Chapter 480 Splenomegaly

Amanda M. Brandow, Bruce M. Camitta

Clinical Manifestations

A soft, thin spleen is palpable in 15% of neonates, 10% of normal children, and 5% of adolescents. In most individuals, the spleen must be 2-3 times its normal size before it is palpable. The spleen is best examined when standing on the right side of a supine patient by palpating across the abdomen as the patient inspires deeply. A splenic edge felt more than 2 cm below the left costal margin is abnormal. An enlarged spleen might descend into the pelvis; when splenomegaly is suspected, the abdominal examination should begin at a lower starting point. Superficial abdominal venous distention may be present when splenomegaly is a result of portal hypertension. Radiologic detection or confirmation of splenic enlargement is done with ultrasonography, CT, or technetium-99 sulfur colloid scan. The latter also assesses splenic function.

Differential Diagnosis

Specific causes of splenomegaly are listed in Table 480-1. A thorough history with a focus on systemic complaints (fever, night sweats, malaise, weight loss) in combination with a complete blood count and careful review of the peripheral smear can help guide diagnosis. Unique problems are discussed next.

Table 480-1 DIFFERENTIAL DIAGNOSIS OF SPLENOMEGALY BY PATHOPHYSIOLOGY

ANATOMIC LESIONS

Cysts, pseudocysts

Hamartomas

Polysplenia syndrome

Hemangiomas and lymphangiomas

Hematoma or rupture (traumatic)

HYPERPLASIA CAUSED BY HEMATOLOGIC DISORDERS

Acute and Chronic Hemolysis*

Hemoglobinopathies (sickle cell disease in infancy with or without sequestration crisis and sickle variants, thalassemia major, unstable hemoglobins)

Erythrocyte membrane disorders (hereditary spherocytosis, elliptocytosis, pyropoikilocytosis)

Erythrocyte enzyme deficiencies (severe G6PD deficiency, pyruvate kinase deficiency)

Immune hemolysis (autoimmune and isoimmune hemolysis)

Paroxysmal nocturnal hemoglobinuria

Chronic Iron Deficiency

Extramedullary Hematopoiesis

Myeloproliferative diseases: chronic myelogenous leukemia (CML), juvenile CML, myelofibrosis with myeloid metaplasia, polycythemia vera

Osteopetrosis

Patients receiving granulocyte and granulocyte-macrophage colony–stimulating factors

INFECTIONS^†

Bacterial

Acute sepsis: Salmonella typhi, Streptococcus pneumoniae, Haemophilus influenzae type b, Staphylococcus aureus

Chronic infections: infective endocarditis, chronic meningococcemia, brucellosis, tularemia, cat-scratch disease

Local infections: splenic abscess (S. aureus, streptococci, less often Salmonella species, polymicrobial infection), pyogenic liver abscess (anaerobic bacteria, gram-negative enteric bacteria), cholangitis

Viral*

Acute viral infections, especially in children

Congenital cytomegalovirus (CMV), herpes simplex, rubella

Hepatitis, A, B, and C; CMV

Epstein-Barr virus (EBV)

Viral hemophagocytic syndromes: CMV, EBV, HHV-6

Human immunodeficiency virus (HIV)

Spirochetal

Syphilis, especially congenital syphilis

Leptospirosis

Rickettsial

Rocky Mountain spotted fever

Q fever

Typhus

Fungal/Mycobacterial

Miliary tuberculosis

Disseminated histoplasmosis

South American blastomycosis

Systemic candidiasis (in immunosuppressed patients)

Parasitic

Malaria

Toxoplasmosis, especially congenital

Toxocara canis, Toxocara cati (visceral larva migrans)

Leishmaniasis (kala-azar)

Schistosomiasis (hepatic-portal involvement)

Trypanosomiasis

Fascioliasis

IMMUNOLOGIC AND INFLAMMATORY PROCESSES*

Systemic lupus erythematosus

Rheumatoid arthritis

Mixed connective tissue disease

Systemic vasculitis

Serum sickness

Drug hypersensitivity, especially to phenytoin

Graft vs host disease

Sjögren syndrome

Cryoglobulinemia

Amyloidosis

Sarcoidosis

Autoimmune lymphoproliferative syndrome (ALPS)

Post-transplant lymphoproliferative disease (PTLD)

Large granular lymphocytosis and neutropenia

Histiocytosis syndromes

Hemophagocytic syndromes (nonviral, familial)

MALIGNANCIES

Primary: leukemia (acute, chronic), lymphoma, angiosarcoma, Hodgkin disease

Metastatic

STORAGE DISEASES

Lipidosis (Gaucher disease, Niemann-Pick disease, infantile GM₁ gangliosidosis)

Mucopolysaccharidoses (Hurler, Hunter-type)

Mucolipidosis (I-cell disease, sialidosis, multiple sulfatase deficiency, fucosidosis)

Defects in carbohydrate metabolism: galactosemia, fructose intolerance

Sea-blue histiocyte syndrome

CONGESTIVE*

Heart failure

Intrahepatic cirrhosis or fibrosis

Extrahepatic portal (thrombosis), splenic, and hepatic vein obstruction (thrombosis, Budd-Chiari syndrome)

G6PD, glucose-6-phosphate dehydrogenase; HHV-6, human herpesvirus 6.

* Common.

^† Chronic or recurrent infection suggests underlying immunodeficiency.

From Kliegman RM, Greenbaum LA, Lye PS: Practical strategies in pediatric diagnosis and therapy, ed 2, Philadelphia, 2004, Elsevier, p 347.

Pseudosplenomegaly

Abnormally long mesenteric connections may produce a wandering or ptotic spleen. An enlarged left lobe of the liver, a left upper quadrant mass, or a splenic hematoma may be mistaken for splenomegaly. Splenic cysts may contribute to splenomegaly or mimic it; these may be congenital (epidermoid) or acquired (pseudocyst) after trauma or infarction. Cysts are usually asymptomatic and are found on radiologic evaluation. Splenosis after splenic rupture or an accessory spleen (present in 10% of normal individuals) may also mimic splenomegaly; most are not palpable. The syndrome of congenital polysplenism includes cardiac defects, left-sided organ anomalies, bilobed lungs, biliary atresia, and pseudosplenomegaly (Chapter 425.11).

Hypersplenism

Increased splenic function (sequestration or destruction of circulating cells) results in peripheral blood cytopenias (thrombocytopenia, neutropenia, anemia), increased bone marrow activity, and splenomegaly. It is usually secondary to another disease and may be cured by treatment of the underlying condition or, if absolutely necessary, moderated by splenectomy.

Congestive Splenomegaly (Banti Syndrome)

Splenomegaly may result from obstruction in the hepatic, portal, or splenic veins leading to hypersplenism. Wilson disease (Chapter 349.2), galactosemia (Chapter 81.2), biliary atresia (Chapter 348), and α-1-antitrypsin deficiency (Chapter 349.6) may result in hepatic inflammation, fibrosis, and vascular obstruction. Congenital abnormalities (absence or hypoplasia) of the portal or splenic veins may cause vascular obstruction. Septic omphalitis or thrombophlebitis (spontaneous or as a result of umbilical venous catheterization in neonates) may result in secondary obliteration of these vessels. Splenic venous flow may be obstructed by masses of sickled erythrocytes leading to infarction. When the spleen is the site of vascular obstruction, splenectomy cures hypersplenism. However, since obstruction usually is in the hepatic or portal systems, portacaval shunting may be more helpful, because both portal hypertension and thrombocytopenia contribute to variceal bleeding.

Bibliography

Aslanidou E, Fotoulaki M, Tsitouridis I, et al. Partial splenic embolization: successful treatment of hypersplenism, secondary to biliary cirrhosis and portal hypertension in cystic fibrosis. J Cyst Fibros. 2007;6:212-214.

Hilmes MA, Strouse PJ. The pediatric spleen. Semin in Ultrasound CT MR. 2007;28:3-11.

Kumar PV, Monabati A, Raseki AR, et al. Splenic lesions: FNA findings in 48 cases. Cytopathology. 2007;18:151-156.

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Subhasis RC, Rajiv C, Kumar SA, et al. Surgical treatment of massive splenomegaly and severe hypersplenism secondary to extrahepatic portal venous obstruction in children. Surg Today. 2007;37:19-23.