Comprehensive review of fetal adenocarcinoma of the lung

Abstract

Fetal adenocarcinoma of the lung (FLAC) is a rare tumor. It accounts for ~0.1%–0.5% of all pulmonary neoplasms. Due to its rarity, much of the world literature regarding FLAC comes from case reports and case series. FLAC is an adenocarcinoma resembling developing fetal lung in its pseudoglandular stage (8–16 weeks of gestation). It is distinguishable from pulmonary blastoma (PB) because it lacks the mesenchymal component which is a hallmark finding in PB. Due to differences in histopathology and clinical course, FLAC has been further categorized into low-grade (L-FLAC) and high-grade (H-FLAC) forms. L-FLAC displays low nuclear atypia and prominent morule formation and has a pure pattern. H-FLAC typically presents with at least 50% fetal morphology, and is often associated with other conventional types of lung adenocarcinoma. FLAC expresses neuroendocrine markers and thyroid transcription factor 1 in most cases. L-FLAC has an aberrant nuclear/cytoplasmic expression of β-catenin and presents mutations in this gene. H-FLAC overexpresses p53. These tumors have a very low frequency of mutations in KRAS and EGFR; it is thought that they are different from a molecular point of view to conventional lung adenocarcinomas. Approximately 25%–40% of patients are asymptomatic at presentation; most of them are incidental findings on chest radiographs. H-FLAC is more common in elderly male patients, with a heavy smoking history. L-FLAC tends to occur in young females. Patients with L-FLAC are usually diagnosed with stage I–II disease, while patients with H-FLAC usually present with a more advanced-stage disease. Poor prognostic factors for FLAC are thoracic lymphadenopathy, metastases at diagnosis, and tumor recurrence; however, the 10-year survival for FLAC is estimated at 75%.

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

“…Aberrant β-catenin nuclear/cytoplasmic staining pattern has been considered as a hallmark of LG-FLAC. 1 , 7 Another valuable IHC marker is p53, which is expressed strongly in HG-FLAC, but is nearly absent in LG-FLAC. It had been shown that ~80% of HG-FLACs display IHC evidence of neuroendocrine differentiation.…”

“…Fetal adenocarcinoma of the lung (FLAC) is a rare malignant lung tumor, accounting for 0.1% to 0.5% of all pulmonary neoplasms. 1 It was reported as a subtype of pleuropulmonary blastoma lacking a sarcomatous component in 1982, 2 and the term “well differentiated fetal adenocarcinoma of the lung” was introduced afterwards. 3 As the name implies, FLAC morphologically resembles a developing fetal lung during the pseudoglandular phase: complex glandular components with tubules are lined by glycogen-rich, nonciliated cells.…”

<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>

“…2 The two FLAC subtypes, L-FLAC and H-FLAC, differ in multiple aspects, including histopathology and clinical characteristics. 5 L-FLAC is commonly detected in female patients in the third-fourth decade of their lives. Typically, the initial diagnosis of L-FLAC occurs during the early stages (I-II).…”

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

“…Due to their different clinicopathological features, biological behavior and clinical outcome, FLACs are classified into low‐grade fetal adenocarcinoma (L‐FLAC) and high‐grade fetal adenocarcinoma (H‐FLAC) 2,3 . It has been reported that the incidence of FLAC in all pulmonary neoplasms accounts for an estimated 0.1% –0.5% 4,5 . One study recently revealed that the prevalence of L‐FLAC and H‐FLAC was 0.32% and 0.54% in Chinese patients, respectively 6 …”

“…2 , 3 It has been reported that the incidence of FLAC in all pulmonary neoplasms accounts for an estimated 0.1% –0.5%. 4 , 5 One study recently revealed that the prevalence of L‐FLAC and H‐FLAC was 0.32% and 0.54% in Chinese patients, respectively. 6 …”