Ann Thorac Surg 2007;83:214-215
© 2007 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Invited commentary
Giuseppe Pelosi, MDa,
Juan Rosai, MDb
a Istituto Europeo di Oncologia (IEO), Via G Ripamonti 435, Milan, I-20141 Italy
b Centro Diagnostico Italiano (CDI), Via Saint Bon, 20, Milan, I-20147 Italy
(Email: giuseppe.pelosi{at}ieo.it; rosai{at}cdi.it).
Pulmonary adenocarcinoma, the most prevalent subtype of lung cancer worldwide, can present in a variety of major morphological growth patterns (ie, acinar, papillary, solid with mucin, and bronchioloalveolar [BAC]), either in pure form or admixed. Several minor histologic variants also exist, such as fetal, mucinous, signet ring, and clear cell. The mixed subtypes, which make up approximately 80% of all resected cases, are morphologically heterogeneous neoplasms characterized by various combinations of histologic patterns, varying degrees of differentiation, different cell types, and variable cytological atypia, with each of these features often varying from field to field and from section to section in the same case. Therefore, rethinking lung adenocarcinoma according to a more dynamic and clinically relevant model is clearly warranted, keeping account of both tumor histogenesis (in turn related to the anatomical location) and prognostic and therapeutic implications. Within this frame of mind, dividing pulmonary adenocarcinomas into replacing (adenocarcinomas mixed with a BAC component, the latter being an in situ tumor) and nonreplacing types (with little or no recognizable BAC component), as proposed by Noguchi and colleagues [1], and as revisited in the study by Sakao and colleagues [2], is a conceptually reasonable and diagnostically reproducible approach. In fact, it could prove useful not only for identifying patients’ subsets with longer life expectations and amenable to more conservative surgery, but also for providing the pathologic correlates for the findings of common computed tomographic scans, such as ground glass opacities, air bronchograms, bubble-like areas, and solid components.
Recently, innovative histologic criteria have been proposed for the diagnosis of early invasive small lung adenocarcinomas [3] and the measurement of stromal invasion [4]. In addition, several studies have stressed the impact of various tumor characteristics (eg, tumor grade, vascular invasion, cell proliferative activity, tumor necrosis, lymphocytic infiltration, central scarring, and so forth) in forecasting patients’ survival. In this scenario, the article by Sakao and colleagues [2] provides original arguments on the theme of the prognostic impact of the non-BAC components in small adenocarcinomas of the lung. In particular, the authors [2] indicate that the nonreplacing-type growth patterns (ie, pure invasive tumors with acinar, papillary, or solid with mucin components and little or no recognizable BAC) run a more aggressive clinical course when compared with replacing type tumors, even for lesions sized 2 cm or smaller. Moreover they show that the former tumor category is associated with a greater prevalence of vascular invasion and lymph node metastases, thus emerging as an independent adverse prognostic factor. Another intriguing implication of Sakao and colleagues’ [2] findings is that tumor diameter in the replacing type lesions is not per se an indicator of vascular or lymph node invasiveness when considered as a whole (ie, including the BAC component), whereas tumor size excluding the BAC component is a significant factor in this regard. This finding is worth emphasizing, because it could have relevant implications for the TNM staging system of pulmonary small adenocarcinoma. In the current scheme, pT1 tumors are defined according to their gross diameter considered as a whole (ie, independently of the presence or amount of a BAC component). In the proposal of Sakao and colleagues [2], pT class assignment of small (up to 2 cm) adenocarcinomas would be dependent on or influenced by the extent of the nonreplacing component, defined as the central scarred portion of the tumor, in which the neoplastic cells have acquired invasive properties. The problem is that currently there is no consensus for assessing the extent of a central scar in mixed adenocarcinomas as an indicator of tumor invasiveness, being that collapsed lung parenchyma with no invasive carcinoma may also participate in the final formation of that scar. Therefore, Sakao and colleagues [2] have adopted a simple and reproducible method for measuring tumor size, which consists of incorporating into such measurement the scar, the carcinoma components other than BAC, the necrotic areas, and the inflammatory changes, finding that this value is more relevant as a prognostic factor for small adenocarcinomas than the whole tumor size. A direct implication of this finding is that it may become feasible to establish direct correlations with the findings of the computed tomographic scan, inasmuch as the nonreplacing type component may correspond to the tumor dimension as determined using the mediastinal window setting on computed tomography thus providing important clinical information to decide on the most appropriate treatment. To sum it up, the intriguing findings of Sakao and colleagues [2] may be viewed as an operational starting point for planning prospective clinical trials, especially when evaluating the impact of tumor size and tumor growth patterns on new treatment options.
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References
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- Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung: histologic characteristics and prognosis Cancer 1995;75:2844-2852.[Medline]
- Sakao Y, Miyamoto H, Sakuraba M, et al. Prognostic significance of a histologic subtype in small adenocarcinoma of the lung: the impact of nonbronchioloalveolar carcinoma components Ann Thorac Surg 2007;83:209-215.[Abstract/Free Full Text]
- Sakurai H, Maeshima A, Watanabe S, et al. Grade of stromal invasion in small adenocarcinoma of the lung: histopathological minimal invasion and prognosis Am J Surg Pathol 2004;28:198-206.[Medline]
- Terasaki H, Niki T, Matsuno Y, et al. Lung adenocarcinoma with mixed bronchioloalveolar and invasive components: clinicopathological features, subclassification by extent of invasive foci, and immunohistochemical characterization Am J Surg Pathol 2003;27:937-951.[Medline]
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