What is the initial workup for a patient presenting with splenomegaly?

Initial Workup for Splenomegaly

The initial workup for a patient presenting with splenomegaly should include complete blood count with differential, comprehensive metabolic panel, peripheral blood smear examination, and abdominal imaging, preferably ultrasound. 1

Laboratory Tests

First-Line Laboratory Tests

• Complete blood count (CBC) with differential
  • Evaluate for cytopenias (anemia, thrombocytopenia, leukopenia) or elevated cell counts
  • Peripheral blood smear examination to assess for abnormal cells
• Comprehensive metabolic panel
  • Liver function tests (AST, ALT, alkaline phosphatase, bilirubin)
  • Renal function (BUN, creatinine, electrolytes)
• Serum protein electrophoresis (SPEP) and immunofixation
  • To identify monoclonal proteins suggesting lymphoproliferative disorders 1

Second-Line Laboratory Tests

• Viral studies
  • Hepatitis panel (HBsAg, hepatitis B surface antibody, HBcAb, HBcAb IgM, HCV antibodies)
  • EBV serology (for suspected infectious mononucleosis)
  • HIV testing
• Flow cytometry of peripheral blood
  • For immunophenotyping of abnormal lymphocytes in suspected lymphoproliferative disorders 1
• Genetic testing
  • MYD88 (L265P) mutation for suspected Waldenström macroglobulinemia 1
  • BRAF V600E mutation for hairy cell leukemia 2

Imaging Studies

First-Line Imaging

• Abdominal ultrasound
  • Confirms splenomegaly (>13 cm in vertical length) 2
  • Assesses liver parenchyma, biliary tract, and portal vein 1
  • Non-invasive and cost-effective initial imaging modality

Second-Line Imaging

• CT scan with contrast
  • More detailed assessment of spleen size and morphology
  • Evaluation of lymphadenopathy
  • Detection of focal lesions within the spleen
• PET-CT
  • Particularly useful for suspected lymphoma
  • Can detect bone marrow involvement and splenic infiltration 2

Diagnostic Procedures

Bone Marrow Evaluation

• Bone marrow aspiration and biopsy
  • Essential for suspected hematologic malignancies
  • Particularly important in myeloproliferative disorders, lymphomas, and leukemias 1
  • Should include cytogenetic and molecular studies as appropriate

Specialized Testing

• For suspected myeloproliferative neoplasms:
  • JAK2, CALR, and MPL mutation testing
• For suspected lymphoproliferative disorders:
  • Immunophenotyping by flow cytometry
  • Cytogenetic and FISH analysis

Diagnostic Algorithm

1. Confirm splenomegaly: Physical examination followed by abdominal ultrasound

2. Categorize based on CBC findings:

   • If cytopenias present → consider hypersplenism, bone marrow infiltration
   • If cytosis present (elevated counts) → consider myeloproliferative disorders
   • If normal counts → consider early disease or non-hematologic causes

3. Further categorization based on additional findings:

   • Abnormal liver function tests → consider hepatic causes (cirrhosis, portal hypertension)
   • Monoclonal protein on SPEP → consider lymphoproliferative disorders
   • Fever, night sweats → consider infection or lymphoma
   • Massive splenomegaly (>20 cm) → consider chronic myeloid leukemia, myelofibrosis, lymphoma

4. Definitive diagnosis:

   • Bone marrow examination for suspected hematologic disorders
   • Liver biopsy for suspected hepatic disorders with inconclusive non-invasive testing
   • Consider splenic biopsy only in rare cases when diagnosis remains elusive after extensive workup

Common Pitfalls and Considerations

• Failing to recognize malignant infiltration in patients with massive hepatosplenomegaly 1
• Overlooking splenic sequestration as a life-threatening complication in sickle cell disease 1
• Performing splenectomy in patients with severe thrombocytopenia, which may be a marker of impending leukemic transformation 1
• Underestimating the risks of contact sports in patients with splenomegaly, which increases risk of splenic rupture 3
• Missing tropical causes such as malaria and schistosomiasis in patients with relevant travel history 3

Special Considerations

• In patients with suspected lymphoma, PET-CT is more sensitive than bone marrow biopsy for detecting bone marrow involvement 2
• Patients with splenomegaly should refrain from participating in contact sports to decrease risk of splenic rupture 3
• Consider splenic irradiation for symptomatic relief in patients with hematologic disorders and painful splenomegaly 4
• In patients with myelofibrosis being considered for hematopoietic cell transplantation, splenomegaly ≥5 cm below the left costal margin may require treatment before transplantation 5

By following this systematic approach to the evaluation of splenomegaly, clinicians can efficiently identify the underlying cause and initiate appropriate management to improve patient outcomes.