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a Istituto Europeo di Oncologia ed Università degli Studi di Milano, Via G. Ripamonti, 435, Milan, I-20141 Italy
b Centro Diagnostico Italiano, Via Saint Bon, 20, Milan, I-20147 Italy
(Email: giuseppe.pelosi{at}ieo.it; rosai{at}cdi.it).
The inherent biological aggressiveness of lung cancer renders its control ineffectual in most instances if the disease is already symptomatic, locally advanced, or metastatic, or a combination of these. These attributes indicate high morbidity and mortality rates and a disappointing outcome to multimodality therapy [1]. Therefore, efforts have been aimed at detecting cancer early under the assumption that the lower the stage, the more curable the cancer [2–5]. This approach requires an accurate tumor staging according to the time-honored and still effective, anatomically-defined TNM system, which was developed in France by Pierre Denoix in the 1940s. The system classifies cancer according to the extent of local (tumor), regional (node), and distant (metastasis), and it continues to play a fundamental role in lung cancer management as the most powerful and reliable predictor of prognosis. Moreover, TMN staging represents the operational basis for choosing the most appropriate therapy and for evaluating the efficacy of different therapeutic methods by comparison of expected survival rates. In other words, cancer staging still remains an essential component of patient care and of cancer research and control activities, even in light of impressive progress in clinical management and molecular medicine.
We, as physicians, have always attempted to improve our knowledge of tumor biology and to refine the instruments we use for patient management. This reflects the irrepressible desire of the human mind for knowledge, which was masterfully depicted in the Ulysses character by Dante in The Divine Comedy (Inferno XXVI). Continuing revisions of the TNM staging system reflect this tendency, as demonstrated by the several updated versions that have followed one another unceasingly. In the fifth edition [6], which was left almost unchanged in the sixth edition [7], stage I and II lung cancers were subcategorized into A and B subgroups according to tumor size (using a cut-off of 3 cm), visceral pleura infiltration and regional (N1) lymph node involvement. This shifted T3N0M0 tumors from stage IIIA (as they were listed in the fourth edition) to stage IIB. The use of a single cut-off threshold of 3 cm, however, was questioned regarding discriminant power in evaluating the T-factor, and this led to a proposal by the International Association for the Study of Lung Cancer to introduce several substantial changes to the TNM staging system in 2007. One change was to split the tumor size cut-off into several categories (T1a 
2cm; T1b > 2 to 3 cm; T2a > 3 to 5 cm; T2b > 5 to 7 cm) [8, 9]. Also, as visceral pleura infiltration was found to be an important prognostic factor [10, 11], this was acknowledged into the proposed seventh edition of the TNM staging system by placing a tumor in the T2a category if less than 5 cm in greatest dimension [8]. These criteria were equated to main bronchus involvement 
2 cm distal to the carina or in association with atelectasis or obstructive pneumonitis extending to the hilar region but not involving the entire lung. It was agreed that pleural infiltration should not affect T2b tumor classification, which was defined on the basis of tumor size alone [8], as it was in the sixth edition [7].
Against this background, the proposal by Sakakura and colleagues' [12] in this issue of The Annals of Thoracic Surgery to divide the T-factor according to a combined evaluation of tumor size and type of visceral pleural involvement (the latter according to a well-codified three-tiered and four-tiered system) [12, 13], is an appealing, conceptually reasonable and reproducible approach in routinely stained sections. In particular, tumors > 3 to 5 cm and no pleural invasion (P0), or tumors invading the pleura but without surface exposure (P1), were found to have a significantly less aggressive clinical course (5-year survival [59.5%]) than tumors greater than 5 cm or with surface exposure (P2) (5-year survival [37.5% and 47.3%, respectively]). The authors categorized the former as T2a and the latter as T2b, and staged them as IB and IIA, respectively. The 5-year survival rate for IB was 70.6% and for IIA 60.4%, respectively, which is in partial agreement with the recent International Association for the Study of Lung Cancer (IASLC) proposal that showed a 5-year survival of 58% for IB stage and 46% for IIA stage [8]. Therefore, it is reasonable to assume that the extent of pleural involvement is relevant to prognosis, as stated in the article by Sakakura and colleagues' [12]. This being the case, the fact that this apparently important feature was not evaluated in the recent IASLC proposed revision of TNM stage grouping [8] and T descriptors [9], because of a small number of patients, inconsistent clinical and pathologic results, or lack of validation [9], is disturbing. In other words, according to Sakakura and colleagues' [12] well-constructed scheme, P2 tumors would be classified as T2b and staged as IIA (if N0) or IIB (if N1), independently of tumor size. The T2a category would be reserved for P0 to P1 tumors > 3 to 5 cm. In the IASLC proposal contained in the forthcoming (seventh) edition of TNM classification of malignant tumors, T2 lung carcinomas with pleural invasion are classified as T2a if 5 cm and T2b if 5 to 7 cm in greatest dimension [8]. In this fashion, the type of pleural involvement, which is assessable on hematoxylin and eosin-stained sections according to a three-tiered and four-tiered method, rather than pleural involvement per se would represent a prognostic discriminator in the listing of T-descriptors for better forecasting prognosis. In the event of tumors ranging from 3 to 5 cm, these would become T2b lesions whenever tumor cells were exposed to the pleural surface.
In summary, the intriguing findings by Sakakura and colleagues [12] have great merit for attracting attention to the significance of the extent of pleural involvement when staging lung cancer. These findings should be regarded as operational starting points for planning clinicopathologic studies to stratify lung cancers into better defined risk categories whenever large cohorts are revised for staging purposes.
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