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Abstract : Immunohistochemistry is a technique that uses antigen-antibody interactions to detect specific proteins in cells. This technique has several essential applications in lymphoma diagnosis, including identifying the cell lineage and phase of maturation, detecting specific genetic alterations, visualizing the degree of cell proliferation, and identifying therapeutic targets. CD3 is a pan T-cell marker expressed on most of the mature T/NK-cell lymphomas, except for anaplastic large cell lymphoma, whereas CD20 is a pan B-cell marker that is expressed on most of the mature B-cell lymphomas. CD79a may be a good alternative to CD20, compensating for its loss owing to the plasmocytic differentiation of tumor cells or history of rituximab administration. CD56, a neuroendocrine marker, is used as an NK cell marker in lymphoma diagnosis. Characteristic translocations occurring in follicular lymphoma (BCL2) and mantle cell lymphoma (CCND1) can be detected by the overexpression of Bcl-2 and cyclin D-1 in immunohistochemistry, respectively. Ki-67 reflects the degree of tumor cell proliferation by indicating cells in cell cycle phases other than G0. With the development of immunotherapy, several antibodies against markers such as programmed death-ligand 1 (PD-L1), CD19, and CD30 have been used as biomarkers to identify therapeutic targets. It is critical to properly fix the specimens to obtain accurate immunohistochemical results. Therefore, all processes, from tissue collection to the final pathological diagnosis, must be performed appropriately for accurate lymphoma diagnosis.

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Abstract : Plasma cell leukemia (PCL) is a rare and highly aggressive plasma cell neoplasm developing in 0.5?4% of patients with multiple myeloma (MM). The diagnostic criteria were recently revised from 20% to ≥5% of circulating plasma cells in peripheral blood smears. PCL is classified as primary or secondary; primary PCL is when it presents in patients with no MM. Primary PCL shows clinical and laboratory features at presentation that differ from MM and exhibits a dismal prognosis even with the use of effective agents against MM. Therefore, intensive chemotherapy should be initiated immediately after diagnosis, and autologous stem cell transplantation is recommended for transplant-eligible patients. Maintenance therapy after transplantation may reduce the rate of early relapses. We reviewed the definitions of PCL, revised diagnostic criteria, clinical features, and appropriate initial treatments for primary PCL.

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Abstract : The history of human acute myeloid leukemia stem cells (AMLSCs) began in a seminal study performed by Lapidot and Dick, proving that only CD34+CD38- human primary acute myeloid leukemia (AML) cells can repopulate in severe combined immunodeficient mice. The concept of leukemic stem cells (LSCs) has impeded a huge change in the treatment strategy against AML from killing proliferating leukemic cells to eradicating quiescent/dormant LSCs. As next-generation sequencing technologies have developed, multiple and recurrent genetic mutations have been discovered in large cohorts of patients with AML, and the updated understanding of leukemogenesis has improved the old concept of LSC to a revised version of a serial developmental model of LSC; that is, pre-LSCs are generated as seeds by the first hit on epigenetic regulators, and then, leukemia-initiating LSCs emerge from seeds by the second hits on genes involved in transcription and signaling. Dreams for universal and targetable AMLSC biomarker sparing healthy hematopoietic stem cells have weakened after the confrontation of significant heterogeneity of AMLSCs from genomic and immunophenotypic viewpoints. However, there is still hope for effective targets for AMLSCs since there is evidence that grouped gene signatures, such as 17-gene LSC score, and common epigenetic signatures, such as HOXA clusters, independent of various gene mutations, exist. Recently, the LSC niche in the bone marrow has been actively investigated and has expanded our knowledge of the physiology and vulnerability of AMLSCs. Presently, an applicable treatment that always works in AMLSCs is lacking. However, we will find a way, we always have.

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Abstract : The accurate assessment of initial disease status and therapeutic responses is critical to the optimal management of patients with lymphoma. Currently, staging and treatment response evaluation for lymphoma has been standardized into the Lugano classification. Lugano classification incorporates positron emission tomography (PET) into the existing response criteria, and response assessment using FDG-PET/CT has been proven to predict the prognosis in various lymphoma subtypes effectively. We will briefly review the current staging and response evaluation system and explore the role of functional imaging in the field of lymphoma.

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Abstract : Thrombocytopenia, defined as platelet count ＜150×10⁹/L, is frequently observed by physicians during pregnancy, with an incidence of approximately 10% of all pregnancies. Most of the cases of thrombocytopenia in pregnancy are due to gestational thrombocytopenia, which does not confer an increased risk of maternal bleeding. However, because other causes can be associated with life-threatening events, such as severe bleeding, that can affect to maternal and fetal outcomes, differentiating other cause of thrombocytopenia, which includes preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, acute fatty liver of pregnancy, immune thrombocytopenia, hereditary thrombocytopenia, antiphospholipid syndrome, thrombotic thrombocytopenic purpura, and atypical hemolytic uremic syndrome, is important. Understanding the mechanisms and recognition of symptoms and signs are important to decide an adequate line of investigation. In this review, the approach to diagnosis and the management of the thrombocytopenia commonly observed in pregnancy are presented.

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Abstract : Inherited bone marrow failure syndrome (IBMFS) is a group of clinically heterogeneous disorders characterized by significant hematological cytopenias of one or more hematopoietic cell lineages and is associated with an increased risk of cancer. The genetic etiology of IBMFS includes germline mutations impacting several key biological processes, such as DNA repair, telomere biology, and ribosome biogenesis, which may cause four major syndromes: Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Although the clinical features of some patients may be typical of a particular IBMFS, overlapping and atypical clinical manifestations and variable penetrance pose diagnostic challenges. Here, we review the clinical and genetic features of the major forms of IBMFS and discuss their molecular genetic diagnosis. Next-generation sequencing-based gene panel testing or whole exome sequencing will help elucidate the genetic causes and underlying mechanisms of this genetically heterogeneous group of diseases.

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Abstract : Technologies in laboratory diagnostics are changing fast with progress in understanding and therapy of diseases. Unfortunately, new analyzers are often needed to be installed in a clinical laboratory to implement such techniques. The demand for new hardware is a bottleneck in improving the diagnostic services for many facilities with limited resources. In this regard, hemostasis laboratories take a slightly different position. Because many in vitro diagnostic tests target the functional aspects of hemostasis, further meaningful information can be obtained from the same analyzers as in current use. Automated coagulometers are good candidates for such further utilization. Clot waveform analysis is a leading example. Behind the simple values reported as clotting time, clotting curves exist that represent the process of fibrin clot formation. Clot waveform analysis examines the clotting curves and derives new parameters other than clotting times. The clot waveform parameters are now in active use in assessing the hemostatic potential of hemorrhagic patients. Clinical application of coagulometers can also be widened by modifying the reagent formulation. For example, the chromogenic factor VIII assay with bovine source reagent compositions has recently been introduced for hemophilia A patients on emicizumab prophylaxis. Also, new immunoturbidimetric functional assays for von Willebrand factor have been developed recently. Thus, new clinically relevant information can be mined from the automated coagulometers that are based on old technology.

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Abstract : Invasive fungal infections (IFIs) are common causes of mortality and morbidity in patients with hematologic diseases. Delayed initiation of antifungal treatment is related to mortality. Aspergillus sp. is the leading cause of IFI followed by Candida sp. Diagnosis is often challenging owing to variable conditions related to underlying diseases. Clinical suspect and prompt management is important. Imaging, biopsy, and non-culture-based tests must be considered together. New diagnostic procedures have been improved, including antigen-based assays and molecular detection of fungal DNA. Among hematologic diseases, patients with acute myeloid leukemia, myelodysplastic syndrome, recipients of hematopoietic stem cell transplantation are at high risk for IFIs. Antifungal prophylaxis is recommended for these high-risk patients. There are continuous attempts to achieve ideal management of IFIs. Scoring system for quality control has been developed with important recommendations of current guidelines. Higher adherence to guidelines is related to decreased mortality in IFIs.

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Abstract : Immune thrombocytopenia (ITP) is isolated thrombocytopenia characterized by autoimmune-mediated disruption of platelet without other etiologies. Treatments for chronic ITP consist of corticosteroids, intravenous immunoglobulins, anti-D immunoglobulin, rituximab, thrombopoietin receptor agonists, immunosuppressants and splenectomy. Although current therapies are effective in over two-thirds of patients, some patients are refractory to therapies or fail to achieve long-term responses. Recently, great advance has been made in identifying various mechanisms involved in ITP pathogenesis, and new treatments targeting these pathways are being developed. Novel agents such as splenic tyrosine kinase inhibitor, Bruton kinase inhibitor, plasma cell targeting therapies, neonatal Fc receptor inhibitor, platelet desialylation inhibitor, and inhibition of the classical complement pathway are expected to be effective for ITP treatment. This review summarizes current strategies and emerging therapies of ITP.

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Abstract : Treatment of indolent lymphoma has improved significantly in recent decades since the advent of rituximab (anti-CD20 monoclonal antibody). Although, some patients with limited disease can be cured with radiation therapy alone, most patients experience disease progression and recurrence during follow-up despite early initiation of treatment. Thus, watch-and-wait is still regarded the standard for asymptomatic patients. Patients with indolent lymphoma have a significant heterogeneity in terms of tumor burden, symptoms (according to anatomical sites) and the need for instant therapy. Therefore, the initiation of treatment and treatment option should be decided with a clear goal in each patient according to the need for therapy and clinical benefits with the chosen treatment. In this review, we cover the current treatment of follicular lymphoma and marginal zone lymphoma.