Concordance among hematopathologists in classifying blasts plus promonocytes: A bone marrow pathology group study.

Enumeration of blasts and promonocytes is essential for World Health Organization (WHO) classification of myelomonocytic neoplasms. The accuracy of distinguishing blasts, promonocytes and monocytes, including normal vs abnormal monocytes, remains controversial. The objective of this analysis is to assess concordances between experienced hematopathologists in classifying cells as blasts, promonocytes, and monocytes according to WHO criteria.

Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study.

Objectives: To assess bone marrow (BM) sampling in academic medical centers.

Methods: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed.

Results: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%).

Most Myeloid Neoplasms With Deletion of Chromosome 16q Are Distinct From Acute Myeloid Leukemia With Inv(16)(p13.1q22): A Bone Marrow Pathology Group Multicenter Study.

Objectives: Isolated deletion of the long arm of chromosome 16 (del(16q)) is rare in myeloid neoplasms (MNs) and was historically considered a variant of inv(16)(p13.1q22) (inv(16)), a subtype of acute myeloid leukemia (AML) associated with CBFB-MYH11 rearrangement and favorable prognosis. This study aims to determine clinicopathologic characteristics of patients with isolated del(16q) in MNs in comparison to AMLs with isolated inv(16).

Myeloid Neoplasms with Germline Predisposition: A New Provisional Entity Within the World Health Organization Classification.

The forthcoming update of the World Health Organization (WHO) classification of hematopoietic neoplasms will feature "Myeloid Neoplasms with Germline Predisposition" as a new provisional diagnostic entity. This designation will be applied to some cases of acute myeloid leukemia and myelodysplastic syndrome arising in the setting of constitutional mutations that render patients susceptible to the development of myeloid malignancies. For the diagnostic pathologist, recognizing these cases and confirming the diagnosis will demand a sophisticated grasp of clinical genetics and molecular techniques.

Lymphocytosis, lymphadenopathy: benign or malignant?

The increasing use of immunophenotypic and molecular analysis in the routine evaluation of patients with lymphocytosis, lymphadenopathy, or other hematologic disorders has led to the identification of unexpected small clonal lymphoid populations. These clones, sometimes with disease-specific markers, such as the t(14;18), are especially challenging for the clinician because of their unknown biologic potential and uncertain clinical behavior. Study of these early lymphoid lesions is providing important clues to the process of lymphomagenesis, and may provide the rationale for preemptive therapy in the future.

GATA family transcriptional factors: emerging suspects in hematologic disorders.

GATA transcription factors are zinc finger DNA binding proteins that regulate transcription during development and cell differentiation. The three important GATA transcription factors GATA1, GATA2 and GATA3 play essential roles in the development and maintenance of hematopoietic systems. GATA1 is required for the erythroid and megakaryocytic commitment during hematopoiesis.

Flow cytometric detection of altered signaling in myelodysplastic syndrome and cytopenia.

Multiparameter flow cytometric analysis allows for precise evaluation of growth factor stimulated intracellular signaling in distinct immunophenotype defined hematopoetic populations. Our analysis of intracellular phosphoprotein in response to major hematopoietic growth factors or cytokines showed several interesting findings. Although there was no characteristic signaling abnormality that was diagnostic for MDS, MDS cases were often associated with more signaling aberrancies involving more cellular populations.

Flow cytometric analysis of lymphoid enhancer-binding factor 1 in diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma.

Objectives: Nuclear overexpression of lymphoid enhancer-binding factor 1 (LEF1) assessed by immunohistochemistry has been shown to be highly associated with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) among small B-cell lymphomas. The purpose of this study was to evaluate the utility of flow cytometric analysis of LEF1 in the diagnosis of CLL/SLL.

Methods: Normal peripheral blood was used to validate the test.

Heritable GATA2 mutations associated with familial AML-MDS: a case report and review of literature.

A 50-year-old woman was diagnosed with acute myeloid leukemia (AML). She has history of thrombocytopenia for 25 years and a significant family history of thrombocytopenia, affecting her mother, siblings and their children, as well as her own children. Both her mother and maternal aunt died from myelodysplastic syndrome (MDS).

Phase II study of alemtuzumab-rituximab therapy in previously untreated patients with chronic lymphocytic leukemia: short- and long-term outcomes.

We investigated the safety, efficacy, and long-term outcomes of alemtuzumab and rituximab (AR) combination therapy in previously untreated patients with CLL. Thirty patients, ages 28-80 years, 47% older than 60 years, 90% Rai clinical stages II-IV, and 67% without favorable cytogenetics received AR. Based on the NCI-WG 1996 criteria, OR was 100%, with 60% CR.

Bone marrow involvement by subcutaneous panniculitis-like T-cell lymphoma: a report of three cases.

Subcutaneous panniculitis-like T-cell lymphoma is a rare subtype of cutaneous T-cell lymphoma. Virtually all cases are confined to the subcutaneous adipose tissue. In this report, we describe the first small series of subcutaneous panniculitis-like T-cell lymphoma (three patients) with bone marrow involvement.

Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death.

We hypothesized that the high early death rate (EDR) due to bleeding in acute promyelocytic leukemia (APL) is in part attributable to delays in all- trans retinoic acid (ATRA). We conducted a retrospective analysis of the timing of ATRA administration. 204 consecutive patients with newly diagnosed APL between 1992 and 2009 were identified.

Nuclear protein dysregulation in lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia.

Waldenström macroglobulinemia (WM) is characterized by monoclonal gammopathy, usually IgM, in association with lymphoplasmacytic lymphoma (LPL). Little is known of the expression of nuclear proteins involved in B-cell development in LPL/WM. In this study, the expression patterns of PAX5/BSAP, MUM1/IRF4, and PRDM1/BLIMP1 were analyzed in plasma cells and lymphocytes in 29 cases of newly diagnosed LPL/WM by double immunohistochemical staining with CD138 and CD22.

Early lesions in lymphoid neoplasia: Conclusions based on the Workshop of the XV. Meeting of the European Association of Hematopathology and the Society of Hematopathology, in Uppsala, Sweden.

The increasing use of immunophenotypic and molecular techniques on lymphoid tissue samples without obvious involvement by malignant lymphoma has resulted in the increased detection of "early" lymphoid proliferations, which show some, but not all the criteria necessary for a diagnosis of malignant lymphoma. In most instances, these are incidental findings in asymptomatic individuals, and their biological behaviour is uncertain. In order to better characterize these premalignant conditions and to establish diagnostic criteria, a joint workshop of the European Association for Haematopathology and the Society of Hematopathology was held in Uppsala, Sweden, in September 2010.

Clinical, morphologic, immunophenotypic, and molecular cytogenetic assessment of CD4-/CD8-γδ T-cell large granular lymphocytic leukemia.

γδ T-cell large granular lymphocytic (T-LGL) leukemia of the CD4-/CD8- subtype is rare, and data are limited in the literature. This study evaluated the clinical, morphologic, immunophenotypic, and molecular cytogenetic features of 7 cases of CD4-/CD8- γδ T-LGL leukemia. Although this variant shares several clinical and morphologic features with the more common T-LGL leukemias, the incidences of autoimmune hemolytic anemia and pure red cell aplasia are higher.

Nuclear overexpression of lymphoid-enhancer-binding factor 1 identifies chronic lymphocytic leukemia/small lymphocytic lymphoma in small B-cell lymphomas.

Lymphoid-enhancer-binding factor 1 (LEF1), coupling with β-catenin, functions as a key nuclear mediator of WNT/β-catenin signaling, which regulates cell proliferation and survival. LEF1 has an important role in lymphopoiesis, and is normally expressed in T and pro-B cells but not mature B cells. However, gene expression profiling demonstrates overexpression of LEF1 in chronic lymphocytic leukemia, and knockdown of LEF1 decreases the survival of the leukemic cells.

Therapy-related myelodysplastic syndrome presenting as fulminant heart failure secondary to myeloid sarcoma.

Rapidly progressive heart failure is commonly caused by an extensive myocardial infarction, a mechanical complication of infarction, myocarditis, or acute valvular insufficiency. We present an unusual case that was caused by a diffuse infiltration of the myocardium with leukemic cells (myeloid sarcoma). The patient presented with episodic shortness of breath, he was anemic and thrombocytopenic, and his bone marrow biopsy revealed myelodysplastic syndrome from treatment for oligodendroglioma.

Immunophenotypic variations in mantle cell lymphoma.

Mantle cell lymphoma (MCL) expresses pan-B-cell antigens and is usually CD5+/CD10-/CD23-/FMC7+. In this study, we evaluated 52 patients with confirmed diagnoses of MCL and identified variant immunophenotypes in 21 patients (19/48 classical and 2/4 variant MCLs), including CD5- in 6 (12%) of 52, CD10+ in 4 (8%) of 50, CD23+ in 10 (21%) of 48, and FMC7- in 4 (11%) of 37 cases. Three cases showed variations in 2 antigens, including CD5-/CD23+, CD10+/FMC7-, and CD23+/FMC7-; they were all classical MCLs.