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Acute myeloid leukemia (AML) is characterized by a clonal expansion of undifferentiated myeloid precursors resulting in impaired hematopoiesis and bone marrow failure. In 2016, the World Health Organization (WHO) published revisions to the classification of myeloid neoplasms and acute leukemias. Similar to the 2008 classification, the updated classification incorporates clinical features, morphology, immunophenotyping, and cytogenetics, with greater emphasis on molecular genetics, to define disease entities. This brief review addresses the various components of pathologic assessment to establish a diagnosis of AML and to help risk stratify patients, with an emphasis on newer techniques used in the detection of mutations with prognostic significance, as well as assays employed in the evaluation of minimal residual disease following treatment., (© 2017 Wiley Periodicals, Inc.)

Primary mediastinal large B-cell lymphoma (PMBL) is a distinct subtype of diffuse large B-cell lymphoma (DLBCL) that shows overlap with classical Hodgkin lymphoma (CHL) and a favorable prognosis compared to mediastinal gray-zone lymphoma (MGZL). We performed immunohistochemistry on initial diagnostic specimens of 49 cases of uniformly treated PMBL to determine the frequency and clinical significance of expression of antigens commonly seen in CHL and MGZL, along with markers previously shown to be prognostic in DLBCL, not otherwise specified. The median age was 37 years with a female:male ratio of 2.3. After a median follow-up of 78 months, 24% of patients had relapsed or refractory disease and 22% had died; the 5-year PFS was 70%. Variable CD15 expression was seen in 31% of cases, but was not associated with adverse outcome. Hans cell-of-origin, proliferation index, and MYC/BCL2 coexpression were not associated with outcome, while low PDL1 (P = 0.011) and high MUM1 (P = 0.065) staining were each associated with shorter PFS. A biologic risk score (one point each for low PDL1 and high MUM1) stratified patients into three prognostic risk groups for PFS (P = 0.001) and OS (P = 0.032). On separate multivariate models, low PDL1 was independent of R-IPI risk group for PFS (HR 6.0, P = 0.023), as was a biologic risk score of 2 (HR 5.6, P = 0.011). Incorporation of the biologic risk score sub-stratified patients within R-IPI groups for both PFS (P < 0.001) and OS (P < 0.001). In summary, we characterize the immunophenotypic spectrum of PMBL and identify PDL1 and MUM1 as prognostic biomarkers for high-risk disease. Am. J. Hematol. 91:E436-E441, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Flow cytometry (FCM) is an adjunct study to routine analysis of cerebrospinal fluid (CSF) to investigate for involvement by a hematologic malignancy. However, in our experience, FCM only infrequently detects abnormalities in CSF. To help optimize resources without forfeiting clinically important data, we sought to determine evidence-based indications and criteria for performing FCM on CSF. FCM results of 316 consecutive CSF specimens were retrospectively reviewed and correlated with clinical history, total nucleated cell (TNC) counts, and results of concurrent cytologic review. Of 255 samples adequate for analysis, 54% were from patients with a prior history of hematologic malignancy, of which 12% (17 cases) were abnormal by FCM. Corresponding TNC counts among samples with abnormal FCM ranged from 0-1050 cells/µL, and only 44% showed abnormal morphology on concurrent cytology. Of the remaining 46% of samples from patients with no known history of hematologic malignancy who had CSF sampling for neurological indications, only one (1%) was abnormal by FCM. This specimen had an elevated TNC count (39 cells/µL) but lacked clearly abnormal findings on concurrent cytology. These results support the use of CSF FCM only in patients with a history of hematologic malignancy or, in the absence of such a history, in samples showing pleocytosis. If these criteria were applied to the current cohort using a TNC count cut-off of >5 cells/µL, 23% of samples would have been deferred from testing, resulting in decreased cost, improved efficiency, and reduction in the need for unnecessary testing without a negative impact on clinical care., (© 2014 Wiley Periodicals, Inc.)