|Ahead of print publication
A rare and unusual presentation of Epstein–Barr virus-associated diffuse large B-cell lymphoma involving colon as the primary site
Varun Modi, Nikki Bajaj, Saraswathi Lakkasani, Hamid S Shaaban, Gunwant Guron
Department of Medical Oncology, St Michael's Medical Center (an Affiliate of New York Medical College), Newark, New Jersey, USA
|Date of Submission||01-Mar-2017|
|Date of Acceptance||12-Nov-2018|
|Date of Web Publication||28-Jan-2020|
Hamid S Shaaban,
111 Central Avenue, Newark, New Jersey 07102
Source of Support: None, Conflict of Interest: None
Lymphoproliferative malignancies can involve both nodal- and extra-nodal tissues. The most common extranodal site involved is the gastrointestinal (GI) tract, and it is secondary to the widespread primary nodal disease. However, about 33% of non-Hodgkin's lymphoma primarily arise from tissues other than lymph nodes, spleen, or bone marrow, for example, GI tract, skin, or the central nervous system and are called primary extranodal lymphomas. The most common site of GI localization is stomach (50%–60%) followed by small bowel. Primary colonic lymphoma is seen only in 6% of GI lymphomas and up to 0.5%–1% of all colon malignancies. Hence, primary GI lymphoma is extremely rare, and primary colonic lymphoma is an even rarer occurrence. There is clearly a paucity of cases reported in literature resulting in unclear treatment protocol. Here, we report a case of a 51-year-old man who presented with abdominal pain, weight loss, and bright red blood per rectum. A colonoscopy revealed diffuse bleeding ulcers involving the entire colon. Pathology was consistent with primary diffuse large B-cell lymphoma arising from the colon. The patient was started on treatment with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone.
Keywords: Colorectal, diffuse large B-cell lymphoma, primary
|How to cite this URL:|
Modi V, Bajaj N, Lakkasani S, Shaaban HS, Guron G. A rare and unusual presentation of Epstein–Barr virus-associated diffuse large B-cell lymphoma involving colon as the primary site. J Can Res Ther [Epub ahead of print] [cited 2020 Feb 29]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=277102
| > Introduction|| |
Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin's lymphoma (NHL)., The most common site of primary extranodal occurrence is the gastrointestinal (GI) tract, with stomach and small bowel being involved more commonly than the colon. Cecum is the most frequent site of primary colorectal lymphoma (PCL). The etiology of PCLs is not clear, but some risk factors and predisposing conditions have been identified such as immunodeficiency and inflammatory bowel diseases.,,, Here, we review the literature and discuss a rare and unusual case of DLBCL of the colon in a 51-year-old African-American male, presenting clinically with a GI bleed.
| > Case Report|| |
A 51-year-old African-American male, with past medical history of colon carcinoma with excision followed by adjuvant chemotherapy (2002), penile carcinoma (2011), HIV diagnosed in 2013, on highly active antiretroviral therapy, history of tuberculosis in 1996, hypertension, and asthma, presented to the hospital because of diarrhea accompanied with bright red blood in stool for about 2 weeks. The patient reported cramping abdominal discomfort, loss of appetite, and unintentional weight loss of about 20 lbs over the past 2–3 months. He denied any other associated complaints including nausea, vomiting, fever, and night sweats. He quit smoking in 2002 prior to which he smoked ½ pack a day for 20 years and 1 year ago quit smoking cocaine and marijuana. Physical examination was free of significant findings. In the emergency department, he was found to have serum calcium of 7.7 mg/dl, hemoglobin of 7.7 g/dl, and hematocrit of 24.5%. C-reactive protein was 5.890 mg/dl. The rest of the blood work was unremarkable. A computed tomography (CT) abdomen/pelvis with contrast showed bowel-wall thickening of the colon involving the splenic flexure and descending colon. A colonoscopy [Figure 1]a, [Figure 1]b, [Figure 1]c, was performed to correlate the findings, which demonstrated multiple ulcerated bleeding masses in the rectosigmoid portion of the descending colon. Biopsies were obtained. Surgical pathology reports indicated multiple fragments of the ulcerated colonic mucosa involved by an Epstein–Barr virus (EBV)-associated DLBCL. Immunohistochemical staining revealed positivity for CD20 [Figure 2]a, PAX-5, BCL-2 [Figure 2]b, BCL-6 [Figure 2]c, CD45, and CD30. In addition, in situ hybridization analysis for EBV-encoded small RNAs (EBERs) was carried out on paraffin sections with fluorescein-conjugated peptide nucleic acid probes, and they were positive confirming the involvement of the virus in the pathogenesis of this rare entity. Bone marrow biopsy did not reveal any lymphomatous involvement of the bone marrow by malignant B-cells. The patient was discharged in stable condition for follow-up. He is currently being treated with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone.
|Figure 1:(a-c) Multiple ulcerated bleeding masses? Noted in rectum sigmoid and descending colon-boxes taken from descending colon at 70 cm-colon|
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|Figure 2:(a) CD20 staining positive. (b) BCL-2 staining positive. (c) BCL-6 staining on colon biopsy specimen positive|
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| > Discussion|| |
PCL is a rare malignancy and comprises only about 0.5%–1.2% of colon malignancies.,,,, The cecum and ileocecal region are typically the site of origin (more than 50% cases), mostly due to their abundance of lymphoid tissue. NHL is the most common type, with DLBCL being the most common subtype. Dawson et al. in 1961 reported the first case of colorectal lymphoma. Predisposing factors have not been identified or clearly defined. However, in general, there is an increased incidence in immunosuppressed individuals and patients with HIV and inflammatory bowel disease.,
Patients usually present with weight loss, abdominal pain, change in bowel movement, GI bleed, or, in some cases, perforation. Men are at higher risk for this disease entity; in fact, they are affected twice as often as women with the mean age of clinical presentation at 55 years., The most common symptoms in more than half of the patients are abdominal pain and weight loss or change in bowel habits.
CT scan is the initial diagnostic study. Colonoscopy is required to obtain tissue to confirm the diagnosis, but this may not always be the case if the biopsy specimen is inadequate. Tumor histology plays a major prognostic role.,,, Flow cytometry and immunohistochemistry play an eminent role in further defining the subtype of lymphoma. In 1961, the diagnostic criteria of PCLs were first established which included the following: (1) no enlarged superficial lymph nodes at the patient's first clinical encounter; (2) chest radiographs with absence of obvious enlargement of the mediastinal lymphadenopathy; (3) the white blood cell counts, both total and differential, are within normal range and bone marrow biopsy is also normal; (4) at exploratory laparotomy, only regional lymph nodes are affected by disease; and (5) the liver and spleen are free of lymphoma.
DLBCL cells generally express pan B-cell markers such as CD20, CD19, CD22, CD45, and CD79a;,, BCL-6 protein is expressed in 70% of the cases and CD10 is expressed in 30%–60% of cases. In our case, the lymphoma cells were strongly positive for CD20, Bcl-2, and Bcl-6. EBER was also positive. EBV infection, like c-Myc rearrangement, has a strong association with Burkitt's lymphoma; however currently, both factors have been found to be positive in DLBCL. More research is needed to identify the exact pathogenetic role of this molecular marker, to expand this disease entity and to improve its prognosis.
The optimal treatment approach is debatable. On briefly reviewing the literature, it is seen that a multidisciplinary approach has been used in the past including chemotherapy, radiation, and surgery. The role and extent of surgery has not been established. However, a lot of cases underwent surgical resection either due to initial presentation as perforation or for diagnosis., Some authors debate that, due to high risk of spontaneous perforation (45%), surgery is advisable. As in the case of our patient, there was diffuse involvement of the colon by lymphoma, excluding surgery as an option.
Chemotherapy remains the mainstay of treatment, especially in the advanced stage. By far, cyclophosphamide, doxorubicin, vincristine, and prednisone regimen has been shown to have maximal improvement in overall survival compared to other chemotherapy agents. Addition of rituxan has shown to increase survival with no added side effects.,, Surgery alone may be adequate therapy for low-grade NHL limited to the submucosa. Perioperative chemotherapy and/or radiation therapy have been used in the past showing varied outcomes.
In 1995, Shimono et al. suggested the use of neoadjuvant radiation therapy. They reported a case of primary rectal lymphoma treated successfully with preoperative radiation and intraluminal hyperthermia followed by abdominoperineal rectal amputation. However, Quayle et al. suggested that radiation therapy should not be used in colonic lymphoma due to the debilitating complication involving small and large bowels. In 2000, a study by Fan et al. revealed that there was a significant improvement in the overall survival in patients with Stage IIE lymphoma treated with adjuvant chemotherapy. Increased median survival from 36 to 53 months has been reported in patients who underwent adjuvant chemotherapy. In 2005, Bilsel et al. described a case of high-grade primary rectal lymphoma that had an excellent response with complete eradication by treatment with chemoradiation without surgery. Guney et al. presented a similar case in 2007. In a case series published by Pricolo et al., good results were obtained with postoperative chemoradiation.
On the other hand, surgical resection followed by radiation is the treatment of choice for indolent lymphomas including mantle cell, follicular cell, or T-cell lymphoma due to decreased sensitivity to chemotherapeutic agents.,,, Due to its rarity of occurrence and the various histology and stages of presentation, only few trials and studies have been conducted so far. The lack of adequate clinical data has resulted in unclear treatment guidelines. Hence, most of the treatment approaches are based on previous case reports and the clinician's personal assessment.
| > Conclusion|| |
PCL is extremely rare, with few cases reported so far. Hence, there is a lack of randomized controlled trials resulting in lack of meaningful data regarding treatment recommendations for lymphoma arising in colon as the primary site. The brief review of literature and retrospective studies has shown that there is no clear treatment protocol. Surgery, chemotherapy, and radiation have been used alone or in combination. However, chemotherapy has been shown to be most effective and remains the mainstay of treatment, especially when colon is diffusely involved by lymphoma.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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