ORIGINAL ARTICLE Low frequency of TERT promoter mutations in a series of well-differentiated follicular-patterned thyroid neoplasms A. Proietti 1 & C. Sartori 2 & E. Macerola 1 & N. Borrelli 2 & G. Materazzi 2 & P. Vitti 3 & F. Basolo 2 Received: 11 May 2017 /Revised: 30 August 2017 /Accepted: 19 September 2017 # Springer-Verlag GmbH Deutschland 2017 Abstract The diagnostic and clinical approaches to follicular-patterned thyroid neoplasms often create dilemmas for pathologist and clinicians. The molecular analysis of these tumors could be a useful tool to overcome diagnostic limita- tions. The most frequent molecular alterations are point mu- tations of RAS family genes. Nevertheless, other molecular markers should be taken into account for their prognostic role, as BRAF mutations and the recently described telomerase re- verse transcriptase (TERT) promoter mutation. We investigat- ed the prevalence and the possible role of TERT promoter, BRAF , and RAS mutations in a series of low-risk well-differ- entiated follicular-patterned thyroid neoplasms. We evaluated 60 follicular adenomas (FA), 29 minimally invasive follicular carcinomas (MIFTC), 82 papillary carcinomas, follicular var- iant (FVPTC), and 16 noninvasive follicular thyroid neo- plasms with papillary-like nuclear features (NIFT-P) for the molecular status of BRAF , H-, N-, K-RAS, and TERT and cor- related it with clinic-pathological parameters of tumors. Fifty- seven (30.5%) follicular neoplasms were mutated. In particu- lar, we found 44 RAS mutated neoplasms (23.5%), specifically three FAs, 29 FVPTCs, five NIFT-Ps, and seven FTCs. BRAF mutations were found in ten FVPTCs. Finally, TERT promoter mutations were observed in three FVPTCs and three FTCs; three of them harbored also N-RAS mutations. We confirmed the absence of TERT promoter mutations in benign follicular neoplasms and found a low frequency of TERT promoter mu- tations in our selected cohort of low-risk follicular-patterned malignancies, speculating their role in the progression and de- differentiation of thyroid cancer. Keywords Thyroid cancer . Follicular neoplasm . TERT . Molecular pathology . Cellular biology Introduction Over the last four decades has been dramatically increasing the incidence of small or subclinical thyroid nodules detected by thyroid ultrasonography and by other imaging techniques; however, increased incidence of thyroid tumors of all size has also been reported [1, 2]. Follicular cell-derived thyroid neoplasms can be classified into several histological types. Benign thyroid tumors are far more common than thyroid cancers. Among cancers the most common types are papillary thyroid cancer (PTC) and follic- ular thyroid cancer (FTC), which account for 85–90% and 10– 15% of all thyroid cancers, respectively [3, 4]. These neo- plasms are generally indolent differentiated thyroid cancer (DTCs). However, approximately 10% of patients are des- tined for a progressive disease course with aggressive tumor behaviors and high recurrence and mortality rates [5, 6]. This wide spectrum of disease behavior often creates dilemmas in clinical risk stratification and decision making for the manage- ment of thyroid tumors with follicular architecture. In partic- ular, the follicular variant of PTC (FVPTC) presents several diagnostic and clinical challenges. Most FVPTCs are encap- sulated tumors (EFVPTCs) and are difficult to be definitely distinguished from benign follicular lesions such as follicular A. Proietti and C. Sartori these authors contributed equally. * F. Basolo fulvio.basolo@med.unipi.it 1 Division of Pathological Anatomy, University Hospital of Pisa, via Roma 67, 56126 Pisa, Italy 2 Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, via Roma 57, 56126 Pisa, Italy 3 Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Pisa, via Paradisa 2, 56124 Pisa, Italy Virchows Arch DOI 10.1007/s00428-017-2236-6