Atypical goblet cell hyperplasia occurs in CPAM 1, 2, and 3, and is a probable precursor lesion for childhood adenocarcinoma

Mucinous adenocarcinoma arising in congenital pulmonary airway malformation: clinicopathological analysis of 37 cases

“…There is an ongoing debate concerning the appropriate terminology for describing these mucinous cell proliferations, with many reports using the World Health Organization (WHO) terminology of 'mucinous adenocarcinoma' (including our study), 9,10,14,16,30 and two recent studies using the terms 'AGCH' and 'mucinous cell clusters (MCCs)' to describe the mucinous cells. 7,27 Although some have argued that these proliferations should not be classified with the use of a malignant or premalignant term, this view seems to be primarily based on a lack of malignant behaviour if complete resection is performed. 27 However, these proliferations are morphologically indistinguishable from those in adults, and this study shows evidence of recurrence and metastasis if complete resection is not performed, albeit with a very slow growth rate.…”

“…27 However, these proliferations are morphologically indistinguishable from those in adults, and this study shows evidence of recurrence and metastasis if complete resection is not performed, albeit with a very slow growth rate. In addition, genetic analysis has demonstrated that these mucinous cells frequently harbour mutations of KRAS, most commonly exon 2 G12D (c.35G>A), G12V (c.35G>T) and G12C (c.34G>T) mutations, 7,9,10,[13][14][15][16][30][31][32] which are similar to the KRAS mutations commonly found in mucinous adenocarcinomas arising de novo, typically in smokers. [33][34][35][36][37] In addition to KRAS mutations, Lantuejoul et al demonstrated loss of heterozygosity at the tumour suppressor genes FHIT, Rb, and p16 INK4 , not only in the A B C D Figure 1.…”

“…A proliferation of cytologically bland mucinous cells within the cyst lining is observed in approximately one-third of cases, 3 mostly in type 1 CPAMs, but also rarely in type 2 and 3 CPAMs. 5,7 These lesions have historically been classified as goblet or mucous cell hyperplasia, 8 mucinous epithelial proliferation, 9 mucinous metaplasia, 10 and atypical goblet cell hyperplasia (AGCH). 7,11,12 Occasionally, the mucinous cells also grow along the alveolar septa into the adjacent, sometimes underdeveloped, alveoli; this is microscopically indistinguishable from mucinous adenocarcinoma in situ (AIS) or invasive mucinous adenocarcinoma (IMA), depending on size, invasion, and multifocality.…”

“…5,7 These lesions have historically been classified as goblet or mucous cell hyperplasia, 8 mucinous epithelial proliferation, 9 mucinous metaplasia, 10 and atypical goblet cell hyperplasia (AGCH). 7,11,12 Occasionally, the mucinous cells also grow along the alveolar septa into the adjacent, sometimes underdeveloped, alveoli; this is microscopically indistinguishable from mucinous adenocarcinoma in situ (AIS) or invasive mucinous adenocarcinoma (IMA), depending on size, invasion, and multifocality. With KRAS mutations having been reported in mucinous cells both within the cyst and in the adjacent alveoli, 7,9,10,[13][14][15][16] and rare reports of associated metastases and mixed mucinous and non-mucinous adenocarcinoma, 17,18 these lesions are now accepted by some pathologists as neoplastic (either as AIS or IMA).…”

EpCAM+CD73+ mark epithelial progenitor cells in postnatal human lung and are associated with pathogenesis of pulmonary disease including lung adenocarcinoma

“…Lung tumors associated with CPAM in children range from rhabdomyosarcoma (RMS), pleuro-pulmonary blastoma (PPB), whereas in the adult, bronchioalveolar carcinoma (BAC) and adenocarcinoma are more common (6). Goblet cell proliferation, which has been described in CPAM may represent a precursor lesion to lung adenocarcinoma in children (13). Along these lines, various changes in several notable genes including FGF10, FGFR2b, SOX2 and mutations in KRAS at codon 12 was associated with adenocarcinoma.…”