The term splenomegaly generally denotes a palpably enlarged spleen. However, it may also refer to an enlarged spleen detected by an imaging test. Splenomegaly can be found in 3% of the normal population.  Prevalence in other populations varies according to diverse etiologies.
It is difficult to create a stepwise algorithmic approach to the patient with splenomegaly.  For example, categorization by presentations such as massive splenomegaly, isolated splenomegaly, or accompanying symptoms could be considered. However, these categories encompass diverse diagnoses. For example, thalassemia, CML, Gaucher disease, hairy cell leukemia, myelofibrosis, or malaria may present with a markedly enlarged spleen. Isolated splenomegaly is a feature of varied diagnoses such as splenic marginal lymphoma or benign splenic neoplasms. Accompanying symptoms such as fever are features of lymphomas, malaria, endocarditis, or infectious mononucleosis.
Splenomegaly is usually determined by physical exam. It may be difficult to palpate an enlarged spleen in the settings of obesity, a muscular abdominal wall, or the inability to sufficiently relax the abdominal musculature. In these cases, spleen size may need to be determined by radiographic tests. It is not uncommon for a radiologist interpreting a chest x-ray to comment that the spleen seems enlarged (usually considered an incidental finding). If splenomegaly is suspected, an ultrasound of the LUQ can be helpful, with the advantage of lack of exposure to radiation. Two further tests that may also be helpful (but do expose the patient to radiation) are CT scan and nuclear medicine studies (liver-spleen scan). CT and nuclear imaging may be complementary. A CT scan may confirm an enlarged spleen, whereas a liver-spleen scan may contribute valuable information about the presence of colloid shift, signifying portal hypertension.
In selected patients, especially those with portal vein or splenic vein thrombosis, further imaging studies may be necessary to determine whether veins draining the spleen are affected by clots (portal vein thrombosis, splenic vein thrombosis). These may be seen on MRI or Doppler venous studies.
Fine-needle aspiration of splenic lesions can be accomplished in selected cases but may expose the patient to risk of splenic rupture. It should be performed only by an experienced interventional radiologist, with surgical support in case of splenic laceration or rupture. Ultimately, some splenic lesions can be diagnosed only by splenectomy with pathologic exam of the removed organ.