The spleen is part of the hepatoportal system and is the largest organ of the lymphatic system. Functions of the spleen include removing aging or abnormal blood cells, storing platelets and red blood cells, and producing and distributing immune cells and antibodies.¹ The spleen is a major site of blood production outside of the bone marrow, especially during times of stress.^1–3 Several general pathophysiologic mechanisms cause splenic enlargement. Hyperplasia and hypertrophy cause splenomegaly due to increased function of the spleen. Infiltrative processes can cause accumulation of abnormal cells in the spleen, which can be malignant, benign, or caused by glycogen storage disorders. Congestive processes result in blood pooling due to blockage of venous outflow.^2,3 These mechanisms can lead to transient splenomegaly, such as with blood loss, infection, and during pregnancy, but in these cases the spleen returns to normal size after the condition resolves.^2,4

In the United States, the most common etiologies of splenomegaly are chronic liver disease, malignancies, and infections.³ Malignancies—usually leukemia or lymphoma—are common causes of splenomegaly, seen in close to one-third of affected patients.³ As many as one-third of patients with splenomegaly have cirrhosis, where abnormal liver parenchyma leads to congestive splenomegaly.^3,5 Several infections can lead to splenomegaly. In the United States, infectious mononucleosis is a common etiology of splenomegaly in adolescents and young adults.³ Splenomegaly is common in patients with HIV, as a response to the virus or because of secondary infections.⁶ People who are born in tropical regions, global travelers, and military personnel deployed to tropical regions are at risk for parasitic infections that can lead to splenomegaly, most commonly schistosomiasis and chronic malaria.⁷ Common disorders associated with splenomegaly are shown in Table 1.^2,3

Splenomegaly is a common finding in college freshman in North America, with rates of up to 3%, because of the high prevalence of infectious mononucleosis.³ Splenomegaly can affect up to 80% of people in tropical areas where malaria and schistosomiasis are endemic.⁷ People who have recently immigrated from overseas, children who are adopted from endemic areas, refugees, and travelers with splenomegaly often have chronic parasitic infections.⁷

Pertinent History

Personal and family history can suggest the etiology of splenomegaly (Table 2^3,8–17). Early satiety and fullness in the left upper quadrant can be due to an enlarged spleen.^2,8 Family history of malignancies, liver disease, lipid storage disorders, or hematologic diseases can suggest an etiology for splenomegaly.^2,8 Personal history may contain risk factors for splenomegaly, including alcohol consumption, intravenous drug use, and high-risk sexual behavior. Immigration from or travel to tropical areas increases the risk of infectious diseases such as malaria or schistosomiasis. Medical history of cancer, hematologic disorders, heart failure, or chronic liver disease increases the chance of splenomegaly (Table 1^2,3). Recent flulike symptoms, sore throat, abdominal pain, fever, weight loss, night sweats, and fatigue can suggest infection or malignancies, whereas bleeding, easy bruising, pallor, jaundice, and petechial rashes can be attributable to hematologic etiologies.