EBV-associated lymphoproliferative disorder involving the gastrointestinal tract which mimic IBD in immunocompetent patients: case reports and literature review

A previously healthy 44-year-old man presented with intermittent fever, abdominal pain, and bloody, mucoid bowel movements persisting for 3 months. The patient did not have any personal or family history of immunodeficiency. Physical examination revealed mild tenderness over the right lower abdominal quadrant. Laboratory tests revealed mild anemia (hemoglobin level, 11.9 g/dL), leukocytosis (white blood cell count, 17.1 × 10⁹/L) with a normal differential, elevated level of serum C-reactive protein (CRP, 98 mg/dL), elevated erythrocyte sedimentation rate (ESR, 60 mm/h), moderate hypoalbuminemia (blood albumin level, 30 g/L; normal, 40–55 g/L), and normal globulin level. The results of the liver function tests were normal. T-SPOT® test was negative. Furthermore, the tests for human immunodeficiency virus, cytomegalovirus antibody IgM, and EBV antibody IgM were negative. Stool examination revealed the presence of a large number of red and white blood cells. However, stool culture, tests for Clostridium difficile toxins, and tests for stool parasites were negative. A computed tomography scan of the abdomen and pelvis revealed diffuse colonic thickening and normal appearance of the liver and spleen. Colonoscopy revealed the presence of multiple, intermittent deep ulcers across the entire length of the colon (Fig. 1a). Histological examination of the biopsy samples showed lymphoid and inflammatory hyperplasia of granulation tissues. The diagnosis was initially considered to be Crohn’s disease, and accordingly, prednisone (50 mg/day) and mesalazine (4 g/day) were administered. The treatment brought about a rapid improvement in the patient’s symptoms, and the dosage of prednisone was quickly reduced. However, once the dose reached 30 mg/day, there was a recurrence of fever and bloody stools. The patient was again admitted to our hospital. The results of the laboratory tests were as follows: leukocyte count, 6.7 × 10⁹/L; hemoglobin level, 10.0 g/dL; CRP level, 8 mg/L; and ESR, 11 mm/h. We thought that the recurrence of fever was due to the rapid dose reduction of prednisone, and increased the dose to 50 mg/day. This reduced the patient’s fever and restored his bowel movement to normal, although the stool was still positive for occult blood. Colonoscopy was repeated, which revealed the presence of multiple, intermittent ulcers along the complete length of the colon, although the ulcers appeared to be less severe than before (Fig. 1b). Histological examinations of the biopsy samples revealed interstitial fibrous tissue hyperplasia, granulation tissue formation, and atypical lymphocyte cell infiltration (Fig. 2a). The samples subjected to immunohistochemical staining were positive for CD3 and CD5, but negative for CD56. Many of the atypical cells were positive for Epstein-Barr encoding region (EBER) in situ hybridization (Fig. 2b). Although the EBV-CA-IgM of serum was normal, serum EBV DNA level was 5.3 × 10³ copies/mL. On the basis of these tests, EBV + T-LPD with colonic involvement was diagnosed. The patient was then treated with DEP (doxorubicin, etoposide, and methylprednisolone) chemotherapy regimen, with a gradual reduction in prednisone dosage. After the second chemotherapy cycle, the patient developed severe fungal pneumonia. Therefore, chemotherapy was discontinued. During the 18-month follow-up period, the patient remained asymptomatic and did not require any medicine.

A previously healthy 48-year-old man presented with diarrhea and abdominal pain persisting for one and a half years. Colonoscopy revealed multiple, diffuse, deep ulcers along the right colon. Under the diagnosis of Crohn’s disease, the patient was treated with and hydrocortisone (100 mg/day) for 8 days. A marked improvement in the symptoms was noted, and the dosage of hydrocortisone was gradually reduced. Eight months after the initiation of treatment, the patient underwent a repeated colonoscopy in our hospital to evaluate the status of the disease. Colonoscopy revealed that deep ulcers in the ileocecal valve and ascending colon persisted (Fig. 3). Laboratory tests revealed the following: leukocyte count, 5.8 × 10⁹/L; hemoglobin level, 11.7 g/dL; CRP level, 21 mg/L; ESR, 26 mm/h; mild hypoalbuminemia, (38.4 g/L); and normal globulin level. Furthermore, stool occult blood, stool culture, tests for stool parasites, and tests for Clostridium difficile toxins were all negative. In addition, T-SPOT® test was negative. Moreover, tests for the detection of human immunodeficiency virus, cytomegalovirus antibody CMVAb-IgM, and EBVAb-IgM were negative. Serum EBV DNA level was 8.6 × 10³ copies/mL. Abdomen and pelvis computed tomography scans showed ileocecal intestinal thickening. Histological examinations of the biopsy samples of the colon showed the abundant infiltration of slightly atypical lymphocyte cells. Immunohistochemical staining showed that cells were positive for CD3, partially positive for CD5, and negative for CD56. Many of the atypical cells were positive for EBER in situ hybridization. On the basis of these findings, the diagnosis was established as EBV + T-LPD with colonic involvement. Since the patient was asymptomatic, chemotherapy was not initiated. Four months after being discharged from our hospital, the patient developed high fever. He was admitted to another hospital and died 2 weeks later.