The College of American Pathologists Foundation's See, Test & Treat Program®: an Evaluation of a One-Day Cancer Screening Program Implemented in Mississippi.

Women in Mississippi experience significant barriers to healthcare that results in high incidence rates of late-stage breast, cervical, and oropharyngeal cancer. We implemented See, Test, & Treat, a cancer screening and education program, that was aimed at increasing access to cancer screening for underserved women in the Jackson Metropolitan Area. During the event, 103 women between the ages of 21 and 69 years old received breast, cervical, and/or oral cancer screenings. Quantitative and qualitative data were collected to evaluate the effect of the program on the participants' cancer screening knowledge, self-efficacy to obtain medical check-ups, and intentions to engage in health-enhancing behaviors. Of the 57 women who received a mammogram, 18 had abnormal results that required follow-up care. None of the women who received a Pap test had abnormal results, but 8 women were diagnosed with trichomoniasis. One woman was diagnosed with stage 4 oral cancer. The evaluation data indicated that participants found that free cancer screenings and receipt of results on the same day were primary benefits of the program.

#InSituPathologists: how the #USCAP2015 meeting went viral on Twitter and founded the social media movement for the United States and Canadian Academy of Pathology.

Professional medical conferences over the past five years have seen an enormous increase in the use of Twitter in real-time, also known as "live-tweeting". At the United States and Canadian Academy of Pathology (USCAP) 2015 annual meeting, 24 attendees (the authors) volunteered to participate in a live-tweet group, the #InSituPathologists. This group, along with other attendees, kept the world updated via Twitter about the happenings at the annual meeting. There were 6,524 #USCAP2015 tweets made by 662 individual Twitter users; these generated 5,869,323 unique impressions (potential tweet-views) over a 13-day time span encompassing the dates of the annual meeting. Herein we document the successful implementation of the first official USCAP annual meeting live-tweet group, including the pros/cons of live-tweeting and other experiences of the original #InSituPathologists group members. No prior peer-reviewed publications to our knowledge have described in depth the use of an organized group to "live-tweet" a pathology meeting. We believe our group to be the first of its kind in the field of pathology.

Pulmonary sclerosing papillary adenoma.

Pulmonary papillary adenomas are very rare benign neoplasms, with approximately 24 cases reported in the English literature. They typically do not contain any more than an occasional focal area of sclerosis. Indeed, sclerotic interstitium within a sclerosing hemangioma has been reported to be a criterion used to distinguish it from pulmonary papillary adenoma. We present a case of pulmonary sclerosing papillary adenoma, with extensive sclerotic stroma and scattered areas containing typical papillary architecture.

Understanding Factors Associated With Anaplastic Lymphoma Kinase Testing Delays in Patients With Non-Small Cell Lung Cancer in a Large Real-World Oncology Database.

CONTEXT.­: With multiple therapeutic options available for patients with advanced non-small cell lung cancer, the timely ordering and return of results to determine therapy are of critical importance. OBJECTIVE.­: To assess factors impacting anaplastic lymphoma kinase (ALK) test ordering and time to result delivery. DESIGN.­: A retrospective study using a de-identified electronic health record database was performed. Postdiagnosis ALK tests (n = 14 657) were analyzed from 14 197 patients with advanced non-small cell lung cancer diagnosed between January 2015 and May 2019. Time from non-small cell lung cancer diagnosis to ALK sample receipt in the laboratory was a surrogate for test order time. Test ordering was considered delayed if order time was more than 20 days. Turnaround time from sample received to test result was calculated and considered delayed if more than 10 days. Multivariable logistic regression was used to assess factors associated with order time and turnaround time delays. RESULTS.­: Median ALK test order time was 15 days, and 36.4% (5342) of all 14 657 orders were delayed. Factors associated with delays were non-fluorescence in situ hybridization testing, send-out laboratories, testing prior to 2018, nonadenocarcinoma histology, and smoking history. Median turnaround time was 9 days, and 40.3% (5906) of all 14 657 test results were delayed. Non-fluorescence in situ hybridization testing, tissue sample, and orders combining ALK with other biomarkers were associated with delayed ALK result reporting. CONCLUSIONS.­: This study provides a snapshot of real-world ALK test ordering and reporting time in US community practices. Multiple factors impacted both test ordering time and return of results, revealing opportunities for improvement. It is imperative that patients eligible for targeted therapy be identified in a timely fashion.

tPA regulates pulmonary vascular activity through NMDA receptors.

Tissue-type plasminogen activator (tPA) is a potent fibrinolytic enzyme used to treat acute coronary artery obstruction. However, tPA has shown limited utility in other disorders caused by thrombotic vascular occlusion, such as pulmonary embolism. We found that tPA caused dose-dependent effects on the contractility of pulmonary arterial rings that may affect its effectiveness as a thrombolytic agent. At low concentrations (1 nM), tPA stimulated pulmonary vascular contraction in response to phenylephrine, whereas at higher concentrations (20 nM) tPA inhibited pulmonary arterial contractility and promoted pulmonary vascular permeability through an interaction between its "docking site" and N-methyl d-aspartate receptor type 1 (NMDA-R1) expressed by pulmonary arteries. A hexapeptide derived from plasminogen activator inhibitor type 1 that blocked the docking site of tPA, but not its catalytic activity, inhibited its interaction with NMDA-R1, abolished inhibition of pulmonary artery contractility, attenuated vascular permeability, and facilitated fibrinolysis in a murine model of pulmonary embolism. Similar outcomes were seen using a tPA variant that lacks the docking site but retains catalytic activity. These data suggest that it is feasible to attenuate the deleterious extrafibrinolytic effects of tPA and improve its benefit:risk profile in the management of pulmonary embolism.

Pathology of the pleura: what the pulmonologists need to know.

Primary and metastatic pleural neoplasms, and non-neoplastic pleural diseases, can have similar clinical, radiographic and gross features. However, treatments and prognoses of these diverse pleural conditions vary greatly. Accurate diagnosis of pleural disease is therefore extremely important, and histological interpretation of pleural biopsies is vital to rendering an accurate diagnosis. Smaller biopsies contribute to the difficulties in accurately characterizing pleural lesions, and immunostains are frequently employed in their assessment. Diffuse malignant mesothelioma, the most common primary pulmonary neoplasm, is rare; however, other less common primary pleural neoplasms, including solitary fibrous tumour, the most common benign primary pleural neoplasm, occur. These neoplasms are discussed. Also, non-neoplastic pleural diseases, including granulomatous pleuritis, eosinophilic pleuritis and fibrous and fibrinous pleuritis, among other diseases, are discussed.

Anaplastic lymphoma kinase rearrangement prevalence in patients with advanced non-small cell lung cancer in the United States: retrospective real world data.

OBJECTIVE: This study assessed the prevalence of anaplastic lymphoma kinase (ALK) rearrangements in US oncology practices. MATERIALS AND METHODS: Using a nationwide real-world database, we included adults with advanced non-small cell lung cancer (aNSCLC, stage IIIB- IV) diagnosed January 2015 - May 2019, with documented ALK testing results and smoking status. Rearrangement prevalence was assessed overall and then stratified by patient characteristics. RESULTS: The cohort included 19,895 eligible patients with a mean age 68.5 years, majority ever-smokers (85.5%) and from community centers (92.2%). The overall ALK rearrangement prevalence was 2.6%. Positivity rate varied by histology and smoking status; it was the highest among non-smoking patients with non-squamous histology (9.3%). Differences in ALK status also varied by age and race, with young patients (18-39 years) having a higher prevalence (21.6%) vs. older patients (age ≥55 = 2.2%); Asian patients had a prevalence of 6.3%. Patients that were positive for other mutations or rearrangements had a lower ALK positivity rate (0.5%) and patients positive for PD-L1 had a rate of 3.0%. CONCLUSIONS: The likelihood of finding an ALK translocation was highest in younger patients and nonsmokers; however, age and smoking history were not discriminative enough to exclude testing based on clinical variables.

Regulation of airway contractility by plasminogen activators through N-methyl-D-aspartate receptor-1.

Reactive airway disease is mediated by smooth muscle contraction initiated through several agonist-dependent pathways. Activation of type 1 N-methyl-D-aspartate receptors (NMDA-R1s) by plasminogen activators (PAs) has been linked to control of vascular tone, but their effect on airway smooth muscle contractility has not previously been studied to our knowledge. We observed that NMDA-R1s are expressed by human airway smooth muscle cells and constitutively inhibit the contraction of isolated rat tracheal rings in response to acetylcholine (Ach). Both tissue-type PA (tPA) and urokinase-type PA (uPA) bind to NMDA-R1 and reverse this effect, thereby enhancing Ach-induced tracheal contractility. Tracheal contractility initiated by Ach is reduced in rings isolated from tPA(-/-) and uPA(-/-) mice compared with their wild-type counterparts. The procontractile effect of uPA or tPA was mimicked and augmented by the nitric oxide synthase inhibitor, l-NAME. uPA and tPA further enhanced the contractility of rings denuded of epithelium, an effect that was inhibited by the NMDA-R antagonist, MK-801. Binding of PAs to NMDA-R1 and the subsequent activation of the receptor were inhibited by PA inhibitor type 1, by a PA inhibitor type 1-derived hexapeptide that recognizes the tPA and uPA docking domains, as well as by specific mutations within the docking site of tPA. These studies identify involvement of PAs and NMDA-R1 in airway contractility, and define new loci that could lead to the development of novel interventions for reactive airway disease.

Philip T. Cagle, MD-Editor-in-Chief of the Archives of Pathology & Laboratory Medicine, 2005-2019.

• The Archives of Pathology & Laboratory Medicine was first published in 1926 as a specialty journal of the American Medical Association. It became the official journal of the College of American Pathologists in 1995. Under the dynamic leadership of its most recent editor-in-chief, Philip T. Cagle, MD, the Archives has dramatically increased its impact factor and become the most widely read general pathology journal. Dr. Cagle has consistently added leading pathologists to the editorial board, and the collective expertise of these individuals is clearly evident in new, cutting-edge journal masthead sections. The Archives has featured innovative content in the field of digital pathology, including articles on the utilization of smart phones in pathology and the incorporation of whole-slide images and videos into the content of articles. During the current editorial board's tenure, special sections were introduced and have proven immensely popular with the journal's readership. As the Archives celebrates its 94th anniversary, its editorial board remains committed to providing insightful and relevant medical knowledge. The journal's open access Web site ( www.archivesofpathology.org ) allows the dissemination of this information to every corner of the globe at no expense to those who wish to expand their knowledge or improve their medical practice. Dr. Cagle, with support from the editorial board and journal staff, has worked tirelessly during his tenure as Archives editor-in-chief to greatly enhance the content of the journal and its stature within pathology and laboratory medicine.

Update on emerging biomarkers in lung cancer.

There has been considerable progress made in identifying oncogenic driver mutations in advanced lung cancer. The recognition that lung cancer is actually an umbrella classification that is comprised of multiple molecular subgroups has had a profound impact on how medical oncologists make treatment decisions. These mutations are clinically important as available targeted therapies can achieve significant responses and prolonged disease control. This review will summarize the current guidelines for biomarker testing and available therapeutic agents.

"Please Help Me See the Dragon I Am Slaying": Implementation of a Novel Patient-Pathologist Consultation Program and Survey of Patient Experience.

CONTEXT.­: Pathologists evaluate human disease and teach medical students, residents, and clinicians. Historically recognized as the "doctor's doctor," pathologists are well suited to be a direct patient resource of individualized, accurate information. OBJECTIVE.­: To develop and implement a pathology consultation service whereby patients review their tissue slides directly with pathologists. DESIGN.­: A pathologist conducted patient consultations, reviewing biopsy or surgery findings on a multiheaded microscope or computer screen. The pathologist evaluated patients' understanding of their disease and invited patients to ask specific questions. We recorded patient demographic data and assessed utilization with a short patient satisfaction survey using 6 questions with a 5-point Likert scale and 2 questions for open response. RESULTS.­: A total of 31 patients came for consultation; 39% (12 of 31) were accompanied by a friend or family member. Patients' median age was 59 years, with a strong female predominance (90%; 28 of 31). The majority of patients had breast cancer (58%; 18 of 31) or hematologic malignancy (19%; 6 of 31). Of the 31 patients, the survey response rate was 58% (18 of 31). Top-box scoring demonstrated program support, with 89% (16 of 18) of respondents strongly recommending the experience to another patient. Additionally, 78% (14 of 18) strongly agreed that they felt more empowered after seeing their disease. Mean scores for Likert-based questions all were higher than 4.0. CONCLUSIONS.­: To our knowledge, this study is the first report of direct patient-pathologist consultation. Early data suggest that the program may provide effective patient-specific education. The high response rate and favorable assessment of the program suggest that it may be a valuable resource for some patients.

The Legal Aspects of Diversity in Academic Pathology.

Diversity and inclusion in academic pathology center on building a diverse, inclusive pathology faculty. Understanding the basics of federal law, and the US Supreme Court cases that interpret those laws, allows one to consider good practices in diversity hire recruitment and retention that protects the pathology chair, the pathology department, and the institution. Consideration of inclusion and unconscious bias are helpful in building and sustaining robust, valuable academic pathology faculty diversity.

Rapid On-Site Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspirations for the Diagnosis of Lung Cancer: A Perspective From Members of the Pulmonary Pathology Society.

CONTEXT: - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a very useful tool in the field of diagnostic respiratory cytology. Rapid on-site evaluation (ROSE) of EBUS-TBNA not only has the potential to improve diagnostic yield of the procedure but also to triage samples for predictive molecular testing to guide personalized treatments for lung cancer. OBJECTIVE: - To provide an overview of the current status of the literature regarding ROSE of EBUS-TBNA in the diagnosis of lung cancer. DATA SOURCES: - An electronic literature search in PubMed and Google databases was performed using the following key words: cytology, lung cancer, on-site evaluation, rapid on-site evaluation, and ROSE EBUS-TBNA. Only articles published in English were included in this review. CONCLUSIONS: - Rapid on-site evaluation can ensure that the targeted lesion is being sampled and can enable appropriate specimen triage. If available, it should be used with EBUS-TBNA in the diagnosis of lung cancer because it can minimize repeat procedures for additional desired testing (ie, molecular studies). Some studies have shown that ROSE does not adversely affect the number of aspirations, total procedure time of EBUS-TBNA, or the rate of postprocedure complications; it is also helpful in providing a preliminary diagnosis that can reduce the number of additional invasive procedures, such as mediastinoscopy. As EBUS technology continues to evolve, our knowledge of the role of ROSE in EBUS-TBNA for the diagnosis of lung cancer will also continue to grow and evolve.

Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group.

CONTEXT: - Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. OBJECTIVE: - To provide updated, practical guidelines for the pathologic diagnosis of MM. DATA SOURCES: - Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks. CONCLUSIONS: - There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included.

Immunohistochemistry of Pulmonary Biomarkers: A Perspective From Members of the Pulmonary Pathology Society.

The use of immunohistochemistry for the determination of pulmonary carcinoma biomarkers is a well-established and powerful technique. Immunohistochemisty is readily available in pathology laboratories, is relatively easy to perform and assess, can provide clinically meaningful results very quickly, and is relatively inexpensive. Pulmonary predictive biomarkers provide results essential for timely and accurate therapeutic decision making; for patients with metastatic non-small cell lung cancer, predictive immunohistochemistry includes ALK and programmed death ligand-1 (PD-L1) (ROS1, EGFR in Europe) testing. Handling along proper methodologic lines is needed to ensure patients receive the most accurate and representative test outcomes.

Hypersensitivity Pneumonitis A Perspective From Members of the Pulmonary Pathology Society.

CONTEXT: - Hypersensitivity pneumonitis (HP) is a lung disease that develops in susceptible individuals after inhalational exposure to an organic antigen or chemical compound. Pathogenesis is attributed to a combination of type III (immune complex-mediated) and type IV (delayed) hypersensitivity reactions to the inciting agent. OBJECTIVE: - To provide an overview of the current status of the medical literature regarding hypersensitivity pneumonitis. DATA SOURCES: - A literature search was performed using PubMed and Google search engines. The terms "hypersensitivity pneumonitis" and "extrinsic allergic alveolitis" were used, with the search starting on January 9, 2017, and concluding March 8, 2017. CONCLUSIONS: - As a pathologist, it is important to consider hypersensitivity pneumonitis when examining lung specimens because it is often clinically and pathologically overlooked. Recognizing the often subtle findings and correlating them with the patient's history or suggesting a thorough clinical investigation of potential exposures can be of help in identifying the underlying condition so that the patient can be appropriately managed.

Twenty-First Century Pathologists' Advocacy.

Pathologists' advocacy plays a central role in the establishment of continuously improving patient care quality and patient safety, and in the maintenance and progress of pathology as a profession. Pathology advocacy's primary goal is the betterment of patient safety and quality medical care; however, payment is a necessary and appropriate component to both, and has a central role in advocacy. Now is the time to become involved in pathology advocacy; the Medicare Access and Children's Health Insurance Program (CHIP) Reauthorization Act of 2015 (MACRA) and the Protecting Access to Medicare Act of 2014 (PAMA) are 2 of the most consequential pieces of legislation impacting the pathology and laboratory industry in the last 20 years. Another current issue of far-reaching impact for pathologists is balance billing, and yet many pathologists have little or no understanding of balance billing. Pathologists at all stages of their careers, and in every professional setting, need to participate. Academic pathologists have a special obligation to, if not become directly involved in advocacy, at least have a broad and current understanding of those issues, as well as the need and responsibility of pathologists to actively engage in advocacy efforts to address them, in order to teach residents the place of advocacy, and its value, as an inseparable and indispensable component of their professional responsibilities.