1. Morphologic, Immunohistochemical, and Genetic Differences Between High-grade and Low-grade Fetal Adenocarcinomas of the Lung
- Author
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Xiao-yan Wu, Xin-hua Yang, Fang Wang, Shao-yan Xi, Yue Li, and Juan-juan Yong
- Subjects
Adult ,Male ,Ribonuclease III ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Adolescent ,mutational profile ,DNA Mutational Analysis ,CTNNB1 DICER1 ,Adenocarcinoma of Lung ,Biology ,medicine.disease_cause ,Pathology and Forensic Medicine ,DEAD-box RNA Helicases ,Young Adult ,Predictive Value of Tests ,MYCN ,Biomarkers, Tumor ,medicine ,Humans ,Child ,beta Catenin ,Aged ,Retrospective Studies ,Aged, 80 and over ,N-Myc Proto-Oncogene Protein ,Fetus ,Mutation ,Lung ,Fetal adenocarcinoma ,High-Throughput Nucleotide Sequencing ,Original Articles ,Middle Aged ,medicine.disease ,Immunohistochemistry ,fetal adenocarcinoma of the lung ,Staining ,medicine.anatomical_structure ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Adenocarcinoma ,Female ,Surgery ,Neoplasm Grading ,Anatomy - Abstract
Supplemental Digital Content is available in the text., Fetal adenocarcinoma of the lung (FLAC) is a rare lung tumor classified into low-grade fetal adenocarcinoma of the lung (LG-FLAC) and high-grade fetal adenocarcinoma of the lung (HG-FLAC). It remains debatable whether HG-FLAC is a subset of FLAC or a distinct subtype of the conventional lung adenocarcinoma (CLA). In this study, samples of 4 LG-FLAC and 2 HG-FLAC cases were examined, and the clinicopathologic, immunohistochemical (IHC), and mutational differences between the 2 subtypes were analyzed using literature review. Morphologically, LG-FLACs had a pure pattern with complex glandular architecture composed of cells with subnuclear and supranuclear vacuoles, mimicking a developing fetal lung. In contrast, HG-FLACs contained both fetal lung-like (FLL) and CLA components. With regard to IHC markers, β-catenin exhibited a nuclear/cytoplasmic staining pattern in LG-FLACs but a membranous staining pattern in HG-FLACs. Furthermore, p53 was expressed diffusely and strongly in HG-FLACs, whereas in LG-FLACs, p53 staining was completely absent. Using next-generation sequencing targeting a 1021-gene panel, mutations of CTNNB1 and DICER1 were detected in all 4 LG-FLAC samples, and a novel mutation, MYCN P44L, was discovered in 2 LG-FLAC samples. DNA samples of the FLL and CLA components of HG-FLACs were separately extracted and sequenced. The FLL component harbored no CTNNB1, DICER1, or MYCN mutations; moreover, the FLL genetic profile largely overlapped with that of the CLA component. The morphologic, IHC, and genetic features of HG-FLAC indicate that it is a variant of CLA rather than a subset of FLAC. Thus, HG-FLAC should be treated differently from LG-FLAC.
- Published
- 2021