Evidence for non-mucinous pulmonary lesions with adenocarcinoma in situ morphology exceeding the current 3 cm WHO threshold

Abstract

CONTEXT: The World Health Organization (WHO) recognizes adenocarcinoma in situ (AIS) of the lung for tumors up to 3 cm in size. Larger tumors with a lepidic growth pattern are classified as invasive lepidic predominant adenocarcinoma. OBJECTIVE: The aim of this study was to demonstrate that pulmonary non-mucinous lesions with adenocarcinomas in situ morphology, but larger than 3 cm and even larger than 7 cm exist. MATERIAL AND METHODS: From two patients with an extensive pneumonia-like pattern on radiological imaging, complete histological embedding of the affected lobe was performed. In addition, from a nationwide retrospective pT3N0M0 cohort a subset of 112 adenocarcinoma patients, characterized by tumors exceeding 7 cm in diameter, was subjected to further analysis. Follow-up data for potential non-invasive cases were collected, their radiological findings reviewed, and comparisons made with matched controls. RESULTS: In two patients the entire lobe was examined, with 130 and 312 tissue blocks, respectively. The histological diagnosis was lepidic growth, without any signs of invasion, as seen in AIS. Both cases had a pT size of 16 cm. In a subset of the T3N0 cohort, 3 out of 112 cases were retrospectively identified as purely non-invasive lepidic proliferations. Radiological imaging revealed consolidation and ground-glass pattern, like that observed in pneumonia and follow-up showed a recurrence-free survival. CONCLUSIONS: Pulmonary non-mucinous proliferation with adenocarcinoma in situ morphology may become much larger than the 3 cm WHO threshold for AIS and may present with a pneumonia type pattern on CT imaging. The restriction of the 3 cm size criterion for AIS may therefore be reconsidered. A serious consequence for the pathology practice is that the whole lesion of such cases needs to be sampled, to exclude invasion.