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Morphologic, Immunohistochemical, and Genetic Differences Between High-grade and Low-grade Fetal Adenocarcinomas of the Lung
- Source :
- The American Journal of Surgical Pathology
- Publication Year :
- 2021
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2021.
-
Abstract
- Supplemental Digital Content is available in the text.<br />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.
- 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
Subjects
Details
- ISSN :
- 01475185
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- American Journal of Surgical Pathology
- Accession number :
- edsair.doi.dedup.....9db4e75b524fa31dd23b6f3f8664e3bb