Acquired amegakaryocytic thrombocytopenia and red cell aplasia in a patient with thymoma progressing to aplastic anemia successfully treated with allogenic stem cell transplantation

Association of pure red-cell aplasia with thymoma is well documented. However, acquired amegakaryocytic thrombocytopenia (AAMT) has been rarely associated with thymoma with only five reported cases in literature. We report a patient with thymoma complicated by pure red cell aplasia (PRCA) and AAMT who progressed to develop aplastic anemia (AA). The patient was refractory to 10-months of immunosuppressive therapy with cyclosporine, prednisone, and antithymocyte globulin. She was eventually treated with allogeneic stem cell transplantation (allo-SCT). On Day +323 the patient continues to be transfusion-independent. This case illustrates how in patients with thymoma and AAMT may herald development of AA. This is also the first report of a patient with AAMT progressing to thymoma-associated AA being successfully treated with allo-SCT. The successful outcome suggests allo-SCT as a feasible option similar to other AA patients.     

Experience with surgery for thymoma associated with pure red blood cell aplasia. Report of three cases

We present three cases of thymoma associated with pure red blood cell aplasia in which thymomectomy and thymectomy were performed. Case 1, a patient with pure red blood cell aplasia and hypogammaglobulinemia, was treated after surgery with immunosuppressive agents. She did not show any remission and died eight months after the operation. Case 2, a patient with pure red blood cell aplasia alone, showed transient erythropoiesis only in the early post-operative period and died one year and seven months after the operation. Patient 3 had pure red blood cell aplasia alone before surgery and was treated after surgery with prednisolone and fluoxymesterone. He showed good remission from the aplasia after these treatments; however, myasthenia gravis appeared seven months after the operation. These results seem to show that such combined therapy as applied in case 3 may be effective for some of the patients with pure red blood cell aplasia and thymoma; however, the effects of thymomectomy or thymectomy (or both) are still controversial for the treatment of pure red blood cell aplasia.     

Relapse of autoimmune hemolytic anemia in Evans syndrome after thymectomy for pure red cell aplasia

A 81-year-old woman was referred to our hospital with pure red cell aplasia (PRCA) associated with a thymoma in May 2005. She had previously suffered from Evans syndrome which had been improved by prednisolone in 1999. She underwent a thymectomy, however her anemia subsequently got worse. Reticulocytopenia was noted and a marrow erythroid series was aplastic. Furthermore, both direct and indirect Coombs tests were positive, and the serum haptoglobin level was low. Based on these findings, the patient was diagnosed as having PRCA complicated with relapsed autoimmune hemolytic anemia (AIHA). The PRCA and AIHA were successfully treated with prednisolone and cyclosporine. To our knowledge, only one case of the PRCA complicated with AIHA after thymectomy has been reported. FoxP3 positive regulatory T-cells (Treg), which maintain immunological self-tolerance, were readily detectable in the excised thymoma. Thus, thymectomy resulted in removal of the Treg pool and might explain the autoimmune activation, believed to be one of the mechanisms of the post-thymectomy recurrence of the AIHA in this case.     

Successful treatment of thymoma-associated pure red cell aplasia with intravenous immunoglobulins

Repeated cycles of intravenous immunoglobulins (IVIG) have been reported to be successful in a few patients with idiopathic pure red cell aplasia (PRCA) or associated with another pathology. The efficacy of this treatment for PRCA with thymoma has not been reported previously. We describe here the case of a 75-yr-old man who presented with PRCA associated with a benign thymoma. After failure of thymectomy, corticosteroids and octreotide, a complete durable remission was obtained after a single 5-d cycle of IVIG.     

Clonal rearrangement of intratumoral T-cell receptor beta-chain gene in two patients with thymoma accompanied by pure red cell aplasia]

We encountered two cases of thymoma accompanied by pure red cell aplasia and demonstrating clonal rearrangement of the T-cell receptor beta-chain gene (TCR-beta) in lymphocytes. Patient 1 was a 55-year-old man and Patient 2 was a 43-year-old woman. Both had severe anemia and mediastinal tumors. Bone marrow aspiration was performed and pure red cell aplasia diagnosed. Thymoma was the presumptive diagnosis for the mediastinal tumors, and extended thymectomy was performed. The post-operative diagnosis was invasive thymoma (spindle-cell type) in Patient 1 and non-invasive thymoma (mixed lympho-epithelial type) in Patient 2. The cell compositions (%) obtained with T-cell surface marker analysis were as follows: [table: see text] Southern blot analysis disclosed clonal rearrangement of TCR-beta genes in thymoma thymocytes from both patients.     

Pure red cell aplasia associated with thymoma

A case of thymoma with mixed spindle and lymphocytic variety along with acquired, secondary, chronic pure red cell aplasia is an uncommon entity. The presented case is a case of anterior mediastinal tumour with marked anemia. On histopathologic and hematological examinations, it proved to be a case of thymoma along with pure red cell aplasia. High index of suspicion, bone marrow examination, radiological including CT scan examination, total thymectomy after preparation with repeated blood transfusion remains the mainstay of treatment. Prolonged corticosteroid therapy leads to remission for upto ten months after operative intervention.     

Effect of tacrolimus in a patient with pure red-cell aplasia

A 78-year-old woman has suffered from pure red-cell aplasia (PRCA) associated with generalized myasthenia gravis and thymoma. Cyclosporin A (CyA) with corticosteroid increased numbers of erythroid cells in her bone marrow cells but she required monthly blood transfusions. Administration of tacrolimus as a substitution for CyA inhibited progression of anemia without the need for further blood transfusion. No serious side effects were observed. This case demonstrates that tacrolimus is another option of treatment for PRCA in patients who fail to respond to CyA.     

Complete remission of pure white cell aplasia associated with thymoma,autoimmune thyroiditis and type 1 diabetes

Pure white cell aplasia (PWCA) is a rare disorder of unknown origin, often associated with thymoma, characterized by selective neutropenia or pure agranulocytosis, and absence of granulocyte precursors in the bone marrow, but with normal erythroblasts and megakaryocytes. We report a case of PWCA associated with thymoma. Unusual findings in this case report included simultaneous presence of autoimmune thyroiditis, type 1 diabetes, anti-striated muscle antibodies, and the presence in the peripheral blood of CD8+ T cells that expressed a homogeneous naive phenotype. Neutrophil count became normal on immunosuppressive therapy after thymectomy.     

Thymoma-associated systemic lupus erythematosus, exacerbating after thymectomy. A case report and review of the literature

SIR, Myasthenia gravis (MG), pure red cell aplasia and acquiredhypogammaglobulinaemia are well recognized to be associatedwith thymoma, but systemic lupus erythematosus (SLE) can alsobe a manifestation of thymoma. The literature on the featuresof thymoma-associated SLE and the effect of thymectomy on SLEdisease activity is conflicting. A 76-yr-old Caucasian woman presented with malaise and weightloss of 10 kg over the past 6 months. Clinical examination atthat time revealed a low body weight of 46 kg and a body lengthof 160 cm. Laboratory examination showed     

Marrow-Suppressing Factors in the Blood in Pure Red-Cell Aplasia, Thymoma and Hodgkin''s Disease

1. A stem cell suppressing factor has been found in the serum of a patient with Hodgkin's disease, a thymic tumour and pure red-cell aplasia. This factor disppeared when active erythropoiesis returned following radiotherapy to the tumour.
2. The suppressing activity was assayed in mice by measuring the capacity of their bone marrow to restore erythropoiesis in heavily irradiated recipients.
3. Failure to demonstrate a raised erythropoietin level, as well as the finding that IgA and IgM immunoglobulins were reduced, suggested that autoimmune processes might be involved. However, it appeared unlikely that the factor was an autoantibody since suppressing activity was destroyed by storage at −20° C.
4. The sera of nine other patients, one with a thymoma associated with erythroid and megakaryocyte aplasia, three with anterior mediastinal tumours and five with secondary marrow aplasia, were assayed. Three of these showed mild suppressing activity, but this could have been due to non-specific causes, the nature of which is discussed.     

Pure red cell aplasia and thymoma: demonstration of persisting inhibition of erythropoiesis after thymectomy and resolution after immune suppressive treatment

A 61 year-old woman presented with general malaise, hair loss, pure red cell aplasia (PRCA) and thymoma: no growth of erythropoietic colonies in vitro (BFU-E) was observed in the presence of her own serum. The thymoma was removed: after the operation no improvement of her anaemic condition was observed and colony growth was very poor, although T-depleted narrow preparations showed a modest BFU-E formation in autologous serum. Following treatment with azathioprine, a complete recovery was seen, associated with normal BFU-E formation in vitro. This observation suggests that a complex inhibition of erythropoiesis may operate in PRCA involving both humoral and cellular factors; thymectomy alone may not be sufficient to restore haemopoiesis, but has to be followed by immune suppressive treatment.     

Pure red-cell aplasia secondary to pregnancy, characterization of a syndrome

The aim of this study was to characterize the syndrome of pure red-cell aplasia (PRCA) secondary to pregnancy. All published cases of PRCA induced by pregnancy were reviewed. Additionally, we reported a patient who developed PRCA on three occasions; two were triggered by pregnancy and one after medroxyprogesterone administration. Ten patients with 13 pregnancy-induced PRCA episodes were reported. The PRCA occurred at any gestational age. All patients received blood transfusions, and six of them were treated corticosteroids. The PRCA resolved in all subjects postpartum. Five women had subsequent pregnancies; three were complicated by PRCA, one was normal, and one had spontaneous abortion without PRCA. One subject developed a PRCA after long-term exposure to medroxyprogesterone. Infant blood values were normal in the nine reported cases. Pregnancy-induced PRCA is a self-limited syndrome with a high risk for relapse during subsequent pregnancies. It can be managed by blood transfusions. Progestins might cause PRCA in these women. The authors have nothing to disclose. This study was not funded by any source and there is no proprietary interest of any kind.     

Macrocytic anemia and thrombocytosis associated with thymoma: a case report

Thymomas are often associated with autoimmune disorders. We report on a 45-year-old female patient with thymoma and hypogammaglobulinemia (Good's syndrome) who developed symptomatic macrocytic anemia (Hb 4.4 g/dl, MCV 112 fl) and thrombocytosis (Plt 442 G/l). Besides hypogammaglobulinemia (IgG 589 mg/dl), an inverted ratio of CD4(+)/CD8(+) cells was seen. The bone marrow biopsy showed a slightly hypercellular bone marrow with normal granulopoiesis, normal megakaryopoiesis and a mild dyserythropoiesis without any ring-sideroblasts. The in-vitro stem cell culture from the bone marrow revealed an atypical growth of macroclusters, reduced BFU-E and CFU-GEMM colony growth, whereas the CFU-GM colony growth was within the normal range. The chromosomal analysis showed a normal karyotype. The plasma vitamin B(12) and folate levels were within normal ranges, and we could not detect any autoantibodies. These findings excluded the differential diagnoses pure red cell aplasia (PRCA) and pernicious anemia. After resection of the thymoma of mixed cell type, the macrocytic anemia and thrombocytosis disappeared. The clinical course was complicated by a cerebral palsy and a life-threatening fungal septicemia after surgery. In the third year after thymectomy, hyporegenerative macrocytic anemia and thrombocytosis reappeared and an immunosuppressive treatment with prednisolone (1 mg/kg BW) was started. After initiation of the prednisolone therapy, reticulocyte counts increased and macrocytic anemia as well as thrombocytosis disappeared. The normalization of these laboratory parameters during glucocorticoid therapy suggests that in rare cases the constellation of macrocytic anemia, thrombocytosis and hypogammaglobulinemia may be due to an underlying immunologic mechanism.     

Cyclosporin improved pure red cell aplasia associated with thymoma and tended to decrease thymoma size: a case report]

The case was a 56-year-old man who underwent extended thymothymectomy in 1993 because of an invasive thymoma classified as Masaoka IIa. The tumor was disseminated through the right thoracic cavity in 1994. Although the chemotherapy was repeated, the disseminated thymoma tended to increase in size. The patient was suffering from severe anemia, and pure red cell aplasia was diagnosed in September 2002. The administration of cyclosporin was initiated, and not only brought about improvement of pure red cell aplasia but also tended to shrink the thymoma. Cyclosporin may be an effective drug for the reduction of thymoma as well as for pure red cell aplasia.     

Malignant thymoma complicated by amegakaryocytic thrombocytopenic purpura

We report the case of a 41-year-old man with malignant thymoma complicated by amegakaryocytic thrombocytopenia 10 years after diagnosis of myasthenia gravis. A bone marrow aspirate showed an absence of megakaryocytes with normal maturation and differentiation of myeloid precursors. Three months later, severe neutropenia occurred, and a bone marrow examination confirmed the diagnosis of severe aplastic anemia. Associations between thymoma and myasthenia gravis, between thymoma and pure red cell aplasia, and between thymoma and aplastic anemia are well documented. Amegakaryocytic thrombocytopenia is not a recognized paraneoplastic syndrome complicating thymoma. Amegakaryocytic thrombocytopenia complicating thymoma may be a very early presentation of impending aplastic anemia.     

Pure Red Cell Aplasia and Thymoma: Loss of Serum Inhibitor of Erythropoiesis Following Thymectomy

A 32-yr-old black female with pure redcell aplasia and thymoma showed complete hematologic remission after thymectomy. Bioassay of preoperative serumand urine in exhypoxic polycythemicmice revealed the presence of significantlevels of erythropoiesis-stimulating factor(ESF or erythropoietin). Antierythropoietin completely neutralized the erythropoietic effect of these samples. Utilizingboth normal and exhypoxic polycythemicmice, the preoperative serum and urinewere also found to contain a potent inhibitor of erythropoiesis. However, nosuch activity was demonstrated in salineextracts of the tumor tissue. The inhibitor was present in the serum IgGfraction. Serum to which excess ESF hadbeen added, after prior neutralization ofendogenous ESF with anti-ESF, failedto stimulate erythropoiesis in the polycythemic mouse.

Submitted on January 10, 1971 Revised on June 9, 1971 Accepted on June 15, 1971     

Diphenylhydantoin-induced severe yet reversible anemia during pregnancy

Diphenylhydantoin (DPH) therapy, often used in treating epileptic seizures, can cause anemia in some patients. A 26-year-old female suffered from convulsions due to encephalitis and was placed on DPH therapy. About two months after the initiation of DPH therapy, her hemoglobin level was 3.8 g/dL. Her anemia improved after the discontinuation of DPH, confirming that the anemia was caused by DPH. Pure red-cell aplasia (PRCA) combined with hemolytic anemia was indicated by results such as erythroid aplasia, an increased LDH level, and a decreased haptoglobin level. PRCA complicated by hemolytic anemia could be responsible for anemia associated with DPH.     

A case of mixed connective tissue disease complicated with thymic carcinoma and Hashimoto's thyroiditis

We report the case of a 63-year-old woman who suffered from mixed connective tissue disease (MCTD) complicated with thymic carcinoma and Hashimoto's thyroiditis. Although many systemic syndromes associated with thymoma and thymic carcinoma, i.e., myasthenia gravis, pure red cell aplasia, hypogammaglobulinemia, and Hashimoto's thyroiditis, are known, this is the first report of MCTD complicated with thymic carcinoma. It was suggested that MCTD may be a paraneoplastic syndrome associated with thymic carcinoma.     

Acquired pure red-cell aplasia associated with an increase of T cells bearing receptors for the Fc of IgG

A case of steroid-resistant acquired pure red-cell aplasia associated with a relative and absolute increase of TG cells is described. Removal of T cells enhanced erythroid colony and burst formation in vitro, and it is suggested that TG cells may be implicated in the pathogenesis of this case of acquired pure red-cell aplasia.     

A case of systemic lupus erythematosus complicated by pure red cell aplasia and idiopathic portal hypertension after thymectomy

We describe a 49-year-old woman who presented in 2002 with pure red cell aplasia (PRCA), systemic lupus erythematosus (SLE), and idiopathic portal hypertension (IPH) that developed following a thymectomy. She underwent a thymectomy at 40 years of age to treat myasthenia gravis. PRCA developed 3 years after the thymectomy and she was successfully treated with cyclosporin. Systemic lupus erythematosus and IPH were diagnosed 6 years later. We conclude that immunological dysfunction resulting from the thymectomy contributed significantly to the subsequent development of PRCA, SLE, and IPH in this patient. This is the first report to describe this extremely rare occurrence.