Department of Pathology and Laboratory Medicine, Johns Hopkins University, Baltimore, MD.
Objectives: A clinical laboratory management (CLM) curriculum that can objectively assess the Accreditation Council for Graduate Medical Education pathology systems-based practice milestones and can provide consistent resident training across institutions is needed.
Methods: Faculty at Emory University created a curriculum that consists of assay verification exercises and interactive, case-based online modules. Beta testing was done at Emory University and Johns Hopkins. Read More
Objectives: Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups.
Methods: MDS-U cases were reviewed at four major academic institutions. Read More
Objectives: To review how changes in the pathologic definitions for papillary tumors of the thyroid during recent decades have affected outcomes for patients with these tumors.
Methods: Forty-nine previous reports or studies involving collectively 53,606 patients were reviewed, and new analyses were performed on the data to include analyses of agreement, incidence, survival, and diagnostic categories.
Results: The past emphasis on cytologic features to define papillary tumors has not resulted in ideal pairwise agreement between pathologists and has produced incidence and survival data suggesting overdetection and overdiagnosis. Read More
Objectives: To curtail inappropriate plasma transfusions, we instituted clinical decision support as an alert upon order entry if the patient's recent international normalized ratio (INR) was 1.7 or less.
Methods: The alert was suppressed for massive transfusion and within operative or apheresis settings. Read More
Objectives: Accurate diagnosis of malignant peripheral nerve sheath tumor (MPNST) is often challenging on fine-needle aspiration (FNA) or core needle biopsy. Recurrent mutations in EED and SUZ12, which encode subunits of polycomb repressive complex 2 (PRC2), have been identified in 70% to 92% of MPNSTs; PRC2 inactivation leads to loss of trimethylation of lysine 27 of histone H3 (H3K27me3). We evaluated the utility of H3K27me3 immunohistochemistry for distinguishing MPNST from its cytomorphologic mimics. Read More
Department of Pathology, Wexner Medical Center at The Ohio State University, Columbus.
Objectives: Several specific histologic types of invasive carcinoma of breast, including invasive tubular carcinoma (ITC), invasive mucinous carcinoma (IMC), and classical invasive lobular carcinoma (CILC), are considered low-grade carcinomas with favorable outcomes. We aimed to investigate the utility of Oncotype DX test in these tumors by comparing its recurrence score (RS) with the modified Magee equation RS.
Methods: Oncotype DX RSs were collected and modified Magee equation RSs were calculated in 163 low-grade invasive breast carcinomas, including 105 CILCs, 41 ITCs, and 17 IMCs. Read More
Objectives: Granular cell tumors are rare neoplasms of neural origin. Despite the mesenchymal nature of these tumors, they rarely occur in the soft tissue, and as a result, this subset is not well characterized. We present the largest case series to date comprising 50 patients with benign and atypical soft tissue granular cell tumors in an effort to better define the pathologic features in this subset of lesions. Read More
Objectives: For over 60 years, Harborview Medical Center (HMC) in Seattle has received its blood components and pretransfusion testing from a centralized transfusion service operated by the regional blood supplier. In 2011, a hospital-based transfusion service (HBTS) was activated.
Methods: After 5 years of operation, we evaluated the effects of the HBTS by reviewing records of hospital blood use, quality system events, blood product delivery times, and costs. Read More
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY.
Objectives: Ki-67 has been proposed to be used as a surrogate marker to differentiate luminal breast carcinomas (BCs). The purpose of this study was to determine the utility of and best approaches for using tissue microarrays (TMAs) and Ki-67 staining to distinguish luminal subtypes in large epidemiology studies of luminal/human epidermal growth factor receptor 2 (HER2)-negative BC.
Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Objectives: This study investigated anal high-risk HPV (HR-HPV) prevalence in HIV-infected women using the Cepheid Xpert HPV assay and compares its performance with that of Hybrid Capture-2 (hc2).
Methods: A total of 199 HIV-infected women were recruited from Helen Joseph Hospital, Johannesburg. Stored ThinPrep anal swabs that had previously been tested using hc2 were tested for HPV using Xpert. Read More
Medical and Scientific Affairs, Roche Molecular Diagnostics, Pleasanton, CA.
Objectives: Health care-associated methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA) infections are continuing problems. Rapidly determining the MRSA colonization status of a patient facilitates practice to reduce spread of MRSA clinical disease. Sensitive detection of all SA prior to surgery, followed by decolonization, can significantly reduce postoperative infection from this pathogen. Read More
Objectives: Previous work in our laboratory identified keratin 17 (K17) as a specific and sensitive biomarker for high-grade squamous intraepithelial lesions and cervical squamous cell carcinoma (SCC). K17, however, has not been previously evaluated in endocervical glandular neoplasia. Based on the similar pathogenesis of squamous and glandular lesions of the cervix, we hypothesized that K17 overexpression could also be a diagnostic and/or prognostic biomarker for endocervical neoplasia. Read More
Objectives: CD200 expression has been well studied in hematopoietic malignancies; however, CD200 expression has not been well-characterized in neuroendocrine neoplasms. We examined CD200 expression in 391 neuroendocrine neoplasms from various anatomic sites.
Methods: Tissue blocks containing pulmonary small cell carcinoma, pulmonary carcinoid, large cell neuroendocrine carcinoma, pancreatic neuroendocrine tumor, gastrointestinal carcinoid, and Merkel cell carcinoma were evaluated for CD200 expression by immunohistochemistry. Read More
Objectives: The expected regional variability in percent human epidermal growth factor receptor 2 (HER2)-positive breast cancers is not currently clear.
Methods: Data from the 2006 to 2011 California Cancer Registry were examined by county and health service area. The influence of demographic and pathologic features was used in a multivariable logistic regression model to compare expected with observed HER2-positive percentages by region. Read More
Objectives: Reporting benign-appearing endometrial cells (nEMCs) in Papanicolaou (Pap) smears of women 40 years and older, introduced in The Bethesda System 2001, may be interpreted as an abnormal finding and lead to unnecessary endometrial biopsies. To our knowledge, this is the first study on the negative predictive value (NPV) of this cytology finding.
Methods: An 11-year database with 1,036,629 Pap test reports and 121,079 surgical pathology reports identified reports of nEMCs in women 40 years and older with follow-up endometrial histopathology within 6 months. Read More
Objectives: Signet ring cells (SRCs) can be seen in a variety of thyroid tumors and can pose a diagnostic pitfall on cytology. This study describes the cytologic, histomorphologic, and molecular aspects of a cohort of primary thyroid tumors with SRCs.
Methods: A search was performed of the Massachusetts General Hospital and Brigham and Women's Hospital (Boston, MA) pathology archives for the keywords thyroid, signet, and signet ring features between 2000 and 2014. Read More
Objectives: To examine and summarize the current literature on the effects of therapeutic plasma exchange on medication levels.
Methods: Literature review was performed via searches of the Cochrane Database and PubMed-MEDLINE (1996 to August 2016) looking for all case reports, case series, and human randomized controlled trials involving therapeutic plasma exchange (TPE)-associated drug removal.
Results: Approximately 60 peer-reviewed articles were identified with the majority being case reports; no randomized controlled trials were identified. Read More
Objectives: The programmed death 1 (PD-1) pathway is upregulated in the immune microenvironment of many cancers. In this study, we examined the PD-1 pathway and the immune microenvironment of small intestinal adenocarcinomas by immunohistochemistry.
Methods: From our department pathology archives we identified 42 small intestinal adenocarcinomas from between 2000 and 2015, with blocks available for IHC studies. Read More
Objectives: Fibromatosis of the breast is an uncommon neoplasm with potential for local recurrence. Treatment has traditionally been surgical excision with current trends toward conservative management. Given the option of observation after diagnosis by core needle biopsy (CNB), we sought to evaluate the accuracy of CNB for diagnosing fibromatosis. Read More
Objectives: Fine-needle aspiration (FNA) of head and neck lymph nodes (LNs) is useful in diagnosing metastatic papillary thyroid carcinoma (PTC) and most commonly shows classic cytologic features of PTC. Metastatic PTC, however, may occasionally present with a pattern unfamiliar to most pathologists: atypical histiocytoid cells (AHCs).
Methods: All PTC thyroidectomy specimens with associated FNA of LNs were retrieved from our files for 2007 to 2013. Read More
Objectives: The increasing cost of clinical laboratory testing is a challenge in our health care system. This study aims to calculate the annual clinical laboratory test costs attributed to patients in a major Canadian city and to correlate them to their sociodemographic variables.
Methods: Retrospective cohort study involving patients who received clinical chemistry, hematology, and microbiology tests in 2011 in Calgary, Canada (n = 610,409). Read More
Objectives: To describe the use of molecular diagnostic techniques for patients with hemoglobin disorders.
Methods: A clinical scenario is presented in which molecular diagnosis is important for genetic counseling. Globin disorders, techniques for their diagnosis, and the role of molecular genetic testing in managing patients with these disorders are described in detail. Read More
Objectives: Pathologist workload in the United States has traditionally been measured by relative value units (RVUs), which is often criticized for providing an inaccurate estimate of actual work. This study compares three methods for measuring workload.
Methods: Surgical pathology and cytopathology workload for 1 representative month at Stanford Health Care was assessed using three different methods: RVUs, Royal College of Pathologists (RCP) point system, and University of Washington-Seattle (UW) slide count method. Read More
Objectives: Patients with hereditary/congenital platelet disorders (HPDs) have a broad range of clinical manifestations and laboratory phenotypes. We assessed the performance characteristics of the International Society on Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT) and clinically validated platelet laboratory tests for diagnosis of HPDs.
Methods: The records of 61 patients with suspected HPDs were reviewed and ISTH-BAT scores calculated. Read More
Objectives: Free light chain (FLC) measurement gained a lot of interest for diagnostic workup of monoclonal gammopathy.
Methods: We evaluated the performance of turbidimetric polyclonal Freelite (The Binding Site, Birmingham, UK) assays on Cobas 6000 (Roche Diagnostics, Rotkreuz, Switzerland) and nephelometric monoclonal N Latex (Siemens Healthcare Diagnostics, Marburg, Germany) assays on BN ProSpec (Dade Behring, Deerfield, IL) vs established nephelometric Freelite assays on BN ProSpec.
Results: Analytical performance was acceptable. Read More
Objectives: The eighth edition of the AJCC Cancer Staging Manual now stratifies the T descriptor for lung cancers by each increasing 1.0 cm increment, up to 5.0 cm, with an additional category for tumor greater than 7. Read More
Objectives: To characterize and quantitate hemoglobin (Hb) variants discovered during biometric hemoglobin A1c (HbA1c) analyses in a large multiethnic population with a focus on the effect of variants on testing method and results.
Methods: In total, 13,913 individuals had their HbA1c measured via ion-exchange high-performance liquid chromatography. Samples that had a variant Hb detected or HbF fraction more than 25% underwent variant Hb characterization and confirmation by gel electrophoresis. Read More
Objectives: An assessment of methods for the accurate measurement of low-density lipoprotein cholesterol (LDL-C) at decreased concentrations has not yet been carried out. We evaluated the performance of the Friedewald equation, a direct enzymatic assay, and a novel equation for determining LDL-C levels in a pediatric population with elevated triglycerides and reduced LDL-C levels.
Methods: LDL-C concentrations of 127 pediatric patients were determined by the Friedewald equation, a direct enzymatic assay, and a novel equation. Read More
Objectives: The importance of distinguishing mature B-cell lymphoproliferative disorders (B-LPDs) is highlighted by the distinct treatments used for and varying prognoses seen in association with these different diseases. Immunophenotyping allows for accurate and efficient differentiation of many B-LPDs. Recently, we showed that CD200 is highly expressed in hairy cell leukemia (HCL) but not in marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), or hairy cell leukemia-variant (HCL-v). Read More
Objectives: To investigate the effects of indirect- and direct-acting anticoagulants on the interpretation of lupus anticoagulant (LAC) assays.
Methods: A retrospective database review was performed to identify all LAC panels from November 2012 to November 2015. The positivity rates for three LAC tests were compared among various anticoagulant medications. Read More
Objectives: A report on the multicenter evaluation of the Bruker MALDI Biotyper CA System (MBT-CA; Bruker Daltonics, Billerica, MA) for the identification of clinically important bacteria and yeasts.
Methods: In total, 4,399 isolates of medically important bacteria and yeasts were assessed in the MBT-CA. These included 2,262 aerobic gram-positive (AGP) bacteria, 792 aerobic gram-negative (AGN) bacteria 530 anaerobic (AnA) bacteria, and 815 yeasts (YSTs). Read More
Objectives: To determine whether V H family usage in B-cell lymphoproliferative disorders can be deduced from polymerase chain reaction (PCR) product-length information obtained through the BIOMED-2 (Invivoscribe, San Diego, CA) clonality assay.
Methods: We develop an algorithm that uses the sizing information of the BIOMED-2 immunoglobulin heavy chain (IGH) clonality assay to deduce V H family usage. PCR with family-specific primers on 51 clinical samples containing 54 rearranged alleles were used to validate the algorithm. Read More
Objectives: To analyze the economic impact of testing for activated protein C resistance (APC-R) due to factor V Leiden (FVL) mutation with APC-R with reflexive FVL genotyping (algorithmic approach) or genotyping alone.
Methods: OptumLabs Data Warehouse (OLDW) data were used to assess testing approaches. Insurance claims for APC-R and FVL in 2013 were compared with the Mayo Clinic database. Read More
Objectives: β-Catenin-activated hepatocellular adenomas have an elevated risk of harboring foci of hepatocellular carcinoma. Inflammatory adenomas also have an increased propensity for malignant transformation and are associated with a systemic inflammatory syndrome. Patients with these two adenoma subtypes benefit from excision. Read More
Objectives: This study aimed to compare a modified Magee equation with Oncotype DX (Genomic Health, Redwood City, CA) recurrence score (RS) and identify patients who are unlikely to benefit from Oncotype DX.
Methods: Magee equation RS was calculated in 438 cases and correlated with Oncotype DX RS.
Results: The Pearson correlation coefficient ( r ) for the Magee equation and Oncotype DX RS was 0. Read More
Objectives: Debate continues on whether leukoreduction alone (LR) is sufficiently similar to leukoreduced cellular products drawn from cytomegalovirus (CMV)-seronegative (SN) donors to minimize the risk of transfusion-transmitted CMV (TT-CMV). We sought to determine the policy, inventory, and practice landscape of the province for TT-CMV mitigation.
Methods: A web-based survey was distributed to hospitals in Ontario by Canadian Blood Services to collect data on their policies with respect to TT-CMV prevention. Read More
Objectives: CD25 expression is associated with t(9;22)(q34;q11)/Philadelphia chromosome translocation (Ph); BCR-ABL1 rearrangement in B lymphoblastic leukemia/lymphoma (B-LL). However, the significance of CD25 expression in Ph negative (Ph-) B-LL regarding residual disease (RD) and genetic abnormalities is largely unknown.
Methods: CD25 expression by flow cytometry (FC) was correlated with Ph status in 95 newly diagnosed B-LL patients and with RD status in day 29 marrow measured by FC in the context of cytogenetic risk stratification in Ph- patients. Read More