How should splenomegaly be evaluated and managed?

Management of Splenomegaly

Diagnostic Definition and Confirmation

Splenomegaly is definitively diagnosed when spleen length exceeds 13 cm measured in the coronal plane on imaging studies, and abdominal ultrasound or CT should be obtained immediately to confirm the diagnosis and assess for associated hepatic or vascular abnormalities. 1

• Physical examination has limited diagnostic accuracy, with hepatomegaly showing only 60% sensitivity and 44% specificity, while splenomegaly detection has 93% sensitivity but only 57% specificity for detecting advanced disease 2
• Abdominal ultrasound is the preferred initial imaging modality due to its non-invasive nature, lack of radiation exposure, and ability to assess liver architecture and portal vasculature 1, 3

Initial Diagnostic Workup

Essential Laboratory Testing

Obtain complete blood count with differential, peripheral blood smear review by a qualified hematologist, reticulocyte count, liver function tests (AST, ALT, alkaline phosphatase, GGT, bilirubin), and platelet count at clinical stability. 2, 1

• Peripheral blood smear is mandatory to identify characteristic cells that establish specific diagnoses, particularly hairy cell leukemia, chronic lymphocytic leukemia, or myeloproliferative disorders 4
• Flow cytometry of peripheral blood should be performed when lymphoproliferative disorders are suspected, looking for CD11c+, CD25+, CD103+, and CD123+ cells (hairy cell leukemia) or other B-cell markers 4

Critical Infectious Disease Screening

Screen all adults for HIV and hepatitis C serology regardless of risk factors, as both infections commonly cause thrombocytopenia with splenomegaly and may precede other symptoms by years. 5

• If any travel to malaria-endemic regions within the past year, obtain three sequential thick and thin blood films spaced 12 hours apart immediately—Plasmodium falciparum can cause death within hours in non-immune patients 5
• Do not start empiric corticosteroids before excluding infectious etiologies, as steroids can precipitate fulminant sepsis in undiagnosed malaria or disseminated tuberculosis 5

Common Etiologies by Geographic Location

Developed Countries (United States/Europe)

The three most common causes are liver disease with portal hypertension, hematologic malignancies, and infections 3

Hematologic malignancies to consider:

• Myeloproliferative neoplasms (chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, primary myelofibrosis) 1, 6
• Indolent lymphomas (chronic lymphocytic leukemia, hairy cell leukemia, splenic marginal zone lymphoma) 6

Tropical Regions

Malaria and schistosomiasis affect up to 80% of people with splenomegaly in endemic areas 3

When to Perform Bone Marrow Biopsy

Bone marrow aspiration and biopsy with flow cytometry and cytogenetics is mandatory in the following scenarios:

• Age >60 years with splenomegaly and any cytopenia 4, 5
• Pancytopenia (involvement of two or more cell lines) 4
• Isolated thrombocytopenia with splenomegaly in patients >60 years to exclude myelodysplastic syndrome 5
• Suspected myeloproliferative neoplasm based on peripheral smear showing leukoerythroblastic picture 4

Disease-Specific Management

Myeloproliferative Neoplasms with Symptomatic Splenomegaly

JAK inhibitors (ruxolitinib) are first-line therapy for symptomatic splenomegaly in myelofibrosis, achieving significant spleen volume reduction and symptom improvement. 1

• Hydroxyurea is an alternative first-line option, achieving spleen volume reduction in approximately 40% of patients 1
• Alternative cytoreductive agents for hydroxyurea-refractory disease include intravenous cladribine (5 mg/m²/day for 5 consecutive days, repeated for 4-6 monthly cycles), oral melphalan (2.5 mg three times weekly), or oral busulfan (2-6 mg/day with close blood count monitoring) 1
• Interferon therapy is poorly tolerated and has limited efficacy in primary myelofibrosis 1

For associated anemia (hemoglobin <10 g/dL):

• Erythropoiesis-stimulating agents, androgens, or danazol may be used, with response rates of 23-60% 1, 4

Splenic Marginal Zone Lymphoma

Rituximab monotherapy is first-line treatment, producing >80% overall response rate with minimal toxicity. 5

Liver Disease with Portal Hypertension

Medical management treating the underlying liver disease and portal hypertension is first-line 5

Monitoring During Treatment

Response Assessment Criteria

For myeloproliferative neoplasms, spleen response is defined as:

• Baseline splenomegaly palpable at 5-10 cm below left costal margin becoming non-palpable, OR
• Baseline splenomegaly palpable >10 cm below left costal margin decreasing by ≥50% 2
• Confirmation by MRI or CT showing ≥35% spleen volume reduction is required 2

For lymphoma patients:

• Spleen must regress by at least 50% in length beyond normal (13 cm) to be considered a partial response 1
• Imaging intervals of 2-3 months during the first year of therapy are recommended, with less frequent imaging thereafter 1

Surgical Considerations

Indications for Splenectomy

Splenectomy may be considered only for:

• Drug-refractory marked splenomegaly (>20 cm below costal margin) causing severe cachexia or pain 1, 4
• Symptomatic portal hypertension with variceal bleeding or ascites 1
• Established transfusion-dependent anemia refractory to medical therapy 1
• Life-threatening or recurrent splenic sequestration in sickle cell disease 1

Critical Surgical Risks

Splenectomy in myeloproliferative disorders carries 5-10% perioperative mortality and up to 50% complication rate—this is a high-risk procedure that should be avoided when possible. 1, 4

• For splenic abscesses, percutaneous drainage is strongly preferred over splenectomy to preserve splenic function 1

Complications and Precautions

Patients with splenomegaly are at risk for:

• Cytopenias due to splenic sequestration 1
• Splenic infarction 1
• Splenic rupture—patients should refrain from contact sports 3
• Infection risk if splenic function is compromised 1

For patients with myeloproliferative disorders and iron overload, consider iron chelation therapy if ferritin exceeds 1000 μg/L. 4

Special Population: Cystic Fibrosis

• Annual abdominal physical examination for hepatosplenomegaly starting at CF diagnosis 2
• Abdominal ultrasound at least every 2 years from age 3 through late adolescence 2
• Splenomegaly in CF indicates advanced liver disease with portal hypertension 2