Mehrad, Mitra

Inverted papilloma (IP) is a benign neoplasm of the nasal cavity and paranasal sinuses, known for its variable risk of recurrence and potential for developing carcinoma. Emerging evidence has shown high rates of activating EGFR mutation, and a smaller subset is associated with low-risk human papillomavirus (lrHPV). While certain morphologic features, including an inverted growth pattern, are well-established, the presence of condylomatous features, such as large fungating lesions with thick undulating surface epithelium, hyperkeratosis, cytoplasmic clearing, raisinoid nuclei, and binucleation (koilocytic changes) in low-risk HPV-associated IP suggests that these tumors may be a distinct subtype of sinonasal papilloma (SP) with features similar to low-risk HPV-associated anogenital condylomas. This study presents a series of SP with condylomatous morphology and explores the association with lrHPV, the clinicopathologic features, and the rates of carcinoma development. In total, 17 cases of SP exhibiting condylomatous morphology were retrospectively identified. We performed lrHPV and high-risk HPV (hrHPV) RNA in situ hybridization and p16 immunohistochemistry and gathered detailed clinical and pathologic data along with treatment, disease follow-up, and outcomes. These condylomatous papillomas almost all developed in active smokers, were large, were primarily located in the nasal cavity (47%), and showed frequent transformation to invasive squamous cell carcinoma (29%). This malignant transformation rate is much higher than what has been reported for inverted, exophytic, and oncocytic papillomas. The tumors were almost uniformly associated with transcriptionally-active lrHPV (94%) and were consistently negative for p16 and hrHPV. This study shows that a subgroup of IPs with condylomatous morphology have a predilection for the nasal cavity, strong association with lrHPV, and high rates of carcinoma. These findings support the concept that these tumors are a distinct (fourth) type of SP with a higher risk of malignant transformation.

AbstractPurposeMultidisciplinary tumor boards (TB) are the standard for discussing complex head and neck cancer cases. During TB, imaging and microscopic pathology is reviewed, but there is typically no visualization of the resected cancer.MethodsA pilot study was conducted to investigate the utility of visual pathology reports at weekly TB for 10 consecutive weeks. Faculty‐level participants completed a pre‐survey and post‐survey to assess understanding of resected cancer specimens.ResultsProviders (n = 25) across seven medical specialties completed pre‐survey and post‐survey. Following intervention, providers reported significant improvement in understanding of anatomic orientation of the specimen and sites of margin sampling (mean 47.4–96.1, p < 0.001), ability to locate the site of a positive margin (mean 69.5–91.1, p < 0.001), and confidence in treatment plans created (mean 69.5–89.2, p < 0.001) with the addition of visual pathology reports.ConclusionsVisual pathology reports improve provider understanding of resected cancer specimens at multidisciplinary TB.

AbstractDue to the anatomic complexity of the head and neck and variable proximity between laboratory and operating room (OR), effective communication during frozen section analysis (FSA) between surgeons and pathologists is challenging. This proof‐of‐concept study investigates an augmented reality (AR) protocol that allows pathologists to virtually join the OR from the laboratory. Head and neck cancer specimens were scanned ex vivo using a 3‐dimensional scanner and uploaded into an AR platform. Eight head and neck specimens were discussed by surgeons and pathologists in an AR environment. AR‐guided intraoperative consultation was used for specimen orientation and discussion of FSA margin sampling sites. One patient had positive initial margins on FSA and was re‐resected to negative final margins. AR‐guided FSA is possible and allows pathologists to join the operating from any location for intraoperative discussion.

Abstract Rationale Heterogeneous characteristics are observed in familial pulmonary fibrosis (FPF), suggesting that nongenetic factors contribute to disease manifestations. Objectives To determine the relationship between environmental exposures and disease characteristics of FPF, including the morphological characteristics on chest computed tomography (CT) scan, and timing of FPF symptom onset, lung transplantation, or death. Methods Subjects with FPF with an exposure questionnaire and chest CT were selected from a prospective cohort at Vanderbilt. Disease characteristics were defined by lung parenchymal findings on chest CT associated with fibrotic hypersensitivity pneumonitis (fHP) or usual interstitial pneumonia (UIP) and by time from birth to symptom onset or a composite of lung transplantation or death. After assessing the potential for confounding by sex or smoking, adjusted logistic or Cox proportional hazards regression models identified exposures associated with fHP or UIP CT findings. Findings were validated in a cohort of patients with sporadic pulmonary fibrosis enrolled in the LTRC (Lung Tissue Research Consortium) study. Results Among 159 subjects with FPF, 98 (61.6%) were males and 96 (60.4%) were ever-smokers. Males were less likely to have CT features of fHP, including mosaic attenuation (FPF: adjusted [for sex and smoking] odds ratio [aOR], 0.27; 95% confidence interval [CI], 0.09–0.76; P = 0.01; LTRC: aOR, 0.35; 95% CI, 0.21–0.61; P = 0.0002). Organic exposures, however, were not consistently associated with fHP features in either cohort. Smoking was a risk factor for honeycombing in both cohorts (FPF: aOR, 2.19; 95% CI, 1.12–4.28; P = 0.02; LTRC: aOR, 1.69; 95% CI, 1.22–2.33; P = 0.002). Rock dust exposure may also be associated with honeycombing, although the association was not statistically-significant when accounting for sex and smoking (FPF: aOR, 2.27; 95% CI, 0.997–5.15; P = 0.051; LTRC: aOR, 1.51; 95% CI, 0.97–2.33; P = 0.07). In the FPF cohort, ever-smokers experienced a shorter transplant-free survival (adjusted hazard ratio, 1.64; 95% CI, 1.07–2.52; P = 0.02), whereas sex was not associated with differential survival (male adjusted hazard ratio, 0.75; 95% CI, 0.50–1.14; P = 0.18). Conclusions In FPF, smoking contributes to shortened transplant-free survival and development of honeycombing, a finding that is also likely applicable to sporadic pulmonary fibrosis. Females are more likely to manifest CT features of fHP (mosaic attenuation), a finding that was incompletely explained by sex differences in exposures. These findings may have implications for pulmonary fibrosis classification and management.

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 clinicopathologic correlation.

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 “cryoprobe” 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.