Incidentally Detected Splenomegaly and Risk of Hematologic Cancer and Liver Disease.

Importance: Splenomegaly is often detected incidentally, but it is unknown at which spleen length or volume risk of hematologic cancer or liver disease is substantially increased, and evidence lacks on when it is beneficial to evaluate individuals with splenomegaly for underlying disease. Objective: To evaluate relative and absolute risks of hematologic cancers, cirrhosis, and liver cancer according to spleen length and volume in individuals with incidentally detected splenomegaly. Design, Setting, and Participants: This prospective cohort study used data from 2 independent general population cohorts from Denmark and the UK. Participants had computed tomography or magnetic resonance imaging scans performed as part of study procedures from January 2012 to February 2020 for Danish individuals and from April 2014 to October 2021 for UK individuals. Data were analyzed from April 2024 to November 2025. Exposures: Spleen volume and spleen length. Main Outcomes and Measures: Hematologic cancers, cirrhosis, and liver cancer during a median follow-up of 5 years after the computed tomography or magnetic resonance imaging scans. Results: Among 8459 included Danish individuals, 4821 (57.0%) were female, and the median (IQR) age at scan date was 61 (54-69) years; among 38 607 included UK individuals, 20 048 (51.9%) were female, and the median (IQR) age at scan date was 65 (58-70) years. Spleen length was measured in 8440 Danish individuals, and spleen volume was measured in 8226 Danish and 38 607 UK individuals. Relative risk of any hematologic cancer was increased for Danish individuals with spleen lengths above the 99th percentile (greater than 134 mm) compared with spleen lengths in the 26th to 74th percentile (hazard ratio, 5.11; 95% CI, 2.00-13.06) and more pronounced for spleen volume above the 99th percentile (greater than 433 mL for Danish individuals; hazard ratio, 11.08; 95% CI, 5.44-22.59; greater than 386 mL for UK individuals; hazard ratio, 11.82; 95% CI, 6.98-20.02). When studying absolute risks using clinically applicable cutoffs, 5-year risks of any hematologic cancer were moderately increased for spleen length of 130 to 139 mm or spleen volume of 400 to 499 mL. Individuals with spleen length of 140 mm or greater had even higher risk, as 5-year risks reached 23% in Danish men and 12% in Danish women 70 years and older. Individuals with spleen volume of 500 mL or greater had particularly high risk, with absolute 5-year risks for any hematologic cancer of 46% and 27% in Danish men and women 70 years and older, respectively, while 5-year risks were 21% and 18% in UK men and women 70 years and older, respectively. Furthermore, absolute 5-year risks of cirrhosis and liver cancer were substantially increased in UK individuals with spleen volume of 400 mL or greater, with 5-year risks for cirrhosis reaching 10.8% in men and 9.3% in women 70 years and older with spleen volume of 500 mL or greater. Five-year risks for liver cancer were 3.2% in men and 1.2% in women 70 years and older with spleen volume of 400 mL or greater. Conclusions and Relevance: In this cohort study, absolute 5-year risks of hematologic cancers, cirrhosis, and liver cancer were calculated according to spleen size, age, and sex. Absolute 5-year risks of any hematologic cancer were moderately increased for spleen length of 130 to 139 mm or spleen volume of 400 to 499 mL and markedly increased in individuals with spleen length of 140 mm or greater or spleen volume of 500 mL or greater, indicating that clinical workup may likely be relevant.