James Huang

BCR-ABL Testing by Polymerase Chain Reaction in Patients With Neutrophilia: The William Beaumont Hospital Experience and the Case for Rational Laboratory Test Requests

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from the fusion of the BCR-ABL genes, forming the Philadelphia chromosome. The diagnosis is often suspected when there is leukocytosis with left shift and basophilia. Confirmation of the diagnosis requires a demonstration of BCR-ABL by polymerase chain reaction. Using data from the William Beaumont laboratory data registry, we conducted a retrospective review of all the orders for BCR-ABL tests sent to the clinical pathology laboratory between March 11, 2014 and September 12, 2014. We concluded that the presence of concurrent neutrophilia and basophilia has a sensitivity of 100% (95% CI, 69.15% to 100%) and specificity of 100% (95% CI, 93.15% to 100%) in the initial diagnosis of CML. Our results suggest that the presence of both neutrophilia and basophilia should be used as a threshold for the placement of orders for BCR-ABL in the initial diagnosis of CML in patients with leukocytosis with left shift and provide a basis for a reduction in health care spending. Restricting BCR-ABL tests to this population would save approximately

Diagnostic Utility of Flow Cytometry Analysis of Reactive T Cells in Nodular Lymphocyte-Predominant Hodgkin Lymphoma

198 million annually in national health care spending.

Significant cytogenomic evolution identified by SNP chromosome microarray analysis accompanies plasmablastic transformation of a hyperdiploid plasma cell myeloma

OBJECTIVESnThis study aims to define the diagnostic utility of flow cytometric features of T cells in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL).nnnMETHODSnCases were retrospectively identified based on diagnosis with NLPHL (n = 30 samples), classic Hodgkin lymphoma (CHL; n = 33), and reactive lymphoid hyperplasia (RLH; n = 43). Pathology slides were reviewed. Flow cytometry list mode data were reanalyzed.nnnRESULTSnThe mean proportion of CD4 + CD8 + T cells (8.4%) in cases of NLPHL was significantly higher than seen in CHL (1.0%) or RLH (0.6%). Of the T cells, 28.4% were CD57 + in NLPHL, significantly higher (P < .05) than in CHL (3.2%) or RLH (3.2%). Based on receiver operating characteristic curve analysis, when using a cutoff of 3.0% of CD4 + CD8 + T cells, the diagnostic sensitivity for NLPHL is 83.3% with a specificity of 97.4%. The diagnostic sensitivity was 96.7% with a specificity of 98.7% when using a cutoff of 12% for CD57 + T cells.nnnCONCLUSIONSnIncreased portions of CD57 + T cells and CD4 + CD8 + T cells are highly suggestive of the possibility of NLPHL. In addition, NLPHL diagnosis appears unlikely if neither CD57 + T cells nor CD4 + CD8 + T cells are increased. Future prospective studies including cases of progressive transformation of germinal center and T-cell/histiocyte-rich large B-cell lymphoma will further define the utility of flow cytometry of T cells in NLPHL.

Secondary acute myelogenous leukemia (AML) with trisomy 10 and del(9q) following precursor B-cell acute lymphoblastic leukemia (ALL) with a hyperdiploid karyotype

Plasma cell myeloma (PCM) is a hematological malignancy involving clonal proliferation of plasma cells in bone marrow. It is the third most common hematolymphoid malignancy in the USA and primarily affects elderly people with a median onset age of 69xa0years and a survival duration ranging from a few months to more than 10xa0years. This variation is due largely to the fact that PCM is a genetically complex and heterogeneous disease. The tumor cells demonstrate a wide range of morphological features, from mature and recognizable plasma cells to pleomorphic forms. In a subset of cases, however, the tumor cells demonstrate plasmablastic morphology which predicts a poor prognosis. We present a patient with an initial diagnosis of plasma cell myeloma with typical morphology and a hyperdiploid karyotype predictive of a favorable outcome. The patient’s disease was unresponsive to chemotherapy and evolved over the course of 43xa0months into a myeloma with plasmablastic features characterized by a highly complex abnormal karyotype demonstrating previously unidentified poor cytogenetic markers including CKS1B gene duplication and p53 gene deletion by fluorescence in situ hybridization (FISH). Post-mortem evaluation by single nucleotide polymorphism (SNP array) chromosome microarray analysis revealed additional structural abnormalities in the diagnostic specimen as well as significant genomic evolution in the plasmablastic myeloma.

Reply to S.E. Langabeer

Acute myelogenous leukemia (AML) secondary to acute lymphoblastic leukemia (ALL) in children is uncommon and usually occurs within 10 years of completing therapy for ALL. A variety of recurrent cytogenetic abnormalities have been described, suggesting significant biological heterogeneity. We report a case of highly refractory secondary AML with trisomy 10 and del(9q) occurring in an adolescent female 12 years after she was treated successfully for precursor B-cell ALL with chemotherapy only.