Background
Splenomegaly is defined as enlargement of the spleen, measured by size or weight. In the past, splenomegaly was a clinical finding, but in recent years, imaging studies have also helped to assess for or confirm mild splenomegaly.
The spleen is a functionally diverse organ with active roles in immunosurveillance and hematopoiesis. It lies within the left upper quadrant of the peritoneal cavity and abuts ribs 9-12, the stomach, the left kidney, the splenic flexure of the colon, and the tail of the pancreas.
In adults, a normal spleen weighs 70 to 200 g and has a craniocaudal length of up to 12 cm. A spleen weight of 400-500 g indicates splenomegaly, while a weight of more than 1000 g is labelled as massive splenomegaly. Poulin et al defined splenomegaly as moderate if the largest dimension is 11-20 cm, and severe if the largest dimension is greater than 20 cm. [1]
Importantly, while lymph nodes can be thought of as the draining secondary lymphoid organs of the respective anatomic compartments via afferent lymphatics (ie the lung drains into the mediastinum), the spleen can be thought of as the primary draining secondary lymphoid organ of the systemic circulatory system with the afferent inflow occurring via the splenic artery instead of afferent lymphatics. [2]
For discussion of splenomegaly in children, see Pediatric Splenomegaly. For discussion of hyperreactive malarial syndrome, see Tropical Splenomegaly Syndrome.
Pathogenesis
Many of the mechanisms leading to splenomegaly are exaggerated forms of normal splenic function. The most important normal functions of the spleen are as follows: [3]
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Filtering both abnormal and senescent red blood cells (RBCs), as well as particulates and microorganisms
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Immune function – Providing an interface between adapative and innate immunity, with synthesis of immunoglobulin M (IgM), properdin (an essential component of the alternate pathway of complement activation), and tuftsin (an immunostimulatory tetrapeptide)
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Erythropoiesis, particularly early in fetal life and as an adaptive response to bone marrow failure
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Providing a resevoir of blood cells, including RBCs and platelets that can be utilized under stress
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Iron metabolism
Eichner et al proposed an early taxonomy for the pathophysiology of splenomegaly as follows [4] :
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Immune response work hypertrophy
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RBC work hypertrophy
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Congestive splenomegaly
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Infiltrative splenomegaly
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Neoplastic splenomegaly
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Miscellaneous
Immune response work hypertrophy
Acute enlargement of the spleen due to various infections or inflammatory processes results from an increase in the defense activities of the organ. The demand for increased antigen clearance from the blood may lead to increased numbers of reticuloendothelial cells in the spleen and stimulate accelerated antibody production, with resultant lymphoid hyperplasia. Examples include splenomegaly from subacute bacterial endocarditis, lupus, and Felty syndrome, and from viral infections such as Epstein-Barr virus–induced mononucleosis.
Red blood cell work hypertrophy
A high rate of removal of abnormal blood cells from the circulation (either cells with intrinsic defects or cells coated with antibody) is the usual source of RBC work hypertrophy. This occurs in thalassemia major, hereditary spherocytosis, and pyruvate kinase deficiency. Another mechanism for splenomegaly in thalassemia major is extramedullary hematopoiesis as a result of intramedullary hemolysis.
Congestive splenomegaly
Cirrhosis with portal hypertension, splenic vein occlusion (thrombosis), or chronic heart failure (CHF) with increased venous pressure causes congestive splenomegaly. In patients receiving oxaliplatin-based chemotherapy, splenomegaly may result from hepatic sinusoidal obstructive syndrome caused by the chemotherapy; use of bevacizumab may reduce the splenomegaly in these cases. [5]
Infiltrative splenomegaly
Infiltrative splenomegaly is the result of engorgement of macrophages with indigestible materials. It may be seen in conditions such as sarcoidosis, Gaucher disease, and amyloidosis.
Neoplastic splenomegaly
Hematologic neoplasms make up the bulk of cancer-related causes of splenomegaly. This category includes both lymphoproliferative neoplasms (eg, lymphomas, leukemias) as well as myeloproliferative ones (eg, chronic myeloid leukemia, primary myeloid fibrosis, essential thrombocythemia, polycythemia vera). Rarely, sarcoma can occur in the spleen, or primary solid tumors can metastasize to the spleen.
Miscellaneous
Additional causes of splenomegaly include trauma, splenic cysts, hemangiomas, abscesses, and certain drugs (eg, Rho[D] immune globulin).
Splenic filtering of blood-borne pathogens, especially encapsulated organisms, may lead to abscess formation. Because many splenic abscesses may be indolent in presentation, splenic size may increase as the abscess enlarges. This is a relatively uncommon, but important, process to recognize and treat.
Acute splenic sequestration crisis (ASSC) is a major cause of morbididty and mortality in children with sickle cell disease and other hereditary hemolytic anemias. ASSC is characterized by sudden enlargement of the spleen due to trapping of a significant proportion of the blood volume, rapid drop in the hematocrit with hypovolemia, and thrombocytopenia. ASSC typically occurs before age 5 years of age, and the median age at first episode is less than 2 years; however, ASSC may occur at a much later age in patients receiving hydroxyurea, possibly because this treatment results in longer preservation of spleen perfusion and function. [6]
Epidemiology
In the United States, one large series reported a palpable spleen in 2% of patients and another in 5.6% of patients. [7] Tropical splenomegaly syndrome occurs most often in persons indigenous to the malarial belt of tropical Africa and in visitors to that region.
Race-, sex-, and age-related demographics
No race predilection is recognized for splenomegaly. However, note that Blacks may have hemoglobin SC disease, a disorder related to sickle cell disease. Unlike sickle cell disease, which results in a small, autoinfarcted spleen, patients with hemoglobin SC disease may have splenomegaly that accompanies their pigment gallstones.
Tropical splenomegaly syndrome (or hyperactive malarial syndrome) has a female-to-male incidence ratio of 2:1. Otherwise, no sex predilection is documented for splenomegaly.
The capsules of older spleens are much thinner than their younger counterparts. The combination of capsular thinning with increased spleen weight and size makes splenic injury more common in elderly persons. These factors account for the increased likelihood of splenectomy for trauma in this subgroup.
Prognosis
The prognosis for patients with splenomegaly is usually excellent and not substantially different from age-matched controls, but it is impacted by the underlying disease state rather than the presence of splenomegaly or the postsplenectomy state.
A prospective study of incidentally detected splenomegaly reported a correlation between spleen size and excess risk for hematologic cancer and liver disease. [8] Results of the study, which used data on approximately 40,000 adults from general population cohorts from Denmark and the United Kingdom, included the following:
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Absolute 5-year risk for any hematologic cancer was moderately increased for spleen length of 130-139 mm or spleen volume of 400-499 mL.
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Risk of hematologic cancer was even greater in individuals age 70 years and older with spleen length of ≥140 mm, reaching 23% in Danish men and 12% in Danish women.
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Risk was particularly high in individuals age 70 years and older with spleen volume of ≥ 500 mL, reaching 46% in Danish men and 27% in Danish women
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Absolute 5-year risks of cirrhosis and liver cancer were substantially increased in UK individuals with spleen volume of ≥400 mL
Morbidity and mortality
Morbidity and mortality in cases of splenomegaly principally stem from associated disease states or surgical procedures, rather than from the splenomegaly itself. The rates for morbidity and mortality vary widely and relate to the presence or absence of comorbidities, hemorrhage, and organ failure.
Patients with enlarged spleens are more likely to have splenic rupture from blunt abdominal or low thoracic trauma. These patients are more likely to be exposed to emergent operative splenectomy and its attendant risks.
