Case of mucinous adenocarcinoma of the lung associated with congenital pulmonary airway malformation in a neonate

Abstract

Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic adenomatoid malformation, is a rare developmental lung abnormality associated with rhabdomyosarcoma, pleuropulmonary blastoma, and mucinous adenocarcinoma of the lung. We report an unusual case of a 10-day-old male newborn with a left lower lobe pulmonary cyst who underwent lobectomy, which revealed type II CPAM complicated by multifocal mucinous adenocarcinoma. KRAS sequencing revealed a somatic mutation in Codon12 (GGT → GAT), suggesting the development of a mucinous adenocarcinoma in the background of mucinous metaplasia. Mucinous adenocarcinoma is the most common lung tumor associated with CPAM, but it generally occurs in older children and adults. Further, all cases in the literature are of type I CPAM. This case in a neonate indicates that malignant transformation can occur very early in type II CPAM.

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.…”

“…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.…”

“…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).…”

Primary Lung Cribriform Adenocarcinoma With Squamoid Morules Harboring Somatic CTNNB1 Mutation in a Never-Smoked Healthy Adolescent

“…There is a well-established association between type 1 CPAM and mucinous adenocarcinoma. 5,6 This association might be related to KRAS mutations in both the mucinous growths in type 1 CPAM and mucinous adenocarcinoma. [17][18][19] Absence of cystic dilatations or mucinous cells in our patient's tumor tissue is in keeping with the KRAS wild-type status in the tumor mutation panels.…”

“…Primary lung adenocarcinomas are extremely rare in pediatric patients. [1][2][3][4] Of the few reported cases, most of them were associated with congenital pulmonary airway malformation (CPAM) 5,6 or identified during treatment for nonpulmonary malignancies, most commonly a sarcoma. 1,7,8 Pediatric pulmonary tumors had identical histologic variants as their adult counterpart.…”