Plasmablastic lymphoma as a rare cause of subocclusive events – case report and review of the literature

Introduction. The most common causes of subocclusive disorders are the adhesion, Crohn's disease and small bowel neoplasms. Plasmablastic lymphoma (PBL) is an aggressive distinct subtype of diffuse large B-cell non-Hodgkin lymphoma initially reported in the oral cavity of the HIV in-fected individuals. Case report. We presented a male patient with PBL of the small intestine as a rare cause of intestinal subocclusion, without HIV infection and negative serology for hepatitis C, hepatitis B, and Epstein-Barr infection. A 73-year-old male was admitted to our Center due to the one-year history of abdominal pain, weigh loss, non-bloody diarrhea, night sweat-ing and pruritus. The patient underwent the ileocolonoscopic examination with the accompanying biopsy specimens. The results, based on the histopathological and immunohistochemical pattern, confirmed a diagnosis of PBL. Following the chemotherapy treatment, our patient underwent the resection of ileum. The postoperative histopathological report confirmed PBL as the final diagnosis. The patient was treated for the following 6 months with the chemotherapy according to the cyc-lophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) protocol. Fatal outcome was due to acute myocardial infarct. Conclusion. PBL of the small intestine is a rare and unusual cause of subocclusive events. In our patient, an accurate histopathological verification of the detected changes in the ileum was of crucial importance for further treatment.

In this case report, we described a patient with symptoms of subocclusion and suspected Crohn's disease of terminal ileum on the endoscopy examination. Since the histopathological findings of the terminal ileum biopsy did not confirm Crohn's disease, an immunohistochemical examination was required. Upon the immunohistochemical analysis, PBL was diagnosed, isolated locally on the terminal ileum. Our patient had the negative serology tests for HIV, Epstein-Barr virus, hepatitis B and hepatitis C, and did not receive immunosuppressive therapy or suffered from any chronic disease.
The Ethics Committee approval for this report was obtained by the Ethics Committee of our Center.

Case report
A 73-year-old male was admitted to our Center with the one-year history of abdominal pain, weight loss, reported non-bloody diarrhea (six times a day), night sweating, and pruritus. His medical history revealed the laparoscopic cholecystectomy in 2012, sinus arrhythmia, hypertension, and benign prostatic hyperplasia. There was no family history of malignancies. The patient was an ex-smoker and had no recent consumption of beverages or drugs.
Six months prior to the admission to our Center, the patient was examined in a regional hospital. However, the results of the previous examinations were unmarkable, except the finding on the radiographic examination of the small intestine which raised suspicion of Crohn's disease of the terminal ileum.
Upon the admission in our center, the general physical examination revealed an abdominal tenderness in the lower abdomen, with no palpable lymphadenopathy or hepa-tosplenomegaly. The patient had an arrhythmic heartbeat with a heart rate of 55-90 beats/min, sinus arrhythmia in electrocardiogram, an atrioventricular block type I and a suspected sick sinus syndrome.
The laboratory data included hemoglobin concentration [113 g/L (normal range: 138-172 g/L)], and normal values for the white blood cell and platelet counts, β2 microglobulin, lactate dehydrogenase, total proteins and albumins. The C-reactive protein (CRP) values (28.2 mg/L) and the erythrocyte sedimentation rate (ESR) (32 mm/h) were elevated (normal range -CRP: less than 5 mg/L; ESR under 20 mm/h). A serum protein electrophoresis did not show the presence of monoclonal protein. Both the serum carcinoembryonic antigen and CA 19-9 were within the normal range. The serological tests for HIV, hepatitis B, hepatitis C, and Epstein-Barr virus were negative. The purified protein derivative (PPD) skin test was also negative. The analyses of stool samples were negative for Campylobacter jejuni, Yersinia enterocolitica, and Clostridium difficile.
The conventional chest X-ray, abdominal ultrasonography and computed tomography (CT) scan showed no abnormalities. Due to the clinical presentation and radiographic signs of subocclusion, the patient was examined by a surgeon who recommended further investigation and conservative treatment. An esophagogastroduodenoscopy revealed a small hiatal hernia and no macroscopic abnormalities of the esophagus, stomach and duodenum. The colonoscopy examination and an accompanying biopsy revealed a normal colon. Endoscopy of terminal ileum showed diffuse erythema and vascular congestion of the mucosal architecture in the terminal ileum with ulcerations as the "skip lesions" between macroscopically normal presented areas of mucosa of terminal ileum.
Relative improvement of clinical symptoms including reduction of abdominal pain and decreasing number of liquid stools was achieved using mesalamine and methylprednisolone. The laboratory data, however, revealed an elevated ESR (66 mm/h) and the fibrinogen values [7.5 g/L (normal range 2-4 g/L)]. Although the histopathology report did not confirm Crohn's disease, the findings of multiple endoscopic biopsies revealed the diffuse infiltration of lymphoid cells. Re-biopsies of terminal ileum and immunohistochemical examination of the terminal ileum were therefore required. The endoscopic features of the terminal ileum during the repeated endoscopy revealed inflamed mucosa with the irregular nodular and polypoid pattern, spontaneous bleeding, and multiple large ulcers (Figure 1 The histopathological examination revealed the abundancy of atypical large lymphoid cells. The immunohistochemical analyses of the biopsied tissue were positive for MUM1, CD38, and CD138, and negative for Pax5, CD20, CD3, bcl2, bcl6, CD56, and CD10; Ki67 was approximately 30% (Figure 2). The results based on the histopathological and immunohistochemical patterns confirmed a diagnosis of PBL. The patient was sent for further hematological investigation and treatment. After completing the clinical staging procedures, the patient received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy. Due to the persistence of abdominal pain, the patient was transferred to the surgery department, where an ileum resection (50 cm in length) was performed. The postoperative histopathology report confirmed PBL as the final diagnosis.
After the postoperative recovery, the patient was receiving chemotherapy according to the CHOP protocol for the following 6 months, when the fatal outcome occurred due to acute myocardial infarction and consequently cardiac insufficiency.

Discussion
Our case report on localized PBL of the ileum presents a rare cause of subocclusive events. The patient was initially admitted to our hospital for further investigation to exclude previously suspected Crohn's disease. Due to the patient's persistent abdominal pain and radiographic signs of subocclusion, a surgical treatment was discussed without previous ileocolonoscopy.
Crohn's disease is the second most common etiological factor of intestinal obstruction that can require a surgical treatment 1 . According to the available literature, approximately 80% of patients with Crohn's disease will undergo an operation during their lifetime 2 . For the patients with Crohn's disease of the small intestine, an intestinal obstruction is the primary surgical indication 3 . During an ileocolonoscopy, the endoscopic features of Crohn's disease of the terminal ileum were described in our patient. The patient was therefore treated with mesalamine and corticosteroids. An explanation for the relative clinical im-provement is that prednisolone is also included in the CHOP therapy. The final PBL diagnosis was based on the histopathology and immunohistochemical analysis with the additional confirmation by the postoperative findings. The case report of our patient once again proves the importance of histopathology and immunohistochemistry in order to establish the final diagnosis.
Although PBL was initially described in the patients with acquired immunodeficiency syndrome (AIDS) predominantly in the oral cavity, the clinical spectrum of this malignancy has since been expanded 4 .
In the largest cohort study so far, conducted on 135 patients with PBL, the most of them were immunocompromised -either HIV-positive, transplanted or previously treated for systemic diseases and carcinoma 16 .
However, there have been a number of patient series and reports including the HIV-negative cases and extraoral localizations. Over one-third of all PBL cases were first noted at extraoral locations, predominantly within the gastrointestinal tract. According to the relevant literature, the HIVnegative patients can have PBL in the stomach, small bowel, and colon 6,9,10,13,14 . PBL of the small intestine is extremely rare. Some Korean authors described the PBL cases of the small intestine associated with other locations, such as the oral cavity, jejunum and thorax 9 . According to a study conducted by some Chinese authors, the patients with localized PBL of the small intestine were immunocompromised from hepatitis B infections and had a recent radiotherapy for maxillary sinus cancer 11 . Our case report is specific because the illness, causing the small bowel obstruction, was localized to 50 cm of ileum in the immunocompetent patient with no previous medical history of radiotherapy or use of immunosuppressant drugs.
A group of Chinese authors analyzed 114 HIV negative patients with PBL from 52 published papers and concluded that PBL was localized in the gastrointestinal tract in only 15.79% of cases 17 .
In a study conducted by the US authors, of 61 patients with PBL, the gastrointestinal tract was affected in 12 patients, of whom only 3 patients were immunocompetent 18 . Although the studies of other authors suggest a very low diagnostic yield terminal ileum intubation during colonoscopy, our case report points to the importance of insisting on the exploration of the small intestine in a patient with subocclusive symptoms in order to establish the final diagnosis 19,20 . Also, in our patient, the crucial importance for further treatment was an accurate histopathological verification of the detected changes in the ileum.

Conclusion
The differential diagnosis of subocclusive events can also include PBL of the small intestine, as a rare and unusual site of the disease, in the HIV-negative patients without a previous medical history of immunosuppression.

Conflicts of interest
The authors state that they have no conflict of interest.