RF17 | PSUN202 DICER1 Gene Mutation: Association With Thyroid Cancer and Other Endocrine Tumors
Authors: Sweis Nadia , Toft Daniel , Pradeep Pallavi 
Published: November 2022

Introduction

DICER1 syndrome is a rare autosomal dominant hereditary tumor predisposition syndrome and is known to have many endocrine manifestations.

Case Description

A 21-year-old female with DICER1 syndrome presented to the clinic to establish care. She had a significant family history of DICER1 mutation in her father and two siblings. She was diagnosed with malignant neuroepithelioma of the uterus at the age of 12 and was treated with cisplatin/cyclophosphamide. Hepatic embryonal rhabdomyosarcoma and pleuropulmonary blastoma type 1 were diagnosed at the age of 16 and she underwent hepatic lobectomy, left lower lung lobectomy, and received additional chemotherapy.

She was first diagnosed with multiple thyroid nodules at the age of 14. Surveillance thyroid ultrasounds were performed biannually over the next 6 years. She also had multiple thyroid nodule FNAs, all showing benign results. Subsequently, CT chest revealed enlarging thyroid nodules with a chest wall lesion which prompted total thyroidectomy. Surgical pathology confirmed a 0.5 cm papillary thyroid carcinoma involving the left superior thyroid lobe; there was no lymph node involvement or extrathyroidal invasion and the surgical margins were intact. Surveillance ultrasounds have not shown any residual or recurrent disease. Excision of chest wall lesion showed nodular epithelia proliferation with rare eccrine duct present in the margin.

She also suffered from secondary amenorrhea from chemotherapy induced ovarian failure. She was started on estrogen patch and cyclical progesterone therapy, following which menstrual cycles resumed.

Discussion

DICER1 encodes an Rnase III endonuclease that processes miRNA precursor hairpins into mature miRNAs. miRNA-mediated effects that lead to this syndrome is due to loss-of-function in tumor suppressor genes or gain of function in oncogenes. This predisposes patients to a variety of different tumors, including many endocrine tumors.

Multiple thyroid nodules, as was seen in our patient, is a common finding in individuals with DICER1 syndrome. Rates of thyroid cancer are 10–20% higher in these patients. Follicular variant of papillary cancer and follicular thyroid cancer are the most common histologies seen. Thyroid cancer in these patients usually follows an indolent course with thyroidectomy typically curative. For screening of thyroid cancer, recommendations include annual thyroid examination, with some authors advocating for thyroid ultrasounds starting at the age 8, with repeated scans every 3 years if normal.

Other endocrine tumors that are associated with DICER1 mutations include pituitary blastomas and pineoblastoma. Patients with pituitary blastomas may present with features of Cushing disease with elevated ACTH. Pineoblastoma can be detected with surveillance brain MRI, but routine screening for these tumors is not currently recommended as these tumors are rare, even within this syndrome.

References

Endocr Relat Cancer. 2018 Mar;25(3): R197-R208.

Presentation: Sunday, June 12, 2022 12:48 p.m. - 12:53 p.m.