Introduction 

• On ultrasonographic examination- if length of the spleen is more than 11cm, it is considered as splenomegaly 

Causes: 

• Congestive 

• Right sided heart failure 
• Budd Chiary syndrome 
• Cirrhosis with portal hypertension 
• Portal/ splenic vein thrombosis 
• Non cirrhotic portal hypertension 
• Hepatic schistosomiasis 

• Infections 

• Viral infections- HIV, Infectious mononucleosis, Dengue fever, Rubella, CMV, Herpes simplex, viral hepatitis 
• Bacterial infections: Subacute bacterial endocarditis, brucellosis, tularemia, malidiosis, listeriosis, plague, secondary syphilis, relapsing fever, psittacosis, ehrlichiosis, tuberculosis, splenic abcess, typhoid, septicemia 
• Rickettsial disease- Rocky mountain spotted fever, Q fever, typhus 
• Fungal infections- Blastomycosis, histoplasmosis, systemic candidiasis 
• Parasitic infections: Malaria, kala-azar, schistosomiasis, babenosis, coccidiodomycosis, paracoccidiodomycosis, trypanosomiasis, toxoplasmosis, ecchynococcosis, cysticercosis, visceral larva migrans  

• Inflammatory/ Autoimmune 

• SLE, Feltry syndrome 
• Juvenile rheumatoid arthritis 
• Autoimmune lymphoproliferative syndrome 
• Hemophagocytic lymphohistiocytosis 
• GVHD 
• Serum sickness 
• LGL leukemia 
• Common variable immunodeficiency 
• Anti D immunoglobulin administration 
• Rheumatic fever 
• Sarcoidosis 
• Tropical splenomegaly 

• Associated with hemolysis 

• Thalassemia 
• Pyruvate kinase deficiency 
• Hereditary spherocytosis 
• AIHA (rarely) 
• Hemoglobinopathies- Sequestration crisis of sickle cell anemia, HbC and other hemoglobinopathies, certain variants of sickle cell anemia 

• Infiltrative 

• Nonmalignant: Splenic hematoma, Littoral cell angioma, lipid storage diseases (Goucher, Neimann Pick), Cystinosis, Amyloidosis, Multicentric Castleman disease, mastocytosis, Hyper eosinophilic syndrome 
• Extrameduallry erythropoiesis- Myelofibrosis, osteopetrosis, thalassemia major 
• Malignant 

• Hematologic- CLL, CML, ALL, AML, PV, HCL, ET, Hepatosplenic lymphoma, HD, SMZL, NHL 
• Non Hematological: Metastasis (rare), Neuroblastoma, Wilm's tumor, Leiomyosarcoma, Fibrosarcoma, Malignant fibrous histiocytoma, hemangiosarcoma, Kaposi's sarcoma, lymphangiosarcoma 

• G-CSF/ EPO administration 

(Causes of massive splenomegaly (enlargement beyond umbilicus) include- Myelofibrosis, CML, HCL, SMZL, CLL, Malaria, Leishmaniasis, Beta thalassemia major, Goucher disease, tropical splenomegaly, AIDS with MAC) 

Investigations: 

• Peripheral smear 

• Pancytopenia- Seen in hypersplenism, lymphoma, HCL, Myelofibrosis, SLE 
• Neutrophilic leucocytosis- Acute infections, inflammations 
• Leucocytosis with premature white cells- CML, MF, MPN/MDS 
• Blasts in acute leukemia 
• Leucoerythroblastic blood picture- MF, BM infiltration 
• Erythrocytosis- Polycythemia vera 
• Atypical lymphocytes- Infectious mononucleosis and other viral infections 
• Thrombocytosis- MPN, chronic infections like tuberculosis 
• Parasites- Malaria, Bartonellosis, Babesiosis 
• Hemolytic picture in hemolytic anemia 
• Lymphocytosis- CLL, Lymphoma spill over 

• Echocardiography- For heart failure, infective endocarditis 
• Abdominal USG with portal venous doppler (splenoportal axis) 
• LFT 
• CXR and sputum AFB for tuberculosis 
• HIV 
• Monospot test 
• Dengue- NS1, IgG and IgM 
• Brucella 
• Serology for Typhus 
• HCV, HBsAg, Widal tests 
• VDRL 
• Rapid malaria test 
• ANA, AntiDs DNA 
• Ferritin, Triglyceride, LDH 
• RA factor 
• SPE for M band and abdominal fat pad- For amyloidosis 
• Hemoglobin HPLC/ Electrophoresis 
• DCT, ICT 
• Blood culture 
• PCR for psittacosis, Rickettsia, TB, CMV 
• Bone marrow aspiration and biopsy- Flow cytometry and molecular studies for MPN if necessary 
• If CT is done, do it with oral and IV contrast 

• Oral contrast- Helps to delineate splenic tissue from stomach, small intestine and colon 
• IV contrast: Better visualization of spleen 

• Upper GI endoscopy- To rule out esophageal varices 
• Stool for schistosoma eggs 
• Splenic aspiration/ core needle biopsy: High false negative rates and has risk of splenic rupture 
• Diagnostic splenectomy: It is done in cases where cause remains undiagnosed after extensive testing 

Diagnostic algorithm: