My source for this article is Iannitto & Tripido, Blood 2011; 17:2585.
The causes of splenomegaly are many. Infections can cause (usually transitory) splenomegaly and include brucellosis, EBV and CMV infections, Leishmaniasis and viral hepatitis. Myeloid neoplasms can be responsible including chronic myeloid leukemia, polycythemia rubra vera, chronic myelomonocytic leukemia and myelofibrosis. Various types of hemolytic anemia, especially AIHA, thalassemia, sickle cell disease in children, certain hemoglobinopathies and hereditary spherocytosis may be the cause. It can be a feature of some inflammatory diseases like SLE, rheumatoid arthritis (Felty's syndrome) and sarcoidosis. It is a feature of portal hypertension caused by cirrhosis of the liver, (always reminds me of a gin palace type of pleasure cruiser called Cirrhosis of the River), or thrombosis of splenic, portal or hepatic vein. There are rare tumors: Littoral cell angiomas, hemangiomas, lymphanghiomas, spindle cell angiomas and various metastases, particularly from melanoma. Then there are some weird diseases like Gaucher's and Amyloidosis.
Most of these have other manifestations as do some lymphomas that affect the spleen like follicular lymphoma, mantle cell lymphoma and Hodgkin's disease, but there is a rare group of lymphomas that cause isolated splenomegaly - perhaps with some effect on the blood and marrow. The splenic lymphomas include splenic marginal zone lymphoma, Hairy Cell Leukemia, Hairy Cell variant, splenic diffuse red pulp B-cell lymphoma, lymphoplasmacytoid lymphoma, primary splenic follicular lymphoma, B- and T-PLL, LGL leukemia and hepatosplenic T-cell lymphoma.
Investigation will always include whole body CT scan to determine if the disease truly is confined to the spleen, and whether it is focal or diffuse. A blood film and flow cytometry will be essential to recognize certain types of lymphoma and bone marrow biopsy with chromosomal as well as cytological and histological examination are essential.
If no diagnosis is obtained or if a high grade lymphoma or mantle cell lymphoma is still a possibility then a diagnostic splenectomy should be performed, but it can be avoided if its only purpose is to distinguish between splenic marginal zone lymphoma, splenic diffuse red pulp B-cell lymphoma and lymphoplasmacytoid lymphoma, since the therapeutic action to any of these diagnoses is likely to be watch and wait, though if the possibility of mantle cell lymphoma persists or the patient has signs of an aggressive lymphoma, (B symptoms, high LDH or Beta 2M) then diagnostic splenectomy should go ahead. It should be remembered that laparoscopic splenectomy, though safer and less traumatic to the patient, will fragment the spleen and make histological examination more difficult.
The treatment of common lymphoma of the spleen should not necessarily be different from the nodal versions of the disease. Splenic follicular lymphoma should be treated with immunochemotherapy with or without splenectomy. Mantle cell lymphoma of the spleen is often more indolent, having a greater likelihood of mutated IGHV genes. After splenectomy, some patients do well with watch and wait. DLBCL is the same dread disease whether or not it is confined to the spleen and requires aggressive therapy.
Nearly 80% with isolated splenic lymphoma have either splenic marginal zone lymphoma or splenic diffuse red pulp B-cell lymphoma. These mainly occur in the elderly and commonly pursue an indolent course with roughly 70% of patients alive at 10 years. Some patients seem to have their disease secondary to an HCV infection and for these treatment with Peg-interferon and Ribavirin is indicated. For others watch and wait until the disease becomes symptomatic or progressive when splenectomy might become applicable. As an alternative, treatment with rituximab might be ventured. It can be very effective and has proved its worth in the closely related cold hemagglutination syndrome. Treatment should be started if Hb <10g/dL, platelets <80,000 of a rising LDH, or if the splenomegaly becomes symptomatic. There is a prognostic scoring system which considers as risk factors a Hb <12 g/dL. a raised LDH and an albumin <3.5 g/dL. If no risk factors are present the overall 5-year survival is 83%, if one, it is 72% and if two or more, it is 56%.
For patients unwilling to consider splenectomy, those with a rapidly rising lymphocyte count, those with abdominal lymph nodes or extranodal involvement and those with AIHA or other autoimmune complications chemotherapy may be indicated. The choice of agent is unclear and there are advocates for FCR, FR and bendamustine.