What laboratory tests should be ordered for a patient with splenomegaly (enlargement of the spleen)?

Laboratory Tests for Splenomegaly Evaluation

The essential laboratory workup for a patient with splenomegaly should include a complete blood count with differential, peripheral blood smear, comprehensive metabolic panel, and lactate dehydrogenase (LDH) levels as the initial diagnostic approach. 1

First-Line Laboratory Tests

• Complete blood count (CBC) with differential to evaluate for cytopenias or abnormal cell populations 1
• Peripheral blood smear review to identify abnormal cells suggestive of hematologic malignancy 1
• Comprehensive metabolic panel to assess liver function 1
• Lactate dehydrogenase (LDH) levels to screen for hemolysis or malignancy 1

Additional First-Line Testing Based on Clinical Suspicion

• Infectious disease workup, including viral studies for EBV, CMV, HIV, and hepatitis 1
• Flow cytometry of peripheral blood for immunophenotyping if lymphoproliferative disorder is suspected 1
• Testing for JAK2, CALR, and MPL mutations if myeloproliferative neoplasm is suspected 1

Imaging Confirmation

• Abdominal ultrasound is the recommended first-line imaging modality to confirm splenomegaly, assess splenic size and echotexture, presence of focal lesions, and evaluate liver size and appearance 1, 2
• Consider CT or MRI of the abdomen if ultrasound findings are equivocal or lymphadenopathy needs further characterization 1

Advanced Testing Based on Initial Findings

• Bone marrow aspiration and biopsy should be performed if abnormal cells are found in peripheral blood, unexplained cytopenias are present, or myeloproliferative or lymphoproliferative disorder is suspected 1, 3
• Consider lymph node biopsy if lymphadenopathy is present and lymphoma is suspected 1
• Serum tryptase and vitamin B12 levels to evaluate for myeloproliferative disorders, particularly in patients with eosinophilia 1

Disease-Specific Testing

• For suspected lymphoproliferative disorders: flow cytometry and immunophenotyping for CD markers 1
• For suspected myeloid/lymphoid neoplasms with eosinophilia: conventional cytogenetics, FISH, and/or RT-PCR to detect tyrosine kinase fusion gene rearrangements 1

Common Pitfalls to Avoid

• Delaying bone marrow evaluation in patients with concerning peripheral blood findings 1
• Assuming ITP is the cause of splenomegaly, as less than 3% of ITP patients have splenomegaly 3
• Performing routine abdominal ultrasound in infectious mononucleosis patients with deranged liver function tests is unnecessary in immunocompetent patients 4
• Failing to consider rare causes such as storage disorders like acid sphingomyelinase deficiency (ASMD), which often has a 4+ year delay in diagnosis due to its rarity 3

Referral Considerations

• Hematology referral for patients with abnormal blood counts or suspected hematologic malignancy 3
• Hepatology/gastroenterology referral if there is evidence of liver disease, portal hypertension, or ascites 3
• Infectious disease referral if infectious etiology is suspected, particularly for patients with fever and splenomegaly 3
• Rheumatology referral if autoimmune disorders are suspected 3
• Medical genetics referral if storage disorders are suspected 3