A familial case of DICER1 syndrome in a patient with pleuropulmonary blastoma

Pleuropulmonary blastoma (PPB) is a very rare tumor of childhood that arises from the mesenchyme of the lung and is associated with mutations in the DICER1 gene. The present article describes a familial case of DICER1 syndrome in a patient aged 3 years and 11 months who underwent investigations and treatment for type II/III PPB of the lower lobe of the left lung at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications. The diagnosis was made based on the results of the pathology investigation of the tissue obtained by open biopsy. Furthermore, the diagnosis was confirmed by the review of histological specimens in the International PPB Registry (Minneapolis, USA). According to the data from the chest CT with intravenous contrast enhancement, the tumor was described as a mass consisting of cystic cavities of various calibers accumulating a contrast agent along the periphery, and a solid component. Specific combination treatment was based on the recommendations of the International PPB Registry and included chemotherapy according to the IVADo/IVA regimen and surgical treatment as a local control. Currently, specific treatment has been completed, the patient is alive with no signs of the disease, the follow-up period was 20 months. As regards the patient's family history, he has a sibling (older brother) who was diagnosed with a cystic nephroma at the age of 1 year and 4 months. Molecular genetic testing of the tumor tissues obtained from the patient (PPB) and his sibling (cystic nephroma) revealed pathogenic somatic variants in the DICER1 gene. Along with the somatic genetic variants, another pathogenic variant was found in both children, the germline status of which was confirmed. The germline variant in the DICER1 gene was inherited from the mother. Thus, the investigations confirmed a familial case of DICER1 syndrome. The case described in this article indicates that families in which DICER1 syndrome was found require special management aimed at early detection of tumors and non-tumor conditions associated with this syndrome in the carriers of pathogenic alleles.