Pulmonary blastoma (PB) comprises a rare heterogeneous group of lung tumours typically containing immature epithelial and mesenchymal structures that imitate the embryonic lung tissue resembling fetal lung of gestational age 10–15 weeks. PB accounts for 0.25–0.5% of all primary pulmonary malignancies. Based on the predominant tissue components, PB is divided into three subtypes:
Well-differentiated fetal adenocarcinoma (WDFA), known as the monophasic pulmonary blastoma, consisting of epithelial component exclusively.
Classic biphasic pulmonary blastoma (CBPB), comprising both epithelial and mesenchymal components, which is the most common subtype and currently considered as part of the spectrum of sarcomatoid carcinomas.
Pleuropulmonary blastoma (PPB), characterized by the presence of mesenchymal components only .
Historically, the term pulmonary blastoma (PB) had included both pure fetal adenocarcinomas, pleuropulmonary blastomas as well as the classic biphasic blastomas. However recent WHO re-classifications separated well-differentiated fetal adenocarcinomas (WDFA) and pleuropulmonary blastomas (PPB) from the biphasic tumours (CBPB). Given the small number of cases and recent classification changes, interpreting the published clinical features and epidemiology of PB is challenging .
PB consists of an epithelial and mesenchymal stroma, where foci of chondrosarcoma, rabdomiosarcoma, osteosarcoma and yolk sac might also be found. Molecular studies indicate that epithelial and mesenchymal components may derive from a single precursor cell. Mutations in various genes (e.g., TP53, EGFR, CTNNB1) may be identified in some pulmonary blastomas . Tumour specimens usually comprise areas of haemorrhage and necrosis, although translucent cytoplasm, tubular glandular cells and hyponuclear vacuoles might be demonstrated. The epithelial component of PB is composed mainly of tubules formed by non-ciliated glycogen-rich cells that mimic the pseudo-glandular stage of fetal lung development and typically does not express cytokeratins . Different immunohistochemical staining methods in PB were studied by Larsen et al. The highest stain sensitivity was found with muscle actin (92%), vimentin (90%), neuron-specific enolase (NSE—83%), α-fetoprotein (AFP—82%), carcinoembryonic antigen (CEA—77%) and epithelial membrane antigen (EMA—71%) .
The aetiology of PB remains unknown, however over 80% of cases are associated with a history of smoking. Abnormalities in laboratory tests are usually non-specific and rare. No specific tumour markers for PB have been found yet. Some reports presented elevated AFP and CEA serum levels .
The most frequent PB symptoms include cough, haemoptysis, chest pain, dyspnoea and fever of unknown origin, although 40% of cases remain asymptomatic and are revealed during incidental chest X-rays. In the vast majority of cases, the tumour is one-sided, with a higher prevalence in superior lobes. The mean tumour diameter at the time of primary diagnosis is 7–10 cm. Typically radiological images show well-circumferenced mass displacing the mediastinum while CT-scans reveal dense and vesical elements with varying contrast uptake. Endobronchial growth is present in approximately ¼ of cases and even rarely pleura invasion is present. Differential diagnosis should include benign lesions such as pleural fibroma or hamartoma as well as other malignancies (primary lung cancers, metastases) [3, 8]. PB symptoms may occur at any age, but 80% of cases are diagnosed in adults, usually in the fourth decade of life and shows a strong female predominance, which is thought to be caused by the influence of estrogen through its receptors overactivated by β-catenin .
Diagnosis is made with transbronchial biopsy but obtaining the representative tissue sample is possible only in approximately 25% of cases because of the PB peripheral nature. Surgery is the preferred method of treatment as pulmonary blastoma typically is a well-demarcated peripheral mass. The range of surgery should be determined individually and depends on the tumour size, pleural invasion, lymph node metastasis and comorbidities. The average survival rate among operated patients is 33 months, as compared to 2 months’ survival in non-operated patients. Limited lobectomies are associated with better survival rates than pneumonectomies, probably due to primary reduced tumour burden .
Larsen et al. reported a 16% response rate to chemotherapy in PB. So far, neither of the agents is more effective than another, although cisplatin is found in most treatment regimens, as it has been proved to improve prognosis in other germ cell tumours . The selection of the most effective chemotherapeutics remains a major problem as the PB often presents biphasic structure with both epithelial and mesenchymal components, sensitive to different lines of treatment .
Overall PB prognosis is poor, the 2-year survival rate is 34%, and the 5-year survival rate is 16%, respectively. Overall prognosis depends primarily on the tumour size and distant organs involvement. Biphasic type of tumour (CBPB), metastatic disease at the time of diagnosis, tumour size exceeding 5 cm, early relapse (within 12 months after treatment) and lymph node involvement contribute to the unfavourable prognosis. At the time of diagnosis distant metastasis is present in 43% of patients and mainly concerns the brain, pleura, mediastinum, diaphragm and liver [12, 13].
Cancer in pregnancy is an increasingly common phenomenon faced by oncologist. This is a consequence of postponed motherhood until a later age and high rates of malignant tumors in the group of young women. Recent studies revealed the lack of knowledge among medical personnel and concerns about possible fetal damage caused by diagnostic radiology. Due to the possibilities of modern diagnostic equipment, also cancer radiological diagnosis in the first trimester of pregnancy is not contraindicated. According to Pereg et al. , performing radiological diagnostic procedures involving fetal exposure to ionizing radiation doses lower than 0.1 or even 0.2 Gy (10–20 cGy) does not increase the risk of congenital defects. The risk of birth defects decreases with increasing gestational age. Minimizing the effects caused by ionizing radiation by further reducing the dose and the residence time, increasing patient’s distance from the radiation source as well as using a thicker shield and a less active radiation source allow the use of radiological imaging methods regardless of the stage of pregnancy [14, 15].
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