KRAS mutation-positive bronchial surface epithelium (BSE)-type lung adenocarcinoma with strong expression of TTF-1: a case providing a further insight as for the role of TTF-1 in the oncogenesis

Abstract

Bronchial surface epithelium (BSE)-type lung adenocarcinoma is a subtype of non-terminal respiratory unit (TRU)-type lung adenocarcinoma originating in the bronchial surface epithelium. However, there are few known cases of BSE-type adenocarcinoma with marked expression of thyroid transcription factor-1 (TTF-1). This paper describes a very rare case of KRAS mutation-positive BSE-type adenocarcinoma that exhibited strong expression of TTF-1 that was putatively involved in oncogenesis. An 84-year-old woman, a never smoker, was referred to our hospital because of an abnormal chest radiograph. Chest computed tomography (CT) showed a solid mass lesion, 15 mm × 10 mm, with a relatively smooth margin in the left upper lobe. The patient underwent partial resection of the left upper lobe for strongly suspected lung cancer with a clinical stage of cT1aN0M0. Histopathological findings showed continuous migration of papillary, hyperplastic, atypical columnar tumor cells originating from normal bronchial surface epithelium, leading to a diagnosis of BSE-type adenocarcinoma. TTF-1 was strongly expressed in almost 100% of the tumor cells, which tested positive for the KRAS mutation. TTF-1 has recently attracted attention as an oncogene, and it is purportedly involved in the carcinogenesis and survival of lung adenocarcinoma cells. There is typically an inverse correlation between the respective expressions of KRAS and TTF-1, but in the present study, they appeared simultaneously and were both putatively involved as oncogenic driver alterations. This case is important in that it sheds some light on the largely unknown pathogenic mechanism of BSE-type adenocarcinoma.

Keywords: BSE-type adenocarcinoma; KRAS; TTF-1.

Figure 1

Chest computed tomography (CT) shows a solid mass lesion, 15 mm × 10 mm, with a relatively smooth margin in the left upper lobe.

Figure 2

A. A 15 mm × 10 mm nodule with central necrosis in the lung parenchyma (hematoxylin and eosin [HE] staining; 12.5 × magnification) is seen; B. The nodule exhibits papillary, hyperplastic, atypical columnar epithelium that was diagnosed as a papillary-predominant invasive adenocarcinoma (HE staining; 200 × magnification). C. Magnifying the edge of the papillary proliferative structure shows serial migration of tumor cells from healthy bronchial surface epithelium and disappearance of the cilia along the border of the tumor cell migration (HE staining; 400 × magnification). Based on these findings, the tumor was diagnosed as a BSE-type adenocarcinoma originating in the bronchial surface epithelium.

Figure 3

The tumor cells are: (A) CK7-positive; (B) strongly TTF-1-positive; (C) MUC4-positive; and (D) p53-positive. Specifically, TTF-1 is expressed in almost 100% of tumor cells and is only weakly expressed in healthy respiratory tract mucosa. TTF-1, Thyroid transcription factor-1.

Figure 4

Direct-sequencing of KRAS gene codons 12 and 13 shows a GGT→GTT mutation at codon 12.