Received: 20 March 2017 Revised: 13 June 2017 Accepted: 14 June 2017 DOI: 10.1002/pbc.26715 Pediatric Blood & Cancer The American Society of Pediatric Hematology/Oncology BRIEF REPORT A case of neuroblastoma in DICER1 syndrome: Chance finding or noncanonical causation? Avi Saskin 1,2,3 Leanne de Kock 2,3 Nelly Sabbaghian 2 Maria Apellaniz-Ruiz 2,3 Ceyhun Bozkurt 4 Dorothée Bouron-Dal Soglio 5 William D. Foulkes 1,2,3,6 1 Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada 2 Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montréal, Québec, Canada 3 Department of Human Genetics, McGill University, Montréal, Québec, Canada 4 Department of Paediatric Oncology, Dr. Sami Ulus Children’s Hospital, Ankara, Turkey 5 Department of Pathology, CHU-Sainte Justine and University of Montreal, Montréal, Québec, Canada 6 Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, Québec, Canada Correspondence William D. Foulkes, Lady Davis Institute, Segal Cancer Centre Room E757, Jewish General Hospital, 3755 Côte-Sainte-Catherine Road, Montreal, QC H3T 1E2, Canada. Email: william.foulkes@mcgill.ca Grant sponsor: C17 and Childhood Cancer Canada Foundation; Grant sponsor: Vanier Canada Graduate Scholarship. Abstract DICER1 syndrome is an inherited disorder associated with at least a dozen rare, mainly pediatric- onset tumors. Its characterization remains incomplete. Some studies suggested that neuroblas- toma (NB) may be involved in this syndrome. Here, we describe the case of a 14-year-old female presenting with a multinodular goiter (MNG) and a collision tumor composed of NB and cystic nephroma (CN). She is a carrier of a deleterious germline mutation in exon 23 of DICER1 and har- bored different somatic mutations in the CN and MNG. However, no second hit was found in the NB, questioning its status as a DICER1-related tumor. KEYWORDS cystic nephroma, DICER1, multinodular goiter, mutation, neuroblastoma, syndrome 1 INTRODUCTION DICER1, a highly conserved RNase endoribonuclease, is an essential enzyme involved in the biogenesis of microRNA and siRNA through the cleavage of precursor double-stranded RNAs. Its important role in human physiology is highlighted by the DICER1 syndrome (Online Mendelian Inheritance in Man [OMIM] #601200), characterized by the occurrence of rare tumors, both benign and malignant in nature, typ- ically presenting before the age of 30 years. Given the rarity of the associated tumors and the variable penetrance, the molecular etiol- ogy underlying the condition was only recently elucidated. The wide spectrum of tumors that can arise in the DICER1 syndrome include pleuropulmonary blastoma, cystic nephroma (CN), nasal chondromes- enchymal hamartoma, ovarian Sertoli–Leydig cell tumors, botryoid embryonal rhabdomyosarcoma of the uterine cervix, ciliary body medulloepithelioma, pineoblastoma, pituitary blastoma, and nodular thyroid hyperplasia, often resulting in multinodular goiter (MNG) and Abbreviations: CN, cystic nephroma; ER, estrogen receptor; LOH, loss of heterozygosity; MNG, multinodular goitre sometimes leading to thyroid carcinoma. 1 Additionally, there are other tumors that through small patient series studies, somatic tumor anal- ysis, and studies of tumor cell lines show evidence of possible asso- ciation with the DICER1 syndrome. 1 One of these tumors is neurob- lastoma (NB). 2–5 Here, we present germline and somatic analysis of DICER1 in three primary tumors—MNG, CN, and NB—occurring in a young female of Turkish descent. The CN and NB were previously pub- lished by Bozkurt et al., without DICER1 mutation data. 6 She also has a brother with a CN, which was not mentioned in the original report. 2 CASE REPORT At the age of 14 months (Fig. 1A), a previously healthy female was admitted for investigations secondary to a right upper quadrant mass. Imaging of the abdomen revealed a right renal mass with 24-hr urine collection revealing elevated vanilylmandelic acid and homovaninilic acid, consistent with an NB. Right radical nephrectomy was performed with the final pathological diagnosis being a well-differentiated col- lision tumor composed of an NB and a CN (Fig. 2, A and B). 6 No Pediatr Blood Cancer. 2017;e26715. c  2017 Wiley Periodicals, Inc. 1 of 4 wileyonlinelibrary.com/journal/pbc https://doi.org/10.1002/pbc.26715