What lab work should be ordered to evaluate splenomegaly?

Laboratory Workup for Splenomegaly Evaluation

The essential laboratory workup for splenomegaly should include a complete blood count with differential, comprehensive metabolic panel, lactate dehydrogenase, peripheral blood smear review, and abdominal ultrasound to confirm the diagnosis and begin investigating the underlying cause. 1

Initial Laboratory Testing

• Complete blood count (CBC) with differential to evaluate for cytopenias, leukocytosis, or abnormal cell populations that may suggest hematologic disorders 1, 2
• Peripheral blood smear review to identify abnormal cells suggestive of hematologic malignancy, including assessment for rouleaux formation 1, 2
• Comprehensive metabolic panel with liver function tests to assess for hepatic causes of splenomegaly 1, 3
• Lactate dehydrogenase (LDH) to screen for hemolysis or malignancy 1, 2
• Serum tryptase and vitamin B12 levels to evaluate for myeloproliferative disorders, particularly in patients with eosinophilia 2

Additional First-Line Testing Based on Clinical Suspicion

• Infectious disease workup including viral studies for EBV, CMV, HIV, and hepatitis testing if infection is suspected 1, 2
• Serum protein electrophoresis (SPEP) and immunofixation to evaluate for monoclonal gammopathies, especially when rouleaux formation is observed on peripheral smear 4
• Serum free light chain assay and quantitative immunoglobulins if multiple myeloma is suspected 4
• Flow cytometry of peripheral blood for immunophenotyping if lymphoproliferative disorder is suspected 1, 2
• Testing for JAK2, CALR, and MPL mutations if myeloproliferative neoplasm is suspected 1

Imaging Studies

• Abdominal ultrasound is the recommended first-line imaging modality to confirm splenomegaly, assess splenic size and echotexture, and evaluate for focal lesions 1, 5
• CT or MRI of the abdomen should be considered if ultrasound findings are equivocal or if lymphadenopathy needs further characterization 1, 6

Advanced Diagnostic Testing

• Bone marrow aspiration and biopsy with immunohistochemistry, cytogenetics, and molecular testing is indicated when:
  • Abnormal cells are found in peripheral blood
  • Unexplained cytopenias are present
  • Myeloproliferative or lymphoproliferative disorder is suspected 1, 2
• Conventional cytogenetics, FISH, and/or RT-PCR to detect tyrosine kinase fusion gene rearrangements in cases of suspected myeloid/lymphoid neoplasms with eosinophilia 2
• Stool ova and parasites testing and gastrointestinal PCR if parasitic infection is suspected, particularly in patients with travel history to endemic areas 2, 5

Disease-Specific Testing

• For suspected myeloproliferative disorders: JAK2, CALR, and MPL mutation analysis 1, 6
• For suspected lymphoproliferative disorders: flow cytometry and immunophenotyping for CD markers 2, 1
• For suspected autoimmune disorders: antinuclear antibodies, rheumatoid factor, and antineutrophil cytoplasmic antibodies 1
• For suspected infectious causes: blood cultures, serologic testing for specific pathogens based on exposure history 1, 5

Common Pitfalls to Avoid

• Failing to confirm splenomegaly with imaging before extensive workup 1, 5
• Overlooking hepatic causes of splenomegaly, which are among the most common etiologies in the United States 5, 3
• Neglecting to assess for hypersplenism complications (thrombocytopenia, anemia, leukopenia) which may require specific management 3, 7
• Delaying bone marrow evaluation in patients with concerning peripheral blood findings 2
• Not considering age-dependent spleen size reference values, particularly in pediatric patients 8

By systematically following this laboratory workup approach, clinicians can efficiently identify the underlying cause of splenomegaly and initiate appropriate management strategies.