Pulmonary pathologic alterations associated with biopsy inserted hydrogel plugs.

The prevention of pneumothorax after percutaneous lung biopsy is a major patient safety concern. The insertion of hydrogel plugs into biopsy sites to mitigate this complication is a new intervention. The histology of the plug has not been previously reported, and in this study the histologic reaction is reported in 13 cases. The hydrogel plug forms a spherical basophilic matrix pool with an adjacent foreign body giant cell reaction and patchy eosinophilia. No extension to the pleural surface is present. The potential diagnostic errors related to the presence of the plug are discussed.

Chronic follicular pleuritis: a B cell-rich form of nonspecific pleuritis/fibrosis.

The parietal pleura is often biopsied in patients with idiopathic pleural effusion, and in up to 40% of cases, a diagnosis of nonspecific pleuritis/fibrosis (NSP) is rendered. The histology of this reaction has not been well described including a pattern of B cell lymphoid hyperplasia described as "chronic follicular pleuritis (CFP)". Thirty-two cases of NSP were studied, of which 13 (41%) corresponded to CFP with the remainder displaying a fibrinous and organizing pleuritis with varying degrees of collagenization. CFP had similar etiologies as NSP with long term follow-up, including cardiac disease, pericarditis, asbestos exposure, and occult malignancy. The importance of recognizing a previously undescribed B cell/plasma cell pleural inflammatory response in reactive pleural disease is discussed.

Outcomes after lung transplantation for patients with occupational lung diseases.

Occupational lung diseases (OLD) including silicosis, asbestosis, and pneumoconiosis progress to end stage lung disease requiring lung transplantation (LT). Prognosis and treatment of OLDs are poorly understood and a paucity of data exists regarding LT outcomes. Additionally, transplant operative complexity for patients with OLD is high. A single center retrospective review of all single and bilateral LT recipients between May 2005 and Oct 2016 was performed. Patients were grouped by OLD, and nearest neighbor matching was performed at a ratio of 1:3 cases to controls. Thirty cases were matched to 88 controls. Seventeen patients (57%) with OLD required intraoperative support with either extra-corporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (P = 0.02), and 5 (17%) required delayed chest closure (P = 0.05) which was more frequent than matched controls. In addition, operative time was significantly longer in patients with OLD (P = 0.03). Despite these factors, there were no significant differences in immediate post-operative outcomes including mechanical ventilator support, post-operative ECMO, and tracheostomy. Chronic lung allograft dysfunction and long-term survival were also similar between cases and controls. OLDs should not preclude LT. The operation should be performed at experienced centers.

Whole-exome sequencing identifies unique mutations and copy number losses in calcifying fibrous tumor of the pleura: report of 3 cases and review of the literature.

Calcifying fibrous tumor of the pleura (CFTP) is a rare mesenchymal tumor of unknown pathogenesis. The diagnosis often requires exclusion of other common entities. Our aim was to determine if genomic changes were associated with CFTP that could contribute to mechanisms underlying tumorigenesis. Three cases of CFTP with their corresponding uninvolved control lung tissue were identified. Two patients were male, and 1 was female (age range, 21-32 years). Tumors were multifocal in 2 cases and solitary in 1. Immunohistochemistry for STAT6, BCL-2, CD34, cytokeratin AE1/AE3, calretinin, desmin, S100, ALK, and ß-catenin was used. All immunohistochemistries were negative in CFTPs. DNA was isolated from all 3 pairs of CFTPs and matching normal lungs for whole-exome sequencing. Damaging, tumor-specific, coding variants were identified in 3 genes including multiple heterozygotic, de novo mutations in the Zinc Finger Protein 717 (ZNF717), fascioscapulohumeral muscular dystrophy-1 (FRG1) and cell division cycle 27 (CDC27) genes. Whole-exome sequencing revealed statistically significant, focal, tumor-specific copy number losses among all CFTPs including a large (302 kb) loss at 6p22.2 comprising 32 genes of the histone cluster 1 family and the hemochromatosis (HFE) gene. This is the first study to evaluate the molecular pathogenesis of CFTP and to identify novel deleterious mutations in ZN717, FRG1, and CDC27 genes as well as significant copy number losses on 8 chromosomes with a large loss common to all samples on chromosome 6. These mutations deleteriously altered coding domains in a manner predicted to be damaging to protein function and may contribute to CFTP tumorigenesis.

Pulmonary Pathologic Manifestations of Anti-Alanyl-tRNA Synthetase (Anti-PL-12)-Related Inflammatory Myopathy.

CONTEXT: - Patients with anti-aminoacyl-tRNA synthetase syndrome (ARS), a subset of idiopathic inflammatory myopathy, have a high prevalence of lung involvement. Autoantibodies directed against alanyl-tRNA synthetase (anti-PL-12 Abs) represent 1 of the 8 autoantibodies currently described under the rubric of ARS. OBJECTIVE: - To describe the clinical, radiographic, and pulmonary histopathologic findings in patients possessing anti-PL-12 autoantibodies. DESIGN: - Patients with anti-PL-12 ARS were identified in the University of Pittsburgh Idiopathic Inflammatory Myopathy registry. Lung biopsies from 10 patients and lung explants from 2 patients with anti-PL-12 ARS were reviewed, together with chest computed tomography and clinical records. RESULTS: - Patients primarily presented with dyspnea and variable combinations of cough, fever, mechanic's hands, Raynaud phenomenon, and skin and muscle involvement. Chest computed tomography most commonly showed lower lung zone-predominant reticular infiltrates and traction bronchiectasis, with or without honeycomb change. Surgical lung biopsies and pneumonectomies for lung transplantation revealed usual interstitial pneumonia in 8 of 12 cases (67%), nonspecific interstitial pneumonia in 2 of 12 cases (17%), and organizing pneumonia in 2 of 12 cases (17%). Lymphoplasmacytic interstitial inflammation with lymphoid aggregates was common. CONCLUSIONS: - Lung disease is often the first manifestation of anti-PL-12 ARS. There are no pathognomonic histopathologic features to distinguish anti-PL-12 ARS-related lung disease from idiopathic variants of diffuse interstitial lung disease. Increased inflammation, lymphoid aggregates, and nonspecific interstitial pneumonia-like areas in a biopsy, as well as clinical features of mechanic's hands, Raynaud phenomenon, arthritis, and fever, should prompt pathologists to suggest involvement by ARS.

Critical diagnoses in cytopathology: Experience at a large medical center.

BACKGROUND: Critical values have been well established and accepted in laboratory medicine, but to the authors' knowledge are less well accepted in anatomic pathology. Herein, the authors used a reporting process whereby reports with critical diagnoses were coded to ensure that the patient's clinical team was promptly notified electronically of this finding. The aim of the current study was to determine whether this coding mechanism was used appropriately for critical cytopathology diagnoses in the study health care system. METHODS: A retrospective review of the University of Pittsburgh Medical Center anatomic pathology laboratory information system was performed to identify cytopathology reports in which a critical diagnosis code (MedTrak notification/CoPath Tissue Code TC66; TC66) was used from 2011 through 2016. TC66-coded cytopathology reports between 2015 and 2016 were reviewed further to determine whether this code was used appropriately. RESULTS: A total of 1687 TC66-coded cytopathology reports were identified. Between 2015 and 2016, a total of 30 of 46 reports (65%) from academic hospitals and 46 of 441 reports (10%) from community hospitals met the critical diagnoses criteria outlined by institutional policy. The remaining TC66-coded cases were predominantly for new diagnoses of malignancy in patients clinically suspected of having cancer. CONCLUSIONS: Use of a code for critical cytopathology diagnoses was found to be occurring increasingly at the study health care system. Pathologists at the academic and community hospitals in the study institution used this code somewhat differently, reflecting the need to satisfy communication with clinicians in different practice settings. Nevertheless, the authors' experiences with using a code for critical diagnoses not only ensured timely patient care but also proposed a model that could be used by other medical specialties to enhance communication and improve quality of care. Cancer Cytopathol 2017;125:726-30. © 2017 American Cancer Society.

Cicatricial variant of cryptogenic organizing pneumonia.

This study of 12 patients focused on a variant of cryptogenic organizing pneumonia (COP) labeled the cicatricial form in which the airspaces of the lung are filled with and consolidated by dense collagenized scar tissue associated with preservation of underlying lung architecture. Patients were predominantly middle-aged men and presented with bilateral lung disease in the majority of cases, often with nodular or reticulonodular disease (10/12; 83%). Patients were usually symptomatic with shortness of breath, cough, and dyspnea on exertion. Fifty-five percent of patients (6/11) had persistent or progressive disease at follow-up (mean, 68.5 months; median, 110 months). The cicatricial variant of cryptogenic organizing pneumonia may be predictive of a more recalcitrant form of COP that needs to be morphologically separated from classical COP, usual interstitial pneumonia, and nonspecific interstitial pneumonia.

Sex steroid receptor expression in idiopathic pulmonary fibrosis.

Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF.

Myositis-associated usual interstitial pneumonia has a better survival than idiopathic pulmonary fibrosis.

Objective: To compare the survival outcomes between myositis-associated usual interstitial pneumonia (MA-UIP) and idiopathic pulmonary fibrosis (IPF-UIP). Methods: Adult MA-UIP and IPF-UIP patients were identified using CTD and IPF registries. The MA-UIP cohort included myositis or anti-synthetase syndrome patients with interstitial lung disease while manifesting UIP on high-resolution CT chest and/or a lung biopsy revealing UIP histology. IPF subjects met American Thoracic Society criteria and similarly had UIP histopathology. Kaplan-Meier survival curves compared cumulative and pulmonary event-free survival (event = transplant or death) between (i) all MA-UIP and IPF-UIP subjects, (ii) MA-UIP with biopsy proven UIP (n = 25) vs IPF-UIP subjects matched for age, gender and baseline forced vital capacity (±10%). Cox proportional hazards ratios compared the survival controlling for co-variates. Results: Eighty-one IPF-UIP and 43 MA-UIP subjects were identified. The median cumulative and event-free survival time in IPF vs MA-UIP was 5.25/1.8 years vs 16.2/10.8 years, respectively. Cumulative and event-free survival was significantly worse in IPF-UIP vs MA-UIP [hazards ratio of IPF-UIP was 2.9 (95% CI: 1.5, 5.6) and 5.0 (95% CI: 2.8, 8.7) (P < 0.001), respectively]. IPF-UIP event-free survival (but not cumulative) remained significantly worse than MA-UIP with a hazards ratio of 6.4 (95% CI: 3.0, 13.8) after controlling for age at interstitial lung disease diagnosis, gender, ethnicity and baseline forced vital capacity%. Respiratory failure was the most common cause of death in both groups. A sub-analysis of 25 biopsy-proven MA-UIP subjects showed similar results. Conclusion: MA-UIP patients demonstrated a significant survival advantage over a matched IPF cohort, suggesting that despite similar histological and radiographic findings at presentation, the prognosis of MA-UIP is superior to that of IPF-UIP.

Histologic Findings of Severe/Therapy-Resistant Asthma From Video-assisted Thoracoscopic Surgery Biopsies.

The histologic changes occurring in severe/therapy-resistant asthma (SA) as defined by the European Respiratory Society/American Thoracic Society guidelines, particularly at the level of the distal airways are unknown. This study describes the clinical, radiologic, and histologic characteristics of 29 SA patients who underwent video-assisted thoracoscopic surgery lung biopsy. Pathologic observations were correlated with clinical features, especially the presence of autoimmune disease (AID) (15/29, 51.7%). Ten biopsies (10/29, 34.5%) showed only small airway manifestations of asthma, whereas in 19 (65.5%) asthmatic granulomatosis, manifested by asthmatic bronchiolitis supplemented by an alveolar septal mononuclear infiltrates with non-necrotizing granulomas, was present. SA patients without asthmatic granulomatosis showed more striking small airway injury, subbasement membrane thickening, and neutrophilic infiltrates. Cases with concurrent AID had a tendency to more parenchymal eosinophilic inflammation, more bronchiolocentric granulomas, and a suggestion of increased responsivity to nonsteroidal immunosuppressive therapy. Histologic examination of video-assisted thoracoscopic surgery lung biopsies in SA demonstrates diverse pathologies including cases associated with granulomatous inflammation in addition to eosinophilic infiltrates. This spectrum of histologies may link to a high incidence of AID.

Survey for human polyomaviruses in cancer.

Over the past 8 years, the discovery of 11 new human polyomaviruses (HPyVs) has revived interest in this DNA tumor virus family. Although HPyV infection is widespread and largely asymptomatic, one of these HPyVs, Merkel cell polyomavirus (MCV), is a bona fide human tumor virus. JC virus (JCV), BK virus, HPyV7, and trichodysplasia-spinulosa virus (TSV) can cause nonneoplastic diseases in the setting of immunosuppression. Few specific reagents are available to study the biology of the newly discovered HPyVs. We developed a pan-HPyV-screening method using a cocktail of 3 antibodies that, when combined, recognize T antigen proteins of all HPyVs. We validated detection characteristics of the antibody cocktail by immunoblotting and immunohistochemistry and screened 1,184 cases, including well-defined diseases and tumor tissue microarrays. This assay robustly detected MCV, TSV, JCV, and HPyV7 in etiologically related diseases. We further identified WU polyomavirus in a case of chronic lymphocytic lymphoma-associated bronchitis. Except for scattered, incidentally infected cells in 5% of lung squamous cell carcinomas and colon adenocarcinomas, a broad panel of tumor tissues was largely negative for infection by any HPyV. This method eliminates known HPyVs as suspected causes of cancers investigated in this study. Pan-HPyV survey can be applied to identify diseases associated with recently discovered polyomaviruses.

Changes in Resident Graduate Characteristics in a Large Pathology Training Program, 1994 to 2013.

The field of pathology has changed dramatically over the recent decades and has become more complex with emphasis toward subspecialization. These changes potentially influence resident training as programs and trainees search for cutting-edge skills in the evolving field. Over the last 20 years, our institution's residency education was modified profoundly to emphasize subspecialty practice. Furthermore, efforts were made to search for and recruit candidates who desired such training. In this study, we examined a 20-year time period to determine how these changes may have influenced the characteristics of our resident graduates. For each trainee who graduated from our pathology residency program (1994-2013), the following parameters were evaluated: highest academic degree, gender, graduating medical school, type of training, number of publications during residency, enrollment in fellowships, and type of career position. The data collected were divided into 4 time periods. Fisher exact test and 2-tailed t test were used for statistical analyses comparing the first half (1994-2003) to the latter half (2004-2013) of the study. In the second half, there were more graduates who pursued single track pathology training-anatomic pathology or clinical pathology versus combined anatomic/clinical pathology training (P = .035), more first author and total publications per graduate during residency (P < .001), more graduates who enrolled in fellowships (P < .001), and a greater tendency toward an academic career position than all other types combined (P = .034). In parallel to the subspecialization trends in our department, we witnessed changes in the characteristics of our resident graduates whose interests and career choices have become more focused.

Enhancing Autophagy with Drugs or Lung-directed Gene Therapy Reverses the Pathological Effects of Respiratory Epithelial Cell Proteinopathy.

Recent studies have shown that autophagy mitigates the pathological effects of proteinopathies in the liver, heart, and skeletal muscle but this has not been investigated for proteinopathies that affect the lung. This may be due at least in part to the lack of an animal model robust enough for spontaneous pathological effects from proteinopathies even though several rare proteinopathies, surfactant protein A and C deficiencies, cause severe pulmonary fibrosis. In this report we show that the PiZ mouse, transgenic for the common misfolded variant α1-antitrypsin Z, is a model of respiratory epithelial cell proteinopathy with spontaneous pulmonary fibrosis. Intracellular accumulation of misfolded α1-antitrypsin Z in respiratory epithelial cells of the PiZ model resulted in activation of autophagy, leukocyte infiltration, and spontaneous pulmonary fibrosis severe enough to elicit functional restrictive deficits. Treatment with autophagy enhancer drugs or lung-directed gene transfer of TFEB, a master transcriptional activator of the autophagolysosomal system, reversed these proteotoxic consequences. We conclude that this mouse is an excellent model of respiratory epithelial proteinopathy with spontaneous pulmonary fibrosis and that autophagy is an important endogenous proteostasis mechanism and an attractive target for therapy.

Relationship between fibroblastic foci profusion and high resolution CT morphology in fibrotic lung disease.

BACKGROUND: Fibroblastic foci profusion on histopathology and severity of traction bronchiectasis on highresolution computed tomography (HRCT) have been shown to be predictors of mortality in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the relationship between fibroblastic foci (FF) profusion and HRCT patterns in patients with a histopathologic diagnosis of usual interstitial pneumonia (UIP), fibrotic non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity pneumonitis (CHP). METHODS: The HRCT scans of 162 patients with a histopathologic diagnosis of UIP or fibrotic NSIP (n = 162) were scored on extent of groundglass opacification, reticulation, honeycombing, emphysema and severity of traction bronchiectasis. For each patient, a fibroblastic foci profusion score based on histopathologic appearances was assigned. Relationships between extent of fibroblastic foci and individual HRCT patterns were investigated using univariate correlation analysis and multivariate linear regression. RESULTS: Increasing extent of reticulation (P < 0.0001) and increasing severity of traction bronchiectasis (P < 0.0001) were independently associated with increasing FF score within the entire cohort. Within individual multidisciplinary team diagnosis subgroups, the only significant independent association with FF score was severity of traction bronchiectasis in patients with idiopathic pulmonary fibrosis (IPF)/UIP (n = 66, r(2) = 0.19, P < 0.0001) and patients with chronic hypersensitivity pneumonitis (CHP) (n = 49, r(2) = 0.45, P < 0.0001). Furthermore, FF score had the strongest association with severity of traction bronchiectasis in patients with IPF (r(2) = 0.34, P < 0.0001) and CHP (r(2) = 0.35, P < 0.0001). There was no correlation between FF score and severity of traction bronchiectasis in patients with fibrotic NSIP. Global disease extent had the strongest association with severity of traction bronchiectasis in patients with fibrotic NSIP (r(2) = 0.58, P < 0.0001). CONCLUSION: In patients with fibrotic lung disease, profusion of fibroblastic foci is strikingly related to the severity of traction bronchiectasis, particularly in IPF and CHP. This may explain the growing evidence that traction bronchiectasis is a predictor of mortality in several fibrotic lung diseases.

Pathobiology of severe asthma.

Severe asthma (SA) afflicts a heterogeneous group of asthma patients who exhibit poor responses to traditional asthma medications. SA patients likely represent 5-10% of all asthma patients; however, they have a higher economic burden when compared with milder asthmatics. Considerable research has been performed on pathological pathways and structural changes associated with SA. Although limitations of the pathological approaches, ranging from sampling, to quantitative assessments, to heterogeneity of disease, have prevented a more definitive understanding of the underlying pathobiology, studies linking pathology to molecular markers to targeted therapies are beginning to solidify the identification of select molecular phenotypes. This review addresses the pathobiology of SA and discusses the current limitations of studies, the inflammatory cells and pathways linked to emerging phenotypes, and the structural and remodeling changes associated with severe disease. In all cases, an effort is made to link pathological findings to specific clinical/molecular phenotypes.

The pulmonary histopathology of anti-KS transfer RNA synthetase syndrome.

CONTEXT: The clinical spectrum of the antisynthetase syndromes (AS) has been poorly defined, although some frequently present with pulmonary manifestations. The anti-KS anti-asparaginyl-transfer RNA synthetase syndrome is one in which pulmonary interstitial lung disease is almost always present and yet the histopathologic spectrum is not well described. OBJECTIVE: To define the morphologic manifestations of pulmonary disease in those patients with anti-KS antiasparaginyl syndrome. DESIGN: We reviewed the connective tissue disorder registry of the University of Pittsburgh and identified those patients with anti-KS autoantibodies who presented with interstitial lung disease and had surgical lung biopsies. RESULTS: The 5 patients with anti-KS antisynthetase syndrome were usually women presenting with dyspnea and without myositis, but with mechanic's hands (60%) and Raynaud phenomenon (40%). They most often presented with a usual interstitial pneumonia pattern of fibrosis (80%), with the final patient displaying organizing pneumonia. CONCLUSIONS: Pulmonary interstitial lung disease is a common presentation in patients with the anti-KS-antisynthetase syndrome, who are often women with rather subtle or subclinical connective tissue disease, whereas the literature emphasizes the nonspecific interstitial pneumonia pattern often diagnosed clinically. Usual interstitial pneumonia and organizing pneumonia patterns of interstitial injury need to be added to this clinical differential diagnosis.

De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation.

BACKGROUND: The development of human leukocyte antigen (HLA) antibody responses has been associated with worse clinical outcomes, such as bronchiolitis obliterans syndrome (BOS) and death, in lung transplant recipients (LTRs). However, the role of donor-specific HLA antibody (DSA) responses as a risk factor for poor outcomes remains controversial. METHODS: We prospectively screened 445 LTRs for DSA at our institution at the time of surveillance bronchoscopies for the first 2 years after transplantation between 2003 and 2008, and evaluated clinical outcomes. For this purpose, we used the combination of panel-reactive antibodies (PRA) by enzyme-linked immunosorbent assay (ELISA) and the Luminex single-antigen bead (SAB) assay (One Lambda, Canoga Park, CA). RESULTS: We detected de novo DSA (dnDSA) in 58 of 445 (13%) LTRs in our cohort. Freedom from BOS was significantly reduced in LTRs with dnDSA versus those without dnDSA (p < 0.001). Using a Cox proportional hazards model, the development of dnDSA was associated with a significantly increased hazard ratio (HR = 6.59 [4.53 to 9.59]; p < 0.001) for BOS and high-grade BOS (Stage ≥ 2) (HR = 5.76 [3.48 to 9.52]; p < 0.001). Freedom from death was significantly reduced in LTRs with dnDSA (p < 0.001), including mortality attributable to BOS (HR = 9.86 [4.91 to 19.78]; p < 0.001). CONCLUSIONS: Taken together, our findings provide evidence that dnDSA is associated with accelerated BOS kinetics and severity, as well as death due to BOS after lung transplantation. In addition, these data support regular monitoring for the development of dnDSA in LTRs and underscore the need for novel strategies to mitigate the increased risk of poor outcomes associated with dnDSA.

Smartphone adapters for digital photomicrography.

BACKGROUND: Photomicrographs in Anatomic Pathology provide a means of quickly sharing information from a glass slide for consultation, education, documentation and publication. While static image acquisition historically involved the use of a permanently mounted camera unit on a microscope, such cameras may be expensive, need to be connected to a computer, and often require proprietary software to acquire and process images. Another novel approach for capturing digital microscopic images is to use smartphones coupled with the eyepiece of a microscope. Recently, several smartphone adapters have emerged that allow users to attach mobile phones to the microscope. The aim of this study was to test the utility of these various smartphone adapters. MATERIALS AND METHODS: We surveyed the market for adapters to attach smartphones to the ocular lens of a conventional light microscope. Three adapters (Magnifi, Skylight and Snapzoom) were tested. We assessed the designs of these adapters and their effectiveness at acquiring static microscopic digital images. RESULTS: All adapters facilitated the acquisition of digital microscopic images with a smartphone. The optimal adapter was dependent on the type of phone used. The Magnifi adapters for iPhone were incompatible when using a protective case. The Snapzoom adapter was easiest to use with iPhones and other smartphones even with protective cases. CONCLUSIONS: Smartphone adapters are inexpensive and easy to use for acquiring digital microscopic images. However, they require some adjustment by the user in order to optimize focus and obtain good quality images. Smartphone microscope adapters provide an economically feasible method of acquiring and sharing digital pathology photomicrographs.

Pulmonary pathologic manifestations of anti-glycyl-tRNA synthetase (anti-EJ)-related inflammatory myopathy.

AIMS: Antisynthetase syndromes are a subset of the idiopathic inflammatory myopathies characterised by the presence of autoantibodies to aminoacyl transfer-RNA synthetases (ARS) and monotypic clinical features including Raynaud phenomenon, fever, non-erosive inflammatory arthritis and hyperkeratotic skin changes ('mechanic's hands'). Interstitial lung disease (ILD) is particularly common in ARS syndromes, affecting up to 90% of patients. METHODS: Four patients with ARS syndrome who possessed anti-glycyl-tRNA synthetase (anti-EJ) autoantibodies were retrieved from the University of Pittsburgh database. We report their clinical, radiographic and histopathologic findings. RESULTS: Patients presented with dyspnoea accompanied by Raynaud phenomenon and 'mechanic's hands'. Lung disease was the first manifestation in all four patients (100%) who were all amyopathic. High-resolution CT of the chest showed patchy opacities and consolidations in two patients (50%) whose surgical lung biopsies revealed organising diffuse alveolar damage (DAD), and lower lung zone predominant reticular infiltrates and traction bronchiectasis without honeycomb change in two patients (50%) whose surgical lung biopsies revealed usual interstitial pneumonia (UIP). Mild lymphoplasmacytic inflammation and few scattered lymphoid aggregates were present, but we found no pathognomonic histopathologic features of anti-EJ ARS syndrome. Serologic testing revealed no other autoantibodies. All patients responded to immunosuppressive therapy. CONCLUSIONS: Identifying ARS-associated autoantibodies in ILD patients with or without myopathy is desirable because patients may respond well to immunosuppressive therapy, and their prognosis is better than that of patients with idiopathic forms of DAD or UIP.

Pocket pathologist: A mobile application for rapid diagnostic surgical pathology consultation.

INTRODUCTION: Telepathology allows the digital transmission of images for rapid access to pathology experts. Recent technologic advances in smartphones have allowed them to be used to acquire and transmit digital images of the glass slide, representing cost savings and efficiency gains over traditional forms of telepathology. We report our experience with developing an iPhone application (App - Pocket Pathologist) to facilitate rapid diagnostic pathology teleconsultation utilizing a smartphone. MATERIALS AND METHODS: A secure, web-based portal (http://pathconsult.upmc.com/) was created to facilitate remote transmission of digital images for teleconsultation. The App augments functionality of the web-based portal and allows the user to quickly and easily upload digital images for teleconsultation. Image quality of smartphone cameras was evaluated by capturing images using different adapters that directly attach phones to a microscope ocular lens. RESULTS: The App was launched in August 2013. The App facilitated easy submission of cases for teleconsultation by limiting the number of data entry fields for users and enabling uploading of images from their smartphone's gallery wirelessly. Smartphone cameras properly attached to a microscope create static digital images of similar quality to a commercial digital microscope camera. CONCLUSION: Smartphones have great potential to support telepathology because they are portable, provide ubiquitous internet connectivity, contain excellent digital cameras, and can be easily attached to a microscope. The Pocket Pathologist App represents a significant reduction in the cost of creating digital images and submitting them for teleconsultation. The iPhone App provides an easy solution for global users to submit digital pathology images to pathology experts for consultation.