Expression-Based Diagnosis, Treatment Selection, and Drug Development for Breast Cancer.

There is currently no gene expression assay that can assess if premalignant lesions will develop into invasive breast cancer. This study sought to identify biomarkers for selecting patients with a high potential for developing invasive carcinoma in the breast with normal histology, benign lesions, or premalignant lesions. A set of 26-gene mRNA expression profiles were used to identify invasive ductal carcinomas from histologically normal tissue and benign lesions and to select those with a higher potential for future cancer development (ADHC) in the breast associated with atypical ductal hyperplasia (ADH).

The Value Proposition for Pathologists: A Population Health Approach.

The transition to a value-based payment system offers pathologists the opportunity to play an increased role in population health by improving outcomes and safety as well as reducing costs. Although laboratory testing itself accounts for a small portion of health-care spending, laboratory data have significant downstream effects in patient management as well as diagnosis. Pathologists currently are heavily engaged in precision medicine, use of laboratory and pathology test results (including autopsy data) to reduce diagnostic errors, and play leading roles in diagnostic management teams.

Benchmarking Subspecialty Practice in Academic Anatomic Pathology: The 2017 Association of Pathology Chairs Survey.

Assessment of physician workloads has become increasingly important in modern academic physician practice, where it is commonly used to allocate resources among departments, to determine staffing, and to set the compensation of individual physicians. The physician work relative value unit system is a frequently used metric in this regard. However, the application of this system to the practice of pathology has proven problematic.

Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study.

Respiratory exposure to multiwalled carbon nanotubes (MWCNT) or asbestos results in fibrosis; however, the mechanisms to reach this end point may be different. A previous study by our group identified pulmonary effects and significantly altered messenger RNA (mRNA) signaling pathways following exposure to 1, 10, 40, and 80 µg MWCNT and 120 µg crocidolite asbestos on mouse lungs over time at 1-month, 6-month, and 1-year postexposure following pulmonary aspiration. As a continuation to the above study, this current study took an in-depth look at the signaling pathways involved in fibrosis development at a single time point, 1 year, and exposure, 40 µg MWCNT, the lowest exposure at which fibrosis was pathologically evident.

The Role of Human Papillomavirus in Oropharyngeal Squamous Cell Carcinoma.

Context: - Human papillomavirus (HPV) is implicated in the development of oropharyngeal squamous cell carcinomas (OPC), particularly those cancers developing in tonsillar tissue.

Objectives: - To review the prevalence, subtypes, and methods of detecting HPV in OPC and to review the epidemiology, histology, staging, management, and prevention of these cancers.

Data Sources: - The study comprised a review of the literature.

The Importance of High-Risk Human Papillomavirus Types Other Than 16 and 18 in Cervical Neoplasia.

Context: - Types 16 and 18 are the most widely studied high-risk types of human papillomavirus (HPV). However, other high-risk HPV types (HPV non-16/18) also play a significant role in cervical neoplasia. Currently, screening and management algorithms separate out HPV 16/18 from all other HPV non-16/18 types.

Chronic exposure to electronic cigarettes results in impaired cardiovascular function in mice.

Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure to E-cig vapor on vascular function. The purpose of this study was to determine the cardiovascular consequences of chronic E-cig exposure. Female mice (C57BL/6 background strain) were randomly assigned to chronic daily exposure to E-cig vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group).

Quality Improvement Intervention for Reduction of Redundant Testing.

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (-) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced.

Use of Pathology Data to Improve High-Value Treatment of Cervical Neoplasia.

We investigated the influence of pathology data to improve patient outcomes in the treatment of high-grade cervical neoplasia in a joint pathology and gynecology collaboration. Two of us (B.S.

Benchmarking Academic Anatomic Pathologists: The Association of Pathology Chairs Survey.

The most common benchmarks for faculty productivity are derived from Medical Group Management Association (MGMA) or Vizient-AAMC Faculty Practice Solutions Center (FPSC) databases. The Association of Pathology Chairs has also collected similar survey data for several years. We examined the Association of Pathology Chairs annual faculty productivity data and compared it with MGMA and FPSC data to understand the value, inherent flaws, and limitations of benchmarking data.

Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study.

Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-μg crocidolite asbestos group was incorporated as a positive control for comparative purposes.

Positron emission tomography in Warthin's tumor mimicking malignancy impacts the evaluation of head and neck patients.

Purpose: 1) To determine SUVs and PET/CT characteristics of Warthin's tumors in patients presenting to a head and neck cancer clinic. 2) To analyze the impact of PET/CT on the clinical course of these patients.

Materials And Methods: This is a single-institution retrospective analysis of patients with proven Warthin's tumors who underwent PET/CT done at or near the time of diagnosis and presented to a head and neck cancer practice.

Breast cancer pathology, receptor status, and patterns of metastasis in a rural appalachian population.

Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns.

Gynecologic cytology proficiency testing failures: what have we learned?: observations from the college of american pathologists gynecologic cytology proficiency testing program.

Context: In 2006, the first gynecologic cytology proficiency tests were offered by the College of American Pathologists. Four years of data are now available using field-validated slides, including conventional and liquid-based Papanicolaou tests.

Objective: To characterize the pattern of error types that resulted in initial proficiency-test failure for cytotechnologists, primary screening pathologists, and secondary pathologists (those whose slides are prescreened by cytotechnologists).

Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs.

Early-life respiratory infection with Pseudomonas aeruginosa is common in children with cystic fibrosis or immune deficits. Although many of its clinical manifestations involve neural reflexes, little information is available on the peripheral nervous system of infected airways. This study sought to determine whether early-life infection triggers a neurogenic-mediated immunoinflammatory response, the mechanisms of this response, and its relationship with other immunoinflammatory pathways.

Vital signs: how early can resident evaluation predict acquisition of competency in surgical pathology?

Objectives: To determine whether a longitudinal, case-based evaluation system can predict acquisition of competency in surgical pathology and how trainees at risk can be identified early.

Design: Data were collected for trainee performance on surgical pathology cases (how well their diagnosis agreed with the faculty diagnosis) and compared with training outcomes. Negative training outcomes included failure to complete the residency, failure to pass the anatomic pathology component of the American Board of Pathology examination, and/or failure to obtain or hold a position immediately following training.

Silicosis in lymph nodes: the canary in the miner?

Objectives: To investigate evidence that lymph node silicosis can precede parenchymal silicosis.

Methods: The study population was comprised of 264 deceased male uranium miners for whom two or more of four pathologists agreed on the presence or absence of silicosis in lymph nodes and lung parenchyma. We had work histories and silica exposure estimates.

A liquid concept--do classic preparations of body cavity fluid perform differently than ThinPrep cases? Observations from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

Context: Newer liquid-based preparations differ morphologically from classic preparations (smears, filters, and cytocentrifuged preparations). Is adenocarcinoma more readily detected in liquid-based preparations? We reviewed responses from 16,750 fluid challenges of adenocarcinoma distributed in 2005 in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology (CAP NGC).

Objective: To compare the performance of body cavity fluid liquid-based preparations with adenocarcinoma to that in classic preparations in the CAP NGC.

Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells.

Background: Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of the toxicity, biopersistence, pathogenicity, and ability of SWCNTs to translocate to subpleural areas. These results compel studies of potential interactions of SWCNTs with mesothelial cells.

Self-test device for cytology and HPV testing in rural Appalachian women: an evaluation.

Objective: To determine the efficacy of a self-test device for obtaining vaginal/cervical samples for HPV DNA and cytologic testing.

Study Design: We recruited 878 Appalachian women; 775 were able to submit a self-test sample and a provider-collected sample. Each specimen was assessed for cytologic abnormalities and for high-risk HPV infection.

CD99 immunoreactivity in atypical fibroxanthoma and pleomorphic malignant fibrous histiocytoma: a useful diagnostic marker.

Atypical fibroxanthoma (AFX), a benign lesion, and pleomorphic malignant fibrous histiocytoma (MFH) are thought to represent points along the same neoplastic spectrum but with different prognoses and treatments. Diagnosis based on histology and clinical parameters alone is sometimes difficult, and a reliable cost-effective immunohistochemical marker to help distinguish these lesions would be beneficial. The diagnosis of AFX or MFH was based upon published clinical and microscopic criteria.

Papanicolaou tests with mixed high-grade and low-grade squamous intraepithelial lesion features: distinct performance in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytopathology.

Context: Previous studies have shown that in gynecologic cytology, cases of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) perform differently on interpretive review. The performance of cases with mixed LSIL and HSIL features is unknown.

Objective: To compare the performance of gynecologic cytology cases of "pure" LSIL and HSIL with cases showing mixed LSIL and HSIL features.

Longitudinal case-based evaluation of diagnostic competency among pathology residents: a statistical approach.

Context: Accreditation Council for Graduate Medical Education guidelines require the evaluation of residents in 6 competencies. Pathology residents demonstrate medical knowledge, patient care, communication, and practice-based learning competencies in their attainment of competency in surgical pathology diagnosis.

Objective: To implement a prospective case-based approach to longitudinally evaluate the acquisition of competency in surgical pathology diagnosis by trainees.

Malignant mixed tumors of the salivary gland: a study of loss of heterozygosity in tumor suppressor genes.

Carcinosarcomas and carcinoma ex pleomorphic adenoma of the salivary glands are rare tumors that fit into the broader category of malignant mixed tumors. Although most evidence has suggested that the different morphologic components arise from a common clonal origin, there are very few studies that have provided molecular evidence for this clonality. In this study, we examined a set of seven carcinosarcomas and four carcinomas ex pleomorphic adenoma for tumor suppressor gene loss of heterozygosity, in order to assess the clonal patterns in the varying components.