Cytomorphologic features of thyroid disease in patients with DICER1 mutations: A report of cytology–histopathology correlation in 7 patients

Abstract

BACKGROUND: Germline and somatic mutations of DICER1 have been identified in various types of neoplastic lesions, with germline DICER1 mutation being linked to autosomal dominant hereditary pleiotropic tumor syndrome (DICER1 syndrome). Patients with DICER1 syndrome are at increased risk of developing thyroid disease, including thyroid cancer. The goal of this study was to identify diagnostic cytologic features in thyroid fine-needle aspiration (FNA) samples from patients with DICER1 mutation. METHODS: Cytology cases of thyroid FNA from 7 patients with DICER1 mutation were identified. Clinical, imaging, cytomorphologic, and molecular data were analyzed. RESULTS: Cytologic preparations from reviewed cases showed thyroid lesions of follicular derivation with scant colloid, moderate cellularity, uniform follicular cells with round nuclei and inconspicuous nucleoli arranged in small crowded groups and microfollicles. Follicular neoplasm was diagnosed in 4 cases and follicular lesion of undetermined significance in 3 cases, based on the Bethesda System for Reporting Thyroid Cytopathology. Histopathological analysis of thyroid tissue confirmed neoplastic process in 6 out of 7 cases: follicular carcinoma (FC, 3 cases), papillary thyroid carcinoma (2 cases), poorly differentiated thyroid carcinoma (PDTC, 1 case). Genetic studies identified 3 different somatic variants of DICER1 gene, including transcript consequence c.5428G>T, which was detected in FC and PDTC (and has been described previously in multinodular goiter). CONCLUSION: DICER1 mutation in all analyzed patients was identified as a result of thyroid FNA evaluation, emphasizing the critical role of FNA in the screening of patients with thyroid nodules, proper diagnosis of thyroid disease, and monitoring of patients with DICER1 mutation. Cancer

Probability of malignancy as determined by ThyroSeq v3 genomic classifier varies according to the subtype of atypia

“…DICER1 mutation reportedly has been associated with a spectrum of thyroid neoplasms, including FA, FTC, PTC, OCA, poorly differentiated thyroid carcinoma, and anaplastic thyroid carcinoma, as well as an associated thyroid cancer predisposition syndrome when present in a germline setting. 37,38 The FC-CA subcategory is associated with a significantly higher frequency of genetic alterations than FC-A, but not the FC-C subcategory. FC-CA showed the highest MDROM, ROM, and frequency of genetic alterations.…”

“…Other alterations found in FC‐A include DICER1 mutation, GEA, and multiple high‐level DNA CNAs. DICER1 mutation reportedly has been associated with a spectrum of thyroid neoplasms, including FA, FTC, PTC, OCA, poorly differentiated thyroid carcinoma, and anaplastic thyroid carcinoma, as well as an associated thyroid cancer predisposition syndrome when present in a germline setting 37, 38 …”

Cytomorphologic features of thyroid nodules harboring thyroid adenoma‐associated fusion: A single institutional review of 11 cases

“…Darbinyan et al examined 7 FNA and corresponding histologic sections of thyroid lesions harboring DICER1 mutations. 16 Six of their patients had a family history of neoplastic lesions. On their smears and ThinPrep ® slides, all seven cases demonstrated architectural atypia with a predominant microfollicular pattern or crowding of cells.…”

“…The cytomorphologic findings of our THADA ‐fusion cohort are not entirely specific and is shared among tumors with other RAS ‐like alterations, such as RAS , PAX8::PPARgamma , DICER1 or PTEN alterations. Darbinyan et al examined 7 FNA and corresponding histologic sections of thyroid lesions harboring DICER1 mutations 16 . Six of their patients had a family history of neoplastic lesions.…”

DICER1 gene alterations in thyroid diseases

“…In this issue of Cancer Cytopathology , Darbinyan et al 10 describe their experience with the cytomorphological features of lesions in patients with DICER1 mutations. The identification of DICER1 mutation in thyroid cytology is of crucial importance, particularly in pediatric patients, because it serves as a screening tool in patients with thyroid nodules.…”