Colorectal cancer is the second leading cause of cancer death in the United States for both men and women, and the third most commonly diagnosed cancer, with a global burden that is expected to increase by 60% by 2030.1,2 Lymphomas are classified as Hodgkin and non-Hodgkin lymphoma (NHL), which are further divided into nodal and extranodal NHL. Primary lymphomas of the gastrointestinal (GI) tract, involving only regional lymph nodes without systemic disease, are extremely rare, accounting for 1%–4% of GI neoplasms.3 The stomach is the predominant site of GI lymphoma, involved in 60%–75% of the cases, whereas rectal lymphoma was only seen in 2% of reported cases.4,5 We report a case of a patient with a history of long-standing ulcerative colitis (UC), diagnosed with primary diffuse large B-cell lymphoma of the rectosigmoid colon. The patient was never treated with immunomodulators or biologic agents.
A 74-year-old man with a medical history of UC, as well as mechanical aortic and mitral valves was admitted for a surveillance colonoscopy with preprocedural anticoagulation bridging. At the time of presentation, the patient had UC for 16 years and no family history of cancer. His UC was controlled with oral mesalamine and rectal enemas. He maintained adequate follow-up with his primary gastroenterologist and was never treated with immunomodulators or biologics. Before his admission, the patient had 6 surveillance colonoscopies, annual or biennial, revealing only mildly active inflammation without dysplasia on pathology. His inpatient surveillance colonoscopy revealed mild inflammation in the distal transverse, descending, and sigmoid colon, unchanged from previous examinations. Also, a single circumferential serpentine ulcer about 10 cm in length was found in the proximal rectum and rectosigmoid colon, extending from 8 to 20 cm from the anal verge (Figure 1).
Biopsies taken from the edge and center of the ulcer revealed colonic mucosa with ulceration and sheets of large atypical B cells, most compatible with diffuse large B-cell lymphoma (germinal center B-cell subtype). The neoplastic cells were positive for CD20 and BCL6 and were negative for CD3, CD5, CD10, BCL1, BCL2, MUM1, CD30, c-MYC, CD138, and LMP1 (EBV-encoded latent membrane protein 1), with a proliferation index (Ki-67) of about 70%–80%, reflecting a highly proliferative and aggressive tumor (Figure 2). Staging thoracic, abdominal, and pelvic computed tomography (CT) scan revealed thickening of the rectum and sigmoid colon, small retroperitoneal lymph nodes, and a 1.0 × 0.8-cm mesenteric lymph node. Otherwise, no significant lymphadenopathy or organomegaly suspicious for involvement by lymphoma was seen.
A positron emission tomography–CT scan showed increased fluorodeoxyglucose (FDG) avidity involving the sigmoid colon up to the anal region with corresponding thickening on low-dose CT. Results were compatible with the patient's newly diagnosed lymphoma in the background of colitis. A mildly avid left external iliac node, suspicious for disease involvement, was also noted. No other areas of FDG uptake were found. Bone marrow biopsy was significant for variable cellular marrow (30%–60%) with trilineage hematopoiesis and no morphologic or immunophenotypic evidence of involvement by lymphoma. Given the above findings, the patient was diagnosed with primary colorectal, early-stage, diffuse large B-cell lymphoma. He was treated with 6 cycles of systemic chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisone. Posttreatment positron emission tomography–CT showed significant interval decrease in FDG uptake and wall thickness of the rectosigmoid colon. It also demonstrated interval decrease in the size and activity of the previously noted left external iliac node (Figure 3).
One year after the index colonoscopy, posttreatment colonoscopy was performed, revealing mild circumferential inflammation from the rectum to sigmoid. Notably, severe stenosis was seen in the rectum measuring 3 cm in length, extending from 10 to 13 cm from the anal verge, with ulceration and nodules within the stenosis. Hematopathology was compatible with benign lymphoid aggregate with no definite large atypical B cells identified.
Primary rectal lymphoma is very rare, accounting for only 0.05% of all primary rectal malignancies.6 It typically involves only regional lymph nodes.7 Aggressive diffuse large B-cell lymphoma accounts for 44.5% of GI NHL and is associated with a less favorable prognosis than patients with mucosa-associated lymphoid tissue.8 The treatment for primary GI lymphoma is usually chemotherapy followed by radiation when feasible, with surgery reserved for patients with life-threatening bleeding, bowel obstruction, or perforation. Complete response has been achieved in 67.5% of patients either by surgery or by chemotherapy.9
Primary GI lymphomas have been associated with Helicobacter Pylori infection, celiac disease, and autoimmune diseases such as rheumatoid arthritis and Sjögren syndrome.10,11 Although inflammatory bowel disease (IBD) confers a 1.5 to 2 times greater risk of colorectal cancer than the general population, the association with GI lymphomas is still unclear.12 Published in 2012, a prospective study revealed an increased incidence of primary intestinal lymphoma with IBD, especially middle-aged male Crohn's patients after 8 years of disease, in the setting of chronic inflammation and Epstein-Barr virus infection.13 Unlike this evidence supporting an association with primary intestinal lymphoma, studies show conflicting data regarding the association between IBD and primary colorectal lymphoma. Some studies associated IBD itself and primary colorectal lymphoma.14,15 Other studies suggest that sustained treatment with thiopurines, methotrexate, or tumor necrosis factor-α antagonists are the possible causes for primary GI lymphoma seen in patients with IBD.16–20
The association between IBD and primary colorectal lymphoma is yet to be established. Given the rarity of this phenomenon, more data should be gathered before declaring that no such association exists. One should recognize that primary colorectal lymphoma can present in long-standing UC, despite no use of immunomodulators or biologic therapies.
Author contributions: BB Mulat, K. Boroda, and H. Guddati wrote the manuscript. N. Kiyici revised the manuscript for intellectual content. BB Mulat is the article guarantor.
Financial disclosure: None to report.
Previous presentation: This case was presented at the American College of Gastroenterology Annual Scientific Meeting; October 5–10, 2018; Philadelphia, Pennsylvania.
Informed consent was obtained for this case report.
1. Keum N, Giovannucci E. Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol 2019;16(12):713–32.
2. Arnold M, Sierra M, Laversanne M, et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017;66(4):683–91.
3. Loehr WJ, Mujahed Z, Zahn FD, et al. Primary lymphoma of the gastrointestinal tract: A review of 100 cases. Ann Surg 1969;170:232.
4. Bautista-Quach MA, Ake CD, Chen M, et al. Gastrointestinal lymphomas: Morphology, immunophenotype and molecular features. J Gastrointest Oncol 2012;3(3):209–25.
5. Olszewska-Szopa M, Wróbel T. Gastrointestinal non-Hodgkin lymphomas. Adv Clin Exp Med 2019;28(8):1119–24.
6. Dodd GD. Lymphoma of the hollow abdominal viscera. Radiol Clin North Am 1990;28:771–83.
7. Dawson IM, Cornes JS, Morson BC. Primary malignant lymphoid tumours of the intestinal tract. Report of 37 cases with a study of factors influencing prognosis. Br J Surg 1961;49:80–9.
8. Koch P, del Valle F, Berdel WE, et al. Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92. J Clin Oncol 2001;19:3861.
9. Jiang C, Gu L, Luo M, et al. Primary rectal lymphoma: A case report and literature review. Oncol Lett 2015;10(1):43–4.
10. Aull MJ, Buell JF, Peddi VR, et al. MALToma: A Helicobacter pylori
-associated malignancy in transplant patients: A report from the Israel Penn International Transplant Tumor Registry with a review of published literature. Transplantation 2003;75:225.
11. Smedby KE, Akerman M, Hildebrand H, et al. Malignant lymphomas in coeliac disease: Evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma. Gut 2005;54:54.
12. Herrinton LJ, Liu L, Levin TR, et al. Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory bowel disease from 1998 to 2010. Gastroenterology 2012;143:382–9.
13. Sokol H, Beaugerie L, Maynadié M, et al. Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease. Inflamm Bowel Dis 2012;18:2063–71.
14. Palli D, Trallori G, Bagnoli S, et al. Hodgkin's disease risk is increased in patients with ulcerative colitis. Gastroenterology 2000;119:647.
15. Wong NA, Herbst H, Herrmann K, et al. Epstein-Barr virus infection in colorectal neoplasms associated with inflammatory bowel disease: Detection of the virus in lymphomas but not in adenocarcinomas. J Pathol 2003;201(2):312–8.
16. Kotlyar DS, Lewis JD, Beaugerie L, et al. Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: A meta-analysis. Clin Gastroenterol Hepatol 2015;13(5):847–58.e4.
17. Mariette X, Cazals-Hatem D, Warszawki J, et al. Lymphomas in rheumatoid arthritis patients treated with methotrexate: A 3-year prospective study in France. Blood 2002;99:3909–15.
18. Siegel CA, Marden SM, Persing SM, et al. Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's disease: A meta-analysis. Clin Gastroenterol Hepatol 2009;7:874–81.
19. Loftus EV Jr, Sandborn WJ. Lymphoma risk in inflammatory bowel disease: Influences of referral bias and therapy. Gastroenterology 2001;121:1239.
20. Lewis JD, Bilker WB, Brensinger C, et al. Inflammatory bowel disease is not associated with an increased risk of lymphoma. Gastroenterology 2001;121:1080.