Search

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. Results: We found that low T cell percentages in all viable cells and low ratios of T cells to abnormal B cells correlated with significantly poorer survival, whereas higher percentages of normal B cells among total B cells (or high ratios of normal B cells to abnormal B cells) and high percentages of NK cells among all viable cells correlated with significantly better survival in patients with DLBCL. After excluding a small number of patientswith low T cell percentages, the normal B cell percentage among all B cells, but not T cell percentage among all cells, continued to show a remarkable prognostic effect. Data showed significant positive correlations between T cells and normal B cells, and between granulocytes and monocytes. Furthermore, we constructed a prognostic model based on clinical and flow cytometry factors, which divided the DLBCL cohort into two equal groups with remarkable differences in patient survival and treatment response. Summary: TILs, including normal B cells, T cells, and NK cells, are associated with favorable clinical outcomes in DLBCL, and flow cytometry capable of quantifying the TIME may have additional clinical utility for prognostication. [ABSTRACT FROM AUTHOR]

Chronic myelogenous leukaemia (CML) can progress from a slow growing chronic phase to an aggressive blast crisis phase (1), but the molecular basis of this transition remains poorly understood. Here we have used mouse models of CML (2,3) to show that disease progression is regulated by the Musashi-Numb signalling axis (4,5). Specifically, we find that the chronic phase is marked by high levels of Numb expression whereas the blast crisis phase has low levels of Numb expression, and that ectopic expression of Numb promotes differentiation and impairs advanced-phase disease in vivo. As a possible explanation for the decreased levels of Numb in the blast crisis phase, we show that NUP98-HOXA9, an oncogene associated with blast crisis CML (6,7), can trigger expression of the RNA-binding protein Musashi2 (Msi2), which in turn represses Numb. Notably, loss of Msi2 restores Numb expression and significantly impairs the development and propagation of blast crisis CML in vitro and in vivo. Finally we show that Msi2 expression is not only highly upregulated during human CML progression but is also an early indicator of poorer prognosis. These data show that the Musashi-Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for the therapy of aggressive leukaemias., Chronic myelogenous leukaemia (CML) is initiated by the BCR-ABL translocation, which leads to myeloid cell expansion while allowing differentiation (8-11). Secondary translocations such as NUP98-HOXA9 or AML1-EVI1, or mutations in [...]

The article presents a case study of a 79-year-old female patient with delirium and auditory and visual hallucinations for several weeks. Topics include patient presenting to a hospital outside the institution with nausea and vomiting diagnosed as having acute kidney injury (AKI); and having a history of hypertension, hyperlipidemia, chronic diastolic congestive heart failure, peripheral vascular disease, meningioma.

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.sup.+] monoclonal B cells and to outline the differential diagnostic possibilities, suggest a workup for correct diagnosis, and examine clinical outcome. Design.--Fifteen cases that met the diagnostic criteria were identified from pathology databases at 4 participating institutions. Morphologic findings were reviewed, additional immunohistochemical stains performed, and flow cytometric, cytogenetic, and relevant laboratory and clinical information was summarized. Previously published cases were searched from electronic databases and cross-references. Results.--Most patients (13 of 15) were older males. Often (11 of 15) they presented clinically with myeloma, yet had both monotypic plasma cells and B cells in the diagnostic marrow. In 4 patients, myeloma developed 24 months or later after chronic lymphocytic leukemia. In 7 patients, myeloma and [CD5.sup.+] B cells showed identical immunoglobulin light-chain restriction. Primary differential diagnoses include lymphoplasmacytic lymphoma, marginal zone lymphoma, and chronic lymphocytic leukemia with plasmacytoid differentiation. CD56 and/or cyclin D1 expression by plasma cells was helpful for correct diagnosis. Most patients in our cohort and published reports were treated for plasma cell myeloma. Conclusions.--Concomitant detection of myeloma and chronic lymphocytic leukemia in the bone marrow is a rare event, which must be carefully differentiated from lymphomas with lymphoplasmacytic differentiation for correct treatment. (Arch Pathol Lab Med. 2013;137:503-517; doi: 10.5858/arpa.2011-0696-OA), Plasma cell myeloma (PCM) (or multiple myeloma) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are both common hematologic neoplasms, each constituting about 10% to 11% of all hematologic malignancies. (1,2) [...]

* Context.--Marginal zone lymphomas (MZLs) are the most common lymphomas encountered in the orbit and ocular adnexa. The accurate categorization of these lymphomas is critical to avoid undertreatment or overtreatment. Objective.--To identify features of orbital MZLs that distinguish them from other lymphomas and reactive lymphoid infiltrates and support the categorization of orbital MZL as mucosa-associated lymphoid tissue (MALT)-type MZLs. Design.--Biopsies from 149 patients with lymphoid lesions of ocular adnexa were examined. Additional immunohistochemical stains and fluorescence in situ hybridization study for the MALT1 locus were performed in selected cases, and patient charts were reviewed. Results.--A total of 115 lymphomas and 34 reactive infiltrates were identified, of which B-cell lymphomas constituted 92% and MZLs constituted 54% of all lymphomas. Certain clinical features (young age, race, bilaterality) favored a reactive infiltrate, but none were diagnostic. Histologic features, such as infiltrative lesions, reactive B-cell follicles, and lymphoepithelial lesions, overlapped between reactive infiltrates and conjunctival MZL. In contrast to conjuctival MZL, orbital MZL infrequently showed reactive follicles, rarely showed epithelial tissue, and did not show lymphoepithelial lesions. Cytogenetic abnormality involving the MALT1 locus was demonstrated in only 15% of ocular adnexal MZLs. Conclusion.--Many MZLs of orbital soft tissue lack key features associated with MALT-type MZL, and the designation MALT lymphoma should be avoided in their diagnosis. (Arch Pathol Lab Med. 2008;132:1405-1416), Lymphoid infiltrates of the conjunctiva and orbit occur frequently, and it has long been recognized that the differentiation of benign infiltrates from malignant lymphomas can be challenging not only for [...]