Pulmonary adenocarcinoma with high-grade fetal adenocarcinoma component has a poor prognosis, comparable to that of micropapillary adenocarcinoma

Abstract

Fetal adenocarcinoma is a rare variant of lung adenocarcinoma, which is subcategorized into low-grade and high-grade forms. High-grade fetal adenocarcinoma confers worse prognosis than low-grade fetal adenocarcinoma, but the prognostic differences between high-grade fetal adenocarcinoma and conventional lung adenocarcinoma are unknown. We reviewed tissue sections of 3719 cases of surgically resected primary lung cancers and found 53 lung cancers with a high-grade fetal adenocarcinoma component. We analyzed their clinicopathological and immunohistochemical features, and performed a prognostic analysis of adenocarcinomas with the fetal-type component. We further analyzed the prognostic differences between adenocarcinomas with the fetal-type component and conventional adenocarcinomas without the fetal-type component. Lung cancers with the fetal-type component predominantly occurred in elderly men with a smoking history. Twenty-nine patients had stage I disease, 13 patients had stage II, and 11 patients had stage III. The fetal-type histology was combined with conventional-type adenocarcinoma (41 cases), squamous cell carcinoma (5 cases), large cell neuroendocrine carcinoma (5 cases), enteric adenocarcinoma (2 cases), and small cell carcinoma (1 case). The fetal-type component showed immunopositivity for α-fetoprotein (39%), glypican-3 (37%), and SALL4 (17%). The 5-year overall survivals of fetal-type-predominant and fetal-type-nonpredominant patients were 44 and 56%, respectively (P = 0.962). The 5-year overall survivals of lepidic-, acinar-, papillary-, solid-, and micropapillary-predominant adenocarcinomas, invasive mucinous adenocarcinomas, and adenocarcinomas with the fetal-type component were 94, 82, 77, 69, 57, 83, and 41%, respectively (P < 0.001). Univariate and multivariate analyses showed that adenocarcinomas with the fetal-type component had a significantly lower overall survival rate than the other histological subtypes, except for the micropapillary-predominant subtype. Our study demonstrated that adenocarcinomas with the fetal-type component had a poor prognosis that was comparable to that of micropapillary adenocarcinoma. The presence of the high-grade fetal adenocarcinoma component in lung adenocarcinomas is an important prognostic marker.

<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>

“…However, H-FLAC, generally displays fetal morphology (over 50%), together with other common types of lung adenocarcinomas. 8 Moreover, H-FLAC commonly demonstrates prominent nuclear atypia and nucleoli, accompanied by necrosis and a high frequency of mitosis. In the current case, no prominent nuclear atypia, necrosis, or a direct transition to conventional adenocarcinoma was observed.…”

Pulmonary high‐grade fetal adenocarcinoma associated with cystic airspace: A case report

“…Although cigarette smoke genetically contributes to dysregulation of cell‐cycle and tumor progression, distinctive molecular features of the pure form remain to be investigated . A recent study suggested a high‐grade fetal adenocarcinoma component (≥5%) in lung adenocarcinomas is significantly associated with a poor prognosis . All six patients with pure high‐grade fetal adenocarcinomas had stage IIB–IV disease after surgery, most experiencing recurrence within two years; however, post‐surgically, the present case was of the lowest level, stage IA.…”

“…Immunohistochemically, the fetal component is often positive for oncofetal and neuroendocrine markers. High‐grade fetal adenocarcinoma is defined as a diagnosis when >50% fetal morphology is present according to the 2015 World Health Organization classification . Furthermore, high‐grade fetal adenocarcinomas consist of pure (entirely fetal morphology) or mixed forms.…”

“…High‐grade fetal adenocarcinomas represent aggressive biological behavior . Although cigarette smoke genetically contributes to dysregulation of cell‐cycle and tumor progression, distinctive molecular features of the pure form remain to be investigated .…”

“…Previous CT images were unavailable; however, the cystic airspaces may have preceded the cancer, given a history of bullous emphysema. A total of 10 patients (19%) with high‐grade fetal adenocarcinoma showed severe pulmonary emphysematous changes . As solid components increase with time, cystic airspaces (eg, emphysematous bullae) may gradually decrease in size, finally giving way to a completely solid lesion.…”