Multinodular Goiter in Children: an Important Pointer to a Germline DICER1 Mutation Rath SR 1,2 , Charles A 3 , Powers N 4 , Baynam G 2,5,6 , Jones T 1,2,7 , Priest J 8 , Foulkes WD 9 , Choong CSY 1,2 1. Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children; 2. School of Paediatrics and Child Health, University of Western Australia; 3. Department of Pathology, Princess Margaret Hospital for Children; 4. Department of Diagnostic Imaging, Princess Margaret Hospital for Children; 5. Genetic Services of Western Australia, Princess Margaret and King Edward Memorial Hospitals; 6. Institute for Immunology and Infectious Diseases, Murdoch University; 7. Telethon Institute for Child Health Research, Perth, WA; 8. Minneapolis, MN, USA; 9. Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, QC A 9 year old boy with history of cystic nephroma ex- cised at 20 months of age (Figure 1) presented with a neck swelling. Examination revealed a 30 mm x 30 mm firm, nontender mass in the left lobe of the thyroid. There were no associated compressive or obstructive findings and no cervical lymphadenopathy. Thyroid function and thyroid autoantibody titers were normal. Ultrasound demonstrated the thyroid gland replaced by cysts and nod- ules (Figure 1, Supplemental Figure 1). Fine needle aspi- ration of the dominant nodule was categorised as inde- terminate according to the Bethesda Thyroid Cytopathology Reporting System (1), however cytopatho- logical features favored a colloid nodule as part of a multi- nodular goitre (MNG)showing papillary hyperplasia (Supplemental Figure 2.). Twelve months earlier, the proband’s father had noted a similar neck swelling and MNG was diagnosed based on clinical and radiological findings (Supplemental Figure 3). FNA demonstrated a benign cytologic pattern consistent with colloid nodules. The deceased paternal grandfather had a verbally reported but unconfirmed history of thy- roidectomy. Neither the proband nor his father had thy- roid surgery, electing instead to undertake regular thyroid sonographic surveillance. Review of the proband’s chest CT scans (performed at 20 months of age), identified pulmonary cysts consistent with pleuropulmonary blastoma (PPB) type Ir. Notably, his father had been diagnosed with a lung cyst at age 13, following presentation with acute chest pain, likely also PPB type Ir (figure 2). Both individuals provided informed consent for insti- tutionally-approved genetic research and this case report. They were found to carry a novel germ line DICER1 mu- tation: c.5221 5232delAACAACACCATC. DICER1 syndrome is a recently described, highly pleio- tropic, variably penetrant, autosomal dominant tumor predisposition syndrome (2), caused by inactivating germ line DICER1 mutations (3). It is associated with rare can- cers and dysplasias, occurring typically from birth to age 20 years: most frequently PPB (4), CN, ovarian Sertoli- Leydig cell tumors and MNG (5). Thyroid disease (nod- ular hyperplasia, cysts, MNG) may emerge as the most frequent presentation of this syndrome. DICER1 is a cytoplasmic RNAse III endoribonuclease, producing mature microRNAs: small, noncoding RNAs that post-transcriptionally modulate messenger RNA (mRNA) expression and are critical in early somatic de- ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2014 by the Endocrine Society Received October 29, 2013. Accepted March 4, 2014. Abbreviations: Figure 1. A. Gross pathology of proband’s nephrectomy specimen: multiloculated cysts, effacing normal parenchyma (arrows) consistent with CN. CN is strongly associated with PPB and DICER1 mutations. B. Ultrasound of proband’s thyroid (left lobe), demonstrating multiple large cysts and nodules. doi: 10.1210/jc.2013-3932 J Clin Endocrinol Metab jcem.endojournals.org 1 The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 15 May 2014. at 20:17 For personal use only. No other uses without permission. . All rights reserved.