#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.

Emerging Biomarkers in Personalized Therapy of Lung Cancer.

The two clinically validated and Food and Drug Administration approved lung cancer predictive biomarkers (epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) translocations) occur in only about 20 % of lung adenocarcinomas and acquired resistance develops to first generation drugs. Several other oncogenic drivers for lung adenocarcinoma have emerged as potentially druggable targets with new predictive biomarkers. Oncologists are requesting testing for ROS1 translocations which predict susceptibility to crizotinib, already approved for ALK positive lung cancers. Other potential biomarkers which are currently undergoing clinical trials are RET, MET, HER2 and BRAF. Detection of these biomarkers includes fluorescent in situ hybridization and/or reverse transcriptase polymerase chain reaction (ROS1, RET, HER2), mutation analysis (BRAF) and immunohistochemistry (MET). Screening by immunohistochemistry may be useful for some biomarkers (ROS1, BRAF). Targeted next generation sequencing techniques may be useful as well. These five biomarkers are under consideration for inclusion in revised lung cancer biomarker guidelines by the College of American Pathologists, International Association for the Study of Lung Cancer and Association for Molecular Pathology.

Ultrasensitive immuno-detection using viral nanoparticles with modular assembly using genetically-directed biotinylation.

We report a novel, modular approach to immuno-detection based on antibody recognition and PCR read-out that employs antibody-conjugated bacteriophage and easily-manipulated non-pathogenic viruses as affinity agents. Our platform employs phage genetically tagged for in vivo biotinylation during phage maturation that can easily be linked, through avidin, to any biotinylated affinity agent, including full-length antibodies, peptides, lectins or aptamers. The presence of analyte is reported with high sensitivity through real-time PCR. This approach avoids the need to clone antibody-encoding DNA fragments, allows the use of full-length, high affinity antibodies and, by having DNA reporters naturally encapsulated inside the bacteriophage, greatly reduces nonspecific binding of DNA. We validate the efficacy of this new approach through the detection of Vascular Endothelial Growth Factor, a known angiogenic cancer biomarker protein, at attomolar concentrations in bronchoalveolar lavage fluid.

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.

Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis.

Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A Streptococcus genome that is epidemiologically associated with decreased human necrotizing fasciitis ("flesh-eating disease"). Working from this clinical observation, we find that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that mtsR inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress prsA or lack speB had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the DeltamtsR mutant strain in mice and monkeys. mtsR inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research.

Lack of a major role of Staphylococcus aureus Panton-Valentine leukocidin in lower respiratory tract infection in nonhuman primates.

Panton-Valentine leukocidin (PVL) is a two-component cytolytic toxin epidemiologically linked to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, including serious invasive infections caused by the epidemic clone referred to as strain USA300. Although PVL has long been known to be a S. aureus virulence molecule in vitro, the relative contribution of this leukotoxin to invasive CA-MRSA infections such as pneumonia remains controversial. We developed a nonhuman primate model of CA-MRSA pneumonia and used it to test the hypothesis that PVL contributes to lower respiratory tract infections caused by S. aureus strain USA300. The lower respiratory tract disease observed in this monkey model mimicked the clinical and pathological features of early mild to moderate S. aureus pneumonia in humans, including fine-structure histopathology. In this experiment using a large sample of monkeys and multiple time points of examination, no involvement of PVL in virulence could be detected. Compared with the wild-type parental USA300 strain, the isogenic PVL deletion-mutant strain caused equivalent lower respiratory tract pathology. We conclude that PVL does not contribute to lower respiratory tract infection in this nonhuman primate model of human CA-MRSA pneumonia.

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.

Clinical Utility of Reflex Ordered Testing for Molecular Biomarkers in Lung Adenocarcinoma.

INTRODUCTION: In order to standardize and expedite molecular biomarker testing, we implemented reflex ordered testing of targeted gene alterations in newly diagnosed lung adenocarcinomas within our hospital system. PATIENTS AND METHODS: Reflex ordered testing of specific molecular biomarkers at the time of pathologic diagnosis of lung adenocarcinoma was approved and adopted system-wide in our hospital during 2017. Through institutional review board approval, we retrospectively looked at cohort of patients whose specimens received a diagnosis of lung adenocarcinoma, with molecular biomarker testing performed at Houston Methodist Hospital between 2016 and 2018. We compared average turnaround time (TAT) from 2016 (prior to reflex ordered testing) to 2017 and 2018 (post reflex ordered testing). RESULTS: Standard molecular testing performed on 39 patients in 2016 had an average TAT of 52.6 days, whereas reflex ordered molecular testing in 2017 yielded an average TAT of 26.5 days (n = 127) and 15.6 days in 2018 (n = 54). The average TAT for reporting of molecular results significantly decreased by 37 days (P = .0002) within our hospital system post adoption of reflex ordered testing for lung adenocarcinoma. Reflex ordered testing also resulted in a higher variant detection rate than standard molecular biomarker ordering practices (48.8% vs. 25.6%; P < .05). Overall, the frequencies and types of variants identified among our cohort were similar to previous reports. CONCLUSIONS: Reflex ordered testing of molecular biomarkers in lung adenocarcinoma led to significantly decreased TAT within our hospital system and higher detection rates of targeted gene alterations.

Pulmonary epithelioid hemangioendothelioma mimicking mesothelioma.

An intrathoracic mass was discovered on magnetic resonance imaging (MRI) of the spine in a 37-year-old Caucasian man with a 1 year history of progressively severe upper back pain. A subsequent chest CT scan indicated a 4 cm left hilar mass, extending to the apex and encasing a portion of the left bronchus and pulmonary artery. Initial bronchoscopic and transthoracic biopsies failed to obtain diagnostic material. The patient underwent thoracotomy and was found to have a locally advanced, surgically unresectable lung tumor, involving the pleura, pericardium and diaphragm. The patient failed to respond to radiochemotherapy, and died 11 months following the diagnosis with tamponade and metastasis to the skin of the thoracoabdominal wall. Histologically the tumor had an epithelioid and spindled appearance, without high-grade histological features, and was initially thought to represent biphasic diffuse malignant mesothelioma. Positive immunohistochemistry for vascular markers (CD31, CD34, and FLI-1) disclosed the vascular nature of the tumor. Mesothelioma markers were universally negative and cytokeratin was focally reactive only in some epithelioid cells. Epithelioid hemangioendothelioma is a rare tumor in the lung that can mimic other more common pathological entities, and should be included in the differential diagnosis of unusual pulmonary neoplasms with epithelioid or biphasic morphology.

Correlation Between Programmed Death Receptor-1 Expression in Tumor-Infiltrating Lymphocytes and Programmed Death Ligand-1 Expression in Non-Small Cell Lung Carcinoma.

CONTEXT.­: The interaction between programmed death ligand-1 (PD-L1) and programmed death receptor-1 (PD-1) on activated T cells sends an inhibitory signal that dampens the immune response. Tumors can express PD-L1 and evade the immune system. In advanced non-small cell lung carcinoma, expression of PD-1 in tumor-infiltrating lymphocytes (TILs) correlates with PD-L1 expression in tumor cells (TCs). However, this relationship has not been thoroughly explored in early disease. OBJECTIVE.­: To investigate the correlation of PD-1 and PD-L1 in non-small cell lung carcinoma tumor samples, with emphasis on stage I disease. DESIGN.­: Whole tissue sections from non-small cell lung carcinoma tumors were retrospectively evaluated by immunohistochemistry for PD-1 and PD-L1 expression. The scoring was based on the percentage of cells positive for PD-1 in TILs and PD-L1 in TCs and tumor-infiltrating immune cells (ICs). RESULTS.­: Expression of PD-1 in TILs was observed in 147 of 161 non-small cell lung carcinoma cases (91%). The majority of cases negative for PD-1 also lacked PD-L1 in TCs. The 68 cases with highest PD-1 expression in TILs included 33 (49%) with expression of PD-L1 in TCs and ICs. Strong correlations were observed in patients with elevated PD-1 expression in TILs and PD-L1 in TCs ( P = .01) and ICs ( P = .003). Expression of PD-1 also correlated with increased PD-L1 in TCs and ICs when the 2 were grouped together ( P < .001). Finally, stage I patients with negative PD-1 and PD-L1 expression showed trends toward increased disease-specific survival. CONCLUSIONS.­: Expression of PD-1 in TILs correlates with PD-L1 expression in both TCs and ICs. Furthermore, negative expression of PD-1 and PD-L1 suggest trends toward disease-specific survival, even in early disease stages.

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.

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.

Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.

CONTEXT: In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. OBJECTIVE: To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. DESIGN: The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. RESULTS: Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. CONCLUSIONS: The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes (ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to "rule in" targetable mutations when tissue is limited or hard to obtain.

Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.

CONTEXT: In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. OBJECTIVE: To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. DESIGN: The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. RESULTS: Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. CONCLUSIONS: The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes (ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to "rule in" targetable mutations when tissue is limited or hard to obtain.

Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.

CONTEXT: - In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. OBJECTIVE: - To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. DESIGN: - The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. RESULTS: - Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. CONCLUSIONS: - The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes ( ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR T790M mutations in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to "rule in" targetable mutations when tissue is limited or hard to obtain.

Interpathologist Diagnostic Agreement for Non-Small Cell Lung Carcinomas Using Current and Recent Classifications.

CONTEXT.­: Measurement of interpathologist diagnostic agreement (IPDA) should allow pathologists to improve current diagnostic criteria and disease classifications. OBJECTIVES.­: To determine how IPDA for pathologists' diagnoses of non-small cell lung carcinoma (NSCLC) is affected by the addition of a set of mucin and immunohistochemical (IHC) stains to hematoxylin-eosin (H&E) alone, by recent NSCLC reclassifications, by simplification of these classifications, and by pathologists' practice location, pulmonary pathology expertise, practice duration, and lung carcinoma case exposure. DESIGN.­: We used a Web-based survey to present core images of 54 NSCLC cases to 22 practicing pathologists for diagnosis, initially as H&E only, then as H&E plus mucin and 4 IHC stains. Each case was diagnosed according to published 2004, 2011, and 2015 NSCLC classifications. Cohen's kappa was calculated for the 231 pathologist pairs as a measure of IPDA. RESULTS.­: Twenty-two pathologists diagnosed 54 NSCLC cases by using 4 published classifications. IPDA is significantly higher for H&E/mucin/IHC diagnoses than for H&E-only diagnoses. IPDA for H&E/mucin/IHC diagnoses is highest with the 2015 classification. IPDA is estimated higher after collapse of stated diagnoses into subhead or dichotomized classes. IPDA for H&E/mucin/IHC diagnoses with the 2015 World Health Organization classification is similar for community and academic pathologists, and is higher when pathologists have pulmonary pathology expertise, have more than 6 years of practice experience, or diagnose more than 100 new lung carcinoma cases per year. CONCLUSIONS.­: Higher IPDA is associated with use of mucin and IHC stains, with the 2015 NSCLC classification, and with pathologists' pulmonary pathology expertise, practice duration, and frequency of lung carcinoma cases.

Expression of glutathione S-transferase pi and glutathione synthase correlates with survival in early stage non-small cell carcinomas of the lung.

The glutathione S-transferase (GST) family of genes encode for detoxification enzymes that protect against reactive oxygen species and influence host susceptibility to carcinogens, including tobacco smoke. It has not been determined whether isoenzyme GST-pi or glutathione synthase (GSH2) expression by tumor cells bears a relationship to survival. A total of 201 non-small cell lung cancers (NSCLC) with long-term follow-up were immunostained with antibodies to GST-pi and GSH2 using standard immunostaining techniques. Results were graded semiquantitatively using a scale of 0 to 3 (0 < or = 10%; 1 = 10%-50%; 2 = 51%-80%; 3 > or = 80%) for both nuclear and cytoplasmic staining. Results were correlated with patient survival using Kaplan-Meier analysis. Nuclear staining with GST-pi in greater than 10% of the cells was closely associated with decreased survival (P = .02) in stage I and II squamous cell carcinomas (n = 40). Cytoplasmic staining showed a similar trend that did not reach statistical significance. No significant correlation between GST-pi staining and survival was determined for other histologic types of NSCLC. Cytoplasmic GSH2 staining in greater than 80% of tumor cells was associated with a trend toward improved survival for stage I adenocarcinoma (P = .08) but did not show a relationship to survival for other histologic types of NSCLC. GST-pi expression predicts prognosis in stage I and II squamous cell lung carcinoma, and GSH2 expression may indicate better survival in early stage adenocarcinoma of the lung. Manipulation of GST-pi and GSH2 may be a potential basis for treatment of some NSCLC.

Management of the Solitary Pulmonary Nodule.

CONTEXT: - Optimal management of the patient with a solitary pulmonary nodule entails early diagnosis and appropriate treatment for patients with malignant tumors, and minimization of unnecessary interventions and procedures for those with ultimately benign nodules. With the growing number of high-resolution imaging modalities and studies available, incidentally found solitary pulmonary nodules are an increasingly common occurrence. OBJECTIVE: - To provide guidance to clinicians involved in the management of patients with a solitary pulmonary nodule, including aspects of risk stratification, workup, diagnosis, and management. DATA SOURCES: - Data for this review were gathered from an extensive literature review on the topic. CONCLUSIONS: - Logical evaluation and management pathways for a patient with a solitary pulmonary nodule will allow providers to diagnose and treat individuals with early stage lung cancer and minimize morbidity from invasive procedures for patients with benign lesions.

Programmed Death Ligand-1 (PD-L1) Expression in Either Tumor Cells or Tumor-Infiltrating Immune Cells Correlates With Solid and High-Grade Lung Adenocarcinomas.

CONTEXT: - Programmed death ligand-1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC) is heterogeneous and known to be underestimated on small biopsies. Correlation of PD-L1 expression with clinicopathologic features may provide additional useful information. To our knowledge, the clinicopathologic features of NSCLC have not been reported for subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. OBJECTIVE: - To investigate the clinicopathologic characteristics of NSCLC subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. DESIGN: - PD-L1 immunohistochemistry with the SP142 clone was performed on whole-tissue sections and given semiquantitative scores (0/1/2/3) according to percent of PD-L1+ tumor cells (TCs) and percent tumor area with PD-L1+ tumor-infiltrating immune cells (ICs). RESULTS: - Adenocarcinoma cases that were scored either TC 1/2/3 or IC 1/2/3 included most (22 of 34; 65%) high-histologic grade cases and most (25 of 36; 69%) solid subtype cases. Compared with the adenocarcinoma TC 0 and IC 0 subset, the TC 1/2/3 or IC 1/2/3 subset correlated with higher histologic grade (P = .005, χ2 test for trend) and solid subtype (P < .001, Fisher exact test). Compared with the adenocarcinoma TC 0/1 or IC 0/1 subset, the TC 2/3 or IC 2/3 subset correlated with higher histologic grade (P = .002, χ2 test for trend), solid subtype (P < .001, Fisher exact test), and higher smoking pack-years (P = .01, Mann-Whitney test). CONCLUSIONS: - Lung adenocarcinoma subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells correlated with high histologic grade, solid subtype, and high smoking pack-years.