Note-Splenomegaly from any cause can be associated with anemia due to increased splenic sequestration of RBCs (as well as other formed blood elements)

I. Most occurrences of splenomegaly result from one of seven basic mechanisms.

  1. Hyperplasia of cells of the RES system or lymphoid lines.
    1. Acute systemic infections, e.g. infectious endocarditis, tuberculosis, infectious mononucleosis, and histoplasmosis
    2. Autoimmune disease, e.g. Felty's Syndrome and SLE
    3. Thyrotoxicosis
  2. Passive congestive splenomegaly
    1. Usually from hepatic disease, especially cirrhosis (Banti's Syndrome) with portal hypertension.
    2. Thrombosis of the splenic or portal veins and cor pulmonale can have the same effect.
    3. Reactive hyperplasia of the RES cells of the red pulp can occur, adding further to the size of the spleen.
    4. Usually asymptomatic.
  3. Trapping of erythrocytes in red pulp sinusoids
    1. Produces congestive splenomegaly
    2. Causes include:
      1. Abnormal RBC morphology (especially hereditary spherocytosis, thalassemias, and early sickle cell anemia)
      2. Autoimmune hemolytic anemia
      3. Polycythemia vera 
  4. Splenic hematopoiesis
    1. Occurs in states of bone marrow insufficiency, most commonly resulting from myeloid metaplasia and the myelophthisic syndromes
    2. Anemia is generaly present.
  5. Malignancies
    1. Metastatic
    2. Primary to the spleen, most commonly:
      1. Lymphomas (Hodgkin's and non-Hodgkin's)-Generalized lymphadenopathy is often present
      2. Chronic lymphocytic and granulocytic leukemias-Generalized lymphadenopathy is often present
      3. Acute leukemias.
  6. Splenic infiltration
    1. Amyloidosis
    2. "Storage diseases" (e.g. Gaucher's, Neimann-Pick's).
    3. Often complicated by reactive hyperplasia of red-pulp macrophages.
  7. Non-neoplastic space-occupying lesions
    1. Hemangiomas
    2. Cysts
    3. Hematomas
    4. Iinfectious granulomas (in mycobacterial and fungal disease)
    5. Non-infectious granulomas (e.g. in sarcoidosis)
    6. Infarcts (e.g. in sickle cell anemia, due to ischemia from blockage of splenic sinusoids with deformed RBCs; also cardioemboli, usually from valvular vegetations in SBE or from mural thrombi. 99Tc-radionuclide scanning of the spleen is useful in identifying areas of infarct).

II. Clinical evaluation of a patient with splenomegaly

  1. In the setting of acute illness, splenomegaly is likely to be due to reactive hyperplasia or space-occupying lesions. The spleen tends to be soft on palpation, with blunt edges
  2. In chronic illness, the mechanisms of congestion, splenic hematopoiesis, malignancy, or infiltrative processes are more probable. A hard, sharp-edged spleen is often felt.
  3. Presentation of splenomegaly with left-upper quadrant pain and splenic tenderness suggests infarction, subcapsular hematoma, or rupture due to trauma or infection (infectious mononucleosis, typhoid fever, and malaria are known to cause splenic rupture).
  4. Asymptomatic splenomegaly is commonly due to passive congestion.
  5. Fever accompanying splenomegaly points to an infectious etiology; fever, rash, and arthralgias, however, suggest autoimmune disease.

III. Diagnosis:

  1. 99Tc-radionuclide scan--most useful in identifying infarcts
  2. Ultrasonography
  3. CT scanning
  4. Bone marrow aspiration can identify many of the causes of splenomegaly, including leukemia, lymphoma, lipid storage diseases, amyloidosis, disseminated fungal or mycobacterial disease, and metastatic cancer.
  5. In some cases, diagnostic splenectomy is the only way to identify the cause of splenomegaly.

IV. Adams' classification of the causes of splenomegaly by the degree of splenic enlargement is considered to be a useful tool in narrowing the enormous differential in hard-to-diagnose cases. This classification is noteworthy in that causes of splenomegaly which share the same mechanism (e.g. CHF, hepatic cirrhosis, and HPV obstruction) do not fall into the same category of degree of splenic enlargement.