Childhood tumors of the lung are rare malignant tumors accounting for 0.5% to 1% of all primary malignant lung tumors. These tumors are subdivided into 3 subtypes: pulmonary blastoma, fetal adenocarcinoma, and pleuropulmonary blastoma (PPB). An epithelial malignant and immature component characterizes fetal adenocarcinoma. A malignant immature mesenchymal proliferation characterizes the pleuropulmonary blastoma. Biphasic components define the blastoma; a mesenchymal and an epithelial malignant and immature component, that look like a 10- to 16-week gestational lung. In the 2015 World Health Organization Classification, fetal adenocarcinoma belongs to the group of adenocarcinomas, pulmonary blastoma belongs to the group of sarcomatoid carcinoma, and pleuropulmonary blastoma belongs to the group of mesenchymal tumors. Pleuropulmonary blastomas are rare tumors which present non-specific symptoms. Although the importance of the radiologic features to suspect the diagnosis, the positive diagnosis remains based on the microscopic features. Many synonyms of pleuropulmonary tumors exist in the literature including:
Genetic forms have been identified in 40% of the cases. They are called the pleuropulmonary blastoma family tumor and dysplasia syndrome or DICER1 syndrome. Patients suffer from neoplastic and dysplastic disease in the first 5 to 6 years of life with rare cases in adolescence. Germline loss-of-function mutations in DICER 1 have been identified in some families with loss of DICER 1 staining in epithelial cells. Most mutation carriers are unaffected. Genetic forms can be suspected when dealing with patients presenting varying symptoms in association with respiratory symptoms such as irregular menstrual cycles or other symptoms related to sex hormone secretion.
Pleuropulmonary blastomas are mainly diagnosed before 4 years of age. They are divided into:
One of the case series by Vargas et al. found that on cytogenetic analysis, polysomy of chromosome 8 is a constant feature of pleuropulmonary blastoma. In addition, the clonal proliferation in pleuropulmonary blastoma is mainly due to the multiplication of malignant mesenchymal elements, while epithelial components are mostly non-neoplastic.
PPB occurs not only in the lung, but it can also arise from mediastinum, diaphragm and/or pleura. This has led to the possibility that PPB may arise from the splanchnopleural or somatopleural mesoderm. Common metastatic sites include the brain, liver, bone, lymph nodes, kidney, pancreas and adrenal glands.
Gross findings vary according to the types of pleuropulmonary blastomas:
Microscopic findings vary according to the different subtypes:
Morphologic features are mandatory to make the diagnosis, but the immunohistochemical study may be helpful in highlighting the diagnosis. Immunohistochemical studies show the reactivity of the tumor cells to vimentin and the reactivity of rhabdomyoblastic cells with the desmin antibody. Morphologically, Type II is similar to Wilms tumor and therefore, it is sometimes called as “extra-renal Wilms tumor”.
Signs and symptoms vary according to the different subtypes:
Asymptomatic lesions revealed by a chest wall deformity or a tension pneumothorax have also been reported.
Typically, pleuropulmonary blastomas involve the lung and the pleura. The CT-scan shoes either a mass or a consolidation. There may also be multiloculated cystic or solid changes. Fifty percent to 60% of type I lesions are limited to the lungs. Spread beyond the lung is more common in type II and III lesions.
PPB appears to have a constitutional and heritable predisposition to other dysplastic or neoplastic diseases in approximately 25% of the patients. Associated conditions include medulloblastoma, thyroid neoplasia, malignant germ cell tumor and others. Thus, all patients with pleuropulmonary blastomas and their families should be evaluated carefully.
Patients with type I tumors are treated with surgical resection to diagnose the lesion and to treat it. Some authors advocate adjuvant chemotherapy, but there is no consensus. Radiation therapy is not used for type I PPB. If type I pleuropulmonary blastoma recurs in a child as type II or type III PPB, then the treatment options for types II and III disease are used.
Type II and III PPB are both aggressive tumors. For patients with types II and III lesions, surgical resection is recommended if feasible, followed by chemotherapy and/or radiation therapy. Intracavitary chemotherapy has been reported in the literature. There is a benefit of doxorubicin-based regimes. Recurrence is often local.
Radiation therapy can be used on individual basis in PPB patients. In general, if there is a small part of tumor that cannot be removed surgically and is resistant to chemotherapy, then radiation can be considered. Pleuropulmonary blastomas can widely metastasize. When PPB spreads to the brain, surgery followed by radiation therapy is often advised. For recurrent tumors, we recommend high-dose consolidation therapy with autologous stem cell rescue.
The major differential diagnoses are represented by synovial sarcoma, congenital cystic adenomatoid malformations, and fetal lung interstitial tumor.
There is no consensual staging system for pleuropulmonary blastomas. Recommendations are to perform chest and abdominal CT-scan in type I tumors and chest and abdominal CT-scan with head MRI and bone scan in type II and III tumors.
Patients with type I tumors have 80% to 90% 5-year, disease-free survival. Patients with types II and III tumors present a 5-year, disease-free survival inferior to 50%.
Many authors reported gains in chromosome 8, especially trisomy with losses in chromosomes 9 and 11. The DICER1 gene is located on chromosome 14q. Patients with pleuropulmonary blastomas should undergo surveillance in relation to the possibility of the appearance of other tumors. Surveillance of siblings or family members is more controversial due to the need to balance the modest risk of tumor development against the possibility of caused anxiety.
In addition to pleuropulmonary blastoma, DICER1 syndrome can be associated with other tumors such as ovarian tumors including Sertoli-Leydig cell tumors, multinodular goiter, or thyroid carcinomas. The association to these tumors can make the symptoms and signs more challenging and unspecific. Thinking about such a syndrome is mandatory when dealing with a patient presenting respiratory symptoms and other hormonal or extrapulmonary symptoms.
Pleuropulmonary blastomas are very rare tumors in young children. They have a diverse presentation and are best managed by an interprofessional team including oncology nurses. Surgery is the treatment of choice but recent reports suggest chemotherapy. Without any guidelines, each case is managed according to personal experience and available facilities
For patients with types II and III lesions, surgical resection is recommended if feasible, followed by chemotherapy and/or radiation therapy. Intracavitary chemotherapy has been reported in the literature. There is a benefit of doxorubicin-based regimes. Recurrence is often local. Pleuropulmonary blastomas can widely metastasize. For recurrent tumors, we recommend high-dose consolidation therapy with autologous stem cell rescue.
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