Risks for lymphoma and gastrointestinal carcinoma in patients with newly diagnosed adult-onset celiac disease: Consequences for follow-up: Celiac disease, lymphoma and GI carcinoma

Abstract

Background: The association between celiac disease (CD) and the development of lymphoid and gastrointestinal (GI) malignancies have been reported. However, data are scarce yet needed to develop evidence-based follow-up programs.

Objective: The objective of this article is to assess relative (RR) and absolute risks of lymphoma and GI carcinoma for newly diagnosed patients.

Methods: A case-control design to determine RR was performed with cases (lymphoma or GI carcinoma) and controls (melanoma or basal cell carcinoma) diagnosed 1994-2014, retrieved from the Dutch nationwide population-based pathology database (PALGA). Within this population, individuals with histologically proven CD before or simultaneously diagnosed with the malignancy were identified.

Results: A total of 349/301,425 cases (0.1%) and 282/576,971 (0.05%) controls were diagnosed with CD. Risk of T-cell lymphoma, predominantly enteropathy-associated T-cell lymphoma (EATL), was strongly associated with CD diagnosis (RR = 35.8 (95% CI 27.1-47.4)). Although most often synchronously diagnosed, T-cell lymphoma RR ≥ 1 year after CD diagnosis was still elevated (RR = 12.7 (95% CI 7.6-21.3)). Other CD-associated malignancies were small bowel adenocarcinoma (RR = 11.9 (95% CI 8.2-17.2)) and esophageal squamous cell carcinoma (RR = 3.5 (95% CI 2.1-5.8)). Absolute risks were relatively low. Other types of lymphomas and GI carcinomas were not associated with CD.

Conclusion: Increased risk for specific malignancies in CD should alert physicians for EATL (both intestinal and extraintestinal) and small bowel adenocarcinoma in patients with CD diagnosed at age ≥ 50 years.

Keywords: Celiac disease; enteropathy-associated T-cell lymphoma; follow-up; small bowel adenocarcinoma; squamous cell carcinoma.

Figure 1.

Selection process of case and control patients. BCC: basal cell carcinoma; CA: carcinoma, CD: celiac disease; GI: gastrointestinal; NHL: non-Hodgkin lymphoma; NOS: not otherwise specified; PALGA: Dutch nationwide population-based pathology database.

Figure 2.

Absolute risk of malignancies until the age of 80 years by current age or age at time of celiac disease (CD) diagnosis. The risks present the risk for developing the malignancy of interest, i.e. T-cell lymphoma ((a) and (b)), small bowel adenocarcinoma ((c) and (d)) and esophageal squamous cell carcinoma (SCC) (2(e) and (f)), by age 80 years for patients cancer free and diagnosed with CD at age 50, 55, etc. years. As reference, we added the risk for colorectal carcinoma at current age in the general population. Example: The risk of being diagnosed with a T-cell lymphoma from CD diagnosis until the age of 80 years (including synchronous diagnosis) for a male when CD is diagnosed at the age of 60 is 3.6% (95% confidence interval 2.4%–5.3%). The risk for a male without CD developing a T-cell lymphoma between ages 60 and 80 years is 0.1%. The risk for a male from the general population developing colorectal adenocarcinoma between the age of 60 to 80 years is 5.1%.

Figure 3.

Descriptive characteristics of malignancies associated with celiac disease (CD). (a) Time between celiac disease and various malignancies associated with CD. Each dot represents an individual event. ALCL: anaplastic large cell lymphoma; CD: malignancy diagnosed three months before until three months after celiac CD diagnosis; EATL: enteropathy-associated T-cell lymphoma; PTCL: peripheral T-cell lymphoma. (b) Sites of enteropathy-associated T-cell lymphoma involvement. Total n (EATL) = 128. NOS: not otherwise specified.