Hematol. Rep., Volume 2, Issue 1 (January 2010) – 11 articles

Klinefelter’s syndrome is characterized by abnormal karyotype 47, XXY and a phenotype associated with hypogonadism and gynecomastia. Often the disease can be diagnosed accidentally, when carrying out cytogenetic analysis in cases of a malignant blood disease. We present the clinical case of a patient diagnosed with acute myelomonoblastic leukemia- M4 Eo (AML- M4), where by means of classic cytogenetics a karyotype was found corre-sponding to Klinefelter’s syndrome. Three induction courses of polychemotherapy wermade, which led to remission of the disease, documented both flowcytometrically and cytogenetically. Full article

Central nervous system (CNS) lymphoma involving the dura mater is very rare and histologically is usually a subtype of non-Hodgkin’s lymphoma (NHL) termed mucosa-associated lymphoid tissue (MALT) lymphoma. We present a case of a 46-year old woman with dural MALT lymphoma that was found to also involve a lacrimal gland, inguinal lymph nodes, and bone marrow. Magnetic resonance imaging of the brain showed an extra-axial enhancing mass approximately 6 cm in maximum diameter along the right frontotemporal convexity. Histopathology of the resected dural mass showed MALT lymphoma expressing CD20, CD52, CD19, and CD38. Molecular studies of the B-cell receptor heavy chain demonstrated monoclonality at the involved sites. The patient was treated with four cycles of fludarabine, mitoxantrone, and rituximab with complete remission. She had recurrence in the subcutaneous tissue of the back at 12 months but has remained free of intracranial disease for 31 months. A review of the literature reveals 57 cases of dural MALT lymphoma. Only 4 had extra-CNS involvement at presentation, and only 3 had local recurrence of the dural tumor. Because of the indolent behavior of this tumor, the intracranial portion can be treated conservatively after resection with or without chemotherapy. Deferral of brain radiation can be considered with close clinical and neuroimaging follow up. Full article

A 25-year-old man was diagnosised subcutaneous panniculitis-like T-cell lymphoma (SPTCL) through biopsy of a nodule from the anterior chest. After the treatment with prednisone 90 mg 3 weeks and tapered off in 1 month, the disease released, but relapsed together with symptions of hemophagocytic syndrome eight months after the termination of prednisone. CHOEP recipe was given but with unsatisfactory result until cyclosporine was prescribed. Cyclosporine was removed 6 months later. There is no evidence of clinical relapse 1 year later. This case suggest that cyclosporine could be a selectable treatment even in relapsed SPTCL. Full article

We wanted to determine whether autonomic dysfunction in patients with lymphoma is related to chemotherapy or represent a paraneoplastic syndrome. 40 patients with current or cured Hodgkin or non-Hodgkin lymphoma and 40 healthy controls, matched for age, gender, hypertension and diabetes mellitus underwent autonomic evaluation (Deep Breath, Valsalva Maneuver, Hand Grip, Lying to Standing, Tilt Test). Current patients also suffering from diabetes or hypertension, or still on chemotherapy revealed autonomic changes, while cured or healthy subjects did not. Autonomic dysfunction in lymphoma is a transient manifestation of a paraneoplastic syndrome. Full article

We report a case of right-sided leiomyosarcoma of the kidney with concomitant poorly differentiated squamous cell carcinoma of the cervix diagnosed one month after radical nephrectomy in a previously healthy female patient. This is the first reported case of concomitant leiomyosarcoma of the kidney and squamous cell carcinoma of the cervix, and the diagnosis, clinical presentation, prognosis, and treatment are discussed. Full article

Bone marrow infiltration by granulomas rarely presents with cytopenias and is usually a result of atypical infections, lymphomas, or sarcoidosis. Drugs are also an important but often overlooked causal agent of bone marrow granulomas. Although rare, amiodarone has been associated with bone marrow granuloma formation. This case report describes a 73-year-old male who presented with pancyto­penia during a preoperative evaluation. Amiodarone therapy was suspected to be the causal agent after diagnostic evaluation and exclusion of other causes. After cessation of amiodarone, the patient’s pancytopenia gradually resolved over a period of several months. Our report illustrates an often overlooked yet important cause of reversible pancytopenia owing to suspected amiodarone-induced bone marrow granuloma formation, and guides clin­icians in an expected timeline for blood count improvement after cessation of this drug. Full article

Hodgkin’s disease is, in general, a lymph node-based disease. It usually starts in an area within the lymphatic system and spreads, in an orderly manner, along the lymph­atic chain to contiguous lymph node areas. There have been sporadic case reports of acute liver failure caused by hematological malignancies. Generally, liver failure is a feature of stage IV end-stage disease, when it occurs in lymphoma. Thus, hepatic involvement usually occurs late in the course of Hodgkin’s disease or with advanced-stage disease, and primary presentation in the liver with acute liver failure is extremely rare. In most cases, the diagnosis was made at aut­opsy. We describe a patient with Hodgkin’s disease presenting with acute liver failure. This is a very unusual Hodgkin’s disease form of presentation, because the acute liver failure was the presenting feature of the disease. Furthermore, the lymphoma occurred as a very late relapse, twenty years after the first diagnosis. To the best of our knowledge, such a case has not been described to date. Full article

Myelodysplastic syndromes (MDS) traditionally have been grouped together as a disease entity based on clinical phenomena seen in association. Despite the similarities, there is great heterogeneity among the syndromes. Recent insights have shown, however, that there exists a biologically cohesive theme that unifies and thereby validates the conceptual interconnectedness. The first suggestion that such a relationship existed where biology could directly explain the observed cytopenias was the finding of excessive premature apoptosis of hematopoietic cells in MDS marrows. This apoptosis was mediated by paracrine as well as autocrine factors implicating both the seed and the soil in the pathology of the disease. Pro-inflammatory cytokines in the marrow microenvironment were mainly the paracrine mediators of apoptosis, but how the clonal cells committed suicide because of autocrine stimulation had remained a mystery for more than a decade. It has been shown now that deregulation of ribosome biogenesis can initiate a stress response in the cell through the p53 signaling pathway. Congenital anemias had been associated with mutations in ribosomal protein genes. The surprise came with the investigation of 5q- syndrome patients where haplo-insufficiency of the ribosomal protein gene RPS14 was found to be the cause of this MDS subtype. Similar ribosomal deregulation was shown to be present in all varieties of MDS patients, serving as another unifying characteristic. In addition to these findings, there are other DNA-related abnormalities such as uniparental disomy, mutations in the TET2 gene, and epigenetic phenomena that are associated with and occur across all types of MDS. This paper summarizes the themes unifying this heterogeneous group of diseases. Full article

We determined lymphoid enhancer-binding factor-1 (LEF1) mRNA expression in 112 chronic lymphocytic leukemia (CLL) samples and assessed correlations with the prognostic markers ZAP70 and CD38, Binet stages, the percentage of lymphocytes in the peripheral blood, and fibromodulin (FMOD) transcripts. The mean LEF1 relative expression ratios (RER) were 53.72 and 37.10 in ZAP70-positive and ZAP70-negative patients, respectively (p = 0.004). However, we did not observe a significant difference in LEF1 expression between CD38-positive and CD38-negative patients. Moreover, patients requiring treatment showed a mean LEF1 RER of 85.61 whereas patients in recently diagnosed Binet A stage had a mean of only 22.01 (p < 0.001). We also found significant correl­ations of LEF1 with the percentage of lymphocytes and FMOD expression. Our results suggest that high LEF1 expression is associated with poor prognosis and disease progression. Thus, LEF1 might be involved in the process of disease progression and possibly can serve as a molecular parameter for risk assessment and/or monitoring of CLL. Full article

Sickle Cell Disorder (SCD) is a congenital hemoglobinopathy. There is little in literature regarding the psychological variables affecting individuals living with SCD and all of the significant people around them. There are also limited numbers of trained clinical psychologists and genetic counselors to cater for the psychotherapeutic needs of individuals living with SCD. Even among those who have been trained, only a few might have fully grasped the complexities of the disease pathology. Early understanding of its pathological nature, sources, types, complications, pathophysiological basis, and clinical severity of symptoms among clinical psychologists, genetic counselors and psychotherapists, as well as general medical practitioners, could guide them in providing holistic care for dealing with and reducing pain among individuals living with SCD. It could allow risk-based counseling for families and individuals. It could also justify the early use of disease-modifying or curative interventions, such as hydroxyurea (HU), chronic transfusions (CTs), or stem-cell transplantation (SCT) by general medical practitioners. Hence, the need for this paper on the pathophysiology of SCD. Full article

Myelodysplastic syndrome (MDS) represents one of the most challenging health-related problems in the elderly. Characterized by dysplastic morphology in the bone marrow in association with ineffective hematopoiesis, pathophysiological causes of this disease are diverse including genetic abnormalities within myeloid progenitors, altered epigenetics, and changes in the bone marrow microenvironment. The concept that T-cell mediated autoimmunity contributes to bone marrow failure has been widely accepted due to hematologic improvement after immunosuppressive therapy (IST) in a subset of patients. Currently, IST for MDS primarily involves anti-thymocyte globulin (ATG)-based regimens in which responsiveness is strongly associated with younger (under 60 years) age at disease onset. In such cases, progressive cytopenia may occur as a consequence of expanded self-reactive CD8⁺ cytotoxic T lymphocytes (CTLs) that suppress hematopoietic progenitors. Although most hematologists agree that IST can offer durable hematologic remission in younger patients with MDS, an international clinical study and a better understanding of the molecular mechanisms contributing to the expansion of self-reactive CTLs is crucial. In this review, data accumulated in the US, Europe, and Asia will be summarized to provide insight and direction for a multi-center international trial. Full article