Initial Workup for Splenomegaly
Begin with abdominal ultrasound to confirm splenomegaly (>13cm is clinically significant), followed immediately by complete blood count with differential and peripheral blood smear review to identify hematologic malignancies or cytopenias. 1, 2
Confirming the Diagnosis
- Perform abdominal ultrasound as the first-line imaging modality to confirm splenomegaly, assess for focal lesions, evaluate liver size and appearance, and look for lymphadenopathy 1
- Measure spleen size: 11-13cm represents mild splenomegaly, while >13cm is clinically significant 1
- Physical examination should include careful percussion and palpation with measurement of liver span at the mid-clavicular line, though imaging is required for confirmation 1
- Consider CT or MRI if ultrasound findings are equivocal or if lymphadenopathy requires further characterization 1
Essential Laboratory Testing (Order Immediately)
Hematologic evaluation:
- Complete blood count with differential to evaluate for cytopenias (anemia, thrombocytopenia, leukopenia) or abnormal cell populations 1, 2
- Peripheral blood smear review to identify abnormal cells suggestive of hematologic malignancy - this is critical and should not be delayed 1
- Flow cytometry of peripheral blood for immunophenotyping if lymphoproliferative disorder is suspected based on CBC or smear findings 1, 2
Metabolic and organ function:
- Comprehensive metabolic panel to assess liver function 1, 2
- Lactate dehydrogenase (LDH) to screen for hemolysis or malignancy 1
Targeted Testing Based on Clinical Context
For suspected myeloproliferative neoplasms:
- JAK2, CALR, and MPL mutation testing 1
- Serum tryptase and vitamin B12 levels, particularly if eosinophilia is present 2
For suspected infectious causes:
- Viral studies for EBV, CMV, HIV, and hepatitis 1
- This is particularly important in patients with fever, recent travel, or immunosuppression 2, 3
For suspected portal hypertension:
- Doppler ultrasound to assess portal blood flow velocity - decreased velocity suggests portal hypertension 2
- Evaluate for ascites and other signs of liver disease 2
When to Proceed to Bone Marrow Evaluation
Bone marrow aspiration and biopsy with immunohistochemistry, cytogenetics, and molecular testing is indicated when: 1, 2
- Abnormal cells are found in peripheral blood
- Unexplained cytopenias are present
- Myeloproliferative or lymphoproliferative disorder is suspected
- Patient is older than 60 years with systemic symptoms
- Conventional cytogenetics, FISH, and/or RT-PCR should be performed to detect tyrosine kinase fusion gene rearrangements in suspected myeloid/lymphoid neoplasms 2
Critical Pitfalls to Avoid
- Do not delay bone marrow evaluation in patients with concerning peripheral blood findings - this is a common error that can delay diagnosis of malignancy 2
- Do not assume immune thrombocytopenia (ITP) if splenomegaly is present - less than 3% of ITP patients have splenomegaly, and moderate to massive enlargement suggests an alternative diagnosis requiring prompt evaluation 2
- Do not miss storage disorders (Gaucher disease, acid sphingomyelinase deficiency) which often have 4+ year diagnostic delays - consider referral to medical genetics if suspected 2
- Sudden left upper quadrant pain requires urgent evaluation for splenic infarction or rupture 2
Referral Algorithm
Refer to hematology if: 2
- Abnormal peripheral blood findings or flow cytometry results
- Suspected myeloproliferative or lymphoproliferative disorder
- Symptomatic splenomegaly without clear etiology 1
Refer to hepatology/gastroenterology if: 2
- Evidence of liver disease, portal hypertension, or ascites
- Cirrhosis is suspected
Refer to infectious disease if: 2
- Fever with splenomegaly and infectious etiology suspected
Refer to rheumatology if: 2
- Autoimmune disorders suspected (SLE, rheumatoid arthritis with Felty syndrome)
Most Common Etiologies in the United States
The three most common causes are liver disease, malignancy, and infection 4. Specifically consider: