What is the initial workup for a patient presenting with splenomegaly (enlargement of the spleen)?

Workup for Splenomegaly

Begin with abdominal ultrasound to confirm splenomegaly (>11-13cm is clinically significant), followed immediately by complete blood count with differential, peripheral blood smear, comprehensive metabolic panel, and LDH to guide further targeted testing based on initial findings. 1

Step 1: Confirm Splenomegaly

Physical examination alone is insufficient and requires imaging confirmation. 1, 2

• Perform careful percussion and palpation of the entire liver and spleen with measurement of liver span at the mid-clavicular line 1
• Order abdominal ultrasound as the first-line imaging modality to confirm splenomegaly, assess for focal lesions, evaluate splenic echotexture, and characterize liver appearance 1
• Spleen length 11-13cm represents mild splenomegaly; >13cm is clinically significant 1
• Advance to CT or MRI if ultrasound findings are equivocal or if lymphadenopathy requires further characterization 1

Step 2: Essential Laboratory Panel (Order Simultaneously)

These tests should be obtained in all patients regardless of suspected etiology: 1

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

Step 3: Targeted Testing Based on Clinical Context

If Infectious Etiology Suspected:

• Viral studies for EBV, CMV, HIV, and hepatitis 1
• Note that in the United States, infection is one of the three most common causes alongside liver disease and malignancy 3

If Lymphoproliferative Disorder Suspected:

• Flow cytometry of peripheral blood for immunophenotyping and CD markers 1
• This should be performed early if peripheral blood shows abnormal lymphocytes 1

If Myeloproliferative Neoplasm Suspected:

• JAK2, CALR, and MPL mutation testing 1
• Serum tryptase and vitamin B12 levels, particularly with eosinophilia 1

Step 4: Bone Marrow Evaluation (When Indicated)

Do not delay bone marrow aspiration and biopsy if any of the following are present: 1

• Abnormal cells found in peripheral blood 1
• Unexplained cytopenias 1
• Suspected myeloproliferative or lymphoproliferative disorder 1
• Include immunohistochemistry, cytogenetics, and molecular testing with the bone marrow procedure 1
• Conventional cytogenetics, FISH, and/or RT-PCR to detect tyrosine kinase fusion gene rearrangements in suspected myeloid/lymphoid neoplasms with eosinophilia 1

Step 5: Additional Tissue Diagnosis

• Consider lymph node biopsy if lymphadenopathy is present and lymphoma is suspected 1

Common Diagnostic Pitfalls to Avoid

The most critical error is delaying bone marrow evaluation when peripheral blood findings are concerning. 1

• Physical examination has poor sensitivity for detecting splenomegaly; always confirm with imaging 1, 2
• In adults, hematological malignancies account for 37% of cases requiring hematological workup 4
• Bone marrow examination may reveal malarial parasites even when peripheral smears are negative (20.5% of cases in some series) 4
• Patients with splenomegaly should avoid contact sports due to rupture risk 3

Algorithmic Approach Summary

The three most common etiologies in the United States are liver disease, malignancy, and infection, which should frame your differential diagnosis. 3

1. Confirm with ultrasound (not clinical exam alone) 1
2. Obtain core laboratory panel (CBC, smear, CMP, LDH) in all patients 1
3. Add targeted testing based on clinical suspicion (infectious studies, flow cytometry, or mutation testing) 1
4. Proceed to bone marrow biopsy if abnormal cells, cytopenias, or suspected hematologic malignancy 1
5. Refer to hematology for symptomatic splenomegaly without clear etiology 1