Controversies and challenges in the histologic subtyping of lung adenocarcinoma

Abstract

Lung adenocarcinomas differ in prognosis based on their histologic growth pattern. Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) both have an excellent prognosis when completely resected, whereas solid and micropapillary-predominant adenocarcinomas do not, with other patterns falling in between. In recent years, it has become apparent that even within histologic patterns, there are differences in appearance that are clinically important, such as complex acinar formations and highly variable-sized papillae. This review highlights prognostically important histologic features in lung adenocarcinoma that have emerged since implementation of the current World Health Organization (WHO) classification of lung adenocarcinoma.

Keywords: Lung adenocarcinoma; classification; histologic; pathology; subtyping.

Figure 1

Pulmonary AIS, which is defined by pure lepidic growth of neoplastic pneumocytes along alveolar septa (A), may exhibit sclerosis/stromal collapse of the alveolar framework that can be mistaken for invasion (B) (HE stain, ×200). AIS, adenocarcinoma in situ.

Figure 2

Elastic stains can sometimes aid in the distinction between pulmonary AIS and MIA by highlighting breaks (arrows) in the alveolar elastic framework in MIA (Verhoeff-Van Gieson elastin stain, ×200). AIS, adenocarcinoma in situ; MIS, minimally invasive adenocarcinoma.

Figure 3

Lung adenocarcinomas in which complex acinar formations (B) or cribriform arrangements (C) predominate have a worse prognosis that tumors composed predominantly of simple acinar structures (A) (HE stain, ×400).

Figure 4

The degree of atypia and architectural complexity in papillary lung adenocarcinoma can vary considerably, ranging from slightly atypical cells and “pseudolepidic” papillae (A, ×200) to medium-sized papillary thyroid carcinoma-like papillae (B, ×400) to complex papillae with marked atypia (C, ×400) (HE stain).

Figure 5

The micropapillary pattern in lung adenocarcinoma includes a variety of appearances, ranging from the classic form in which tumor cells lacking fibrovascular cores are arranged in papillary tufts, florets, and intraalveolar clusters (A) to the filigree form with its delicate lacelike narrow stacks of tumor cells (B) and the stromal form featuring infiltrating clusters of tumor cells within cleft-like spaces surrounded by stroma (not shown) (HE stain, ×400).

Figure 6

Based on data that have emerged since the current lung adenocarcinoma classification was introduced, some patterns will likely need to be regrouped in future moderations to better align with their risk of recurrence.