Wilms tumor, pleuropulmonary blastoma, and DICER1: case report and literature review
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Pleuroblastoma (PPB) is a rare pediatric tumor which, in 30% of cases, is associated with cystic nephroma. It has been recently linked to the DICER1 mutation as part of a predisposition syndrome for various tumors. However, if DICER 1 anomalies have been reported in patients with Wilms tumor (WT), to date, no cases of PPB, WT, and DICER1 mutations have been reported in the same patient.
We report the case of a 3-year-old patient, initially managed for metastatic WT. During his clinical course, the diagnosis of a PPB was made after detecting the DICER1 mutation and subsequent management was therefore modified.
This case highlights that in case of simultaneous discovery of a renal tumor and a pulmonary lesion in a child, the DICER 1 mutations should be looked for as these could help adapt management and schedule the surgical procedures.
KeywordsDICER 1 Pleuropulmonary blastoma Wilms tumor
Pleuropulmonary blastoma (PPB) is a rare pediatric tumor with around 500 cases reported . Its association with cystic nephroma is classically reported and occurs in 30% of patients . Moreover, it has been linked to the mutation of DICER1 as part of a predisposition syndrome for different types of tumors . Wilms tumor is another well-known pediatric tumor with an incidence of seven per one million cases per year . Predisposition genetic syndromes and multiple mutations associated with Wilms tumor have been reported including DICER 1 anomalies. However, to date, there have been no cases of PPB, WT, and DICER1 mutations in the same patient reported in the literature.
A left pleuro-pneumonectomy with intra-pericardic ligature of the vessels and without cardiac assistance was performed. The early postoperative course was uneventful. The pathologist confirmed the diagnosis of type 3 PPB with R0 resection. Postoperative chemotherapy consisted of eight courses (27 weeks) of vincristine, actinomycin, and doxorubicin. After 1-year follow-up, the patient remains asymptomatic and is considered to be in remission.
The association of DICER 1 mutations and PPB is reported in approximatively 66% of recorded cases . Among all patients with a PPB, 30% also presented with cystic nephromas . Moreover, WT can be associated with DICER1 mutations . However, our report is the first described case of WT, PPB, and DICER1 mutation.
Our experience underlines two aspects. First, in case of associated renal and pulmonary tumors, preoperative chemotherapy could help determine the nature of the renal lesion. In our case, the WT could be easily removed without preoperative treatment because of its anatomic localization, but we considered it as metastatic disease because of the lung tumor. The diagnosis of DICER1 mutation after the nephrectomy brought us to consider the possibility of two synchronous lesions. It would have been helpful to determine this earlier as it could have modified the surgical strategy. We could also have combined both procedures, but it seemed too difficult for the patient to cope with such an operation.
Secondly, DICER 1 mutations and WT have been reported in the genotype of tumor cells as in patients with PPB . However, this is the first reported case. It confirms that DICER1 is implicated in microRNA biosynthesis in nephrogenesis and that the loss of MIRNA processing enzymes can lead to an activation of progenitor cells from stem cells, as in WT1 mutation [3, 7].
Surgical decisions were linked to the evolution of the tumor after chemotherapy. The acute lung symptoms could have been due to necrosis of the tumor inducing massive pleural effusion or by rapid tumor growth. The emergency surgical procedure was meant more to improve the child’s breathing than to actually cure her, because we thought that local invasion would mean the tumor was not resectable. Surprisingly, complete excision of the PPB was possible despite what the preoperative workup suggested.
Finally, this case should help inform parents with PPB and DICER1 mutations that WT can also occur in these circumstances and that ultrasound scan should be performed more easily in these patients to avoid late diagnosis.
This yet unreported association highlights that in case of simultaneous discovery of a renal tumor and a pulmonary lesion in a child, DICER 1 mutation research could help adapt management and schedule surgery.
Many thanks to Dr. Luke Harper, from CHU of Bordeaux (France), for his correction of the English language.
All authors have participated in the making of the manuscript and the presented patient management. All authors have read and approved the final manuscript.
Ethics approval and consent to participate
Informed consent was properly documented by both the patient’s parents. Ethical approval by the local hospital ethical committee was given properly.
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