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Objectives In this feasibility study, we explored the combined use of circulating tumor human papillomavirus (HPV) DNA (ctHPVDNA) and HPV serology as diagnostic tests for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods Among patients with research-banked serum or plasma at diagnosis, IgG antibodies to oncoproteins from HPV types 16, 18, 31, 33, 35, 45, 52, and 58 were detected with multiplex serology. Positivity for HPV 16 was defined based on detection of combinations of anti-E6, E1, E2, and E7 and for other high-risk types on detection of anti-E6 and anti-E7. Circulating tumor HPV DNA was detected by custom digital droplet polymerase chain reaction (ddPCR) assays for HPV types 16, 18, 33, 35, and 45. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization (ISH) using a cocktail of 18 high-risk HPV types were performed on tissue. Results Of 75 patients, 67 (89.3%) were HPV-associated (p16 and HPV RNA ISH positive) and 8 (10.7%) were HPV-independent. All 8 HPV-independent patients were seronegative and negative for ctHPVDNA (100% specificity). Serology was positive in 53 (79.1%) of 67 HPV-associated patients, while ddPCR was positive for ctHPVDNA in 59 (88.6%) of 67 HPV-associated patients. Requiring both tests to be positive resulted in a sensitivity of 50 (74.6%) of 67 while combining assays (either positive) improved sensitivity to 62 (92.6%) of 67. Conclusions Compared to HPV RNA ISH, HPV serology and ctHPVDNA are sensitive and highly specific biomarkers for HPV-associated OPSCC at the time of presentation. [ABSTRACT FROM AUTHOR]

* Context.--Vaping is the inhalation of heated aerosol from a small battery-powered device as a method to deliver nicotine or other substances. A recent outbreak of severe respiratory illness primarily in the United States has put a spotlight on vaping and its potential risks. Objective.--To familiarize pathologists with vaping, the cytologic and histopathologic features of vaping-associated acute lung injury, and the role of pathology in this diagnosis. Data Sources.--A targeted literature review was performed. Conclusions.--Most cases of vaping-associated lung injury have been linked to vaping products containing tetrahydrocannabinol or other cannabinoids. Lung biopsies show a spectrum of nonspecific acute lung injury patterns (organizing pneumonia, diffuse alveolar damage, acute fibrinous, and organizing pneumonia, or combinations of the above), accompanied by prominent, foamy macrophage accumulation. Injury is usually accentuated around small airways. Lipid-laden macrophages can be identified in bronchioloalveolar lavage fluid in most patients and these can be highlighted using lipid stains, such as oil red O, but the clinical utility of this finding remains unclear, as lipid-laden macrophages can be seen in a wide variety of processes and should not be relied upon to make the diagnosis. Classic histologic features of exogenous lipoid pneumonia have not been identified in tissue samples. Lightly pigmented macrophages, similar to those seen with traditional cigarette smoking, are present in some cases but are usually a minor feature. To date, no specific pathologic features for vaping-related injury have been identified, and it remains a diagnosis of exclusion that requires clinic-pathologic correlation. doi: 10.5858/arpa.2020-0024-RA, WHAT IS VAPING? A PRIMER ON DEVICES, CONTENTS, AND TERMINOLOGY 'Vaping' is the inhalation of an aerosol (vapor) generated by heating a liquid in a small batterypowered device. (1-3) This [...]

* Context.--Transbronchial cryobiopsy is an emerging procedure to obtain lung tissue for diagnosis of interstitial lung disease and has gained popularity because it is less invasive and has a lower rate of complications compared with nonselective surgical lung biopsy. Objective.--To provide an overview of the status of the medical literature regarding transbronchial cryobiopsy. Data Sources.--A literature search was performed using PubMed search engine. The terms 'cryobiopsy' or 'cryo-probe' and 'interstitial lung disease' or 'diffuse parenchymal lung disease' or 'pulmonary fibrosis' were used, with the search concluding at the end of November 2019. Conclusions.--While the diagnostic yield of transbronchial cryobiopsy is slightly lower than surgical lung biopsy, a growing amount of literature suggests that with a multidisciplinary approach cryobiopsy provides diagnostic and prognostic information approaching that of surgical lung biopsy with lower morbidity and mortality. doi: 10.5858/arpa.2020-0007-RA, Diffuse interstitial lung diseases (ILD) are a heterogeneous group that differ widely in their pathogenesis, clinicopathologic features, therapeutic options, and prognosis. In approximately 30% of ILD patients, the specific diagnosis [...]

* Context.--Given the growing clinical significance of human papillomavirus status in oropharyngeal squamous cell carcinoma, the College of American Pathologists established a set of evidence-based recommendations for high-risk human papillomavirus testing for publication in a guideline. Objective.--To evaluate the impact of the recommendations on human papillomavirus ancillary test ordering habits by comparing compliance before and after the guideline was published. Design.--We retrospectively reviewed head and neck squamous cell carcinoma biopsy or resection specimens from outside institutions during a 2.5-year period around guideline publication to determine whether human papillomavirus testing was performed in accordance with the guideline. Results.--Human papillomavirus testing deviated from the guideline in 45 of 107 cases (42.1%) before and 93 of 258 cases (36.0%) after its publication (P = .29). This included 6 of 26 cases of oropharyngeal squamous cell carcinoma (23.1%) before and 5 of 55 cases (9.1%) after (P = .16), with 5 of 5 (100.0%) after due to not performing p16 immunohistochemistry. This also included 30 of 68 cases of nonoropharyngeal carcinoma (44.1%) before and 69 of 163 (42.3%) after the guideline was published (P = .88), with 29 of 30 (96.7%) before and 67 of 69 (97.1%) after due to unnecessary use of p16 immunohistochemistry. Nodal metastasis testing deviated in 9 of 13 cases (69.2%) before and 19 of 40 cases (47.5%) after (P = .21) with marked variability in testing, including 3 of 9 (33.3%) before and 8 of 19 (42.1%) after, for not confirming certain p16 immunohistochemistry-positive tumors with human papillomavirus-specific testing. Conclusions.--Pathologists continue to deviate from the testing guideline significantly in everyday practice. Further education and discussion about the appropriate handling of head and neck cancer specimens may be needed. (Arch Pathol Lab Med. 2021;145:1123-1131; doi: 10.5858/arpa.2020-0220-OA, High-risk human papillomavirus (HR-HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is an increasingly common subset of head and neck squamous cell carcinoma (HNSCC). (1-4) Histologically, HR-HPV-positive OPSCCs typically exhibit nonkeratinizing morphology, [...]

Objectives: Virtual 3D specimen mapping of oncologic surgical specimens provides a visual record of the specimen and margin sampling sites which can be utilized in a variety of cancer care settings. Our objective was to perform a retrospective review of head and neck surgical oncology cases where the specimen was mapped post‐operatively and to evaluate the utility of these 3D specimen maps amongst the multidisciplinary cancer care team. Methods: A retrospective review of our 3D specimen model biorepository was performed. Surgical specimens were 3D scanned and then graphically annotated (or "mapped") during routine pathologic processing. The resulting 3D specimen maps were distributed to the multidisciplinary oncologic care team. Final margin status and any use of the 3D specimen maps were recorded. Results: A total of 28 cases were included. Virtual 3D specimen maps were utilized by the cancer care team in 8 cases (29%), including 2 positive margin cases, 2 close margin cases, and 4 indeterminate margin cases. 3D specimen maps were used to visualize positive margin sites for pathologist‐surgeon communication as a visual reference during tumor board discussions and to inform radiation treatment planning. Conclusion: Post‐operative virtual 3D specimen mapping of oncologic specimens creates a permanent visual record of the specimen and the margins sampled and may serve as a beneficial tool for communication amongst the multidisciplinary cancer care team. Level of Evidence: 4 Laryngoscope, 134:191–197, 2024 [ABSTRACT FROM AUTHOR]

* Context.--Different testing algorithms and platforms for EGFR mutations and ALK rearrangements in advanced-stage lung adenocarcinoma exist. The multistep approach with single-gene assays has been challenged by more efficient next-generation sequencing (NGS) of a large number of gene alterations. The main criticism of the NGS approach is the detection of genomic alterations of uncertain significance.Objective.--To determine the best testing algorithm for patients with lung cancer in our clinical practice.Design.--Two testing approaches for metastatic lung adenocarcinoma were offered between 2012-2015. One approach was reflex testing for an 8-gene panel composed of DNA Sanger sequencing for EGFR, KRAS, PIK3CA, and BRAF and fluorescence in situ hybridization for ALK, ROS1, MET, and RET. At the oncologist's request, a subset of tumors tested by the 8-gene panel was subjected to a 50-gene Ion AmpliSeq Cancer Panel.Results.--Of 1200 non-small cell lung carcinomas (NSCLCs), 57 including 46 adenocarcinomas and NSCLCs, not otherwise specified; 7 squamous cell carcinomas (SCCs); and 4 large cell neuroendocrine carcinomas (LCNECs) were subjected to Ion AmpliSeq Cancer Panel. Ion AmpliSeq Cancer Panel detected 9 potentially actionable variants in 29 adenocarcinomas that were wild type by the 8-gene panel testing (9 of 29, 31.0%) in the following genes: ERBB2 (3 of 29, 10.3%), STK11 (2 of 29, 6.8%), PTEN (2 of 29, 6.8%), FBXW7 (1 of 29, 3.4%), and BRAF G469A (1 of 29, 3.4%). Four SCCs and 2 LCNECs showed investigational genomic alterations.Conclusions.--The NGS approach would result in the identification of a significant number of actionable gene alterations, increasing the therapeutic options for patients with advanced NSCLCs.(Arch Pathol Lab Med. 2018;142:353-357; doi: 10.5858/arpa.2017-0046-OA), Therapeutic successes with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutated advanced lung adenocarcinoma revolutionized the treatment of lung cancer. (1-4) Shortly after the discovery of EGFR mutations, ALK rearrangements were reported [...]

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.(Arch Pathol Lab Med. 2018;142:120-126; doi: 10.5858/arpa.2017-0138-SA), Hypersensitivity pneumonitis (HP, also referred to as extrinsic allergic alveolitis in the medical literature) can develop after inhalational exposure to a particular antigen or chemical in a susceptible individual. Hypersensitivity [...]

BACKGROUND. Patients with [p16.sup.+] oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for [p16.sup.+] OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in [p16.sup.+] OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability. METHODS. We present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in [p16.sup.+] OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated [p16.sup.+] OPSCC were acquired from 6 institutions for optimization and validation of the MuNI. RESULTS. The MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in [p16.sup.+] OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately. CONCLUSION. MuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with [p16.sup.+] OPSCC. These data support further confirmation of the MuNI in prospective trials. FUNDING. National Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government., Introduction The continued increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the setting of declining rates of tobacco use has been attributed to HPV, with almost 70% [...]

Background: Numerous challenges exist in determining surgical margin status. Communication between surgeons and pathologists is crucial for specimen orientation and accurate margin assessment. Methods: A prospective study to determine feasibility of incorporating three‐dimensional (3D) scanning into surgical pathology workflow was performed. A structured‐light 3D scanner captured the photorealistic surface topography of fresh surgical specimens. Computer‐aided design (CAD) software was used to document sites of margin sampling and sectioning. Surveys were distributed among faculty and staff stakeholders to assess feasibility. Results: A series of 40 cases were 3D‐scanned. Median image acquisition time was 8 min. The majority of respondents agreed that the experimental 3D system helped achieve clearer communication. 3D specimen maps assisted in the communication of a focally positive or close margin in 4 of 17 cases. Conclusions: Routine 3D scanning and specimen mapping is feasible and represents an innovative approach to intraoperative and final pathology documentation, margin analysis, and surgeon–pathologist communication. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a multifactorial syndrome with high morbidity and mortality rates, characterized by deficiency in gas exchange and lung mechanics that lead to hypoxemia, dyspnea, and respiratory failure. Histologically, ARDS is characterized by an acute, exudative phase, combining diffuse alveolar damage and noncardiogenic edema, followed by a later fibroproliferative phase. Despite an enhanced understanding of ARDS pathogenesis, the capacity to predict the development of ARDS and to risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the greatest risk of developing ARDS, to evaluate response to therapy, to predict outcome, and to improve clinical trials. The ARDS pathogenesis is presented in this article, as well as concepts and information on biomarkers that are currently used clinically or are available for laboratory use by academic and practicing pathologists and the developing and validating of new assays, focusing on the assays' major biologic roles in lung injury and/or repair and to ultimately suggest innovative, therapeutic approaches. (Arch Pathol Lab Med. 2017;141:1719-1727; doi: 10.5858/arpa.2017-0115-SA), Effective gas exchange in the lung requires thin alveolar septa with a minimum distance between the alveolar epithelium and the endothelium of the microvasculature to facilitate simple diffusion of those [...]