Initial Workup for Splenomegaly
Begin with abdominal ultrasound to confirm splenomegaly (>13 cm is clinically significant), followed immediately by complete blood count with differential, peripheral blood smear review, comprehensive metabolic panel, and lactate dehydrogenase. 1, 2, 3
Confirming Splenomegaly
Physical examination alone is insufficient - while palpation and percussion should document exact spleen size below the costal margin and liver span at the mid-clavicular line, physical exam has only 93% sensitivity and 57% specificity for detecting splenomegaly. 1, 3
Abdominal ultrasound is mandatory as the first-line imaging modality to:
- Confirm splenomegaly and measure splenic size 1, 2, 3
- Assess for focal lesions within the spleen 1, 2
- Evaluate hepatomegaly and liver appearance 1, 2, 3
- Identify lymphadenopathy 1, 2, 3
Spleen size thresholds:
- 11-13 cm = mild splenomegaly 1, 2, 3
13 cm = clinically significant, warrants aggressive workup 1, 2, 3
Essential First-Line Laboratory Testing
Complete blood count with differential to identify:
- Cytopenias (thrombocytopenia, anemia, leukopenia) 1, 2, 3
- Leukocytosis or lymphocytosis 1, 3
- Abnormal cell populations suggesting hematologic malignancy 1, 2, 3
Peripheral blood smear review is critical - this must be performed to identify blasts, atypical lymphocytes, or other abnormal cells suggestive of leukemia or lymphoma. 1, 2, 3
Comprehensive metabolic panel including liver function tests - liver disease is one of the three most common causes of splenomegaly in the United States. 1, 2, 3
Lactate dehydrogenase (LDH) to screen for hemolysis or malignancy. 1, 2
Infectious Disease Workup
Test for EBV, CMV, HIV, and hepatitis viruses as infectious causes are among the top three etiologies in developed countries. 1, 2
Hematologic Malignancy Evaluation
Flow cytometry of peripheral blood for immunophenotyping should be performed immediately if lymphoproliferative disorder is suspected based on CBC findings. 1, 2, 3
JAK2, CALR, and MPL mutation testing if myeloproliferative neoplasm is suspected, particularly with leukocytosis, thrombocytosis, or unexplained splenomegaly. 1, 2, 3
Bone marrow aspiration and biopsy is indicated when:
- Abnormal cells are found in peripheral blood 1, 2, 3
- Unexplained cytopenias are present 1, 2, 3
- Myeloproliferative or lymphoproliferative disorder is suspected 1, 2, 3
Advanced Imaging
CT or MRI of the abdomen should be obtained if:
- Ultrasound findings are equivocal 1, 2, 3
- Lymphadenopathy needs characterization 1, 2
- Focal splenic lesions are present requiring tissue diagnosis 1
Critical Pitfalls to Avoid
Do not delay bone marrow evaluation in patients with concerning peripheral blood findings including blasts, significant cytopenias, or abnormal cell populations. 1, 2, 3
Do not miss lymphoma-associated hemophagocytic lymphohistiocytosis (HLH) - approximately 40-70% of adult HLH cases are malignancy-associated, particularly with Hodgkin lymphoma, diffuse large B-cell lymphoma, and T-cell lymphomas. 1, 3
Consider PET-guided imaging and repetitive tissue sampling if lymphoma is suspected but initial biopsies are negative, as tumor-infiltrating reactive lymphocytes can mask underlying lymphoma. 1
Do not assume alcoholic liver disease in patients with alcohol use - other causes must be excluded through appropriate testing. 1
Immediate Hematology Referral Criteria
Refer immediately for:
- Peripheral smear showing blasts or abnormal lymphocytes beyond typical reactive changes 1, 3
- Presence of cytopenias 1, 3
- Symptomatic splenomegaly without clear etiology after initial workup 1, 3
Additional Testing in Acute Presentations
Disseminated intravascular coagulation panel (D-dimer, fibrinogen, PT, PTT) in acute presentations, particularly when acute leukemia is suspected. 1
Tumor lysis syndrome panel (uric acid, potassium, phosphates, calcium) when malignancy is suspected. 1