Mucinous cells in type 1 pulmonary congenital cystic adenomatoid malformation as mucinous bronchioloalveolar carcinoma precursors.
Type 1 congenital cystic adenomatoid malformation (CCAM), the most frequent malformation of the lung, is the only type to present intracystic mucinous cell clusters, which may form beyond the cysts extracystic mucinous proliferation resembling mucinous bronchioloalveolar carcinomas (BACs). As mucinous BACs are increasingly described in the literature in young patients with CCAM, we hypothesized that type 1 CCAM mucinous cells could represent BAC precursors. We reviewed 7 cases of type 1 CCAM including 6 with intracystic mucinous cell clusters, 3 with extracystic mucinous proliferations, and 4 with mucinous BAC or mixed adenocarcinoma with predominant BAC. K-ras mutations at codon 12 were detected in 3/3 intracystic mucinous cell clusters, in 2/3 extracystic mucinous proliferations, and in 3/4 BAC. Loss of heterozygosity (LOH) at p16(INK4) locus, with microsatellite alterations in 3 cases, was observed in 2/3 intracystic mucinous cell clusters, in 2/3 extracystic mucinous proliferations, and in all BAC. Two extracystic mucinous proliferations showed LOH at FHIT and Rb loci, respectively. P16(INK4) expression was lost in 2 intracystic mucinous cell clusters, 1 extracystic mucinous proliferation, and 1 BAC. Neither epidermal growth factor receptor mutation on exons 18, 19, and 21 nor P53 accumulation was observed. All lesions expressed MUC5AC, but were negative for MUC2, CDX2, and TTF-1. In conclusion, type 1 CCAM mucinous cells share the same differentiation profile with corresponding mucinous BAC, consistent with a common bronchial origin. Moreover, the high frequency of K-ras mutation and LOH and/or microsatellite alterations at p16(INK4) locus presented by these mucinous cells justifies their consideration as BAC precursors.
Lantuejoul
Sylvie
S
Department of Pathology and Lung Cancer Research Group, INSERM U578, CHU A Michallon, Grenoble, France. SLantuejoul@chu-grenoble.fr
Nicholson
Andrew G
AG
Sartori
Giuliana
G
Piolat
Christian
C
Danel
Claire
C
Brabencova
Eva
E
Goldstraw
Peter
P
Brambilla
Elisabeth
E
Rossi
Giulio
G
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015615:Cystic Adenomatoid Malformation of Lung, Congenital / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000150:complications / Q000235:genetics* / Q000473:pathology