Morphological and Molecular Characteristics in Low Grade Fetal Adenocarcinoma of the Lung: Two Case Reports and Literature Review

Abstract

Background: Low-grade fetal adenocarcinoma of the lung is a rare pulmonary tumor resembling fetal lung histologically. Due to its rarity, there is limited information regarding the pathogenesis and biological characteristics of low-grade fetal adenocarcinoma of the lung. Here, we describe two cases of low-grade fetal adenocarcinoma of the lung treated at our hospital and summarize cases of low-grade fetal adenocarcinoma of the lung reported in the literature. Case presentation: We examined two cases (one woman and one man; 30 and 67 years old, respectively). Histologically, tumor tissues from both cases had a complex glandular component with clear cuboidal and columnar cells that resembled the histological features of fetal lung. In some areas, squamous morules were prominent. Immunohistochemically, nuclear/cytoplasmic expression of β-catenin was detected in both cases. Mutation analysis revealed a CTNNB1 mutation in both cases and a DICER1 mutation in 1 case. No mutations in EGFR, BRAF, KRAS, or PIK3CA were found. Conclusions: Low-grade fetal adenocarcinoma of the lung showed a high frequency of CTNNB1 mutations and low frequencies of EGFR, KRAS, BRAF, and PIK3CA mutations in our examined cases and in previous studies. This rare tumor has unique clinicopathological characteristics with specific genetic aberrations involving the Wnt pathway. These results provide a molecular basis for development of new therapies to treat these tumors.

Fetal Type Morphologies Suggest the Presence of DICER1 Hotspot Mutations in Non–small Cell Lung Cancer

“…DICER1 hotspot-negative NSCLC cases harbored a typical mutational landscape of NSCLC, with the most frequently mutated genes being TP53, KRAS, STK11, CDKN2A and ARID1A, 17,22 whereas DICER1 hotspotpositive cases revealed a strong co-occurrence of CTNNB1 mutations compared with NSCLCs lacking DICER1 hotspots. CTNNB1 mutations have previously been reported in DICER1-associated WDFLACs, 2,15,18,23,24 PB 6,11,25 and rarely, PPB. 10,11 Beta-catenin IHC supported the CTNNB1 sequencing results showing nuclear positivity in 5/7 tumors that harbored a PV in CTNNB1 (4/5 hotspot-positive cases and 1/2 single variant cases), similar to a study by Nakatani et al, 25 which demonstrated nuclear positivity in all 4 cases of classic PB of which 3/4 harbored a CTNNB1 PVs.…”