Differential Diagnosis for Massive Splenomegaly

Single Most Likely Diagnosis

• Chronic Lymphocytic Leukemia (CLL): CLL is a common cause of massive splenomegaly due to the accumulation of malignant lymphocytes in the spleen. The disease often presents with significant splenic enlargement, which can lead to discomfort, early satiety, and other symptoms related to the compression of adjacent organs.

Other Likely Diagnoses

• Lymphoma: Both Hodgkin's and non-Hodgkin's lymphoma can cause significant splenomegaly. The spleen can be involved in the disease process, leading to its enlargement.
• Chronic Myeloid Leukemia (CML): CML is another myeloproliferative disorder that can lead to massive splenomegaly due to the accumulation of granulocytic cells in the spleen.
• Myeloproliferative Neoplasms (MPN): Conditions like primary myelofibrosis, polycythemia vera, and essential thrombocythemia can cause splenomegaly due to extramedullary hematopoiesis or the sequestration of blood cells.
• Sickle Cell Disease: Repeated splenic infarctions in sickle cell disease can lead to autosplenectomy, but in some cases, especially in early stages or with specific sickle cell variants, massive splenomegaly can occur.

Do Not Miss Diagnoses

• Splenomegaly due to Portal Hypertension: While not always massive, splenomegaly from portal hypertension (e.g., due to cirrhosis) is critical to identify because it implies significant liver disease and potential complications like variceal bleeding.
• Infectious Causes (e.g., Kala-Azar, Malaria): Certain infections can cause massive splenomegaly and are crucial to diagnose promptly due to their potential for severe morbidity and mortality if left untreated.
• Lymphatic or Venous Obstruction: Obstruction of the splenic vein or lymphatic vessels can lead to significant splenomegaly and is important to recognize due to its implications for treatment and potential complications.

Rare Diagnoses

• Gaucher's Disease: A lysosomal storage disorder that can lead to splenomegaly due to the accumulation of glucocerebroside in macrophages within the spleen.
• Niemann-Pick Disease: Another lysosomal storage disorder that can cause splenomegaly among other systemic manifestations.
• Primary Splenic Lymphoma: A rare condition where lymphoma arises primarily in the spleen.
• Splenic Metastases: Rarely, metastatic disease can involve the spleen, leading to splenomegaly, although this is much less common than other causes.