A Core Cohort of Adults with Unexplained Splenomegaly: Clinical, Laboratory, and Longitudinal Findings

Abstract

Objective: Splenomegaly is a frequent clinical finding associated with a wide spectrum of infectious, hematologic, hepatic, and systemic disorders. Despite comprehensive diagnostic evaluation, a subset of adult patients remains without an identifiable etiology, creating uncertainty regarding prognosis and follow-up strategies. Data describing well-characterized cohorts with unexplained splenomegaly and longitudinal follow-up remain limited.

Methods: In this retrospective observational study, adult patients with radiologically confirmed splenomegaly who were evaluated at a tertiary care center and remained without an identifiable etiology despite a comprehensive diagnostic assessment were included. Patients with identifiable causes, including hematologic malignancies, chronic liver disease, portal hypertension, infectious, autoimmune, infiltrative, or metabolic disorders, were systematically excluded. Demographic data, radiologic measurements, laboratory parameters, molecular analyses, and longitudinal follow-up findings were reviewed. Patients were stratified according to spleen size to explore the associations with hematologic parameters.

Results: The study cohort consisted of 97 patients (53.6% female), with a median age of 41 years. Median spleen size was 147 mm, and median follow-up duration was 15 months. Hematologic parameters were largely preserved across the cohort. Stratification by spleen size demonstrated a significant inverse association between spleen size and platelet count (P = .0018), while hemoglobin levels remained stable. Neutrophil counts showed modest but significant variation across spleen size categories (P = .0285). Extensive laboratory, molecular, and imaging evaluations, including bone marrow assessment in selected cases, failed to identify a definitive etiology during follow-up.

Conclusion: Adults with unexplained splenomegaly may represent a clinically indolent subgroup characterized by stable hematologic parameters and sequestration-driven cytopenic patterns rather than progressive hematologic disease. The consistent inverse relationship between spleen size and platelet count may serve as a practical marker of hypersplenic physiology. Well-defined cohorts with longitudinal follow-up are essential for refining diagnostic algorithms and guiding risk-adapted surveillance strategies.

Cite this article as: Candan O, Erdoğan B, Candan S, Keskin D, Uysal A. A core cohort of adults with unexplained splenomegaly: clinical, laboratory, and longitudinal findings. Cerrahpaşa Med J. 2026, 50, 0026, doi: 10.5152/cjm.2026.26026.