PB is an extremely rare malignant tumor, which often occurs with distant metastasis and recurrence. The prognosis of patients is poor, which is related to the TNM stage, bidirectional histological type, and recurrence(Shastri and Kundu, 2023). The incidence of metastasis was highest within 2 years of initial treatment. In 1945, Barnett and Barnard first described PB and referred to it as "embryonoma". The pathogenesis of PB is currently unknown, and the origin of the biphasic cell population remains elusive, possibly related to P53 gene mutation and overexpression. The mutation of p53 gene includes the benzopyrene gene associated with smoking, which indirectly indicates that p53 mutation may be one of the molecular biological mechanisms of PB induced by smoking(Nemeh et al., 2017). The clinical symptoms and imaging findings are similar to non-small cell lung cancer, and it is extremely easy to be misdiagnosed clinically. Generally, PB occurs relatively young and is usually a single lesion, with hilar and mediastinal lymph node metastases less common. At present, the treatment of PB is mainly surgical resection. Lobectomy and lymph node dissection are usually performed as routine procedures. Chemoradiotherapy or not, which option is still inconclusive. Some scholars believe that postoperative radiotherapy does not improve the survival rate, but radiotherapy is feasible if there is lymph node metastasis or surrounding tissue invasion. Some studies suggest that patients with early PB do not benefit from postoperative chemotherapy(Kawasaki et al., 2014;Magistrelli et al., 2014;Sakata et al., 2015;Xie et al., 2023). Our study showed that postoperative use of docetaxel and cisplatin could effectively treat PB recurrence and prolong the patient’s survival time. Therefore, establishing clinical diagnosis and treatment guidelines for PB through multi-center collaboration has important scientific value.
The 5th WHO classification of thoracic tumors proposes that PB is a distinct form of lung sarcomatoid carcinoma. The most common general presentation is a nodular mass, 1 to 20cm in diameter, with clear tumor boundaries, no envelope, grayish-brown sections, and necrotic and bleeding areas. Microscopically, the epithelial components are similar to that of the 11-18-week fetal lung, with branched or back-to-back glandular hyperplasia, columnar cells, less cytoplasm, small, uniform, round to oval nuclei, and less atypia. Morula bodies may be found in 40% of cases(Tsamis et al., 2021). Mesenchymal differentiation components consist of primitive oval or spindle cells. Allogenic differentiation, including skeletal muscle, bone, and cartilage, was observed in 25% of cases. Nuclear polymorphism and nuclear fissions are occasionally seen. Adenocarcinoma or poorly differentiated carcinoma areas can also be observed in 30–50% of patients (Bu et al., 2020;Jain et al., 2020).
Due to the complex tissue composition of PB, preoperative pathological diagnosis is very difficult, and puncture specimens are easily misdiagnosed(Xiu et al., 2015). In cytology, there is dimorphism of epithelial cells and mesenchymal cells, and the proportion of the two compartments is different in different cases, which has a certain correlation with the prognosis of patients(Shalini et al., 2009). Immunohistochemical staining is helpful for the pathological diagnosis and differential diagnosis of PB. Tumor cells in the epithelial component were positive for keratin staining (e.g., CAM5.2, CK). EMA and TTF-1 were also positive. Neuroendocrine cells were scattered throughout the tumor, expressing CD56, Syn, or CgA. β-catenin staining of glands and morula bodies was nucleo-positive. Vimentin staining of mesenchymal differentiation components was positive, and other more specific markers may be displayed in heterodifferentiated regions.
CTNNB1 exon 3 missense mutation is often present in PB, which leads to activation of Wnt pathway through abnormal nuclear localization of β-catenin protein. TP53 mutations can also occur. Mutations in ROS1 and EGFR may co-occur with mutations in CTNNB1. DICER1 and CTNNB1 mutations are present in some cases of PB, which may have a potential genetic link to pleuropulmonary blastoma in children(Xiu et al., 2015;de Kock et al., 2016;Zhao et al., 2016). Our results showed that PB in this case had gene mutations of BRCA2 and MET. If necessary, drugs targeting these sequences may be considered in drug selection. Pathologically, PB needs to be distinguished from fetal lung adenocarcinoma, pleuropulmonary blastoma, bidirectional synovial sarcoma, and certain metastatic tumors (especially malignant mixed Miller tumors of female reproductive origin). Fetal adenocarcinoma lacks the mesenchymal embryonic cell component. Bidirectional synovial sarcoma lacks the features of fetal lung adenocarcinoma. Pleuropulmonary blastoma often occurs in children and can form a sac lined with normal respiratory epithelium(Pavlos et al., 2014;Jenkins et al., 2018).