Dept. of Pathology, San Raffaele Scientific Institute, Milan, Italy.
Dept. of Pathology, OLVG LAB BV, Amsterdam, the Netherlands.
Lung Cancer. 2024 Nov;197:107987. doi: 10.1016/j.lungcan.2024.107987. Epub 2024 Oct 5.
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.
识别非侵袭性生长模式对于正确诊断、侵袭性大小确定和切除的非小细胞肺癌 pT 分期是必要的。由于切除后的医源性塌陷，原位腺癌（AIS）和浸润性腺癌之间的区分可能很困难。本研究旨在探讨切除标本中伴有医源性塌陷的非黏液性非侵袭性 AIS 模式的复杂形态，并将其与随访结果相关联。在数学模型中模拟了医源性塌陷对塌陷 AIS 形态的影响。在两个独立的回顾性原发性肺腺癌≤3cm 切除标本队列中应用了三维相关标准，这些标本均具有可获得的随访信息，并采用改良分类，同时使用细胞角蛋白 7 和弹性蛋白作为附加染色。模型表明，肺泡壁的内折发生在医源性塌陷期间，与塌陷程度较小的区域相比，在最大塌陷区域中肿瘤细胞高度显著增加。内折 AIS 的形态与根据 WHO 分类描述的乳头状和腺泡状腺癌模式重叠，需要进行调整。改良分类纳入了对医源性和生物学塌陷、切线切割效应真正浸润和侵袭替代标志物的识别，即灰色区域，涵盖了多层排列但未达到微乳头状、筛状和实性肺泡填充生长。弹性蛋白和 CK7 染色的使用有助于识别医源性塌陷的 AIS 和与浸润性腺癌的区分。在总共 70 个切除标本中，1 例最初被归类为 AIS，9 例被重新归类为医源性塌陷 AIS。在平均随访时间为 69.5 个月后，塌陷 AIS 患者的无复发生存率为 100%。根据目前的 WHO 分类，由于内折，AIS 被过度诊断为浸润性腺癌。改良分类有助于 AIS 的诊断。
