Introduction: The Challenge of the Radiographic Incidentaloma
In the era of high-resolution diagnostic imaging, clinicians are increasingly confronted with the incidentaloma—an unexpected finding discovered during a scan performed for an unrelated purpose. Among these, splenomegaly remains one of the most clinically ambiguous findings. While an enlarged spleen can be a benign anatomical variant or a response to transient infection, it is also a hallmark of serious underlying pathology, including myeloproliferative neoplasms, lymphomas, and advanced liver disease.
Until recently, the clinical community lacked robust, prospective data to guide the management of incidentally detected splenomegaly. At what specific length or volume does a finding transition from a radiological curiosity to a mandate for hematological or hepatological evaluation? A landmark study published in JAMA Oncology by Juhl et al. (2026) provides much-needed clarity, offering precise absolute and relative risk assessments based on two massive general population cohorts.
Study Design and Methodology
This prospective cohort study leveraged data from two independent populations: a Danish cohort (8,459 individuals) and a UK cohort (38,607 individuals). Participants underwent computed tomography (CT) or magnetic resonance imaging (MRI) scans between 2012 and 2021. The researchers meticulously measured spleen length and volume, tracking participants for a median follow-up of five years to observe the development of hematologic cancers, cirrhosis, and liver cancer.
The Danish cohort (median age 61) provided data on both spleen length and volume, while the UK cohort (median age 65) focused primarily on spleen volume. This dual-cohort approach allowed the researchers to validate their findings across different populations and measurement modalities, enhancing the generalizability of the results.
Quantifying the Risk: Relative and Absolute Findings
Relative Risk of Hematologic Cancer
The study found a striking correlation between spleen size and the risk of hematologic malignancy. In the Danish cohort, individuals with a spleen length exceeding the 99th percentile (greater than 134 mm) faced a fivefold increase in the relative risk of developing a hematologic cancer compared to those in the 26th to 74th percentile (Hazard Ratio [HR], 5.11; 95% CI, 2.00-13.06).
When spleen volume was analyzed, the associations were even more pronounced. For individuals with a spleen volume above the 99th percentile—defined as >433 mL in the Danish cohort and >386 mL in the UK cohort—the relative risk surged more than tenfold. The hazard ratios were 11.08 in the Danish group and 11.82 in the UK group, suggesting that spleen volume may be a more sensitive predictor of occult malignancy than length alone.
Absolute 5-Year Risks: A Practical Clinical Guide
For the practicing clinician, absolute risk is often more informative than relative risk. The study provided clear 5-year absolute risk percentages stratified by age, sex, and spleen size:
1. Spleen Length 130–139 mm or Volume 400–499 mL: These individuals showed a moderate increase in risk. While not necessarily requiring immediate invasive workup in all cases, these findings suggest the need for careful clinical monitoring.
2. Spleen Length ≥140 mm: The risk profile shifts dramatically at this threshold. In Danish men aged 70 and older, the 5-year risk of any hematologic cancer reached 23%, while in women of the same age, it was 12%.
3. Spleen Volume ≥500 mL: This represents the highest risk category. For Danish men aged 70 or older, the absolute 5-year risk of hematologic cancer was a staggering 46%. In the UK cohort, the risk for the same demographic was 21%. Even in younger populations, these volumes indicated a substantial clinical burden.
The Liver Connection: Cirrhosis and Hepatocellular Carcinoma
Beyond hematologic concerns, the study highlighted the importance of splenomegaly as a sentinel marker for liver disease. In the UK cohort, individuals with a spleen volume of 400 mL or greater demonstrated a significantly higher risk for cirrhosis and liver cancer.
Specifically, for those with a spleen volume ≥500 mL, the 5-year risk for cirrhosis reached 10.8% in men and 9.3% in women aged 70 and older. Furthermore, the risk of liver cancer was 3.2% in men aged 70+ with a spleen volume of at least 400 mL. These findings underscore that splenomegaly should not only trigger a hematologic review but also a thorough assessment of hepatic health, including liver function tests and potentially non-invasive fibrosis imaging.
Expert Commentary: Interpreting the Data
The implications of this study are twofold. First, it validates the common clinical intuition that a larger spleen is more concerning, but it does so with rigorous statistical backing. Second, it suggests that radiology reports should ideally include spleen volume where possible, as it appears to be a more robust predictor of disease than simple linear measurement.
The difference in risk between men and women, as well as the significant increase in risk with age, suggests that clinical workup should be tailored. A 140 mm spleen in a 75-year-old male carries a much higher immediate threat than the same finding in a 40-year-old female, though both warrant attention.
One limitation noted by researchers is the potential for healthy volunteer bias, particularly in the UK Biobank cohort, which might explain the lower absolute risk percentages compared to the Danish cohort. However, the consistency in relative risks across both populations reinforces the validity of the thresholds identified.
Clinical Recommendations: When to Act
Based on the findings of Juhl et al., a structured approach to incidentally detected splenomegaly is recommended:
1. Threshold for Concern: Any spleen length ≥130 mm or volume ≥400 mL should be noted as a potentially significant finding.
2. Mandate for Workup: A spleen length ≥140 mm or a volume ≥500 mL should trigger a formal clinical evaluation. This should include a detailed history (evaluating for B-symptoms like night sweats or weight loss), physical examination for lymphadenopathy, a complete blood count with peripheral blood smear, and liver function assessment.
3. Referral: Patients meeting the high-risk thresholds, particularly older males, should be prioritized for hematology or hepatology consultation.
Conclusion
Incidentally detected splenomegaly is a frequent clinical dilemma. By providing concrete 5-year absolute risk data, this study moves the field toward a more evidence-based triage system. Recognizing that nearly half of elderly men with a spleen volume over 500 mL may develop a hematologic cancer within five years transforms the way we view ‘incidental’ findings. These measurements are not just anatomical descriptions; they are powerful prognostic indicators that demand clinical action.
