Lung cancer samples preserved in liquid medium: One step beyond cytology

Lung cancer is one of the most common cancer types in men and women worldwide with a high mortality rate. World Health Organization (WHO) classification has accepted biopsy as the primary sample for lung cancer diagnosis, pathological classification and molecular testing for management of patients, yet, the use of alternative sampling procedures is highly encouraged. Bronchial cytological samples require a less invasive collection technique and may be suitable for pathological and molecular analysis and storage in liquid medium. Furthermore, the molecular analysis of bronchial cytological samples allows the detection of molecular biomarkers, which may be useful for the selection of molecular targeted therapies. Thus, the purpose of this review is to describe the usefulness of bronchial cytological samples preserved in liquid medium from lung cancer patients for pathological diagnosis and molecular investigation.     

Reporting lung cancer pathology specimens. Impact of the anticipated 7th Edition TNM Classification based on recommendations of the IASLC Staging Committee

Led by the International Association for the Study of Lung Cancer (IASLC), there are currently several major international collaborative projects underway that will have a significant impact on the future reporting of lung cancer pathology. In particular, the IASLC Staging Committee has just completed an analysis of >100 000 lung cancer cases, providing the basis for proposed revisions of the current TNM staging classification. The purpose of this review is not to provide a comprehensive document on recommendations for specimen processing, but rather to discuss how the anticipated changes in the 7th edition TNM will impact on specimen processing, specifically looking at tumour size, how to deal with multiple tumours and visceral pleural invasion. TNM staging of carcinoid tumours and small cell carcinoma is also discussed.     

The diagnostic value of endobronchial ultrasound‐guided needle biopsy in lung cancer and mediastinal adenopathy

Endobronchial ultrasonography (EBUS) has emerged as a new diagnostic tool that allows the bronchoscopist to see beyond the airway, including pulmonary and mediastinal lesion. The real time EBUS‐guided transbronchial needle aspiration (TBNA) has advanced the diagnostic yield in primary lung pathology and mediastinal lymph node staging of lung carcinoma. Sixty‐four patients (36 males, 28 females, ages ranging from 16 to 86 years) with peribronchial lung lesions and mediastinal and/or hilar lymph node lesions underwent EBUS‐TBNA. All patients had intraoperative cytological assessment by smears on aspiration samples or touch preparation on needle core biopsies. The cytological final diagnoses were categorized as negative, suspicious/positive, and non‐diagnostic. Forty‐nine samples were obtained from lymph node lesions and 15 samples were obtained from lung lesions. In cytology specimens, 32 patients had suspicious/positive diagnoses and 32 patients had negative diagnosis. In follow‐up histology specimens, 35 patients had malignant diagnoses, including 18 adenocarcinomas, 8 small cell carcinomas, 6 squamous cell carcinomas, 1 metastatic hepatocellular carcinoma, 1 metastatic melanoma, and 1 lymphoma. Twenty‐nine patients had negative diagnoses. Sensitivity and specificity were 88.9% and 96.4%, respectively. Positive and negative predictive values were 97.0% and 87.1%, respectively. Diagnostic accuracy was 92.2%. EBUS‐TBNA is an efficient and effective technique for diagnosis of intrapulmonary and mediastinal/hilar lymph nodes. It becomes significantly invaluable on clinical management for staging in those patients with lung cancer of other metastatic malignancies. This technique enables us to obtain tissue samples for quick diagnoses beyond central airway with minimal complications. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Endobronchial ultrasound-guided fine-needle aspiration and liquid-based thin-layer cytology

BACKGROUND: Optimal management of patients with lung cancer requires accurate cell typing of tumours and staging at the time of diagnosis. Endobronchial ultrasound-guided lymph node aspiration as a method of diagnosing and staging lung cancer is a relatively new technique. AIM: To report the use of liquid-based-thin-layer cytology for the processing and reporting of these specimens. METHODS: The specimens obtained from 80 patients were processed using the ThinPrep system, with the remainder of the samples being processed as a cell block. RESULTS: 40 of the 81 procedures yielded malignant cells (30 non-small cell carcinoma, 8 small-cell carcinoma and 2 combined small-cell carcinoma/non-small-cell carcinoma). The cell blocks were found to contain sufficient material to allow the immunohistochemical characterisation of tumour cells with a range of antibodies. CONCLUSION: The use of liquid-based-thin-layer cytological techniques provides high-quality specimens for diagnostic purposes. When used in conjunction with cell blocks, sufficient material may be obtained to allow immunohistochemical studies to confirm the tumour cell type. Given the current move towards centralisation of pathology services, this approach gives the pathologist high-quality specimens without the need for direct onsite support at the time of the procedure.     

Pulmonary small cell carcinoma: Review,common and uncommon differentials,genomics and management

Lung cancer is the leading cause of cancer‐related death worldwide. It is divided into sub‐categories based upon morphology, immunostaining pattern, biology, molecular profile, and/or treatment options. Up until the early 2000s when driver mutations with targeted therapies were identified in a subset of adenocarcinomas, the most critical distinction of lung carcinomas was driven by differences in treatment between small cell carcinoma (SCC) and nonsmall cell lung carcinoma (NSCLC). The distinction between SCC and NSCLC remains critical in the 21st century for management, especially for advanced stage cancer. In the vast majority of cases, morphological features are sufficient to separate SCC from other types of lung cancers. In some instances, however, cytomorphological features and immunohistochemical overlap with other tumors, limited sample availability, and/or crush artifact pose diagnostic challenges. The aim of this review is to highlight salient features of SCC and ancillary studies to distinguish it from common and uncommon potential mimickers, as well as provide updates in genomics and management.     

Synchronous pulmonary adenocarcinoma and extranodal marginal zone/low-grade B-cell lymphoma of MALT type

A case of synchronous adenocarcinoma of lung and extranodal marginal zone/low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is reported. Primary pulmonary non-Hodgkin's lymphoma is relatively rare, however, the majority of these lesions are low-grade B-cell lymphomas of MALT. After the stomach, the lung is the second most common location for such latter lesions. Lung adenocarcinoma in selected countries is fast becoming the leading form of non small-cell lung carcinoma. To our knowledge, this synchronous occurrence in the lung has not been previously reported. Such associations have been primarily limited to gastric lesions where an association with Helicobacter pylori infection has been identified. This case report highlights the importance of adjunctive diagnostic investigations such as molecular techniques in conclusive analysis of synchronous cases such as ours.     

Recurrence of bronchioloalveolar carcinoma in transplanted lungs

BACKGROUND: Bronchioloalveolar carcinoma is a distinctive subtype of typical adenocarcinoma of the lung that tends to metastasize widely throughout the lungs but less commonly elsewhere. Because conventional therapies for intrapulmonary metastatic bronchioloalveolar carcinoma are generally ineffective, we treated seven patients who had intrapulmonary metastatic bronchioloalveolar carcinoma with lung transplantation. METHODS: Seven patients with biopsy-proved bronchioloalveolar carcinoma and no evidence of extrapulmonary disease received transplants of either one or two cadaveric lungs. At transplantation, all native lung tissue was removed and replaced with a donor lung or lungs. The patients received the usual post-transplantation care given at the institution. RESULTS: Four of the seven patients had recurrent bronchioloalveolar carcinoma within the donor lungs; the recurrences appeared from 10 to 48 months after transplantation. All recurrences were limited to the donor lungs. Histologic and molecular analyses showed that the recurrent tumors in three patients originated from the recipients of the transplants. CONCLUSIONS: Lung transplantation for bronchioloalveolar carcinoma is technically feasible, but recurrence of the original tumor within the donor lungs up to four years after transplantation was common.     

Changing trends in the distribution of the histologic types of lung cancer: a review of 4,439 cases

Lung cancer is the second most common cancer and the leading cause of cancer death in both men and women. The purpose of the study is to explore the distribution of the 4 major histologic types of lung carcinoma and the incidence of lung cancer with reference to all other sites of cancer. The clinical and histopathologic data of 4,439 patients with lung carcinoma between January 1980 and December 2003 were reviewed. Adenocarcinoma has become the most frequent histologic type in men and women (36.8% and 46.5%, respectively), followed by squamous cell carcinoma (31.6% and 25.4%, respectively). The incidence of large cell (undifferentiated) carcinoma in men and women is 18.0% and 9.9%, respectively. The incidence of small cell carcinoma in men and women is 13.7% and 18.3%, respectively. In addition, analysis of our data indicates that lung cancer rate is decreasing, relative to all other primary cancer sites. The results of this study suggest that the incidence of lung cancer has decreased in comparison with other sources of cancer in southern Texas. This observation is consistent with the current national trends. In addition, there are significant changes in the distribution of the major histologic types of lung cancer. The results of this study may portend important changes in the selection of targeted therapy and patient management.     

Cytological cell blocks: Predictors of squamous cell carcinoma and adenocarcinoma subtypes

Fine needle aspirations biopsies, CT-guided and endobronchial ultrasound-guided, as a mode of diagnosing and/or staging lung carcinoma, are becoming more frequent. Also, there is greater necessity for classification of lung cancers into subcategories of squamous cell carcinoma and adenocarcinoma for appropriate management. Cytomorphology, based on smears alone, allows this classification in many instances. The aim of the current study was to explore the potential of cell blocks to increase the specificity of diagnosis. The morphological characteristics of sixty-two lung carcinomas were examined. Less well-differentiated squamous cell carcinomas were more readily classified as such on cell blocks. Likewise, cell block sections with architectural patterns including strips of cells, papillae and nests of cells correlated with bronchioalveolar, papillary and acinar/mixed subtypes of adenocarcinoma on follow-up histology. In conclusion, cell blocks provide additional morphological clues and material for ancillary studies for classification of lung carcinomas.     

Ultrastructural and Immunohistochemical Features of Common Lung Tumors: An Overview

Lung cancer is rapidly becoming the most commonly diagnosed malignant neoplasm in the world. Pathologists play a key role in the care of patients with lung cancer by accurately classifying and staging these neoplasms. Immunohistochemistry and electron microscopy have become important tools in the diagnosis of lung tumors, especially those which are histologically undifferentiated. This review discusses the ultrastructural and immunohistochemical features of common lung tumors, with an emphasis on their diagnostic usefulness.     

Oncogenic role of JC virus in lung cancer

The JC virus (JCV) infects a large proportion of the population world wide and can cause progressive multifocal leucoencephalopathy in the context of immunodeficiency. Recent reports provide evidence that it may also be oncogenic. Here, JCV was examined by targeting its T-antigen in lung carcinomas (n=103) and normal lung tissues (n=18) by nested-PCR followed by Southern blot, real-time PCR, immunohistochemistry, in situ hybridization and in situ PCR. Additionally, expression of Ki-67, caspase-3, beta-catenin, p53, and Rb was analysed by immunohistochemistry on tissue microarrays of lung carcinomas. Copy numbers of JCV were compared with clinicopathological features. Normal lung tissue was positive significantly less frequently, and contained a lower copy number of JCV than lung carcinomas (p<0.05), and copies were lower in lung adenocarcinomas than in squamous, small or large cell carcinomas (p<0.05). In situ PCR and immunolabelling revealed JCV positivity in the nuclei of lung carcinoma cells. The JCV copy number correlated closely with sex, and expression of Ki-67 and membrane beta-catenin (p<0.05), but not with age, tumour size, pleural invasion, lymph node metastasis, expression of caspase-3, cytoplasmic beta-catenin, p53 or Rb, prognosis, smoking or cancer family history (p>0.05). Age and UICC staging were independent prognostic factors for lung carcinoma patients. These data suggest that JCV may be involved in lung carcinogenesis, especially in tumour types other than adenocarcinoma. Lung carcinomas with higher JCV copy numbers display high proliferation and down-regulation of cell adhesion mediated by membrane beta-catenin.     

Galectin-3: differential expression between small-cell and non-small-cell lung cancer

AIMS: To compare the histological expression of galectin-3 in different lung cancers, including small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Lung cancer is the leading cause of cancer deaths in the UK. Galectin-3 is a beta-galactoside binding protein with a controversial role in malignant transformation. SCLC metastasizes early and is initially chemosensitive; NSCLC metastasizes later, offering the chance of surgical cure, but is much less chemosensitive. Mixed tumours present a diagnostic and therapeutic problem, with a poorer response to therapy. Insight into the cellular mechanisms that govern metastasis and chemoresistance will profoundly influence the future management of this disease. METHODS AND RESULTS: In this study the histological expression of galectin-3 was assessed in a panel of lung tumour specimens, using the indirect streptavidin-biotin method. A striking difference in galectin-3 expression was observed between tumours, with high expression in NSCLC (42/47 samples) and low expression in SCLC (negative in 13/18, weak in 5/18). CONCLUSION: This differential expression of galectin-3 between histological types of lung carcinoma suggests that galectin-3 may have an important influence on tumour cell adhesion, apoptosis and the response of tumours to chemotherapy.     

Lung cancer imaging

Lung cancer remains the leading cause of cancer-related deaths in the US. Imaging plays an important role in the diagnosis, staging, and follow-up evaluation of patients with lung cancer. With recent advances in technology, it is important to update and standardize the radiological practices in lung cancer evaluation. In this article, the authors review the main clinical applications of different imaging modalities and the most common radiological presentations of lung cancer.     

Clinicopathological classification and traditional prognostic indicators of breast cancer

Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. The objective of this study is to evaluate the value of molecular subtypes in breast cancer management according to a retrospective analysis of breast carcinoma molecular subtypes, histopathological grade, and TNM stage. A retrospective study of 475 paraffin-embedded tissues of breast cancer samples from the First Affiliated Hospital of Guangxi Medical University was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The differences of molecular subtypes of breast cancers in regard to TNM staging and pathological grade were analyzed using χ² tests. Values of P<0.05 were considered statistically significant. The frequency of luminal A, luminal B, HER2-positive luminal B, triple negative and non-luminal HER2-positive subtypes were: 35.5%, 22.5%, 13.1%, 15.2% and 13.7%, respectively. Among the five subtypes of breast cancer, the distribution of pathological grades showed a significant difference (P<0.001). There were significant differences in the distribution of TNM staging among the five subtypes of breast cancer (P<0.001). In addition to traditional prognostic indicators such as TNM staging and pathological grade, molecular subtype may aid clinical practice and research into breast cancer. Different molecular subtypes will lead to different prognosis and therapeutic option. Molecular subtyping is essential for breast cancer management.     

The haematopoietic specific signal transducer Vav1 is aberrantly expressed in lung cancer and plays a role in tumourigenesis

Lung cancer is the leading cause of cancer death worldwide. The spectrum of aberrations affecting signalling pathways in lung cancer pathogenesis has not been fully elucidated. Physiological expression of Vav1 is restricted to the haematopoietic system, where its best‐known function is as a GDP/GTP nucleotide exchange factor for Rho/RacGTPases, an activity strictly controlled by tyrosine phosphorylation downstream of cell surface receptors. Here we find Vav1 expression in 42% of 78 lung cancer cell lines analysed. Moreover, immunohistochemical analysis of primary human lung cancer tissue samples revealed Vav1 expression in 26/59 malignant samples, including adenocarcinoma, squamous cell carcinoma and bronchioloalveolar carcinoma. Stronger Vav1 staining was associated with larger tumour size. siRNA‐mediated knockdown of Vav1 in lung cancer cells reduced proliferation in agar and tumour growth in nude mice, while control siRNA had no effect, suggesting that Vav1 plays a critical role in the tumorigenicity of lung cancer cells. Vav1 is tyrosine‐phosphorylated in lung cancer cells following activation by the growth factors EGF and TGFα, suggesting its participation in signalling events in these cells. Depletion of Vav1 reduced Rac‐GTP activation and decreased expression of TGFα, an autocrine growth factor. These data suggest that Vav1 plays a role in the neoplastic process in lung cancer, identifying it as a potential therapeutic target for lung cancer therapy. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

衰变加速因子在非小细胞肺癌中的表达及其临床意义

目的 检测衰变加速因子（decay accelerating factor，DAF，CD55）在非小细胞肺癌（non-small cell lung carcinoma，NSCLC）中的表达，分析其表达与临床分期、化疗用药及预后的关系。方法 免疫组化法检测8例NSCLC癌旁组织和36例NSCLC手术标本中DAF的蛋白表达，分析临床资料。结果 免疫组化结果显示36例NSCLC标本中，共有18例（50．0％）表达DAF，其中18例肺鳞癌中有15例（83．3％）表达，而16例肺腺癌中有3例（18．8％）表达，两者有显著差异（P〈0．05）；不同的病理分期的DAF免疫组化平均积分光密度表达有显著性差异（P〈0．05）；DAF的表达与无病生存期无相关关系（P〉0．05）。结论 NSCLC中有DAF的表达，尤其是肺鳞癌；提示在NSCLC抗体治疗中应同时阻断DAF的免疫抑制效应。     

Improving radiation therapy for non-small cell lung cancer: molecular imaging and a team-based approach

The successful integration of molecular imaging and radiation therapy has been shown to significantly impact the management of patients with non-small cell lung cancer (NSCLC). The collaboration of multidisciplinary team members, including radiation oncologists, radiation therapists, nuclear medicine physicians and physicists, has enabled PET/CT to be utilised for routine use throughout the radiotherapy treatment trajectory. Applications include disease diagnosis and staging, target volume definition for radiation therapy and monitoring tumour response to treatment. Not only has the adoption of this technology demonstrated benefits for our current patients, it is also opening doors for significant research in the future.     

Radiologic staging of lung carcinoma: A report generator and database system

A checklist used by the radiologist interpreting images on lung carcinoma patients for tumor staging is described. The checklist data is subsequently entered into a user friendly microcomputer program which radiologically stages lung carcinoma according to the updated TNM system, maintains an upgradable relational database and generates printed reports for tumor board meetings.