Clinically relevant pathologic classification of Congenital Cystic Lung Malformations.

Congenital cystic lung malformations encompass a diverse group of lesions that arise during in utero development. A variety of pathologic classification schemes have been proposed, but recent advances suggest that gross and microscopic morphologies can often be explained by the underlying mechanism of cyst development. A subset of congenital pulmonary airway malformations, usually with large cysts, is associated with widespread epithelial oncogenic KRAS mutation. These have a long-term risk of developing mucinous adenocarcinoma. Another subset, more commonly with smaller cysts, are associated with bronchial atresia or other mechanisms of obstruction. The histology of atresia specimens overlaps with that of intra- and extra-lobar sequestrations, which additionally have an extra hilum-like structure suggesting that they arise due to an ectopic portion of lung developing without normal fluid-flow in utero. These lesions are not expected to have a long-term risk of cancer but may become infected due to abnormal clearance. Finally, a subset of lesions associated with DICER1 mutation may arise in utero or after birth and are best classified as cystic pleuropulmonary blastoma. The term congenital pulmonary airway malformation is no longer in use for these cysts, which may progress to a solid aggressive sarcoma or may regress to a bland and benign multiloculated cyst. While surgical management may be the same independent of the underlying pathology (open or thoracoscopic lobectomy), post-natal pathologic examination contributes to patient care by establishing a diagnosis that goes beyond cyst size. This may guide future treatment decisions including monitoring, molecular testing, or genetic counseling.