A Comprehensive Investigation into the Underlying Etiology of Massive Splenomegaly

Background: Massive Splenomegaly is commonly encountered in routine hematology practice. However, a comprehensive analysis of the underlying pathologies driving splenomegaly is lacking and few studies have investigated the epidemiology of this finding. In many cases, splenomegaly is detected incidentally in asymptomatic patients. The numerous potential causes of massive splenomegaly can pose a challenge when evaluating a patient. This study aims to identify the most prevalent etiologies among patients who initially exhibited massive splenomegaly. The objective is to determine outcomes and provide insights to guide clinical decision-making.

Methods: We undertook a retrospective cohort study at the Oregon Health & Science University in Portland OR, including adults between ages of 18-89 years who had documented splenomegaly on their medical problem list or imaging within the last 10 years (January 2012-June 2023). Massive splenomegaly was defined as spleen measuring greater than 20 cm in its largest dimension. The presence of massive splenomegaly was confirmed by direct review of the medical record and available imaging modalities including ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI). Splenic pathology results and splenectomy outcomes were obtained if available.

Results: We identified 224 patients with massive splenomegaly with a mean age of 52.6 years. Of the 224 patients, 113 (50.4%) were ultimately found to have a hematological diagnosis underlying the splenomegaly, while 93 (41.5%) ultimately had a diagnosis related to liver dysfunction. 18 (8%) were idiopathic or representative of a rare disease. Among those with hematologic diagnosis, myeloproliferative neoplasms accounted for 40.7% followed by Leukemia (23%) and lymphoma (21.2%). Among those ultimately diagnosed with some form of liver pathology driving their presentation, cirrhosis was the most common etiology, encompassing 79.6% while the remaining 20.4% had non-cirrhotic pathology including non-alcoholic fatty liver disease without overt cirrhosis (NAFLD), Primary sclerosing cholangitis (PSC), Autoimmune hepatitis or others. Chronic Hepatitis C related cirrhosis (32.3%) followed by Non-alcoholic Steatohepatitis (NASH) related cirrhosis (19.4%) were the most common forms of cirrhosis. Of the 18 cases not specifically related to hematologic or liver disease, 5 (2.2%) were of an unknown etiology, 6 (2.7%) were due to solid organ cancers or metastases and 3 (1.3%) appeared to be related to sequalae of Cystic Fibrosis. The remaining 4 cases were attributed to singular cases of Type 2 Glycogen Storage Disease causing cirrhosis, Autosomal Recessive Polycystic Kidney Disease, Felty Syndrome, and sequelae of motor vehicle accident, respectively.

Conclusion: This large cohort of patients with massive splenomegaly offers many insights into the epidemiology of the underlying differential diagnosis. We found that approximately half of cases involved a hematologic disorder with myeloproliferative neoplasms being the most common etiology. Liver pathology was also a common driver, accounting for approximately 40% of cases. These findings underscore the necessity for appropriate diagnostic workup to better address the diverse etiologies contributing to massive splenomegaly.