Flow cytometry quantification of tumor-infiltrating lymphocytes to predict the survival of patients with diffuse large B-cell lymphoma.

Introduction: Our previous studies have demonstrated that tumor-infiltrating lymphocytes (TILs), including normal B cells, T cells, and natural killer (NK) cells, in diffuse large B-cell lymphoma (DLBCL) have a significantly favorable impact on the clinical outcomes of patients treated with standard chemoimmunotherapy. In this study, to gain a full overview of the tumor immune microenvironment (TIME), we assembled a flow cytometry cohort of 102 patients diagnosed with DLBCL at the Duke University Medical Center.

Methods: We collected diagnostic flow cytometry data, including the proportion of T cells, abnormal B cells, normal B cells, plasma cells, NK cells, monocytes, and granulocytes in fresh biopsy tissues at clinical presentation, and analyzed the correlations with patient survival and between different cell populations.

How to Design and Validate a Clinical Flow Cytometry Assay.

Multiparametric flow cytometry assays are long recognized as an essential diagnostic test for leukemias and lymphomas. Lacking Food and Drug Administration-approved standardized tests, these assays remain laboratory developed tests. The recently published guidelines, CLSI H62, are the most detailed and up-to-date instructions for designing and validating clinical flow cytometry assays.

Evaluation of multiple myeloma measurable residual disease by high sensitivity flow cytometry: An international harmonized approach for data analysis.

Background: Multiple myeloma (MM) measurable residual disease (MRD) evaluated by flow cytometry is a surrogate for progression-free and overall survival in clinical trials. However, analysis and reporting between centers lack uniformity. We designed and evaluated a consensus protocol for MM MRD analysis to reduce inter-laboratory variation in MM MRD reporting.

Myeloid neoplasms in the setting of sickle cell disease: an intrinsic association with the underlying condition rather than a coincidence; report of 4 cases and review of the literature.

Myeloid neoplasms occasionally occur in patients with sickle cell disease, and the underlying connection between the two diseases is unclear. Herein, we retrospectively analyzed four cases of sickle cell disease patients who developed myeloid neoplasm. Age at time of diagnosis ranged from 27 to 59 years with a median of 35.

Lineage Switch Between B-Lymphoblastic Leukemia and Acute Myeloid Leukemia Intermediated by "Occult" Myelodysplastic Neoplasm: Two Cases of Adult Patients With Evidence of Genomic Instability and Clonal Selection by Chemotherapy.

Objectives: Lineage switch occurs in rare leukemias, and the mechanism is unclear. We report two cases of B-lymphoblastic leukemia (B-ALL) relapsed as acute myeloid leukemia (AML).

Methods: Retrospective review of clinical and laboratory data.

Plasmacytic or lymphoplasmacytic infiltrate in lymph nodes: Diagnostic approach and differential considerations.

Plasmacytosis is a common finding in lymph node biopsies and can be seen in diverse circumstances ranging from reactive lymphadenopathy to malignant lymphoma. Familiarity with various histopathologic features of the different entities and awareness of their typical clinical and ancillary study findings are essential for an accurate diagnosis. In this review, we present common and representative nonneoplastic entities and lymphomas that have plasmacytic differentiation or associated plasmacytosis.

Improved detection of diffuse large B-cell lymphoma by flow cytometric immunophenotyping-Effect of tissue disaggregation method.

Background: Flow cytometric immunophenotyping (FCI) is recognized as a rapid, sensitive, and accurate method for diagnosis of B-cell lymphomas. We observed that FCI failed to identify the clonal B-cell population in several cases of large B-cell lymphoma (DLBCL) when tissue samples were prepared by a commercially available mechanical tissue disaggregation method. We tested a manual tissue disaggregation method and compared it with the mechanical method.

Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting.

Background: Major heterogeneity between laboratories in flow cytometry (FC) minimal residual disease (MRD) testing in multiple myeloma (MM) must be overcome. Cytometry societies such as the International Clinical Cytometry Society and the European Society for Clinical Cell Analysis recognize a strong need to establish minimally acceptable requirements and recommendations to perform such complex testing.

Methods: A group of 11 flow cytometrists currently performing FC testing in MM using different instrumentation, panel designs (≥ 6-color) and analysis software compared the procedures between their respective laboratories and reviewed the literature to propose a consensus guideline on flow-MRD analysis and reporting in MM.

Blast phase in chronic myelogenous leukemia is skewed toward unusual blast types in patients treated with tyrosine kinase inhibitors: a comparative study of 67 cases.

Objectives: To compare the features of the blast phase of chronic myelogenous leukemia (CML) in patients treated with tyrosine kinase inhibitors (TKIs) with those in the pre-TKI era.

Methods: Sixty-seven patients with blast phase CML were identified in the Duke Pathology database from 1991 to 2011. The morphology and immunophenotype of blasts were evaluated, along with cytogenetic studies and associated findings in the peripheral blood and bone marrow.

Extranodal Castleman disease of the extremities: a case report and review of the literature.

Castleman disease is a rare lymphoproliferative disorder of unknown etiology that most commonly presents as a mediastinal nodal mass or, in the extranodal form of the disease, a mass located in the mediastinum or retroperitoneum. It is exceptionally uncommon for Castleman disease to present in the extremities. We report a rare case of extranodal Castleman disease presenting as a muscular forearm mass.

Characterization of bone marrow mast cells in acute myeloid leukemia with t(8;21) (q22;q22); RUNX1-RUNX1T1.

Mast cells are often increased in AML with t(8;21). We analyzed characteristics of mast cells to elucidate their relationship with leukemic blasts. In 31 cases in which the results of KIT mutation analysis were available, five cases showed mutations.

Diagnostic and clinical considerations in concomitant bone marrow involvement by plasma cell myeloma and chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis: a series of 15 cases and review of literature.

Context: Plasma cell myeloma and chronic lymphocytic leukemia are both common hematologic malignancies, sharing many epidemiologic features. Concomitant detection of the 2 conditions poses special diagnostic challenges for the pathologist.

Objective: To describe the pathologic findings in cases of concomitant bone marrow involvement by myeloma and CD5(+) monoclonal B cells and to outline the differential diagnostic possibilities, suggest a workup for correct diagnosis, and examine clinical outcome.

Clinically undiagnosed enteropathy associated T-cell lymphoma type II presenting with prolonged lower gastrointestinal tract symptoms: report of an autopsy case and review of diagnostic challenges and clinicopathological correlation.

An elderly patient with watery diarrhea for 3 months received extensive laboratory, radiographic and upper and lower gastrointestinal (GI) endoscopic work up including colonic biopsies, but a diagnosis was not established before death. At autopsy enteropathy associated T-cell lymphoma-type II (EATL-II) with multifocal mucosal involvement of the jejunum was identified. The colon was completely uninvolved grossly and microscopically.

Genetic heterogeneity of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma in adults. The disease exhibits a striking heterogeneity in gene expression profiles and clinical outcomes, but its genetic causes remain to be fully defined. Through whole genome and exome sequencing, we characterized the genetic diversity of DLBCL.

The genetic landscape of mutations in Burkitt lymphoma.

Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors.

Re-induction therapy decisions based on day 14 bone marrow biopsy in acute myeloid leukemia.

Purpose: The decision to re-induce patients with acute myeloid leukemia (AML) based on results of the day 14 bone marrow (BM) biopsy is variable and lacks evidence based data. The aim of our review was to evaluate the accuracy of a day 14 BM biopsy in determining the need for re-induction chemotherapy.

Methods: Seventy-four patients with newly diagnosed de novo AML treated with induction chemotherapy were retrospectively reviewed for the purpose of evaluating treatment decisions and outcomes based on their day 14 BM biopsy.

Lymph node infarction: role of underlying malignancy, tumour proliferation fraction and vascular compromise--a study of 35 cases and a comprehensive review of the literature.

Aims:   To determine the roles of the presence of malignancy, tumour proliferation fraction, vascular compromise and therapeutic and diagnostic manipulations in lymph node infarction (LNI).

Methods And Results:   Thirty-five cases of LNI were identified over a 20-year period. Of the 35 patients, 31 (89%) had an underlying malignancy: 27 of the 31 (87%) were haematologic malignancies, the rest being metastatic carcinoma (two), melanoma, and seminoma.

Lymphomas of the gastro-intestinal tract - pathophysiology, pathology, and differential diagnosis.

The gastrointestinal tract (GIT) is the most commonly involved site of extranodal lymphomas. The close association between chronic inflammation and specific GIT lymphomas not only provide interesting insights into the pathobiology of lymphomas but also poses unique diagnostic challenges. A clear understanding of marginal zone and mucosa associated lymphoid tissue (MALT) in health and disease is helpful to place GIT lymphomas in proper context.

Donor cell-derived leukemias/myelodysplastic neoplasms in allogeneic hematopoietic stem cell transplant recipients: a clinicopathologic study of 10 cases and a comprehensive review of the literature.

We report 10 cases of donor cell leukemia (DCL). All cases except the case of chronic lymphocytic leukemia had anemia, neutropenia, and/or thrombocytopenia when DCL was diagnosed. Eight cases with sex-mismatched hematopoietic stem cell transplant (HCT) showed donor gonosomal complements, suggesting DCL.

Histone H4 acetylation by immunohistochemistry and prognosis in relapsed acute lymphocytic leukaemia (ALL).

Histone H4 acetylation was examined by immunohistochemistry in patients with acute lymphocytic leukaemia (ALL) in first relapse. Univariate and multivariate models identified correlates of complete remission (CR) and overall survival (OS). No variables were associated with achievement of CR.

Feasibility of low-dose interleukin-2 therapy following T-cell-depleted nonmyeloablative allogeneic hematopoietic stem cell transplantation from HLA-matched or -mismatched family member donors.

Introduction: High relapse rates and infections remain primary causes of failure in nonmyeloablative transplantation. Interleukin-2 (IL-2) may stimulate the immune system and improve outcomes. The primary objective of this pilot study was to evaluate the feasibility of administering IL-2 following a T-cell-depleted nonmyeloablative hematopoietic stem cell transplant.