Early Lung Cancer With Lepidic Pattern

Adenocarcinoma in Situ, Minimally Invasive Adenocarcinoma, and Lepidic Predominant Adenocarcinoma

Wilko Weichert; Arne Warth


Curr Opin Pulm Med. 2014;20(4):309-316. 

In This Article

Clinical Implications of the Classification of Tumors With Lepidic Growth

One of the most profound changes in the new ADC classification are the elimination of the term BAC and a concomitant tighter delineation of lesions that were formerly summarized in this category, including solitary small noninvasive AIS, minimal invasive ADCs, mixed subtype invasive ADCs with a lepidic component and tumors now categorized as invasive mucinous carcinomas. This hopefully will lead to a more precise and comparable classification of the respective tumors in the future. Introduction of the new entities AIS and MIA is consistent with tumor biology and in line with the classification of tumors in other organs. Beyond tumor architecture, other parameters like mitotic count or nuclear grading might be helpful for a meaningful prognostic assessment of ADC in the future.[5]

From a clinical point of view, a classification should reflect the patients' prognosis to allow for tailored treatment decisions. This has been achieved with the novel classification. With respect to prognosis of tumors with lepidic growth, it is of utmost importance to delineate between MIA and LPA, whereas the differentiation of AIS and MIA from each other seems to have no prognostic relevance. Concerning staging, AIS and MIA are classified as pTis and pTmia, respectively, and should not be considered for multiple nodule upstaging. For a definite separation of the lepidic tumors, surgical resection is a prerequisite, which, in cases in which a definite classification is necessary, hampers the use of alternative treatment options.

Advances in imaging allow for an early detection of lung cancer, while increasing numbers of precursor lesions are expected to be diagnosed in the future. A large trial demonstrated that small nodules smaller than 10 mm or smaller than 500 mm3 that are clearly 100% pure GGO lesions on CT might be considered for close follow-up rather than immediate resection.[57] Whether some of these lesions can be treated by limited resection is a prevailing question and a subject of intensive investigations.[58] However, although most cases of AIS or MIA will likely be cured by complete resection,[26] a small percentage of LPA will recur. Thus, it is of utmost importance to further characterize these lesions in a multidisciplinary setting in order to identify criteria allowing for risk-adjusted treatment decisions.

With respect to predictive biomarkers used for patient stratification, nonmucinous lepidic growth is significantly associated with mutations in the epidermal growth factor receptor but not V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations.[25,59–62] Tumors with mucinous lepidic growth and papillary projections, now designated as invasive mucinous ADC, are associated with KRAS mutations;[27,62–64] however, these tumors now form a separate entity and are not part of the lepidic tumor spectrum anymore.