Lymphoproliferative Disorders

Lymphoproliferative disorders (LPD) comprise a heterogeneous group of diseases characterized by uncontrolled production of lymphocytes that cause monoclonal lymphocytosis, lymphadenopathy and bone marrow infiltration. These diseases often occur in immunocompromised individuals. There are two subsets of lymphocytes: T and B cells that regenerate uncontrollably to produce immunoproliferative disorders, which are prone to immunodeficiency, a dysfunctional immune system, and lymphocyte dysregulation. Several gene mutations have been described as causes of LPD that can be iatrogenic or acquired. The X-linked LPD is characterized by a mutation in the X chromosome that predisposes to natural killer cell LPD and T-cell LPD. Autoimmune lymphoproliferative syndrome (ALPS) is a type of LPD caused by a mutation in the gene that encodes for a Fas protein which is located in the long arm of chromosome 10. Males with X-linked immunodeficiency syndrome are susceptible to LPD and at risk for acquiring EBV and further development of lymphoma. Individuals with common variable immunodeficiency (CVID), severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, ataxia-telangiectasia, Chediak–Higashi syndrome and viral infections including HIV, are also prone to LPD. Others at risk include patients undergoing tissue transplantation and the use of immunosuppressive drugs such as cyclosporin, sirolimus, and tacrolimus. Invasive fungal infections have also been linked to this pathology. Chronic lymphoproliferative disorders are immuno-morphologically and clinically heterogeneous. Common features of these processes include various immunophenotypes (T, B, and NK cells) and terminal deoxynucleotidyl transferase negativity. The B-cell lymphocytic disorders include B-cell chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, non-Hodgkin lymphoma (including mantle cell lymphoma) in leukemic phase, hairy cell leukemia and splenic lymphoma with villous lymphocytes. The T-cell chronic lymphoproliferative disorders include Sezary syndrome, T-cell prolymphocytic leukemia, adult T-cell leukemia-lymphoma, and large granulated lymphocyte leukemia.