Reprint of: The pathology of pulmonary sarcoidosis: update.

Sarcoidosis is a multi-system disease of unknown etiology, usually affecting the respiratory tract and other organs, and is characterized by the formation of nonnecrotizing epithelioid granulomas. The diagnosis depends on a combination of a typical clinicoradiological presentation, the finding of nonnecrotizing epithelioid granulomas in a tissue biopsy, and exclusion of other possible diseases, especially those of infectious etiology. The granulomas contain epithelioid cells, giant cells, CD4+ T cells in their center, and CD8+ T lymphocytes and B lymphocytes at their periphery.

Lung Adenocarcinoma Staging Using the 2011 IASLC/ATS/ERS Classification: A Pooled Analysis of Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma.

Background: Lung adenocarcinoma accounts for almost 60% of non-small-cell lung cancer. According to the 2011 International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) classification and 2015 World Health Organization classification of tumors of the lung, lepidic-predominant adenocarcinomas ≤ 3 cm in size can be classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma, lepidic predominant. AIS lesions, which are noninvasive, and MIA lesions, which show ≤ 0.

Clinical Validation and Implementation of a Targeted Next-Generation Sequencing Assay to Detect Somatic Variants in Non-Small Cell Lung, Melanoma, and Gastrointestinal Malignancies.

We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq.

Epstein-Barr Virus-Associated Pulmonary Smooth Muscle Tumor After Lung Transplantation.

We report an Epstein-Barr virus (EBV)-associated pulmonary posttransplant smooth muscle tumor arising in the left lung of a 71-year-old bilateral lung transplant recipient nearly 3 years after transplantation, treated with thoracoscopic wedge resection. Four previous smooth muscle tumors have been reported following lung transplantation. To our knowledge, this is the first reported case of an EBV-positive posttransplant smooth muscle tumor within the transplanted lung.

A Translational, Pharmacodynamic, and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer.

Purpose: The altered PI3K/mTOR pathway is implicated in lung cancer, but mTOR inhibitors have failed to demonstrate efficacy in advanced lung cancer. We studied the pharmacodynamic effects of everolimus in resectable non-small cell lung cancer (NSCLC) to inform further development of these agents in lung cancer.

Experimental Design: We enrolled 33 patients and obtained baseline tumor biopsy and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging followed by everolimus treatment (5 or 10 mg daily, up to 28 days), or without intervening treatment for controls.

Pulmonary effects of synthetic marijuana: chest radiography and CT findings.

Objective: The purpose of this article is to present the first chest radiographic and CT descriptions of organizing pneumonia in response to smoking synthetic marijuana.

Conclusion: Chest radiographs showed a diffuse miliary-micronodular pattern. Chest CT images showed diffuse centrilobular nodules and tree-in-bud pattern and a histopathologic pattern of organizing pneumonia with or without patchy acute alveolar damage.

Tumor genetics and survival of thymic neuroendocrine neoplasms: a multi-institutional clinicopathologic study.

Thymic neuroendocrine tumors (TNET) are rare primary epithelial neoplasms of the thymus. This study aimed to determine clinically relevant parameters for their classification and for therapeutic decisions. We performed a comprehensive histological, clinical, and genetic study of 73 TNET cases (13 thymic typical carcinoids [TTC], 40 thymic atypical carcinoids [TAC], and 20 high-grade neuroendocrine carcinomas [HGNEC] of the thymus), contributed by multiple institutions.

Maintaining glycogen synthase kinase-3 activity is critical for mTOR kinase inhibitors to inhibit cancer cell growth.

mTOR kinase inhibitors that target both mTORC1 and mTORC2 are being evaluated in cancer clinical trials. Here, we report that glycogen synthase kinase-3 (GSK3) is a critical determinant for the therapeutic response to this class of experimental drugs. Pharmacologic inhibition of GSK3 antagonized their suppressive effects on the growth of cancer cells similarly to genetic attenuation of GSK3.

Routine intraoperative frozen section analysis of bronchial margins is of limited utility in lung cancer resection.

Background: Residual disease at the bronchial margin after resection of non-small cell lung cancer (NSCLC) adversely affects survival. To ensure an R0 resection, thoracic surgeons commonly use intraoperative frozen section analysis of the bronchial margin. We hypothesize that frozen section of the bronchial margin is rarely positive and seldom changes intraoperative management.

Phase II study of docetaxel in combination with everolimus for second- or third-line therapy of advanced non-small-cell lung cancer.

We conducted a phase II study of docetaxel in combination with everolimus, a mammalian target of rapamycin (mTOR) inhibitor, for salvage therapy of advanced non-small-cell lung cancer (NSCLC) based on promising preclinical and early-phase clinical data. Patients with advanced-stage NSCLC treated with one or two previous systemic therapy regimens were given docetaxel (60 mg/m) and everolimus (5 mg orally once daily on days 1-19) every 3 weeks. Archived tumor specimens were evaluated for markers of mTOR pathway activation (total and phosphorylated mTOR, Akt, S6, eIF4e, and 4EBP1).

Lung cancer staging: pathology issues.

The previous, 6th, American Joint Committee on Cancer and International Union Against Cancer Staging Manual classification of lung cancer was largely unchanged from 5th edition. However, the most recent, 7th, edition has significantly updated the tumor, node, metastasis classification of lung cancer with regards to the inclusion of additional size criteria for T stages and revision of the staging for multiple tumor nodules, and represents the most dramatic change in 30 years. The recommendations for this most recent edition of tumor, node, metastasis classification are derived from a systematic retrospective review of data from a multi-international/institutional database of lung cancers and also incorporate expert opinion, to revise and clarify various staging factors.

Survival analysis of patients with stage I non-small-cell lung cancer using clinical and DNA repair pathway expression variables.

Background: Lung cancer is the leading cause of cancer-related mortality. Understanding patient attributes that enhance survival and predict recurrence is necessary to individualize treatment options.

Methods: Patients (N = 162) were dichotomized into favorable (n = 101) and unfavorable (n = 61) groups based on survival characteristics.

Farnesyl transferase expression determines clinical response to the docetaxel-lonafarnib combination in patients with advanced malignancies.

Background: Lonafarnib (LNF) is a protein farnesyl transferase (FTase) inhibitor that has shown synergistic activity with taxanes in preclinical models and early stage clinical trials. Preclinical findings suggested tubulin acetylation and FTase expression levels may be important determinants of drug sensitivity that would help identify patient populations more likely to benefit from this regimen. This pilot study evaluated the biological effects of LNF and docetaxel (DTX) combination therapy in refractory solid tumors by comparing pretreatment and post-treatment tumor biopsies.

Angiotensin-converting enzyme N-terminal inactivation alleviates bleomycin-induced lung injury.

Bleomycin has potent anti-oncogenic properties for several neoplasms, but drug administration is limited by bleomycin-induced lung fibrosis. Inhibition of the renin-angiotensin system has been suggested to decrease bleomycin toxicity, but the efficacy of such strategies remains uncertain and somewhat contradictory. Our hypothesis is that, besides angiotensin II, other substrates of angiotensin-converting enzyme (ACE), such as the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), play a significant role in controlling fibrosis.

Granulomatous lung disease: an approach to the differential diagnosis.

Context: Granulomas are among the most commonly encountered abnormalities in pulmonary pathology and often pose a diagnostic challenge. Although most pathologists are aware of the need to exclude an infection in this setting, there is less familiarity with the specific histologic features that aid in the differential diagnosis.

Objective: To review the differential diagnosis, suggest a practical diagnostic approach, and emphasize major diagnostically useful histologic features.

Twist: a regulator of epithelial-mesenchymal transition in lung fibrosis.

Background: Several studies have implicated viral infection as an important factor in the pathogenesis of IPF and related fibrotic lung disorders. Viruses are thought to cause epithelial cell injury and promote epithelial-mesenchymal transition (EMT), a process whereby differentiated epithelial cells undergo transition to a mesenchymal phenotype, and considered a source of fibroblasts in the setting of lung injury. We have demonstrated an association between the epithelial injury caused by chronic herpes virus infection with the murine gamma-herpes virus, MHV68, and lung fibrosis.

Dynamics of human regulatory T cells in lung lavages of lung transplant recipients.

Background: Despite advances in the field of lung transplantation, the median survival after lung transplant remains below 5 years. Early rejection is a risk factor for the development of chronic rejection. In animal models of transplant tolerance, regulatory T cells (Tregs) can prevent the establishment of rejection.

Primary yolk sac tumor of the lung.

Yolk-sac tumor mimics the yolk sac of the embryo, and the presence of alpha fetoprotein in the tumor cells is highly characteristic. We present an 18-year-old boy with primary pulmonary yolk-sac tumor diagnosed postoperatively. A computed tomographic scan revealed a huge intrathoracic soft tissue mass 20 x 25 cm occupying most of the left hemithorax.

Characteristics of second primary lung malignancy in patients with known breast cancer.

Background: As breast cancer survival improves, the incidence of additional malignancies will likely rise. Identification of a lung nodule in a patient with known breast cancer poses a challenging diagnostic problem. This study outlines the management of such patients and identifies factors that correlate with survival.

Efficacy of oral ribavirin in lung transplant patients with respiratory syncytial virus lower respiratory tract infection.

Background: Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infection (LRI) and is a risk factor for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Currently, the most widely used therapy for RSV is inhaled ribavirin. However, this therapy is costly and cumbersome.

Prognostic factors for hospital mortality and ICU admission in patients with ANCA-related pulmonary vasculitis.

Background: The objective of this study was to evaluate the factors predictive of 28-day mortality and admission to Intensive Care Unit (ICU) in patients with ANCA-related pulmonary vasculitis.

Methods: We reviewed the medical records and imaging studies of 65 patients diagnosed with ANCA-related vasculitis hospitalized with pulmonary complications between February 1985 and November 2002. All patients underwent open or video-assisted thoracoscopic lung biopsy, had a positive ANCA serology, and were negative for glomerular basement membrane antibodies.

Management of a patient with stage IIIA (N2) NSCLC.

The appropriate treatment of patients with stage IIIA (N2) nonsmall-cell lung cancer (NSCLC) is unclear. With this case report and review, we address the history, assessment, and management of a 67-year-old patient with this diagnosis, and then discuss the challenges in managing N2 disease, as well as the roles of systemic therapy, surgery, and postoperative radiation therapy.