T-cell large granular lymphocytic leukemia associated with pure red cell aplasia, successfully treated with cyclophosphamide

Authors report effective treatment of T-cell large granular lymphocyte (LGL) leukaemia and secondary pure cell aplasia with cyclophosphamide. The current classification of LGL proliferations is presented, with emphasis on the issues of diagnosis, clinical course and treatment. LGL proliferations are not so rare that previously thought and should be involved in the differential diagnosis of neutropenia, pure red cell aplasia, Felty's syndrome and vasculitis of unknown origin.     

Pure red cell aplasia associated with true thymic hyperplasia

We reported unique magnetic resonance imaging (MRI) findings of a 57-year-old Japanese man who was diagnosed as Vogt-Koyanagi-Harada disease. This patient presented with complaints of a transient severe headache followed by a bilateral loss of visual acuity and truncal ataxia. Magnetic resonance imaging revealed abnormal contrast enhancement of both the uveas and the cerebellar vermis corresponding to his neurological abnormalities. The distribution and the nature of the resolution of this unusual pattern of contrast enhancement suggested that these MRI findings might illustrate transient destruction of the blood brain barrier or vascular extravasations. Such events might be representative of pathophysiology involving the central nervous system that occurred in patients with Vogt-Koyanagi-Harada disease.     

Pure red cell aplasia in autoimmune polyglandular syndrome with T lymphocytosis

We report the onset of pure red cell aplasia (PRCA) in a patient with a history of polyglandular syndrome including Addison's disease, malabsorption syndrome, diabetes type I and gastric hyperplastic polyposis. An autoimmune origin for this complex disorder was not supported by the presence of organ specific antibodies, but T cells were found to be of polyclonal origin, as demonstrated by molecular analysis of T cell receptor (TCR) gene rearrangement. The pathophysiology of this case, based on laboratory findings and response to therapy, is discussed.     

Autoimmune disease and chronic lymphocytic leukemia: autoimmune hemolytic anemia, pure red cell aplasia, and autoimmune thrombocytopenia

Immune dysregulation, a hallmark of chronic lymphocytic leukemia (CLL), manifests itself in three autoimmune diseases: warm autoimmune hemolytic anemia (AIHA); idiopathic thrombocytopenia (ITP); and, pure red cell aplasia (PRCA). AIHA occurs in 11% of advanced stage CLL patients. Prednisone is the first treatment of choice, with 90% responses and 65% complete responses. More than 60% of patients relapse when treatment is stopped. Intravenous immunoglobulin, the next line of treatment, causes responses in 40% of patients. While the data are very limited, cyclosporine A is a reasonable choice for third-line therapy. Alkylating agents, danazol, plasma exchange, immunoabsorption, vincristine-loaded platelets, splenectomy, and splenic irradiation are also reported to cause responses. The data on mechanisms of AIHA are most consistent with immune dysregulation leading to loss of tolerance to a self antigen which in turn leads to the immune-based hemolytic anemia. PRCA is underrecognized in CLL with 6% of CLL patients having PRCA when tested for it. Unlike AIHA, PRCA often occurs in early stage disease. Anemia, reticulocytopenia, and a marrow virtually devoid of red blood cell precursors are hallmarks of PRCA. Corticosteroid therapy is the first line of treatment. If a response is not obtained in 4 weeks, cyclosporine A should be added. Although the data on pathophysiology are very limited, PRCA appears to be the result of an abnormal T cell that both fails in its normal function to support growth and inhibits the growth of erythroid progenitor cells. ITP occurs in 2-3% of CLL patients, occurs in early stage disease and may be a presenting manifestation. Initial therapy for ITP mirrors the guidelines for primary ITP. Initial therapy should consist of prednisone. Seventy percent of patients respond. Splenectomy is a reasonable second-line treatment. Autoimmune phenomena, largely related to blood cells, are based in the immune dysregulation of CLL. Longer survivals in CLL patients, more treatment regimens per patient, and more immunosuppression with modern treatments, allow us to predict an increasing incidence of autoimmune blood cell diseases in CLL.     

Pure red cell aplasia and myasthenia gravis with thymoma: a case report and review of the literature

In women, osteoporosis with fractures can happen between 50 years, the age of the menopause, and 80 years. Over these three decades, the condition of bone metabolism is not the same. The years after menopause present with high bone turnover. During these years, the administration of antiresorptive drugs is promising: Estrogens (plus progestagens), calcitonins, bisphosphonates. About 10 years after the menopause bone turnover slows down to low turnover. Now the administration of bone-formation stimulating agents is to be preferred: fluorides in the first line, perhaps anabolics in single cases. The prominent fracture of women older than 75 years is the hip fracture (type II osteoporosis). Bone turnover mostly is accelerated again, now due to secondary hyperparathyroidism as a consequence of long-lasting calcium and vitamin D deficiency. For treatment, calcium plus vitamin D is recommended. The exact diagnosis of the metabolic status of the skeleton is a prerequisite for the choice of the optimal therapeutic principle.     

Multicentric Castleman''s disease associated with renal amyloidosis and pure red cell aplasia

Researchers have recently proven the ability of computer simulation to predict the behaviour of cerebral aneurysms. Accurately simulating the flow of blood within the aneurysm helps researchers to predict the growth pattern of the aneurysm and the danger of rupturing. As this tool is further developed into a practical diagnostic tool, it is expected to dramatically improve the ability of surgeons to weigh the results of alternate treatment methods. The simulation method used, computational fluid dynamics (CFD), provides much more information than current diagnostic tools, including particularly shear stress levels at various stages of the cardiac cycle, which help to pinpoint areas of aneurysm formation and growth.     

Large granular lymphocyte leukemia associated with hepatocellular carcinoma: a case report

Both primary and metastatic malignancies of the masseter muscle are rare. We report a case of metastatic renal cell carcinoma to the masseter muscle. It was incidentally found as a hypervascular mass in carotid angiography for delineating a recurrent metastatic brain tumour. Prior to surgical removal, intravascular embolization via the left facial artery was performed in order to decrease intra-operative bleeding. The tumour was removed with minimum damage to the muscle fibres by the extraoral method, followed by a transient lower lip palsy. Metastatic intramuscular tumours, which are assumed to be due to haematogenous spread, are generally a sign of poor prognosis.     

Large granular lymphocytic leukemia. Case report with scarce expression in peripheral blood

Evidence is rapidly emerging which suggests that uncoupling protein 2 (UCP2), by virtue of its ubiquitous expression, may be important for determining basal metabolic rate. To assess the functional modulation of UCP2 gene expression in relation to body weight control, we examined the effects of hyperthyroid state induced by chronic treatment with triiodothyronine (T3) on UCP2 mRNA expression in male rats. Daily subcutaneous injection of T3 (37 pmol/100 g body weight) for 7 days increased UCP2 mRNA expression in brown adipose tissue (BAT), white adipose tissue (WAT) and the soleus muscle 1.6-, 1.6- and 1.7-fold compared to the controls, respectively, and increased UCP1 mRNA expression in BAT 1.2-fold. In contrast, the same treatment with T3 decreased both ob mRNA expression in WAT and plasma leptin level 0.5-fold for each. The present results suggest that T3 may directly increase UCP2 expression independently of leptin action.     

Aggressive NK cell lymphoma preceded by a ten year history of neutropenia associated with large granular lymphocyte lymphocytosis

We report a case of aggressive natural killer (NK) cell lymphoma in an 82 year old man who first presented 10 years earlier with neutropenia in association with a large granular lymphocyte (LGL) lymphocytosis. The diagnosis of NK cell lymphoma was made on the basis of morphological and immunological characteristics (CD3-CD56+) found on skin biopsy of one of multiple skin nodules which subsequently developed in association with splenomegaly, thrombocytopenia and continuing neutropenia. In addition there was BM infiltration and a cytogenetic abnormality [add(6)(p25)] was detected. Combination chemotherapy led to an initial clinical response but a relapse occurred shortly afterwards and the patient died 8 months later from infection whilst neutropenic following re-introduction of chemotherapy. Previously reported cases of aggressive NK cell lymphoma have shown a young male predominance with a rapidly progressive clinical course and without evidence of a preceding chronic phase of LGL lymphocytosis and neutropenia.     

Persistence of red cell aplasia despite treatment of malignant thymoma: a case report

Pure cytopenias are well-recognised associations with malignant thymoma. We present a case of pure red-cell aplasia (PRCA) and malignant thymoma where the PRCA continued to persist despite computerised tomographic scan evidence of regression following radiotherapy and chemotherapy.     

Biliary duct granular cell tumor: a rare but surgically curable benign tumor

Granular [correction of Granulosa] cell tumors are rare benign tumors which may be found throughout the body. Rare cases are isolated within the biliary tree. If completely resected, surgical excision is curative. A case of biliary duct granular [correction of granulosa] cell tumor is presented with review of the world's literature on this topic.     

Multidisciplinary treatment for a patient with recurrent thymoma associated with myasthenia gravis (MG), pure red cell aplasia (PRCA), and hypogammaglobulinemia

The patient is 62-year-old female. When she was 43 years old, MG occurred. At age of 49 years thymoma was found and complete thymectomy (stage III) and postsurgical irradiation were performed. At age of 57 years pleural dissemination of the thymoma was found. Chemotherapy was effective but did not obtain total tumor cell kill. Though chemotherapy has been repeated for each tumor regrowth, the regimen used at first recurrence became ineffective and the interval between tumor regrowth became shorter. This year, when she is 62 years old, PRCA and hypogammaglobulinemia were accompanied with the forth tumor regrowth.     

Sudden death in a patient with chronic lymphocytic leukemia

The authors describe a 51-year-old man with chronic lymphocytic leukemia who presented with respiratory distress and then died suddenly while in hospital. Autopsy revealed pulmonary leukostasis and a large intracardiac mass containing mostly mature lymphocytes and fibrin. Although leukostasis and lymphocyte thrombi have been described (albeit rarely) in chronic lymphocytic leukemia, an intracardiac "clot" has not. It seems plausible that this intracardiac mass caused the patient's death.     

Chemotherapy-induced myocardial necrosis in a patient with chronic lymphocytic leukemia

Cardiac toxicity following the administration of chemotherapeutic agents is well documented. Vinca alkaloids, as well as high-dose cyclophosphamide, have been associated with myocardial ischemia. The present report describes a case of acute myocardial infarction occurring in a patient with no antecedent cardiac history who received both vincristine and conventional chemotherapeutic doses of cyclophosphamide for the treatment of chronic lymphocytic leukemia. Physicians should possess a heightened awareness of this potentially serious complication.