DICER1 Syndrome in Twins With Ovarian Sertoli-Leydig Cell Tumor and Papillary Thyroid Carcinoma

DICER1 syndrome is a rare autosomal dominant syndrome resulting in benign and malignant tumors in various organs with tumors in endocrine organs (pituitary, thyroid, adrenal, ovaries, and pancreas). Here we present a rare case of 18-year-old twin sisters with DICER1 syndrome who presented at the age of 15 years with hirsutism, deepening of the voice, and amenorrhea. They were diagnosed with a Sertoli-Leydig cell tumor of the ovary and underwent unilateral oophorectomy, with no evidence of recurrence or metastasis during follow-up. Genetic analysis showed the same germline DICER1 mutation in both cases. They also had large multinodular goiters (nodule size ranging from 1.0 to 2.3 cm) nodules were increasing in size. Fine needle aspiration cytology (FNAC) of thyroid nodules for both the sisters showed atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), and they both underwent total thyroidectomy revealing papillary thyroid carcinoma. No pituitary lesion was observed in the brain magnetic resonance imaging (MRI) of either of them. A chest CT scan showed bilateral sub-pleural benign-looking nodules in both patients. The twin sisters developed some features, such as Sertoli-Leydig cell tumor, multinodular goiter, and papillary thyroid carcinoma, and had positive genetic tests for DICER1 germline mutation. The father and paternal grandfather had a family history of papillary thyroid carcinoma. Both patients require active surveillance due to the increased risk of developing tumors in multiple organs associated with this disease.

[1]  M. Kuhlen,et al.  Surveillance recommendations for DICER1 pathogenic variant carriers: a report from the SIOPE Host Genome Working Group and CanGene-CanVar Clinical Guideline Working Group , 2021, Familial Cancer.

[2]  J. Vredenburgh,et al.  A family with Sertoli-Leydig cell tumour, multinodular goiter, and DICER1 mutation. , 2019, Current oncology.

[3]  Jung Kim,et al.  The prevalence of germline DICER1 pathogenic variation in cancer populations , 2019, Molecular genetics & genomic medicine.

[4]  W. Foulkes,et al.  Clinical and Molecular Characteristics May Alter Treatment Strategies of Thyroid Malignancies in DICER1 Syndrome , 2018, The Journal of clinical endocrinology and metabolism.

[5]  S. Heenan,et al.  Sertoli-Leydig Cell Tumour and DICER1 Mutation: A Case Report and Review of the Literature , 2018, Case reports in obstetrics and gynecology.

[6]  C. Jorcyk,et al.  DICER1 Syndrome: DICER1 Mutations in Rare Cancers , 2018, Cancers.

[7]  W. Foulkes,et al.  DICER1 gene mutations in endocrine tumors. , 2018, Endocrine-related cancer.

[8]  Gretchen M. Williams,et al.  DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies , 2018, Clinical Cancer Research.

[9]  Gretchen M. Williams,et al.  Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model , 2018, F1000Research.

[10]  Gretchen M. Williams,et al.  Quantification of Thyroid Cancer and Multinodular Goiter Risk in the DICER1 Syndrome: A Family-Based Cohort Study , 2017, The Journal of clinical endocrinology and metabolism.

[11]  J. Bedoyan,et al.  Novel DICER1 mutation as cause of multinodular goiter in children , 2013, Head & neck.

[12]  D. Huntsman,et al.  Cancer‐associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse‐strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage , 2013, The Journal of pathology.

[13]  W. Foulkes,et al.  DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. , 2011, JAMA.

[14]  T. Golub,et al.  Impaired microRNA processing enhances cellular transformation and tumorigenesis , 2007, Nature Genetics.

[15]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[16]  J. Geller,et al.  DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association. , 2016, The Journal of clinical endocrinology and metabolism.

[17]  P. Stratton,et al.  DICER1 Tumor Predisposition , 1993 .