Splenic Steatopathy: A Clinical and Experimental Framework for Lipid-Associated Splenic Pathology

The spleen is usually viewed as a hematologic, vascular and immune organ, but rarely within lipid-associated disease. This review proposes splenic steatopathy as a provisional clinical and experimental framework rather than an established diagnosis or a splenic equivalent of fatty liver disease. Evidence is organized into pre-splenic drivers, intra-splenic pathology and post-splenic consequences. Upstream drivers include metabolic dysfunction-associated steatotic liver disease, obesity, severe hypertriglyceridemia, lysosomal storage disorders, drug-induced phospholipidosis, altered lymphatic lipid handling and portal-hemodynamic stress. Spleen-level findings include altered volume, attenuation, stiffness or metabolic activity; lipid-laden histiocytes; lysosomal or phospholipid storage; and immune-cell remodeling. Potential downstream relevance includes cytopenias, immune dysfunction, infection vulnerability, diagnostic redirection, cancer-associated immune biology and perioperative risk. Human evidence currently consists mainly of observational imaging studies and rare tissue reports; animal studies provide mechanistic support, while several proposed clinical links remain hypotheses. No validated diagnostic criteria, imaging thresholds or biomarkers currently exist. The framework may help distinguish unexplained splenomegaly from common mimics and, if validated, support long-term risk stratification for infection and malignancy in patients with metabolic liver disease. Future studies should prioritize spleen-specific imaging methods, tissue-imaging correlation, lipidomics, immune phenotyping and prospective outcome validation.