Comprehensive Workup for Splenomegaly
The workup for splenomegaly should begin with abdominal ultrasound to confirm the diagnosis, followed by targeted laboratory testing including complete blood count with differential, peripheral blood smear, comprehensive metabolic panel, and specific tests based on suspected etiology. 1, 2
Initial Confirmation of Splenomegaly
- Imaging confirmation: Abdominal ultrasound is the first-line imaging modality to confirm splenomegaly suspected on physical examination 1
- Safe in all patients regardless of platelet count
- Allows for accurate measurement of splenic size
- Can detect associated findings (portal hypertension, liver abnormalities)
Laboratory Evaluation
First-line Laboratory Tests
- Complete blood count (CBC) with differential
- Peripheral blood smear examination
- Comprehensive metabolic panel including:
- Liver function tests
- Renal function tests
- Electrolytes
- Calcium and albumin
- Lactate dehydrogenase (LDH)
- Hepatitis B testing (HBsAg and HBcAb) 3
- Hepatitis C testing (especially in high-risk patients and those with suspected splenic marginal zone lymphoma) 3
Second-line Laboratory Tests (Based on Clinical Suspicion)
- Serum protein electrophoresis
- Immunophenotypic analysis by flow cytometry (if hematologic malignancy suspected) 3
- β-microglobulin (if lymphoma suspected) 3
- HIV testing (if status unknown) 3
- Specific infectious disease testing based on exposure history:
- EBV serology (if infectious mononucleosis suspected)
- Malaria testing (if travel to endemic regions)
- Schistosomiasis testing (if travel to endemic regions) 2
Advanced Imaging
CT scan with contrast of chest/abdomen/pelvis if:
- Malignancy suspected
- Need to evaluate for lymphadenopathy
- Need to assess for other visceral involvement 3
PET-CT scan if:
- Lymphoma suspected
- Need to evaluate extent of disease
- Need to distinguish between malignant and non-malignant causes 3
Bone Marrow Evaluation
Bone marrow aspiration and biopsy indicated when:
- Hematologic malignancy suspected
- Unexplained cytopenia present
- Abnormal cells seen on peripheral blood smear 3
Bone marrow evaluation should include:
- Cytology
- Flow cytometry
- Cytogenetic analysis
- Molecular studies as indicated 3
Disease-Specific Evaluations
For Suspected Hematologic Malignancies
- Immunophenotypic analysis using flow cytometry and/or immunohistochemistry 3
- Cytogenetic or molecular genetic analysis to identify characteristic chromosomal translocations 3
- Evaluation for specific mutations (e.g., BRAF V600E for hairy cell leukemia) 3
For Suspected Chronic Myeloid Leukemia
- BCR-ABL1 testing by PCR or FISH 3
For Suspected Lymphoma
- Excisional lymph node biopsy if lymphadenopathy present
- Immunophenotyping panel including Pan-B and Pan-T-cell antigens 3
For Suspected Portal Hypertension
- Doppler ultrasound to assess portal vein flow
- Upper endoscopy to evaluate for varices 4
Special Considerations
- In patients with thrombocytopenia and splenomegaly, abdominal ultrasound is safe regardless of platelet count 1
- Patients with unexplained fevers and splenomegaly may require evaluation for HHV-8-associated conditions with C-reactive protein, HHV-8 serum viral load, and interleukin testing 3
- Diagnostic splenectomy is rarely necessary with current diagnostic modalities 5
Common Pitfalls to Avoid
- Failing to confirm splenomegaly with imaging (physical examination alone has limited sensitivity)
- Not performing peripheral blood smear examination, which can provide valuable diagnostic clues
- Missing underlying liver disease, which is one of the most common causes of splenomegaly in the United States 2
- Neglecting to test for infectious causes in patients with appropriate exposure history
- Performing unnecessary invasive procedures before completing non-invasive workup
By following this systematic approach to the evaluation of splenomegaly, clinicians can efficiently identify the underlying cause and initiate appropriate management.