Bronchocentric granulomatosis associated with pure red cell aplasia and lymphadenopathy.

Bronchocentric granulomatosis developed in a patient with previously diagnosed pure red cell aplasia and lymphadenopathy. There was an excellent response to corticosteroid treatment. An immunological pathogenesis common to bronchocentric granulomatosis and pure red cell aplasia is suggested.     

Concomitant thymectomy and cardiac operation in a patient with pure red cell aplasia

Pure red cell aplasia is a rare condition resulting in severe anemia. Medical therapy is indicated, unless a thymoma is present. In patients with concurrent cardiac pathology requiring operation, simultaneous operation should be contemplated to avoid risky resternotomy. We describe an exceptionally rare case of a patient with pure red cell aplasia secondary to a thymoma who underwent concomitant thymectomy and coronary artery grafting with a successful surgical outcome.     

Microthymoma: definition of the entity and distinction from nodular hyperplasia of the thymic epithelium (so-called microscopic thymoma)

We report 2 cases of microscopic-sized thymoma, which probably represents the earliest phase of thymoma development. The 2 patients presented with pure red cell aplasia and myasthenia gravis, respectively. The thymectomy specimens did not reveal tumor on gross examination, but histologically each contained small thymomas measuring 5 mm and 7 mm in largest dimension, respectively. One of the tumors was unencapsulated and involved a single lobule only, and the other was encapsulated and comprised two lobules. The tumors consisted of ovoid epithelial cells with pale nuclei and distinct nucleoli, scattered in a background of small lymphocytes. Foci of medullary differentiation and perivascular space were identified in the 2 cases, respectively. The lymphocytes were confirmed to be immature T cells on immunohistochemical studies (CD3+, TdT+). Except for the microscopic size, the morphology of the two tumors conforms to conventional type B1/B2 and type B2 thymoma, respectively. We propose calling such incidental small tumor "microthymoma" to distinguish it from the so-called microscopic thymoma, which is composed of small thymic epithelial nests and probably more appropriately termed "nodular hyperplasia" of the thymic epithelium.     

Thymoma

OBJECTIVE: We evaluated the prognostic factors for thymoma that remain controversial. METHODS: We studied 72 consecutive patients treated for thymoma during the period between 1966 and 1997. Recurrence-free interval rates and overall survival rates calculated by the Kaplan-Meier method were compared using log-rank test by the Masaoka stage, extent of surgical resection, histology, or associated disease(s). Multivariate analysis was performed using Cox's proportional hazards model. RESULTS: Thirty-two thymomas were at Masaoka stage I, 9 at stage II, 15 at stage III, and 16 were at stage IV. There were 56 complete resections, 7 incomplete resections (2 at stage III and 5 at stage IV), and 9 biopsies (1 at stage III and 8 at stage IV). Forty-one thymomas were cortical, 16 medullary, and 15 were mixed form. Association of myasthenia gravis was found in 20 patients, and pure red cell aplasia in 7. After an average follow-up period of 103 months, the recurrence-free 5-, 10-, 15-year interval rate was 89%, 80%, 80%, respectively, and overall 5-, 10-, 15-year survival rate was 86%, 71%, 59%, respectively. Factors influencing the recurrence-free interval and overall survival included the Masaoka stage, extent of surgical resection, and association with pure red cell aplasia. Multivariate analysis revealed stage IV tumor and association with pure red cell aplasia as risk factors for recurrence. Pure red cell aplasia indicated poor prognosis for overall survival. CONCLUSIONS: Masaoka stage, extent of surgical resection, and association with pure red cell aplasia were prognostic factors for thymoma. Multidisciplinary treatment for stage IV tumors and better control of pure red cell aplasia, if associated, should be investigated.     

Antibody-mediated pure red cell aplasia in chronic kidney disease patients receiving erythropoiesis-stimulating agents: new insights

Antibody-mediated pure red cell aplasia is a very rare but devastating condition affecting patients receiving treatment with erythropoiesis-stimulating agents. New cases continue to emerge, generally in clusters, consistent with an 'environmental' trigger to its pathogenesis. Defining the causes of antibody-mediated pure red cell aplasia is clearly of importance for patients with chronic kidney disease, but any developments in this area may also have relevance to other disease areas as therapeutic delivery of endogenous proteins rapidly increases. This review focuses on the current knowledge regarding the etiology of antibody-mediated pure red cell aplasia and the current approach to therapy.     

Thymoma

Objective: We evaluated the prognostic factors for thymoma that remain controversial.Methods: We studied 72 consecutive patients treated for thymoma during the period between 1966 and 1997. Recurrence-free interval rates and overall survival rates calculated by the Kaplan-Meier method were compared using logrank test by the Masaoka stage, extent of surgical resection, histology, or associated disease(s). Multivariate analysis was performed using Cox's proportional hazards model.Results: Thirty-two thymomas were at Masaoka stage I, 9 at stage II, 15 at stage III, and 16 were at stage IV. There were 56 complete resections, 7 incomplete resections (2 at stage III and 5 at stage IV), and 9 biopsies (1 at stage III and 8 at stage IV). Forty-one thymomas were cortical, 16 medullary, and 15 were mixed form. Association of myasthenia gravis was found in 20 patients, and pure red cell aplasia in 7. After an average follow-up period of 103 months, the recurrence-free 5-, 10-, 15-year interval rate was 89%, 80%, 80%, respectively, and overall 5-, 10-, 15-year survival rate was 86%, 71%, 59%, respectively. Factors influencing the recurrence-free interval and overall survival included the Masaoka stage, extent of surgical resection, and association with pure red cell aplasia. Multivariate analysis revealed stage IV tumor and association with pure red cell aplasia as risk factors for recurrence. Pure red cell aplasia indicated poor prognosis for overall survival.Conclusions: Masaoka stage, extent of surgical resection, and association with pure red cell aplasia were prognostic factors for thymoma. Multidisciplinary treatment for stage IV tumors and better control of pure red cell aplasia, if associated, should be investigated.     

胸腺瘤合并单纯红细胞再生障碍性贫血(附5例报道)

目的 探讨胸腺瘤合并单纯红细胞再生障碍性贫血（PRCA）的临床特征及外科治疗方法.方法 回顾分析1979年至2004年间5例胸腺瘤合并PRCA病人的临床资料.结果 男2例,女3例;年龄43～68岁,平均54.6岁,均获根治性切除.胸腺瘤合并PRCA者占同期胸腺瘤病人的2.7%（5/185例）.术后早期PRCA情况明显改善,术后长期生存4例,1例复发死亡.结论 胸腺瘤合并PRCA是一种少见疾病,外科治疗是本病的首选治疗手段.对单纯红细胞再生障碍性贫血不能缓解者给予激素和免疫抑制剂治疗,可望取得较好疗效.     

True thymic hyperplasia: a clinicopathological study

In this report, we describe the clinicopathological features of 4 patients with true thymic hyperplasia. This controversial thymic lesion has only recently been defined as a variable, often massive enlargement of the thymus characterized by a nearly normal microscopic structure. Our study of 4 patients and review of the literature indicate that true thymic hyperplasia has a well-defined clinicopathological profile: prevalence in children or young male patients, absence of associated autoimmune diseases, and often presence of respiratory distress or peripheral blood lymphocytosis, or both. True thymic hyperplasia should be considered in the differential diagnosis of anterior mediastinal masses in children and young adolescents.     

Epoetin-induced pure red cell aplasia: diagnosis and treatment

PURPOSE OF REVIEW: Antibody-mediated pure red cell aplasia is now recognized as a rare complication of erythropoiesis-stimulating agent therapy. The incidence of this adverse effect peaked in 2002, but new cases still appear sporadically. The aim of this review is to discuss the latest opinions regarding the detection and management of this condition. RECENT FINDINGS: The diagnosis of classical erythropoiesis-stimulating agent induced pure red cell aplasia is made by a constellation of clinical features, including severe transfusion-dependent anaemia, reticulocytopenia, low or absent erythroblasts in the bone marrow, and the presence of circulating antierythropoietin antibodies. Recently, some cases have been reported in which the bone marrow findings show red cell hypoplasia rather than aplasia; this may represent earlier presentations of the same condition. SUMMARY: Management of pure red cell aplasia as a complication of erythropoiesis-stimulating agent therapy consists of stopping the drug and implementing an immunosuppressive regimen to reduce or abolish erythropoietin antibody production. A recent animal study suggested that a possible alternative strategy may be to administer a novel peptide-based erythropoietin receptor agonist called Hematide that does not cross react with antierythropoietin antibodies, and will allow ongoing stimulation of erythropoiesis; this is the subject of a current clinical trial.     

Anterior mediastinal exenteration for thymoma associated with pure red cell aplasia

A 46-year-old female bad thymoma associated with pure red cell aplasia, a relatively uncommon entity. Anterolateral thoracotomy in supine position offered excellent exposure for exenteration of anterior mediastinum. Steroids and cyclophosphamide were administered postoperatively. She remains stable one year after surgery. The incidence, clinical features, pathology, pathogenesis, management and prognosis of thymoma with pure red cell aplasia are reviewed.     

The role of thymectomy in red cell aplasia.

Red cell aplasia is an unusual cause of anemia. Fifty percent of all patients with red cell aplasia will have a thymoma. Twenty-five to 30% of those who undergo thymectomy will be cured. Data are presented that suggest that any patient with red cell aplasia should have thymectomy through a median sternotomy. One of 3 such patients who underwent the operation has had complete remission for two years.     

Invasive thymoma associated with pure red cell aplasia and liver metastasis: a case report]

A case of invasive thymoma associated with pure red cell aplasia and liver metastasis was reported. A 57-year-old male was admitted to our hospital because of hepatic abnormal shadow on computed tomography. Malignant tumor was suspected by imaging procedures. Left lateral segmental resection of liver was performed and histo-pathological examination proved the tumor to be liver metastasis of thymoma. He was received 50 Gy irradiation after incomplete resection of thymoma. In the course of time he contracted pure red cell aplasia. But he is well controlled medically and alive 7 years after the surgery.     

Epoetin-induced autoimmune pure red cell aplasia

During the first 10 yr of therapy with recombinant human erythropoietin ([EPO]), only three cases of antibody-associated pure red cell aplasia have been described in patients who were treated with EPO, whereas several millions of patients have received this treatment. Thus, the possibility for epoetin to induce the formation of anti-EPO antibodies was considered extremely low. However, since 1998, a significant increase in the number of cases of EPO-induced pure red cell aplasia has been found in patients with chronic kidney disease with a peak in 2001 and 2002. The incidence rate seems now to be back to the baseline level. The change in formulation of epoetin a sold outside the United States seems to be the cause of these antibodies.     

Cyclosporine in the treatment of azathioprine-induced red cell aplasia following renal transplantation

Azathioprine, a well-known immunosuppressive agent, is used extensively in renal transplantation. There have been several case reports of pure red cell aplasia induced by this drug following a successful kidney transplant. Previous management of azathioprine-induced red cell aplasia included reduction of azathioprine dose, or treatment with cyclophosphamide. We propose the substitution of cyclosporine for azathioprine, in this clinical setting. Not only does cyclosporine allow recovery of bone marrow function, but it maintains a level of immunosuppression which stabilizes renal function in the post-transplant patient.     

True thymic hyperplasia in an infant

True thymic hyperplasia is a very rare entity. We present an instance of idiopathic true massive thymic hyperplasia in a 9-month-old girl with a very large left-sided mediastinal mass noted on diagnostic imaging. Percutaneous biopsy revealed normal thymic tissue. Steroids were administered with no response. Surgery may be required in patients with respiratory distress unresponsive to steroids.     

Surgical pathology of the thymus: 20 years'' experience.

Fifty five patients underwent thymic surgery at Papworth Hospital from April 1964 to March 1984. The number presenting and the percentage with symptoms annually remained unchanged during this period. Forty four of these 55 patients had tumours. Twenty eight had thymomas (18% of whom had myasthenia gravis and 7% red cell aplasia), nine Hodgkin's disease, four germ cell tumours, and three secondary carcinomatous tumours. Five tumours were cystic. Six further patients had non-tumourous cystic lesions (four simple, one foregut, one lymphangiectatic). The remaining five patients had follicular hyperplasia; all of these had myasthenia gravis. Complete excision was performed in 41 of the 55 patients. So far survival is 100% in those with benign lesions other than benign thymomas, where the survival was 70% at five years. Those with malignant thymomas had a 60% survival rate at five years and those with Hodgkin's disease 29%.     

Pure red cell aplasia caused by Parvovirus B19 infection in solid organ transplant recipients: a case report and review of literature

Human Parvovirus B19 (PV B19) is one of the several recently described 'emerging viruses' and has been identified as the etiological agent of 'fifth disease' in childhood. Human PV B19, which is the etiological agent of transient erythroblastopenia in hemolytic anemia, is also a recognized rare cause of red cell aplasia in immunocompromised patients, including transplant recipients. To date, 26 cases of PV B19-induced red cell aplasia have been reported in solid organ transplant recipients. Twelve patients had cyclosporine-based immunosuppression and 14 had tacrolimus-based immunosuppression. Sixteen of these patients required treatment with commercial intravenous immunoglobulin alone, 1 required treatment with intravenous immunoglobulin and plasmapheresis, 4 required intravenous immunoglobulin and erythropoietin, 1 required treatment with intravenous immunoglobulin and conversion of tacrolimus to cyclosporine, 1 had improvement in hematocrit with erythropoietin alone and in 3 patients the disease was self-limiting. Herein, we report a case of pure red cell aplasia caused by acute PV B19 infection in a renal transplant recipient in whom the immunosuppressive regimen included prednisone, mycophenolate mofetil and tacrolimus and the red cell aplasia resolved with discontinuation of mycophenolate mofetil.     

Renal and thymic pathology in thymoma-associated nephropathy: report of 21 cases and review of the literature.

BACKGROUND: Acquired thymic disease (malignant thymoma or thymic hyperplasia) is associated with various autoimmune diseases, such as myasthenia gravis (MG), pure red-cell aplasia (PRCA), pemphigus vulgaris or systemic lupus erythematosus (SLE). Renal disease has rarely been observed in association with thymoma. METHODS: This retrospective, multicentric study collected data on patients with thymic disease and biopsy-proven renal involvement. RESULTS: Twenty-one patients were studied (age: 49+/-14 years; male/female ratio: 8/13). Thymic pathology revealed mostly high-grade malignant thymoma (B2 and AB type); two cases were associated with non-malignant thymic hyperplasia. MG was found in nine out of 21 cases, SLE in three, PRCA in three and pemphigus in two. In 47% of these cases, nephropathy occurred after curative treatment of thymoma (108+/-83 months; range: 8-180 months), mainly based on surgical thymectomy associated with radiotherapy. Clinical and laboratory findings included nephrotic syndrome (75%), renal failure (50%), frequent presence of antinuclear antibodies and hypogammaglobulinaemia. Renal pathology showed minimal change disease in 14 patients and focal segmental glomerulosclerosis (FSGS) in one. Membranous nephropathy was observed in four cases, ANCA-associated glomerulonephritis in two and thrombotic microangiopathy in one. Most patients with minimal change disease or FSGS (11/13) were steroid-sensitive. Despite good response to steroids, 38% of patients died from thymoma and 17% developed end-stage renal failure. CONCLUSIONS: Glomerulopathy can be associated with thymoma or thymic hyperplasia. The present series shows that minimal change disease is the most frequent thymoma-associated glomerular lesion and that it may occur several years after thymectomy.     

Triad of thymoma, myasthenia gravis and pure red cell aplasia combined with Sj?gren’s syndrome

A 36-year-old woman complained of cough and high fever. Computed tomographic scans demonstrated a mediastinal mass. A couple of months later, she developed dryness in her eyes and mouth. Biopsy of the lip confirmed the diagnosis of Sj?gren’s syndrome. She underwent thymo-thymomectomy. Pathological findings of the mass revealed thymoma. At two months after surgery, she developed ptosis and dysphagia that were compatible with myasthenia gravis. The clinical symptoms were adequately controlled with prednisolone. At eleven months after surgery, she presented with severe anemia, which led to the diagnosis of pure red cell aplasia. The following treatment with cyclosporin caused hemoglobin concentration to rise. However, she continues to suffer from dryness of her eyes and mouth. The case is the first to be reported with Sj?gren’s syndrome and the triad of thymoma, myasthenia gravis and pure red cell aplasia, and is compared with previously reported cases of the three conditions.     

Triad of thymoma,myasthenia gravis and pure red cell aplasia combined with Sjögren’s syndrome

A 36-year-old woman complained of cough and high fever. Computed tomographic scans demonstrated a mediastinal mass. A couple of months later, she developed dryness in her eyes and mouth. Biopsy of the lip confirmed the diagnosis of Sjögren’s syndrome. She underwent thymo-thymomectomy. Pathological findings of the mass revealed thymoma. At two months after surgery, she developed ptosis and dysphagia that were compatible with myasthenia gravis. The clinical symptoms were adequately controlled with prednisolone. At eleven months after surgery, she presented with severe anemia, which led to the diagnosis of pure red cell aplasia. The following treatment with cyclosporin caused hemoglobin concentration to rise. However, she continues to suffer from dryness of her eyes and mouth. The case is the first to be reported with Sjögren’s syndrome and the triad of thymoma, myasthenia gravis and pure red cell aplasia, and is compared with previously reported cases of the three conditions.