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The current American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association guidelines recommend surgical lung biopsy (SLB) in combination with multidisciplinary discussion among a team [...], Transbronchial lung cryobiopsy involves using a cryoprobe rather than forceps to obtain a bronchoscopic biopsy. Recent studies have shown that transbronchial cryobiopsy provides a larger specimen than conventional transbronchial forceps biopsy, and that the interobserver agreement in the interpretation of cryobiopsy specimens is comparable to that of a surgical lung biopsy. This is encouraging, and transbronchial lung cryobiopsy clearly has a role in the workup and diagnosis of interstitial lung diseases. However, very few patients who have been studied underwent both transbronchial lung cryobiopsy and surgical lung biopsy, and the available data suggest that the diagnostic accuracy of cryobiopsy may not be similar to that of surgical lung biopsy. Further study is needed before transbronchial lung biopsy can be recommended as a replacement for surgical lung biopsy. (Arch Pathol Lab Med. 2016; 140:1281-1284; doi: 10.5858/arpa.2016-0258-SA)

In an era of personalized medicine, with an increasing need for molecular testing, cytologic specimens comprise a crucial component in providing prognostic and predictive information for clinical management of patients [...], * The advent of targeted therapy in lung cancer has heralded a paradigm shift in the practice of cytopathology with the need for accurately subtyping lung carcinoma, as well as providing adequate material for molecular studies, to help guide clinical and therapeutic decisions. The variety and versatility of cytologic-specimen preparations offer significant advantages to molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is critical, not only from a lung cancer diagnosis standpoint but also for the myriad ancillary studies that are necessary to provide appropriate clinical management. A large fraction of lung cancers are diagnosed by aspiration or exfoliative cytology specimens, and thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. This review focuses on the opportunities and challenges of using cytologic specimens for molecular diagnosis of lung cancer and the role of cytopathology in the molecular era. (Arch Pathol Lab Med. 2016;140:1267-1272; doi: 10.5858/arpa.2016-0091 -SA)

Lung cancer is the number 1 cancer killer. Despite recent advances in our understanding of the genomic underpinnings of pulmonary adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, there remain [...], Liquid biopsy has received extensive media coverage and has been called the holy grail of cancer detection. Attempts at circulating tumor cell and genetic material capture have been progressing for several years, and recent financially and technically feasible improvements of cell capture devices, plasma isolation techniques, and highly sensitive polymerase chain reaction- and sequencing-based methods have advanced the possibility of liquid biopsy of solid tumors. Although practical use of circulating RNA-based testing has been hindered by the need to fractionate blood to enrich for RNAs, the detection of circulating tumor cells has profited from advances in cell capture technology. In fact, the US Food and Drug Administration has approved one circulating tumor cell selection platform, the CellSearch System. Although the use of liquid biopsy in a patient population with a genomically defined solid tumor may potentially be clinically useful, it currently does not supersede conventional pretreatment tissue diagnosis of lung cancer. Liquid biopsy has not been validated for lung cancer diagnosis, and its lower sensitivity could lead to significant diagnostic delay if liquid biopsy were to be used in lieu of tissue biopsy. Ultimately, notwithstanding the enthusiasm encompassing liquid biopsy, its clinical utility remains unproven. (Arch Pathol Lab Med. 2016; 140:825-829; doi: 10.5858/ arpa.2016-0163-SA)

Following successful trials and much enthusiasm among the oncology community, the introduction of anti-programmed death receptor-1 (PD-1) and anti-programmed death ligand-1 (PD-L1) immune checkpoint inhibitors into routine practice for the [...], The approval of anti-programmed death receptor (PD)-1 therapies for non-small cell lung cancer has directed the spotlight on programmed death ligand-1 (PD-L1) immunohistochemistry as the latest predictive biomarker potentially required in this disease. Several other drugs in this class will likely be approved in the future and each has been developed with a unique anti-PD-L1 immunohistochemistry test. The prospect of 5 drugs competing in the same treatment area, each possibly requiring PD-L1 immunohistochemistry testing, presents a challenge for pathologists unlike any previously faced. The key issue is whether laboratories will attempt to deliver the trial-validated assays for one or more of these treatments, or introduce instead one or more laboratory developed tests, or attempt to provide a single PD-L1 immunohistochemistry assay for all possible anti-PD-1 and anti-PD-L1 treatments that may be used. This paper discusses some of the issues, challenges, hazards, and possible solutions that have recently emerged in this most complex interface between cancer therapeutics and laboratory biomarker testing. (Arch Pathol Lab Med. 2016; 140:326-331; doi: 10.5858/arpa.2015-0522-SA)

Programmed death receptor-1 (PD-1) is a type 1 membrane protein of the immunoglobulin superfamily (1) that has an important role in restricting immune-mediated tissue damage secondary to inflammation and/or infection. [...], The binding of programmed death ligand-1 and ligand-2 (PD-L1 and PD-L2) to PD-1 blocks T-cell-mediated immune response to tumor. Antibodies that target programmed death receptor-1 (PD-1) will block the ligandreceptor interface, thereby allowing T cells to attack the tumor and increase antitumor immune response. In clinical trials, PD-1 inhibitors have been associated with an approximately 20% overall response rate in unselected patients with non-small cell lung cancer, with sustained tumor response in a subset of patients treated by these immune checkpoint inhibitors. Facing a proliferation of PD-L1 immunohistochemistry clones, staining platforms, and scoring criteria, the pathologist must decide on the feasibility of introducing a newly approved companion diagnostic assay that may require purchase not only of a specific antibody kit but of a particular staining platform. Given the likely reality that clinical practice may, in the near future, demand access to 4 different PD-L1 antibodies coupled with different immunohistochemistry platforms, laboratories will be challenged with deciding among this variety of testing methods, each with its own potential benefits. Another immediate challenge to PD-L1 testing in lung cancer patients is that of access to adequate tumor tissue, given that non-small cell lung cancer samples are often extremely limited in size. With PD-L1 testing it has become clear that the historically used US regulatory approach of one assay-one drug will not be sustainable. One evolving concept is that of complementary diagnostics, a novel regulatory pathway initiated by the US Food and Drug Administration, which is distinct from companion diagnostics in that it may present additional flexibility. Although pathologists need to face the practical reality that oncologists will be asking regularly for the PD-L1 immunohistochemistry status of their patients' tumors, we should also keep in mind that there may be room for improvement of biomarkers for immunotherapy response. The field is rich with opportunities for investigation into biomarkers of immunotherapy response, particularly in the form of collaborative, multidisciplinary studies that incorporate oncologists, pathologists, and basic scientists. Pathologists must take the lead in the rational incorporation of these biomarkers into clinical practice. (Arch Pathol Lab Med. 2016; 140:341-344; doi: 10.5858/arpa.2015-0506-SA)

Traditionally the treatment of advanced non-small cell lung cancer (NSCLC) was limited to radiotherapy, chemotherapy, or a combination of both, depending on tumor stage and patient fitness. (1,2) In recent [...], Context.--Although most primary cancers of the lung carry a heavy mutational load and will potentially present many "nonself" antigens to the immune system, there are a wide range of possible mechanisms for tumors to avoid so-called immune surveillance. One such mechanism is the adoption of immune checkpoints to inhibit the host immune response. Immune checkpoint inhibitors show great promise in the treatment of advanced non-small cell lung cancer. Objective.--To discuss the possibility of biomarker selection of patients for these therapies. This is becoming a much debated issue, and the immunohistochemical detection of Programmed Death Ligand 1 (PD-L1), the ligand for the inhibitory Programmed Death receptor 1 (PD-1) checkpoint, is one possible biomarker. Data so far available show some conflicting results, but PD-L1 immunohistochemistry looks likely to be introduced into clinical use for selecting patients for treatment with anti-PD-1 or anti-PD-Ll therapies. Given that there are 4 such drugs rapidly approaching regulatory approval, each with its own independent PD-L1 immunohistochemistry biomarker test, both oncologists and pathologists face some significant challenges. Data Sources.--Peer-reviewed literature and meeting proceedings, especially during the last 12 months, were used. Conclusions.--The biology of PD-1/PD-L1 is complex, the clinical data for these drugs show considerable variation, the selection performance of the PD-L1 biomarker test is not perfect, and the existence of 4 drug/test combinations adds significantly to the problems faced. This article addresses some of the background to this therapeutic problem and discusses some of the issues ahead. (Arch Pathol Lab Med. 2016; 140:249-254; doi: 10.5858/arpa.2015-0303-SA)

Introduction: Noninvasive ventilation therapy is a common approach in acute respiratory failure as an alternative to invasive mechanical ventilation. Assistive communication strategies are necessary to overcome communication impairments and anxiety caused by oronasal obstruction in pediatric intensive care unit patients undergoing noninvasive ventilation. Clinical Findings and Diagnosis: A 7-year-old girl was admitted with a history of pulmonary arterial hypertension and recurrent respiratory failure requiring bilevel positive airway pressure intervention. The patient experienced initial lack of bilevel positive airway pressure mask compliance due to oronasal mask discomfort. Interventions: The trial of a novel communication device (SPEAX, Ataia Medical) involving a microphone that attaches to the patient's bilevel positive airway pressure mask for enhanced communication. Outcomes: Use of the assistive communication device was associated with increased intelligibility to familiar listeners, mask compliance, enhanced mobility, and reduced patient anxiety levels throughout hospitalization and in later episodes of readmission. Conclusion: The implementation of assistive communication devices can alleviate communication barriers in pediatric bilevel positive airway pressure users, contributing to increased compliance and diminished anxiety for patients and caregivers. Providing a pathway for effective communication may reduce sedation use, minimizing risks of sedation-related delirium and improving overall quality of life in these patients. [ABSTRACT FROM AUTHOR]