<p>Coexistence of Low-Grade Fetal Adenocarcinoma and Adenocarcinoma in situ of the Lung Harboring Different Genetic Mutations: A Case Report and Review of Literature</p>

Abstract

Low-grade fetal lung adenocarcinoma (L-FLAC) is an exceptionally rare pulmonary tumor, presenting with unclear histological and molecular features. In particular, the potential driver genes of L-FLAC remain elusive. To date, only five reports have documented genetic aberrations in L-FLAC. In the current study, we describe an unusual case of L-FLAC coexisting with adenocarcinoma in situ (AIS) of the lung, harboring different genetic mutations. A 39-year-old non-smoker female patient was referred to our hospital with the chief complaint of dyspnea for 20 days. Chest computed tomography (CT) revealed a-2.5×1.5×1.5 cm nodule in the right middle lobe, with no mediastinal lymph node enlargement or distant metastases. Thoracoscopic surgery was performed to remove the nodules. Histopathological analysis of the tissue sections, based on findings from immunohistochemical staining, confirmed a diagnosis of L-FLAC coexisting with AIS of the lung. Nextgeneration sequencing revealed L-FLAC-based mutations in DICER1 and CTNNB1, and AIS harboring KRAS mutations. Currently, the patient remains recurrence-free 17 months after the initial diagnosis. This report presents the first case demonstrating the coexistence of L-FLAC and AIS in the same pulmonary nodule, harboring different genetic mutations. Based on the literature review, this is the second reported case of L-FLAC bearing DICER1 mutations.

Morphologic, Immunohistochemical, and Genetic Differences Between High-grade and Low-grade Fetal Adenocarcinomas of the Lung

“…After a careful review, 12 articles with featured molecular findings 4 , 7 – 9 , 18 , 22 – 25 and/or detailed clinicopathologic, IHC description 4 , 7 , 17 – 20 were included and summarized in Tables 2 – 4 . Clinical features of 77 LG-FLAC and 97 HG-FLAC cases from the published studies and the current study were analyzed (Table 5 ).…”

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

“…25 In some studies, mutations in both DICER1 and CTNNB1 have been found in PB and L-FLAC. 26,27 In these two cases of PB, β-catenin was also mainly expressed in membrane and multifocal cytoplasmic/ nuclear localization. These cases further support the genetic abnormalities shared by L-FLAC and PB, and the mutation of DICER1 may be related to the abnormal expression…”

“…Both L‐FLAC and PB are closely related to CTNNB1 gene mutation 25 . In some studies, mutations in both DICER1 and CTNNB1 have been found in PB and L‐FLAC 26,27 . In these two cases of PB, β‐catenin was also mainly expressed in membrane and multifocal cytoplasmic/nuclear localization.…”

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

“…Therefore, the high prevalence of CTNNB1 mutation is a hallmark of L-FLAC and could serve as a diagnostic marker. Next generation sequencing for L-FLAC cases allowed the detection of DICER1 mutations [8, 10,11]. DICER1 encodes an RNase III family endoribonuclease that plays an essential role in microRNA production [16].…”