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

Abstract

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.

Diagnosing Lung Carcinomas with Optical Coherence Tomography

“…With the advances in targeted therapeutics, physical tissue must be collected for molecular testing to determine whether tumors harbor mutations that would benefit from targeted therapy. This requirement precludes replacement of tissue biopsy with OCT and other in vivo optical biopsy techniques because, to date, they are unable to provide this essential mutational information (5,6).…”

“…New therapeutic discoveries have driven a dramatic effort to subtype poorly differentiated carcinomas as either SCCs or adenocarcinomas even on small tissue specimens (2, 4-6), but one study showed that only 32% of poorly differentiated carcinomas could be accurately subtyped on FNA by morphology alone (45). Immunohistochemical studies can be performed to aid subtyping, but these studies do not always provide a clear answer and there is also significant concern regarding tissue preservation for molecular testing work-ups (2,(4)(5)(6). In this study, the readers were able to correctly diagnose the carcinoma subtype (SCC or adenocarcinoma) with OCT in 71% of poorly differentiated carcinoma cases that could not be subtyped by morphological features on histology.…”

“…biopsy and fine needle aspiration (FNA) are often the only method of diagnosis for many patients with lung cancer (6)(7)(8). However, pathology diagnosis on these small specimens can be difficult because of inadequate tumor volume and/or lack of tissue architecture (1,(7)(8)(9)(10)(11)(12)(13)(14).…”

Diagnosis and Predictive Molecular Analysis of Non–Small-Cell Lung Cancer in the Africa-Middle East Region: Challenges and Strategies for Improvement

“…The majority of patients with pulmonary carcinoma have non-resectable advanced disease [11,12]; as a result, only minimally invasive non-surgical tissue-sampling is often performed. However, diagnostic demands are increasing due to the importance of correctly characterising each malignancy.…”

“…A limited number of IHC stains can be utilised on NSCLC-NOS cases to determine whether such cases represent adenocarcinoma or squamous cell carcinoma, bearing in mind that IHC cannot predict the subtype in approximately one fifth of NSCLC-NOS cases [16] (Table 1). Minimum recommendations for IHC include the use of antibodies for TTF-1 (for adenocarcinoma) and p63 or p40 (for squamous cell carcinoma) [12,17]. It is important to interpret the IHC tests according to validated levels of staining [16]; for example, squamous predictive markers generally require strong, diffuse staining for accurate diagnosis.…”