According to the WHO classification, adenocarcinoma in situ (AIS) is a localised small (≤3 cm) adenocarcinoma whose growth is restricted to neoplastic cells along pre-existing alveolar structures, lacking stromal, lymphovascular, or pleural invasion. There is no evidence to define AIS as having a tumour size of ≤3 cm. It is extremely rare for adenocarcinomas with pure lepidic growth lacking invasion to be >3.0 cm. The biological characteristics of these large AISs should be revealed.
The patient was an 82-year-old asymptomatic woman. Chest computed tomography showed a 6-cm-diameter pure ground-glass opacity in the left lower lung. The patient underwent lobectomy. On histologic examination, the tumour was restricted to neoplastic cells along pre-existing alveolar structures, lacking stromal, vascular, alveolar space, and pleural invasion. Papillary patterns were absent. Initially, the histopathological diagnosis was AIS, but the total tumour diameter exceeded 3 cm. The final pathological diagnosis was lepidic adenocarcinoma lacking an invasive component and harbouring an EGFR exon 20 insertion V774_C775insHV mutation using next-generation sequencing (NGS).
We report a rare case of lepidic adenocarcinoma with a total tumour diameter of 6 cm and without an invasive component. Although EGFR mutations are oncogenic driver mutations, AISs have fewer EGFR mutations than invasive adenocarcinomas do. An adenocarcinoma that progresses to AIS, not stepwise progression, might have uncommon mutations and might be another type of adenocarcinoma. NGS could be useful for detecting uncommon genes that reveal the biological characteristics of AIS, and may contribute to the validation of next TNM classification.

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