Stereologic consequences of iatrogenic collapse: The morphology of adenocarcinoma in situ overlaps with invasive patterns. Proposal for a necessary modified classification of pulmonary adenocarcinomas.

Publisher: Elsevier Scientific Publishers Country of Publication: Ireland NLM ID: 8800805 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8332 (Electronic) Linking ISSN: 01695002 NLM ISO Abbreviation: Lung Cancer Subsets: MEDLINE

Publication: Limerick : Elsevier Scientific Publishers
Original Publication: Amsterdam, The Netherlands : Elsevier, c1985-

Lung Neoplasms*/pathology ; Lung Neoplasms*/diagnosis ; Adenocarcinoma*/pathology ; Neoplasm Invasiveness*; Humans ; Male ; Female ; Aged ; Iatrogenic Disease ; Adenocarcinoma in Situ/pathology ; Adenocarcinoma in Situ/etiology ; Middle Aged ; Adenocarcinoma of Lung/pathology ; Adenocarcinoma of Lung/diagnosis ; Elastin/metabolism ; Retrospective Studies ; Keratin-7/metabolism

Recognizing non-invasive growth patterns is necessary for correct diagnosis, invasive size determination and pT-stage in resected non-small cell lung carcinoma. Due to iatrogenic collapse after resection, the distinction between adenocarcinoma in-situ (AIS) and invasive adenocarcinoma may be difficult. The aim of this study is to investigate the complex morphology of non-mucinous non-invasive patterns of AIS in resection specimen with iatrogenic collapse, and to relate this to follow-up. The effects of iatrogenic collapse on the morphology of collapsed AIS were simulated in a mathematical model. Three dimensional related criteria applied in a modified classification, using also cytokeratin 7 and elastin as additional stains, in two independent retrospective cohorts of primary pulmonary adenocarcinomas ≤3 cm resection specimen with available follow-up information. The model demonstrated that infolding of alveolar walls occurs during iatrogenic collapse and lead to a significant increase in tumor cell heights in maximal collapse areas, compared to less collapsed areas. The morphology of infolded AIS overlaps with patterns described as papillary and acinar adenocarcinoma according to the WHO classification, necessitating an adaptation. The modified classification incorporates recognition of iatrogenic and biologic collapse, tangential cutting effect true invasion and surrogate markers of invasion i.e. grey zone, covering a multilayering falling short of micropapillary, cribriform and solid alveolar filling growth. The use of elastin and CK7 staining aids in the morphologic recognition of iatrogenic collapsed AIS and the distinction from invasive adenocarcinoma. Out of a total of 70 resection specimens 1 case was originally classified as AIS and 9 were reclassified as iatrogenic collapsed AIS. Patients with collapsed AIS showed a 100 % recurrence-free survival after a mean follow-up time of 69.5 months. With the current WHO classification, AIS is overdiagnosed as invasive adenocarcinoma due to infolding. The modified classification facilitates the diagnosis of AIS.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andreas schonau is developer of the pathogate website. None of the other authors declares a conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Keywords: Adenocarcinoma in situ, Elastin, Cytokeratin 7; Collapse stereology; Iatrogenic; Lung adenocarcinoma; Modified classification

9007-58-3 (Elastin)
0 (Keratin-7)

Date Created: 20241010 Date Completed: 20241110 Latest Revision: 20241110

20241114

10.1016/j.lungcan.2024.107987

39388963