Splenomegaly

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Gichoya Judy Wawira [2], Moi University School of Medicine

Synonyms and keywords: Spleen enlargement; enlarged spleen; spleen swelling

Differentiating Splenomegaly from Other Diseases

Category	Disease		Etiology	Clinical manifestations												Para−clinical findings										Gold standard	Associated findings
				Demography	History	Symptoms					Signs					Lab Findings									Imaging
						Fever	Fatigue	Weight	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	CBC			Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology
																WBC	Hb	Plt
Congestive	Cirrhosis		Infection Alcohol Autoimmune	Any, more in elderly	Hepatitis Alcohol use NAFLD	–	+	↑↓	+	+	↓	Nl	+	+	Spider angiomata Palmar erythema Weakness	↓	↓	↓	Nl	↑	↑	↑	Dark urine	Pancytopenia Regenerating nodules of hepatocytes Fibrosis Deposition of connective tissue between these nodules	Small and nodular liver on ultrasound Fibrosis on liver scan	Liver biopsy	Hepatic encephalopathy Gynecomastia Hypogonadism Esophageal varices Caput medusa Dupuytren's contracture
	Heart failure		Coronary artery disease HTN	Elderly	Smoking Sedentary lifestyle Obstructive sleep apnea	–	+	↑↓	–	–	↑	↑	±	+	Dyspnea Weakness Chest pain Heart murmur	↓	↓	↑	Nl	↑	↑	↑	Nl	NA	Normal or low ejection fraction on echocardiography Cardiomegaly on chest x-ray	Echocardiography	Pulmonary edema Hyponatremia Elevated BNP
	Thrombosis of portal, hepatic, or splenic veins		Thrombosis	Any	Inflammation Infection Cirrhosis Cancer	+	+	↑	+	+	↓	Nl	±	+	Weakness Hematemesis Melena	↓	↓	↓	Nl	↑	↑	↑	Dark urine	NA	Reduced or absent blood flow on doppler ultrasonography	Doppler ultrasonography	Portal hypertension Esophageal varices
Malignancy	Lymphoma		Unknown Mutation Infection	Any, most common malignant splenic tumor	Epstein Barr virus Positive family history Smoking HIV Autoimmune diseases	+	+	↓	+	+	Nl	Nl	+	–	Lymphadenopathy Itching Night sweats Anorexia Dyspnea	↓	↓	↓	High ferritin	↑	↑	↑	Nl	Different histopathological features based on types and stages Reed-Sternberg cell Malignant cells	Peritoneal lymphomatosis on CT scan	Lymph node biopsy	Primary immune disorder Post-transplant
	Leukemia		Unknown Mutation Bone marrowinfiltration Ineffective hematopoiesis Immune mediated	Elderly, male>female	History of hematological disorder History of chemotherapy andionizing radiation	+	+	↓	+	+	Nl	Nl	±	+	Pallor Leukemia cutis Bruising Petechiae Ecchymosis Fatigue Bone tenderness Early satiety	↓	↓	↓	High ferritin	↑	↑	↑	Nl	Leukemic blasts Leukoerythroblastic features Giant platelets	NA	Bone marrow examination + clinical manifestation	Infections of variable severity Cranial nerve palsy
	Polycythemia Vera		Autonomous erythrocyteproduction JAK2mutation	Mean age >60 years old	Positive family history	–	+	Nl	+	–	Nl	Nl	–	–	Erythromelalgia Chest pain Stroke-like symptoms Pruritus Dizziness Visual disturbance Facial plethora Painful erythema Lymphadenopathy	Nl to ↑	↑	Nl to ↑	High ferritin	Nl	Nl	Nl	Nl	Elevated normochromic, normocytic RBCs Thrombocytosis Rarely immature cells Leukoerythroblastic picture	NA	WHO criteria for PV	Stroke Venous thrombosis Myelofibrosis Acute leukemia
	Disease		Etiology	Demography	History	Fever	Fatigue	Weight loss	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	WBC	Hb	Plt	Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology	Imaging	Gold standard	Associated findings
	Multiple myeloma		Unknown Mutation Infection	Any, more in adults	Exposure to chemicals Radiation Pre-existent blood disorders	+	+	↓	+	+	Nl	Nl	+	–	Lymphadenopathy Itching Night sweats Anorexia Dyspnea	↓	↓	↓	High ferritin	Nl	↑	↑	Hemoglobinuria	Blast cells		Bone marrow examination	Tumor lysis syndrome Infection CNS involvement DIC
	Essential thrombocythemia		Acquired mutation of JAK2, CALR, or MPL	Mean age >60 years old, female > male	Vascular occlusive events and hemorrhages	±	+	Nl	+	+	Nl	Nl	–	–	Flushing Erythromelalgia Transient ischemic attacks Priapism Decreased visual acuity	↑	↑	↑↑	Nl	Nl	Nl	Nl	Nl	Increased cellularity Hyperplasia and clustering of megakaryocytes Bone marrow reticulin may be increased with no collagen fibrosis	Splenomegaly on abdominal CT VTE on spiral chest CT DVT on ultrasound	Bone marrow biopsy	Thrombosis
	Primary myelofibrosis		Bone marrow fibrosis Mutation in JAK2, CALR, or MPL	Mean age >60 years old, male> female	Other myeloproliferativedisorders Radiation exposure Chemicals exposure	–	+	Nl	+	+	Nl	Nl	+	–	Pallor Bruising Skin nodules Insert paragraph Fatigue Abdominal pain Early satiety Dyspnea Lymphadenopathy	↓	↓	↑/↓	Low iron	Nl	↑	Nl	Dark urine	Proliferation and atypia of megakaryocytes Reticulin or collagen fibrosis Hypercellular bone marrow	Diffuse bone sclerosis on CT	Bone marrow biopsy	Thrombosis Variable risk for development of acute leukemia
	Primary splenic tumors			Rare
	Metastatic solid tumors		Bone marrowinfiltration Ineffective hematopoiesis Immune mediated	Any, more in adults	Exposure to chemicals Radiation Pre-existent blood disorders	+	+	↓	+	+	↓	Nl	±	±	Petechiae Weakness	↓	↓	↓	Low iron, high ferritin	↑	↑	↑	Dark urine	Blast cells		Biopsy	Tumor lysis syndrome Infection CNS involvement DIC
Category	Disease		Etiology	Demography	History	Fever	Fatigue	Weight	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	WBC	Hb	Plt	Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology	Imaging	Gold standard	Associated findings
Infection	Viral	Hepatitis	Infection Autoimmune	Any	High risk behaviors Close contact	+	+	↓	+	+	Nl	Nl	+	+	Lymphadenopathy Muscle weakness Joint swelling Focal neurologic signs Depends on etiology	↓	↓	↓	Nl	↑	↑	↑	Dark urine Hematuria	Pancytopenia		Clinical manifestation + lab tests	Depends on etiology Encephalomyelitis
		Infectious mononucleosis	EBV
		Cytomegalovirus
	Bacterial	Salmonella
		Brucella
		Tuberculosis
	Parasitic	Malaria
		Schistosomiasis
		Toxoplasmosis
		Kala-azar	Visceral leishmaniasis
	Infective endocarditis
	Fungal
	Disease		Etiology	Demography	History	Fever	Fatigue	Weight loss	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	WBC	Hb	Plt	Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology	Imaging	Gold standard	Associated findings
Inflammation	Sarcoidosis		Immune mediated Unknown	Autoimmune disease, more in young African American women	Positive family history	+	+	↓	+	+	Nl	Nl	-	-	Bilateral hilar adenopathy Blurry vision Shortness of breath Cough Erythema nodosum	↑	↓	↑	Nl	Nl	Nl	Nl	Nl	NA	Bilateral hilar adenopathy on chest x-ray	Diagnosis of exclusion	Interstitial lung disease Systemic inflammatorydisease
	Serum sickness
	Systemic lupus erythematosus		Immune mediated bone marrow failure	More in young females	Family history	+	+	↓	+	+	Nl to ↓	Nl	+	+	Skin rash Mouth ulcers Chest pain Lymphadenopathy	↓	↓	↓		↑	↑	↑	Hemoglobinuria Proteinuria	Hypocellular bone marrow		Clinical findings + laboratory studies	Multi organ damage
	Felty syndrome		Immune mediated bone marrow failure	Rare autoimmune disease, more in females 50-70 years old	History of rheumatoid arthritis	+	+	↓	+	+	Nl to ↓	Nl	+	+	Pallor Skin hyperpigmentation Painful, stiff, and swollen joints Keratoconjunctivitis sicca	↓	↓	↓	Nl	Nl	Nl	Nl	Nl	Hypocellular bone marrow		Clinical findings + laboratory studies	Rheumatoid arthritis Infections
Category	Disease		Etiology	Demography	History	Fever	Fatigue	Weight loss	Abdominal pain	Bleeding	BP	JVP	Jaundice	Ascites	Other	WBC	Hb	Plt	Iron	LFT	PT/PTT	BUN/Cr	UA	Histopathology	Imaging	Gold standard	Associated findings
Infiltrative	Gaucher disease		Bone marrowinfiltration	Rare, mostly in children	Family history	-	+	↓	+	+	Nl to ↓	Nl	+	+		↓	↓	↓	Nl	Nl	↑	↑		Hypocellular bone marrow		Clinical findings + laboratory studies
	Niemann-Pick disease
	Amyloidosis
	Langerhans cell histiocytosis
	Hemophagocytic lymphohistiocytosis
	Rosai-Dorfman disease
Hematologic (hypersplenic) states	Hemolytic anemia
	Sickle cell disease
	Granulocyte colony-stimulating factor

Case Studies

Case #1