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

AIMS Mucinous adenocarcinoma arising in congenital pulmonary airway malformation (CPAM) is a rare complication, with little known about its natural course. We describe a series of mucinous adenocarcinomas arising from CPAMs and present its clinicopathological features, genetics, and clinical outcome. METHODS AND RESULTS Thirty-seven cases were collected within a 34 year period, and the subtype of adenocarcinoma and CPAM, tumour location, stage, growth patterns, molecular data, and follow-up were recorded. The cohort comprised of CPAM type 1 (n=33) and type 2 (n=4). Morphologically, 34 cases were mucinous adenocarcinomas (21 in situ, 13 invasive), while 3 were mixed mucinous and non-mucinous adenocarcinoma. Seventeen cases showed purely extracystic (intraalveolar) adenocarcinoma, 15 were mixed extracystic, and 5 showed purely intracystic proliferation. Genetically, 9 of 10 cases tested positive for KRAS mutations, 4 with exon 2 G12V and 5 with G12D mutation. Residual disease on completion lobectomy was observed in two cases, and three cases recurred 7, 15, and 32 years after original diagnosis. Two patients died of metastatic invasive mucinous adenocarcinoma. CONCLUSIONS Most cases of adenocarcinomas arise in type 1 CPAMs, are purely mucinous and have early stage disease. Intracystic proliferation is associated with lepidic growth, absence of invasion, and indolent behaviour, whereas extracystic proliferation may be associated with more aggressive behaviour and advanced stage. Most cases are cured by lobectomy and recurrence/residual disease seems associated with limited surgery. Long-term follow-up is needed as recurrence can occur decades later.