IHC) and in situ hybridization of EBV-encoded miRNA (EBER). IHC revealed that the mild atypical lymphoid cells were positive for (Figure 4B) CD3, (Figure 4A) CD2, (Figure 4E) CD7, and (Figure 4C) CD4 expression. Further, a few atypical cells were also found positive for (Figure 4F) CD8, (Figure 4H) GranzymeB, (Figure 4J) TIAI, TCRGbeta, and TCRgammadelta. The lymphoid cells were negative for CD56. (Figure 4I) Ki-67 positivity was 40-50%. In situ hybridization for (Figure 4K) EBER demonstrated EBV-positive atypical lymphoid cells of 50/HPF.
The patient was recommended to come back to hospital monthly for reexaminations. During these visits, she had signs of relapse every time, including new stoma ulcers and bloody stools. EB viral load test was done during her first follow-up visit, and EBV-DNA was found to be 2.55 x 106 copies/ml for. A post-operative colonoscopy, performed at first relapse, showed multiple aphthous bleeding ulcers scattered from the stoma to about 40 cm away from small intestine, in addition to colonic post-operative anastomositis (Figure 5). Histological examination of biopsy samples confirmed the pathological diagnosis of EBV-T-cell LPD. Treatment with daily prednisolone 10 mg was initiated intravenously for a few days in the hospital. Oral prednisolone, 40 mg/day, was prescribed thereafter, after which it was tapered off slowly. The patient showed significant clinical improvement. Hematochezia was temporarily controlled until when the prednisolone was tapered off to 25 mg, and EBV-DNA decreased to 1.31 x 106 copies/mL. Moreover, nothing remarkable was observed in colonoscopy this time (Figure 6). A bone marrow aspiration was strongly recommended but was not performed because of family refusal.
The last time patient came back to our department for reexamination was 4 months after her initial presentation. During this last visit, bone marrow aspiration was performed and found to be normal. However, liver function tests turned out to be abnormal (ALT 100 IU/L and AST 43 IU/L). EBV-DNA was 1 x 106 copies/mL. The patient was referred to the Oncology Department of our Hospital for evaluation. She was asked to continue with the combination of prednisolone and anti-viral medication, until she presented with persistent fever and hematochezia, and died, 3 months later.