Pure red cell aplasia and thymoma.

In this issue of the Journal, van der Marel et al.1 report a case of pure red cell aplasia (PRCA) and hypogammaglobulinemia complicating a thymoma. After surgical resection of the thymoma, the patient experienced hematopoietic recovery but required ongoing treatment with replacement gamma globulin. This case illustrates two rare paraneoplastic syndromes that can be associated with a thymoma. An association between thymomas and various paraneoplastic syndromes is well recognized, with the most common paraneoplastic syndrome being myasthenia gravis (MG), occurring in 30% to 46% of patients with a thymoma.2,3 There are at least 20 other syndromes that have been reported in association with thymoma, including PRCA, hypogammaglobulinemia, and a wide range of autoimmune disorders. More than 40% of patients with thymoma are afflicted with a so-called parathymic syndrome.4 This commentary focuses on the diagnosis and management of PRCA in association with a thymoma. Among patients with thymoma, fewer than 10% will develop PRCA, whereas fewer than 5% of patients with PRCA have a thymoma. Other known associations with PRCA include medications such as erythropoietin, viral infections including parvovirus, immune disorders, ABO-incompatible hematopoietic stem cell or bone marrow transplantation, and other malignancies. PRCA can also present as a primary, idiopathic disease.5 PRCA is characterized by erythropoietic failure with preserved granulopoiesis and megakaryopoiesis. The diagnosis should be suspected in a patient with isolated anemia and absent reticulocytes and be confirmed with a bone marrow biopsy, which classically shows a selective decrease in erythroid precursors without other diagnostic morphological abnormalities. The pathophysiology of PRCA and thymoma is not entirely understood, but it seems to be related to an autoimmune mechanism. In some cases, there has been evidence for antibodies against erythroblasts blocking differentiation of erythroid progenitors; antibodies directed against native erythropoietin blocking signaling by that cytokine; or cellmediated suppression of erythropoiesis by autoreactive T cells, large granular lymphocytes, or natural killer cells. In cases of drugor virus-induced PRCA, a direct toxic effect of a virus or drug on erythroid precursors is suspected.5–7 Because of the rarity of PRCA in association with thymoma, there are no standard treatment guidelines. At the time of diagnosis, surgical resection of the thymoma is usually undertaken. Some patients experience restoration of normal hematopoiesis after resection of the thymoma, as demonstrated in the case presented in this issue.1 It has been reported that removal of the thymoma leads to remission of PRCA in 25% to 30% of cases,8 but modern series have suggested remission from surgery alone is actually quite rare and that most patients will require some other form of therapy.9 Multiple non-surgical interventions have been attempted in patients with PRCA and thymoma, including systemic corticosteroids, other immunosuppressant drugs, chemotherapy, androgens, splenectomy, and monoclonal antibodies. In our case series of 13 patients, cyclosporine and anti-thymocyte globulin (ATG) were the most effective treatments in achieving transfusion independence.9 However, complications from therapy,