Diagnosis of Lung Cancer in Small Biopsies and Cytology Implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification
The new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification provides, for the first time, standardized terminology for lung cancer diagnosis in small biopsies and cytology; this was not primarily addressed by previous World Health Organization classifications. Until recently there have been no therapeutic implications to further classification of NSCLC, so little attention has been given to the distinction of adenocarcinoma and squamous cell carcinoma in small tissue samples. This situation has changed dramatically in recent years with the discovery of several therapeutic options that are available only to patients with adenocarcinoma or NSCLC, not otherwise specified, rather than squamous cell carcinoma. This includes recommendation for use of special stains as an aid to diagnosis, particularly in the setting of poorly differentiated tumors that do not show clear differentiation by routine light microscopy. A limited diagnostic workup is recommended to preserve as much tissue for molecular testing as possible. Most tumors can be classified using a single adenocarcinoma marker (eg, thyroid transcription factor 1 or mucin) and a single squamous marker (eg, p40 or p63). Carcinomas lacking clear differentiation by morphology and special stains are classified as NSCLC, not otherwise specified. Not otherwise specified carcinomas that stain with adenocarcinoma markers are classified as NSCLC, favor adenocarcinoma, and tumors that stain only with squamous markers are classified as NSCLC, favor squamous cell carcinoma. The need for every institution to develop a multidisciplinary tissue management strategy to obtain these small specimens and process them, not only for diagnosis but also for molecular testing and evaluation of markers of resistance to therapy, is emphasized.
"Strategies have been proposed to allow for subtyping of NSCLC and testing of molecular markers in small biopsy and cytology specimens (59). With any specimen, the first approach is to establish squamous or adenocarcinoma differentiation based on morphology under light microscopy. "
[Show abstract][Hide abstract] ABSTRACT: Lung cancer has entered the era of personalized therapy with histologic subclassification and the presence of molecular biomarkers becoming increasingly important in therapeutic algorithms. At the same time, biopsy specimens are becoming increasingly smaller as diagnostic algorithms seek to establish diagnosis and stage with the least invasive techniques. Here, we review techniques used in the diagnosis of lung cancer including bronchoscopy, ultrasound-guided bronchoscopy, transthoracic needle biopsy, and thoracoscopy. In addition to discussing indications and complications, we focus our discussion on diagnostic yields and the feasibility of testing for molecular biomarkers such as epidermal growth factor receptor and anaplastic lymphoma kinase, emphasizing the importance of a sufficient tumor biopsy.
Frontiers in Oncology 09/2014; 4:253. DOI:10.3389/fonc.2014.00253
[Show abstract][Hide abstract] ABSTRACT: The majority of lung cancer patients are diagnosed at advanced stages of disease. This study evaluated the diagnostic value of ThinPrep (TP) bronchial brushing cytology in lung cancer. A total of 595 patients with suspicious lung cancer were enrolled in this study. The bronchial brushing samples were prepared by TP. The data were then compared to histology of lung tissue samples. Histologically, 479 of these 595 patients were diagnosed with lung cancer, including 223 cases of lung squamous cell carcinoma (SCC), 77 cases of lung adenocarcinoma (ADC), and 152 cases of small cell lung carcinoma (SCLC). The TP cytology revealed a total of 460 cases of lung cancer (including 232 SCCs, 91 ADCs, and 108 SCLCs). The TP cytological technique had 87.06% sensitivity and 62.93% specificity in the diagnosis of lung cancer. Specifically, TP cytology confirmed 195 of 223 SCCs, 47 of 77 ADCs, and 94 of 152 SCLCs. The TP cytology showed 87.44% sensitivity and 90.05% specificity for the diagnosis of SCC, with a Matthew's correlation coefficient (MCC) of 0.820; while the sensitivity was reduced to 61.04% and the specificity was 90.93% for the diagnosis of ADC, with a MCC of 0.464. For the diagnosis of SCLC, the sensitivity was 61.84% and the specificity was 96.84%, with a MCC of 0.648. Thus, this study demonstrated the usefulness of TP bronchial brushing cytology in the early diagnosis of lung cancer, especially the early stage of lung SCC. A prospective clinical trial will verify these data before being translated into the clinic.
PLoS ONE 04/2014; 9(4):e90163. DOI:10.1371/journal.pone.0090163 · 3.23 Impact Factor
"Mucin stain may also be useful for identifying adenocarcinoma, likewise cytokeratin 5/6 (CK5/6) can be valuable for distinguishing squamous cell carcinoma. Napsin A is a highly specific marker for lung adenocarcinoma and p40 is an antibody that recognizes a specific p63 isoform, and is superior to p63 in specificity, with potential to replace p63 as a marker of squamous cell carcinoma8,9,11,12. In general, immunohistochemical panels containing TTF-1, p63, CK5/6, mucin stain or TTF-1, p63, CK5/6, and Napsin A are used to subtype poorly differentiated NSCLC19,20. "
[Show abstract][Hide abstract] ABSTRACT: The emergence of new therapeutic agents for non-small cell lung cancer (NSCLC) implies that histologic subtyping and molecular predictive testing are now essential for therapeutic decisions. Histologic subtype predicts the efficacy and toxicity of some treatment agents, as do genetic alterations, which can be important predictive factors in treatment selection. Molecular markers, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement, are the best predictors of response to specific tyrosine kinase inhibitor treatment agents. As the majority of patients with NSCLC present with unresectable disease, it is therefore crucial to optimize the use of tissue samples for diagnostic and predictive examinations, particularly for small biopsy and cytology specimens. Therefore, each institution needs to develop a diagnostic approach requiring close communication between the pulmonologist, radiologist, pathologist, and oncologist in order to preserve sufficient biopsy materials for molecular analysis as well as to ensure rapid diagnosis. Currently, personalized medicine in NSCLC is based on the histologic subtype and molecular status. This review summarizes strategies for tissue acquisition, histologic subtyping and molecular analysis for predictive testing in NSCLC.
Tuberculosis and Respiratory Diseases 11/2013; 75(5):181-187. DOI:10.4046/trd.2013.75.5.181
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