Viral Infections (e.g., Infectious Mononucleosis): This is often the most common cause of new splenomegaly, especially in younger patients, due to the high prevalence of viral infections such as Epstein-Barr virus (EBV), which causes infectious mononucleosis.

Chronic Liver Disease: Conditions like cirrhosis can lead to portal hypertension, causing splenomegaly due to the backflow of blood into the spleen.
Lymphoma: Both Hodgkin's and non-Hodgkin's lymphoma can cause splenomegaly as the disease progresses.
Chronic Lymphocytic Leukemia (CLL): A type of cancer that affects the blood and bone marrow, often leading to an enlarged spleen.
Myeloproliferative Neoplasms (MPNs): Conditions such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis can cause splenomegaly.

Sickle Cell Disease: Although less common, sickle cell disease can cause splenomegaly, especially in early childhood, due to the sickling of red blood cells within the spleen.
Tuberculosis: While not as common in some regions, tuberculosis (TB) can cause splenomegaly, particularly in areas where TB is endemic.
Histiocytosis: Rare conditions like Langerhans cell histiocytosis can lead to splenomegaly and are critical to diagnose due to their potential impact on prognosis and treatment.

Gaucher's Disease: A genetic disorder that leads to the accumulation of harmful substances within cells, potentially causing splenomegaly.
Amyloidosis: A condition characterized by the deposition of amyloid proteins in various organs, including the spleen, leading to its enlargement.
Sarcoidosis: Although primarily affecting the lungs, sarcoidosis can rarely cause splenomegaly due to the formation of granulomas in the spleen.
Primary Splenic Neoplasms: Tumors originating in the spleen itself are rare and can cause splenomegaly, including splenic lymphoma or angiosarcoma.