Exploring the Association between Lymphoma and Inflammatory Bowel Disease in an Inner-City Academic Institution

Introduction:

The incidence of lymphoma has been increasing over the past several decades, with data showing an estimated annual percentage change of 0.56%. There is evidence suggesting a link between inflammatory bowel disease (IBD) and the development of lymphoma. Over the past two decades, the cumulative incidence of lymphoma has notably increased in patients with Crohn's disease (CD). This trend aligns with the growing use of immunomodulators and biologics. In contrast, this trend has not yet been observed in patients with ulcerative colitis (UC).

Methods:

Data was extracted from electronic health records of patients with an Internal Classification of Disease (ICD) 9 or ICD10 code for Inflammatory Bowel Disease seen between 2012 and 2023 at one of two major tertiary hospital systems in the Southeastern United States. Patients were then categorized into this retrospective, observational study comparing patients with ICD9 or ICD10 codes for lymphoma among the patients with IBD. Statistical analysis was performed on Stata software using the Chi-square test. Patient characteristics such as age, sex, and race, as well as the lymphoma subtype, were analyzed. When analyzing the subset of IBD patients who had comorbid lymphoma, this was further stratified into patients with non-Hodgkin lymphoma and Hodgkin lymphoma. Further sub-stratification was done in the patients with non-Hodgkin lymphoma into “diffuse large B-cell lymphoma,” “marginal zone lymphoma,” “T-cell lymphoma,” “follicular lymphoma,” and “other unspecified type of non-Hodgkin lymphoma.”

Results:

125 out of 6810 UC patients, whereas 160 out of 9577 CD patients had comorbid lymphoma (1.84% vs 1.67%, respectively; p=0.43). Of the 285 patients with diagnoses of both IBD and lymphoma, 40% underwent flow cytometry, and 54% underwent colonoscopy at our institution. In terms of the subset of lymphoma, 0.17% of patients with UC had Hodgkin lymphoma, with the remaining 1.67% having non-Hodgkin lymphoma. Similarly, 0.15% of patients with CD had Hodgkin lymphoma, with the remaining 1.52% having non-Hodgkin lymphoma.

Of the UC with non-Hodgkin lymphoma cohort (1.67%), 0.62% were classified as diffuse large B-cell lymphoma, 0.15% as marginal zone lymphoma, 0.19% as T-cell lymphoma, 0.02% as follicular lymphoma, and 0.79% with other unspecified type of non-Hodgkin lymphoma. Of the CD with non-Hodgkin lymphoma cohort (1.52%), 0.56% were classified as diffuse large B-cell lymphoma, 0.12% as marginal zone lymphoma, 0.11% as T-cell lymphoma, 0.02% as follicular lymphoma and 0.71% as other unspecified type of non-Hodgkin lymphoma.

Conclusion:

This analysis examines the relationship between IBD and lymphoma at a major tertiary hospital system. In our study, the overall prevalence of lymphoma in patients with co-existing IBD was 1.7%. Previous studies have not found a strong link between UC and lymphoma, but a known correlation exists between Crohn's Disease and lymphoma. Although our data did not reach statistical significance, there is clinical utility in knowing there is a higher prevalence of co-existence of lymphoma and UC compared to CD in this population. One must, however, take into consideration that some patients with Crohn's disease may be initially misdiagnosed, with the most common misdiagnosis being that of ulcerative colitis.

In terms of the type of lymphoma, non-Hodgkin lymphoma was far more common in these patients compared to Hodgkin lymphoma, which is expected. Diffuse large B-cell lymphoma was the most common subtype of non-Hodgkin lymphoma, with prevalence rates similar to patients without IBD. However, a significant proportion of these patients were labeled as “other unspecified type of non-Hodgkin lymphoma,” which could have impacted actual sub-stratification. Hodgkin lymphoma made up approximately ten percent of these patients with both IBD and lymphoma, which is in keeping with the general population.

While the overall prevalence of lymphoma in patients with IBD remains low, the incidence is increasing. A higher index of suspicion for lymphoma is required in all patients with a pre-existing diagnosis of IBD, especially in patients who are on immunosuppressive therapies associated with an increased risk of lymphoma. Currently, no screening guidelines exist for lymphoma. Further studies are needed to develop clinical guidance in this area.

No relevant conflicts of interest to declare.