Mucinous Adenocarcinoma With Intrapulmonary Metastasis Harboring KRAS and GNAS Mutations Arising in Congenital Pulmonary Airway Malformation

Am J Clin Pathol. 2021 Jul 6;156(2):313-319. doi: 10.1093/ajcp/aqaa245.

Abstract

Objectives: Mucinous adenocarcinoma arising in unresected congenital pulmonary airway malformation (CPAM) is rare. Underlying driver mutations in addition to KRAS gain-of-function mutations in this setting and the long-term outcomes of these patients are unknown.

Methods: We report a case of metastatic mucinous adenocarcinoma harboring both KRAS and GNAS mutations arising in a type 1 CPAM of a 14-year-old male. A literature review was performed.

Results: Next-generation sequencing revealed identical KRAS (G12V) mutations in both the CPAM and metastatic adenocarcinoma and a missense mutation in the GNAS (R201C) gene in the metastatic adenocarcinoma only. Median survival was 23 and 4 years for patients with localized (no or limited spread within the same lobe of CPAM) and distant involvement (spread to any different lobe of CPAM) of mucinous cells, respectively (95% confidence interval, 23-23 and 1.5-22 years, respectively; P = .017).

Conclusions: Mucinous cell proliferation associated with type 1 CPAM has exceptionally good long-term outcomes if confined within the same lobe of CPAM. A second oncogenic mutation in the GNAS gene may be necessary for progression to malignancy and distant spread.

Keywords: GNAS; KRAS; Congenital pulmonary airway malformation; Mucinous adenocarcinoma.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / pathology*
  • Adolescent
  • Chromogranins / genetics*
  • Cystic Adenomatoid Malformation of Lung, Congenital / genetics
  • Cystic Adenomatoid Malformation of Lung, Congenital / pathology*
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Mutation
  • Proto-Oncogene Proteins p21(ras) / genetics*

Substances

  • Chromogranins
  • KRAS protein, human
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs
  • Proto-Oncogene Proteins p21(ras)