Novel genetic characteristics in low‐grade fetal adenocarcinoma of the lung

Abstract

Background Low‐grade fetal adenocarcinoma of the lung (L‐FLAC) is a rare subtype of lung adenocarcinoma with undetermined histological features and genetic abnormalities. In this study, we attempted to investigate the pathological characteristics and genomic profiles of L‐FLAC. Methods Among 9839 cases of primary lung adenocarcinoma resected at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2011 and June 2016, three cases diagnosed with L‐FLAC were selected. An immunohistochemical profile and whole exome sequencing (WES) using tumor and normal tissues was conducted. The last follow‐up date of patients was January 2021. Results Three cases diagnosed with L‐FLAC were finally screened, suggesting a percentage of 0.03%. All three patients were male and diagnosed as stage I following radical lobectomy. The missense variant was found to be the major gene mutation type using WES. CTNNB1 and DICER1 were the two most frequent gene mutations. All cases demonstrated positive TTF‐1 expression. In addition, two patients showed positive expression of β‐catenin (nuclear/cytoplasmic expression), CgA and Sny. Negative expression of PD‐L1 in tumor cells was observed in all three cases. One case with a relatively high tumor mutation burden (TMB) (2.18 mut/Mb) had an inferior overall survival of 11.5 months. However, the other two cases with a lower TMB (0.12 and 0.74 mut/Mb) still acquired disease‐free status up to the last follow‐up date. Conclusions L‐FLAC has a specific molecular background which is different from lung adenocarcinoma. Furthermore, gene heterogeneity was found and might be the reason for a dramatically different prognosis in these L‐FLAC patients.

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

“…Studies reporting the clinicopathological characteristics of lowgrade fetal lung adenocarcinoma with genetic analyses are summarized in Table 1. [6][7][8][9][10][11][12] To date, 21 low-grade fetal lung adenocarcinomas, including the two in our study, have been reported. All showed β-catenin nuclear/ cytoplasmic staining.…”

“…17 DICER1 mutations have been observed in different types of tumors and could contribute to the development of various cancers. 12 To the best of our knowledge, nine low-grade fetal lung adenocarcinoma cases, including one of our two cases, have been reported to carry DICER1 mutations (Table 1). Among the data we reviewed, only 1 case has been reported to represent familial DICER syndrome.…”

Cytomorphology of pulmonary low‐grade fetal adenocarcinoma in bronchial brushing specimen prepared by BD SurePath: A case report and literature review

“…The characteristic histopathological features includes branch forming tubular glands lined by non‐ciliated columnar cells with a bland cytology and prominent morule formation. LGFA has a specific molecular background which is different from conventional adenocarcinoma 1,2,8 . LGFA has an aberrant nuclear/cytoplasmic expression of β‐catenin and presents mutations in this gene.…”

“…Fetal adenocarcinoma of the lung is extremely rare, accounting for only 0.1%–0.5% of all lung neoplasms 1,2 . It features a morphology resembling the fetal lung during the pseudoglandular stage (8–16 weeks of gestation) 3 .…”

High Frequency of CTNNB1 Mutation in Low Grade Fetal Adenocarcinoma of the Lung: Two Case Series and Literature Review

“…Germline inactivation of DICER1 is associated with familial DICER1 syndrome [17]. DICER1 mutation has been observed in different kinds of tumors and could contribute to the development of various cancers [12].…”