How do you evaluate for splenomegaly?

Evaluation for Splenomegaly

Begin with physical examination using percussion and palpation of the entire spleen with measurement of liver span at the mid-clavicular line, followed immediately by abdominal ultrasound to confirm splenomegaly, then proceed with targeted laboratory testing based on clinical context. 1, 2

Physical Examination Technique

Perform careful percussion and palpation of the entire liver and spleen, measuring liver span at the mid-clavicular line. 1, 2 Document the exact spleen size below the costal margin in centimeters. 2

Performance Characteristics of Physical Examination:

• Splenomegaly detection: 93% sensitivity, 57% specificity 1
• Hepatomegaly detection: 60% sensitivity, 44% specificity 1
• Physical examination alone is relatively insensitive but noninvasive, easily repeatable, and requires minimal time and cost 1
• Sonographic versions of physical examination maneuvers have greater diagnostic accuracy than traditional techniques but take longer to perform 3

Imaging Confirmation

Abdominal ultrasound is the first-line imaging modality to confirm splenomegaly. 2, 4, 5 It should assess splenic size and echotexture, presence of focal lesions, liver size and appearance, and lymphadenopathy. 4

Spleen Size Interpretation:

• 11-13 cm = mild splenomegaly 2, 4
• >13 cm = clinically significant splenomegaly warranting aggressive workup 2, 4

Advanced Imaging Indications:

• CT with intravenous contrast (sensitivity 96-100%, specificity 96-100%) should be obtained if ultrasound findings are equivocal, lymphadenopathy needs characterization, or focal splenic lesions are present 2, 5
• Contrast-enhanced ultrasound (CEUS) can be added if initial ultrasound is non-diagnostic 5
• MRI/MRCP is reserved for specific biliary concerns 5

Essential Laboratory Testing

Order these tests immediately upon confirming splenomegaly:

First-Line Laboratory Panel:

• Complete blood count with differential to identify cytopenias, leukocytosis, lymphocytosis, or abnormal cell populations 2, 4
• Peripheral blood smear review is critical to identify blasts, atypical lymphocytes, or other abnormal cells suggestive of leukemia or lymphoma 2, 4
• Comprehensive metabolic panel to assess liver function, as liver disease is one of the three most common causes of splenomegaly in the United States 2, 4, 6
• Lactate dehydrogenase (LDH) to screen for hemolysis or malignancy 2, 4

Infectious Disease Workup:

Test for EBV, CMV, HIV, and hepatitis viruses as infectious causes are among the top three etiologies in developed countries. 2, 4

Fibrosis Indices (if liver disease suspected):

Calculate AST-to-Platelet Ratio Index (APRI), fibrosis-4, and GGT-to-Platelet Ratio (GPR) to detect advanced fibrosis and portal hypertension. 1 These may be more specific than liver tests alone since they include platelet count. 1

Hematologic Malignancy Evaluation

If lymphoproliferative disorder is suspected based on CBC findings, perform flow cytometry of peripheral blood for immunophenotyping immediately. 2, 4

When to Pursue Aggressive Hematologic Workup:

• Testing for JAK2, CALR, and MPL mutations if myeloproliferative neoplasm is suspected (particularly with leukocytosis, thrombocytosis, or unexplained splenomegaly) 2, 4
• Bone marrow aspiration and biopsy is indicated when abnormal cells are found in peripheral blood, unexplained cytopenias are present, or myeloproliferative or lymphoproliferative disorder is suspected 2, 4
• Serum tryptase and vitamin B12 levels to evaluate for myeloproliferative disorders, particularly in patients with eosinophilia 4

Critical Pitfalls to Avoid

Do not delay bone marrow evaluation in patients with concerning peripheral blood findings (blasts, significant cytopenias, or abnormal cell populations). 2, 4

Do not miss lymphoma-associated hemophagocytic lymphohistiocytosis (HLH): approximately 40-70% of adult HLH cases are malignancy-associated, particularly with Hodgkin lymphoma, diffuse large B-cell lymphoma, and T-cell lymphomas. 2

Do not rely on spleen size alone to determine pathology: ultrasound can identify normal-sized spleens with lymphomatous involvement and enlarged spleens without pathology. 5

Consider PET-guided imaging and repetitive tissue sampling if lymphoma is suspected but initial biopsies are negative, as tumor-infiltrating reactive lymphocytes can mask underlying lymphoma. 2

Referral Threshold

Immediate hematology referral is warranted for:

• Peripheral smear showing blasts or abnormal lymphocytes beyond typical reactive changes 2
• Presence of cytopenias 2
• Symptomatic splenomegaly without clear etiology after initial workup 2, 4

Screening Frequency for Specific Populations

For patients with cystic fibrosis or chronic liver disease, annual physical examination for hepatosplenomegaly starting at diagnosis is recommended. 1 Abdominal ultrasound should be performed at least every 2 years in children from age 3 until late adolescence. 1

For pediatric portal vein thrombosis, start screening with Doppler ultrasound at 6 months after the event, then annually for 5 years to assess for portal hypertension, splenomegaly, and portosystemic collaterals. 1