Differential diagnosis of massive splenomegaly includes myelofibrosis, chronic myelogenous leukemia, lymphoma, hairy cell leukemia, sarcoidosis, Gaucher’s disease, malaria and kala-azar.

May be seen with acquired or inherited hemolytic anemias.

May be seen in severe infections such as infective endocarditis,

sepsis, infectious mononucleosis, toxoplasmosis, leishmaniasis, schistosomiasis and fungal infections.

May be seen in systemic lupus erythematosus, rheumatoid arthritis (Felty’s syndrome), portal hypertension from cirrhosis, congestive heart failure, portal vein thrombosis, portal vein aneurysm of Budd-Chiari syndrome, amyloidosis, and splenic cysts.

Transiently, may result from treatment with IL-2.

Commonly associated with HIV/AIDS.

May be associated with early satiety, abdominal bloating, and left upper quadrant abdominal pain.

Up to 90% of total body platelet mass may be sequestered by the spleen when it is enlarged.

Spleen enlargement can be due to congestion caused by portal hypertension as seen with cirrhosis that may result in sequestration of leukocytes, erythrocytes, and platelets with resultant cytopenias.
Splaine enlargement can be seen with infiltrated processes, such as amyloidosis, sarcoidosis, myeloproliferative processes,  lymphomas, chronic leukemias, , and other hematologic cancers.
Infections caused by Epstein- Barr virus, human immunodeficiency virus, mycobacteria, iautoimmune processes such as rheumatoid arthritis and systemic lupus erythematosus can cause splenomegaly.

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