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

Minimally Invasive Adenocarcinoma

MIA is a small to moderately sized solitary lesion (≤3 cm) with lepidic pattern and circumscribed invasive foci. Mucinous variants of MIA are rare. The number of invasive foci is variable; however, most often only one distinct area of microinvasion is present. By definition, the invasive areas must be 5 mm or smaller in greatest dimension in any one focus. The invasive component to be measured in MIA is defined as being of any histological pattern other than lepidic (i.e. acinar, papillary, micropapillary and/or solid) or comprising single nests of tumor cells infiltrating myofibroblastic stroma. The category MIA is not applied to tumors invading lymphatics, blood vessels, or pleura or to tumors containing necrosis. When multiple independent tumors are present, AIS and MIA should only be diagnosed if the lesions are regarded as synchronous primaries rather than intrapulmonary metastases. Approximately one third of ADCs have a significant lepidic component and of these nearly one third are believed to be minimally invasive.[28]

MIA has been demonstrated to have a 100% 5-year disease-free survival in multiple studies.[3,7,13,14,22–26,29–31] One study reported a slightly diminished 5-year overall survival of 98%.[27]

The delineation of invasive foci in MIA from AIS with sclerotic septal widening or alveolar collapse can be challenging, as the latter two morphologic states might resemble acinar tumor growth. To ease the evaluation of parenchymal invasion, in some cases the use of elastic stains demonstrating a destruction of the elastic structures can be helpful to differentiate true invasion from alveolar collapse.[28] However, early invasion will not necessarily result in a destruction of elastic fibers. Furthermore, a recent study pointed out that one must be aware not to misinterpret biopsy-site changes from prior biopsies as tumor-related stromal reactions.[32] Regardless of these shortcomings, the introduction of MIA as a new entity placed between AIS and LPA is a logical step from the tumor-biological point of view and helpful for pathologists in cases in which the features for stromal invasion versus alveolar collapse are controversial. However, in the strict sense, the definitive delineation of microinvasive foci is not critical from the clinical viewpoint (see below).

In contrast, exact delineation of MIA from LPA is of utmost importance, as both entities are associated with a significantly different prognosis. In addition, Yeh et al.[33] demonstrated that not only invasion per se but also different stromal invasion categories in combination with specific ADC patterns were associated with variations in patient survival. Another work quoted that even small micropapillary components in an MIA might be associated with a worse prognosis.[28] The acinar (91%) and the papillary pattern (9%) were described as the predominant invasive components in a series of 43 MIAs,[26] which further complicates the delineation of MIA from AIS, as both patterns are the ones most readily confused with lepidic tumor growth (see below). This might also explain why there was only a fair reproducibility in the delineation of invasive from noninvasive ADC patterns among international pulmonary pathologists.[15] In frozen sections, the differentiation of AIS from MIA is difficult because of multifactorial reasons (e.g. intraoperative consultation of more than one pathologist necessary; more than one sample of frozen sections needed) as demonstrated by root cause analysis of 224 consecutive cases.[34]