Enlarged lymph nodes may be a marker of occult cancer, but accurate data on cancer risk are limited. We used population-based Danish medical registries to assess cancer risk in a cohort of patients with a first-time inpatient or outpatient hospital contact for enlarged lymph nodes during 1994-2008. Observed cancer incidences were compared with that expected in the general population. We observed 1750 cancers among 11284 patients with enlarged lymph nodes during median follow up of 4.7 years. Only 389 cases were expected. Cancer risk was 11.5% [95% confidence interval (CI): 10.9-12.1%] during the first year of follow up, corresponding to an age- and sex-standardized incidence ratio (SIR) of 21.1 (95% CI: 20.0-22.3). One-year SIRs were more than 100 times increased for head and neck cancer and lymphomas. Beyond one year of follow up, overall cancer risk remained 1.4-fold (95% CI: 1.3-1.5-fold) higher than expected, while risk of lymphoma remained six to 10 times higher. Cancer risk was also elevated among patients with other conditions known to be associated with enlarged lymph nodes, such as infections and rheumatic disorders. We conclude that enlarged lymph nodes are a marker of occult cancer and long-term risk of cancer.

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