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Splenomegaly Differential Diagnoses

  • Author: Neetu Radhakrishnan, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Apr 29, 2016

Diagnostic Considerations

Traditionally, splenomegaly was classified as mild, moderate, or massive. This distinction can help with etiological diagnosis.

Conditions to consider in the differential diagnosis of massive splenomegaly include the following:

  • Leishmaniasis
  • Malaria
  • Myeloproliferative disease
  • Portal vein obstruction/portal hypertension
  • Schistosomiasis
  • Niemann-Pick disease
  • Mucopolysaccharidosis
  • Lymphomas
  • Gaucher disease [10]
  • Hereditary spherocytosis
  • Thalassemias – major, alpha or beta
  • Histiocytosis X

Conditions to consider in the differential diagnosis of mild to moderate splenomegaly include all of the above, as well as the following:

  • Bacterial sepsis
  • Infective endocarditis
  • Sickle cell anemia
  • Splenic abscess
  • Acute infectious illnesses (eg, typhoid, malaria, other tropical diseases)
  • Acute viral infections (eg, infectous mononucleosis)
  • Systemic lupus erythematosus
  • Tuberculosis
  • Angioimmunoblastic lymphadenopathy
  • Banti disease
  • Congestive heart failure
  • Drug reactions with serum sickness syndromes
  • Hyperlipidemias
  • Idiopathic splenomegaly
  • Immune hemolytic anemias
  • Immune thrombocytopenic disorders
  • Leukocyte disorders
  • Ovalocytosis
  • Splenic vein obstruction
  • Symptomatic human immunodeficiency virus (HIV) infection
  • Trypanosomiasis

While certain causes of splenomegaly are usually obvious due to the concurrent illness (eg, endocarditis, malaria, infections), etiologic diagnosis of splenomegaly in the outpatient setting involves extensive history taking, with inquiries about the range of possible causes, including any history of liver disease, hereditary anemias, or infiltrative disorders. The presence of B symptoms and constitutional symptoms may indicate a primary bone marrow malignancy or myeloproliferative disorders.

On laboratory testing, if the sedimentation rate is high, the differential diagnosis includes the following:

  • Infection
  • Acute leukemias
  • Sarcoidosis
  • Other inflammatory disorders

If the sedimentation rate is low, the differential diagnosis includes the following:

  • Chronic myeloproliferative disorders
  • Hereditary hemolytic anemias
  • Infiltrative disorders

Anemia with peripheral smear findings showing spherocytosis, sickle cells, hemoglobin SC, or elliptocytosis would indicate splenomegaly due to these disorders. Anemia with a high lactate dehydrogenase (LDH) or low haptoglobulin level and a high bilirubin level may indicate a hemolytic disorder or liver disease.

An abnormal coagulation profile with high prothrombin time (PT), international normalized Ratio (INR) and PTT usually indicates an associated liver disorder, with cirrhosis and portal hypertension as the etiology of splenomegaly. It may also indicate an underlying acute bone marrow malignancy or disseminated intravascular coagulation (DIC). Portal hypertemsion due to liver disease or a bone marrow neoplastic process is also the likely cause of splenomegaly in patients with thrombocytopenia and a mildly abnormal coagulation profile, indicates splenomegaly.

Splenomegaly  with fevers may indicate one of the following:

  • Epstein-Barr virus (EBV) infection
  • Acute bacterial or fungal infection
  • Acute leukemia or lymphoma

Differential Diagnoses

Contributor Information and Disclosures

Neetu Radhakrishnan, MD Assistant Professor of Medicine, Division of Hematology/Oncology, University of Cincinnati Medical Center; Lab Director, Hematology Lab, University Point, West Chester

Neetu Radhakrishnan, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.


Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Gina M Matacia-Murphy, MD Fellow in Hematology/Oncology, University of Cincinnati College of Medicine

Gina M Matacia-Murphy, MD is a member of the following medical societies: American Society of Clinical Oncology

Disclosure: Nothing to disclose.


Wadie F Bahou, MD Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook

Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

David Coffman, MD Fellow, Department of Surgery, Division of Trauma and Critical Care, Yale University School of Medicine

Disclosure: Nothing to disclose.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Emmanuel N Dessypris, MD Professor of Medicine, Medical College of Virginia; Chief, Medical Service, Hunter Holmes McGuire Department of Veterans Affairs Medical Center

Emmanuel N Dessypris, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society of Hematology, New York Academy of Sciences, Society for Experimental Biology and Medicine, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

David J Draper, MD Fellow, Department of Hematology/Oncology, The University Hospital, University of Cincinnati College of Medicine

Disclosure: Nothing to disclose.

Lewis J Kaplan, MD, FACS, FCCM, FCCP Director, SICU and Surgical Critical Care Fellowship, Associate Professor, Department of Surgery, Section of Trauma, Surgical Critical Care, and Surgical Emergencies, Yale University School of Medicine

Lewis J Kaplan, MD, FACS, FCCM, FCCP is a member of the following medical societies: American Association for the Surgery of Trauma, American College of Surgeons, Association for Academic Surgery, Association for Surgical Education, Connecticut State Medical Society, Eastern Association for the Surgery of Trauma, International Trauma Anesthesia and Critical Care Society, Society for the Advancement of Blood Management, Society of Critical Care Medicine, and Surgical Infection Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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This patient has a splenic abscess due to pneumococcal bacteremia. Note that the massively enlarged spleen is readily visible, with minimal retraction in the left upper quadrant.
Resected specimen from the patient in the previous image. Note the discrete abscesses adjacent to normal parenchyma.
The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18 kg (7 lb) spleen crosses the midline. Inferiorly, it extends into the pelvis.
Massive splenomegaly does not preclude splenectomy through a minimally invasive approach. This photograph depicts a fragmented 3.2 kg (7.05 lb) spleen after removal via a hand-assisted laparoscopic technique.
A portion of a massive spleen is extracted via hand-assisted laparoscopy.
Intraoperative photograph of a laparoscopic splenectomy being taken down using the hanging-pedicle technique. The tip of the spleen is visualized in the background, whereas the stapler is detailed in the foreground across a segment of the pedicle.
A massive spleen that was removed from an elderly woman with lymphoma.
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