Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas.

Small cell lung cancer (SCLC) comprises 14% of all lung cancers, and >30,000 new cases are diagnosed per year in the United States. SCLC is one of the most distinctive malignancies in the entire field of oncology with characteristic clinical properties, responsiveness to specific chemotherapy, genetic features and a highly reliable pathological diagnosis. SCLC is defined by light microscopy, and the most important stain is a good-quality hematoxylin and eosin (H&E)-stained section.

Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations.

Purpose: There is persistent controversy as to whether EGFR and KRAS mutations occur in pulmonary squamous cell carcinoma (SQCC). We hypothesized that the reported variability may reflect difficulties in the pathologic distinction of true SQCC from adenosquamous carcinoma (AD-SQC) and poorly differentiated adenocarcinoma due to incomplete sampling or morphologic overlap. The recent development of a robust immunohistochemical approach for distinguishing squamous versus glandular differentiation provides an opportunity to reassess EGFR/KRAS and other targetable kinase mutation frequencies in a pathologically homogeneous series of SQCC.

Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker.

Purpose: This phase II study was conducted to assess the efficacy of temozolomide in patients with relapsed small cell lung cancer (SCLC).

Experimental Design: Patients with disease progression after one or two prior chemotherapy regimens received temozolomide at 75 mg/m(2)/d for 21 days of a 28-day cycle. The primary endpoint was the overall response rate [ORR; complete response (CR) plus partial response (PR)], which was evaluated separately in sensitive and refractory cohorts.

International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report.

The International Association for the Study of Lung Cancer (IASLC) Board of Directors convened a computed tomography (CT) Screening Task Force to develop an IASLC position statement, after the National Cancer Institute press statement from the National Lung Screening Trial showed that lung cancer deaths fell by 20%. The Task Force's Position Statement outlined a number of the major opportunities to further improve the CT screening in lung cancer approach, based on experience with cancer screening from other organ sites.The IASLC CT Screening Workshop 2011 further developed these discussions, which are summarized in this report.

Predicting pulmonary adenocarcinoma outcome based on a cytology grading system.

Background: Pulmonary adenocarcinoma (AD) has a variety of architectural patterns. Recently, a 3-tiered histological pattern-based grading system was developed for stage I lung AD, stratifying patients into low, intermediate, and high risk for recurrence. However, cytology may serve as the primary method for diagnosis in patients with inoperable disease.

p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma.

Immunohistochemistry has recently emerged as a powerful ancillary tool for differentiating lung adenocarcinoma and squamous cell carcinoma-a distinction with important therapeutic implications. Although the most frequently recommended squamous marker p63 is extremely sensitive, it suffers from low specificity due to its reactivity in a substantial proportion of lung adenocarcinomas and other tumor types, particularly lymphomas. p40 is a relatively unknown antibody that recognizes ΔNp63-a p63 isoform suggested to be highly specific for squamous/basal cells.

Pathology of lung cancer.

This article reviews current concepts in pathologic classification of lung cancer based on the 2004 World Health Organization classification of lung tumors and the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification of lung adenocarcinoma. Preinvasive lesions are discussed. The major changes in lung disease diagnosis affected by the IASLC/ATS/ERS classification are presented.

Large cell neuroendocrine carcinoma of the head and neck.

Large cell neuroendocrine carcinoma is a poorly differentiated neuroendocrine carcinoma that usually occurs in the lung. Although rare in the head and neck, salivary and mucosal subtypes are recognized. This article describes their characteristic light microscopic and immunohistochemical features and highlights the importance of accurate diagnosis, management and prognostic implications.

A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma.

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant pleural mesothelioma in which only staging is prognostic for survival. In this study of epithelioid diffuse malignant pleural mesothelioma, we investigate the prognostic utility of nuclear features. The slides of 232 epithelioid diffuse malignant pleural mesothelioma patients (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed for the following seven nuclear features: nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, intranuclear inclusions, prominence of nucleoli, mitotic count, and atypical mitoses.

The fake fat phenomenon in organizing pleuritis: a source of confusion with desmoplastic malignant mesotheliomas.

We report 9 patients with pleural biopsies referred because of concern about infiltration of what appeared to be chest wall fat by pan-keratin-positive spindled cells, a finding that led to a consideration of desmoplastic mesothelioma. All patients showed pleural effusions/pleural thickening on computed tomographic scan. Pleural biopsy showed a greatly thickened and fibrotic paucicellular pleura with circular fat-like spaces and, sometimes, adjacent oblate spaces mostly deep in the fibrotic area.

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary.

Introduction: The American Thoracic Society is a cosponsor of a newly published lung adenocarcinoma classification.

Methods: An international multidisciplinary panel of experts was formed. A systematic review was performed and recommendations were graded by strength and quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Carcinoma in situ at the bronchial resection margin: a review.

Carcinoma in situ at the mucosal bronchial resection margin is a rarely reported event. At present, such histological findings at the resection margins are classified as R1(is), thus representing an incomplete resection. A review of the English literature on the topic was undertaken to try to better define the significance of such findings and to define possible areas of prospective data acquisition to further define the problem and its management.

Loss of cytoplasmic CDK1 predicts poor survival in human lung cancer and confers chemotherapeutic resistance.

The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer.

Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas: a single institution experience.

Background: Pulmonary large cell neuroendocrine carcinomas (LCNEC) are aggressive neoplasms with poor prognosis. The role of neoadjuvant and adjuvant therapies in these tumors remains uncertain.

Methods: We performed a retrospective review of a prospective database.

Subtyping of non-small cell lung carcinoma: a comparison of small biopsy and cytology specimens.

Background: There is growing evidence that lung adenocarcinoma and squamous cell carcinoma (SQCC) have distinct oncogenic mutations and divergent therapeutic responses, which is driving the heightened emphasis on accurate pathologic subtyping of non-small cell lung carcinoma (NSCLC). The relative feasibility and accuracy of NSCLC subtyping by small biopsy versus cytology is not well established, particularly in current practice where immunohistochemistry (IHC) is becoming routinely used to aid in this distinction.

Methods: Concurrent biopsy and cytology specimens obtained during a single procedure and diagnosed as NSCLC during a 2-year period (n = 101) were reviewed.

Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients.

This study aims to determine whether a semi-quantitative assessment of inflammatory response in tumor and stroma on routine hematoxylin and eosin-stained (H&E) slides can predict survival in patients with epithelioid malignant pleural mesothelioma (MPM). H&E sections of 175 epithelioid MPM specimens from a single institution (1989-2009) were reviewed. Patients who received neoadjuvant chemotherapy were excluded from analysis.

Endotracheal myoepithelioma.

Myoepitheliomas have been described most commonly in salivary glands and have been reported elsewhere but are rare in the lung, with only six previously reported cases. To our knowledge, this represents the first endotracheal myoepithelioma. These tumors have characteristic features that distinguish them from other tumors, and the diagnosis is a pathologic one, based on the morphology and supported by immunohistochemistry.

Prognostic immune markers in non-small cell lung cancer.

Tumor-associated immune responses have polarized effects in regulating tumor growth. Although a clear association has been shown between the tumor immune response and clinical outcome in colorectal and ovarian cancers, the role of immune markers for stratifying prognosis in non-small cell lung cancer (NSCLC) is less defined. Herein, we review the prognostic significance of published immune markers in the tumor microenvironment and peripheral blood of NSCLC patients.

Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens.

Immunohistochemistry is increasingly utilized to differentiate lung adenocarcinoma and squamous cell carcinoma. However, detailed analysis of coexpression profiles of commonly used markers in large series of whole-tissue sections is lacking. Furthermore, the optimal diagnostic algorithm, particularly the minimal-marker combination, is not firmly established.

Terminology and classification of neuroendocrine neoplasms of the larynx.

Objectives: To review the history and literature on neuroendocrine neoplasms of the larynx and discuss the terminology and classification of these tumors.

Study Design: Contemporary review.

Methods: Published journal articles identified through PubMed and conference proceedings were reviewed.

Pathological diagnosis and classification of lung cancer in small biopsies and cytology: strategic management of tissue for molecular testing.

Standardized lung cancer classifications by the World Health Organization have traditionally been based on the histological characteristics of resected tumors with little guidance about diagnosis based on small biopsies and cytology. The focus has mainly been on the separation of small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). Until recently there have been no therapeutic implications to further classification of NSCLC, so little attention has historically been given to the distinction of adenocarcinoma and squamous cell carcinoma in these small tissue samples.

Primary myoepithelial carcinoma of the lung: a rare entity treated with parenchymal sparing resection.

Primary lung myoepithelial carcinomas are rare neoplasms arising from the salivary glands of the respiratory epithelium. Given the rare occurrences and reports of these tumors, appropriate recommendations for resection are difficult to formulate. Although classified as low-grade neoplasms, these tumors have a significant rate of recurrence and distant metastasis.

Pleomorphic epithelioid diffuse malignant pleural mesothelioma: a clinicopathological review and conceptual proposal to reclassify as biphasic or sarcomatoid mesothelioma.

Introduction: In patients with epithelioid diffuse malignant pleural mesothelioma (DMPM), clinical stage is the current primary prognostic factor. We sought to investigate whether histologic subtyping can prognostically stratify patients with epithelioid DMPM.

Methods: Hematoxylin and eosin-stained slides of 232 patients with epithelioid DMPM (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed.