In Compressed Lung Tissue Microscopic Sections of Adenocarcinoma In Situ May Mimic Papillary Adenocarcinoma Open Access

To the Editor.—In 2013 the article “In Compressed Lung Tissue Microscopic Sections of Adenocarcinoma In Situ May Mimic Papillary Adenocarcinoma” was published in this journal.¹  This case report demonstrated that a (pseudo) papillary pattern should not be quickly diagnosed as invasive adenocarcinoma. Recently, the explanation for this adenocarcinoma in situ (AIS) morphology became clear: the alveolar air volume is reduced in resection specimens owing to the iatrogenic collapse. As a smaller volume requires a smaller surface, this will induce adaptation of the underlying morphology by infolding of the alveolar walls.²  Depending on the amount of air left, a pseudopapillary and/or pseudo-acinar pattern may evolve.²  This also explains, to a large extent, the higher interobserver variation of the World Health Organization classification compared to a classification that takes the morphologic effects of iatrogenic collapse into account.³  Thus, the initial message of the 2013 article¹  is still strong. In hindsight, awareness of 2 more issues is relevant for recognition of pulmonary nonmucinous AIS.

Firstly, the diagnostic biopsy of the lesion before resection is likely to have less iatrogenic collapse than the lesion in the resection specimen. The AIS appearance of the biopsied lesion (Figure, A through D) may already hint toward a correct diagnosis for the pseudopapillary appearance in the resection specimen (see Figure 2 in the 2013 article¹ ).

Secondly, the consistency of AIS is soft, not much different from the preexisting parenchyma. This hampers detection with palpation during gross examination by the pathologist. In practice, this lesion was missed after the first gross cutting examination in 2009. Since the initial hematoxylin-eosin sections did not reveal any tumor, a second gross examination revealed its presence in a relatively thick slice after recutting the actual lesion.

In addition, in preparation for this letter, clinical follow-up revealed that a 5-mm lesion in the left lower lobe, observed in 2017, remained stable at the last follow-up in 2023. The long period without recurrence (14 years after resection) also fits with the initial diagnosis of AIS.¹ 

Awareness of the morphologic difference between initial diagnostic biopsy and the iatrogenic collapse in the resection specimen, as well as the soft consistency of tumor, may aid in the diagnosis of collapsed AIS.