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

Lepidic Predominant Adenocarcinoma

LPA typically consists of slightly to moderately atypical neoplastic cells growing along the surface of alveolar walls. Architecture and cytomorphology are comparable with the criteria described for AIS and MIA. However, at least one invasive focus measuring more than 5 mm in greatest dimension must be present. The diagnosis of LPA rather than MIA is also made if the tumor invades lymphatics, blood vessels, or pleura and if the tumor contains necrosis. The average percentage of the lepidic pattern in LPA was recently reported to be 50% (range: 40–85%) with acinar (81%) and papillary (17%) as the predominant accompanying invasive components.[26] In several retrospective studies, 5-year disease-free survival of LPA ranged between 85.7 and 100%;[3,13,14,23–27,33] survival for these tumors is thereby considerably better than for ADC with any other predominant pattern. A higher percentage of the lepidic pattern correlated with a lower risk for recurrence.[26] As multifocality is a typical feature of tumors with predominant lepidic growth, the prognostic impact of synchronous lesions was analyzed by different groups. In a series of 39 patients with multifocal ground glass lesions and negative lymph nodes, Gu et al.[35] recently reported a 100% overall survival after anatomic resection of the dominant tumor and wedge resection of all other accessible ground glass opacities (GGO), which is in line with data from previous studies.[36–39]

The proportion of the lepidic growth in LPA is of high prognostic value. Stratification for survival in dependence of ADC diameter is better when instead of the overall tumor diameter only the adjusted nonlepidic ('invasive') tumor diameter is taken into account.[12] This observation strengthens comparable findings by Yoshizawa et al.[13] and was also underscored by recent data of two series of n = 603[40] and n = 191[24] stage I ADC in which the 'invasive' size was of higher prognostic impact than the total tumor size. In both studies, the total tumor size even failed to reach prognostic relevance, whereas the invasive tumor size was found to be an independent prognosticator in multivariate analysis. This is supported by data of Zhang et al.,[41] who analyzed 215 small peripheral ADC, and Xu et al.,[28] who analyzed 87 resected ADCs with lepidic growth. Both studies found that histomorphological subtyping is more reliable to predict the N0 status than the tumor size. In addition, the size of the invasive foci has been demonstrated as an independent predictor of survival for pulmonary ADC in preceding studies.[42]

If a noninvasive pattern is present in a small biopsy, it should be referred to as lepidic growth. The diagnosis of AIS or MIA cannot be firmly established without entire histologic sampling of the tumor. To achieve this, patients necessarily must be subjected to surgery. For lesions suspicious for AIS or MIA with a diameter of larger than 3 cm (based on imaging analyses; compare Fig. 2), the term 'lepidic predominant ADC' should be applied including a comment that an invasive component cannot be excluded.[43]

Figure 2.

Interplay of histomorphology and radiological imaging. Case of a 72-year-old male with a lung lesion with dominance of ground-glass opacities in segment 10 of the left lower lobe (a). On positron emission tomography (PET)/computed tomography (CT) images, the lesion was found PET-negative (b). Transthoracic core needle biopsy showed a small lung tissue fragment with lepidic growth (c). Subsequent lobectomy accompanied by systematic lymph node dissection revealed an adenocarcinoma in situ (d). CT and PET images were kindly provided by C.P. Heussel and U. Haberkorn, Thoraxklinik and University Hospital Heidelberg, Germany, respectively.