Comparison of the collection approaches of 2 large thyroid fine-needle aspiration practices reveals differing advantages for cytology and molecular testing adequacy rates.

Introduction: At our institution, almost all thyroid fine-needle aspiration (FNA) procedures are performed by either Endocrinology or Radiology personnel. In this study, we compared the cytology and molecular adequacy rates of these 2 thyroid FNA practices, which differ on several aspects of specimen procurement.

Materials And Methods: All thyroid FNA specimens from Endocrinology and Radiology practices between September 2008 and December 2016 were included.

Benign call rate and molecular test result distribution of ThyroSeq v3.

Background: The benign call rate (BCR) is the percentage of cytomorphologically indeterminate cases with subsequent benign or negative molecular results. For rule-out tests, the BCR is an important parameter because these molecular "negative" cases may be managed similarly to those with a benign cytology diagnosis. Although earlier versions of ThyroSeq molecular tests were less effective in excluding malignancy, the extensively expanded v3 version with a high negative predictive value is considered to represent a rule-out test.

Correct extent of thyroidectomy is poorly predicted preoperatively by the guidelines of the American Thyroid Association for low and intermediate risk thyroid cancers.

Background: Recent guidelines from the American Thyroid Association recommend thyroid lobectomy for intrathyroidal differentiated thyroid cancers <4 cm. Our aim was to examine histology from patients with cytologic results that were positive or suspicious for malignancy to assess the extent of initial thyroidectomy based on criteria from the 2015 American Thyroid Association guidelines.

Methods: We studied consecutive patients who had either a positive or suspicious for malignancy cytologic diagnosis and under prior American Thyroid Association guidelines underwent initial total thyroidectomy ± lymphadenectomy.

The influence of the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) resection diagnosis on the false-positive thyroid cytology rate relates to quality assurance thresholds and the application of NIFTP criteria.

Background: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a newly defined entity and recent studies have suggested a decrease of a few percentage points in the rate of malignancy (ROM) for the positive-for-malignancy (PFM) cytology category as a result of NIFTP implementation. However, the distinction between a diagnosis of PFM and one of suspicious for malignancy (SFM) may depend on a variety of factors. In the current study, the authors investigated the ROM for the PFM and SFM diagnoses before and after histologic NIFTP reclassification.

Preoperative detection of RAS mutation may guide extent of thyroidectomy.

Background: Preoperative detection of RAS mutations can contribute to cancer risk assessment in indeterminate thyroid nodules, although RAS is not always associated with malignancy.

Methods: Fine-needle aspiration samples classified in 1 of 3 indeterminate cytology categories were prospectively tested for N-, H-, and K-RAS mutations using next-generation sequencing assay.

Results: In the study, 93 patients with 94 nodules had preoperative RAS detected, of whom 86 patients had an operation (69% total thyroidectomy, 29% lobectomy).

Impact of the Multi-Gene ThyroSeq Next-Generation Sequencing Assay on Cancer Diagnosis in Thyroid Nodules with Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Cytology.

Background: Fine-needle aspiration (FNA) cytology is a common approach to evaluate thyroid nodules. It offers definitive diagnosis of a benign or malignant nodule in the majority of cases. However, 10-25% of nodules yield one of three indeterminate cytologic diagnoses, leading to suboptimal management of these patients.

Significance of what is not sampled: Characteristics of thyroid nonmicrocarcinomas (>1.0 cm) that were not targeted.

Background: Although most unsuspected thyroid carcinomas qualify as microcarcinomas (≤1 cm), larger, nontargeted carcinomas may be found also. This study evaluated the significance of these nonmicrocarcinomas (>1 cm) in the setting of a large-volume thyroid practice.

Methods: Thyroid resection specimens from May 2007 to December 2012 were reviewed.

Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay.

Background: Fine-needle aspiration (FNA) cytology is a common approach to evaluating thyroid nodules, although 20% to 30% of FNAs have indeterminate cytology, which hampers the appropriate management of these patients. Follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN) is a common indeterminate diagnosis with a cancer risk of approximately 15% to 30%. In this study, the authors tested whether the most complete next-generation sequencing (NGS) panel of genetic markers could significantly improve cancer diagnosis in these nodules.

Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS mutations with regard to cytopathologic and histopathologic outcome characteristics.

Background: Mutations in the RAS gene in the thyroid gland result in the activation of signaling pathways and are associated with a follicular growth pattern and the probability of a carcinoma outcome ranging from 74% to 87%. In the current study, the authors investigated the cytopathologic and histopathologic features of common RAS mutation subtypes.

Methods: Malignant, indeterminate, and selected benign thyroid cytology cases were tested prospectively for the presence of NRAS61, HRAS61, and KRAS12/13 mutations.

A clinical algorithm for fine-needle aspiration molecular testing effectively guides the appropriate extent of initial thyroidectomy.

Objective: To test whether a clinical algorithm using routine cytological molecular testing (MT) promotes initial total thyroidectomy (TT) for clinically significant thyroid cancer (sTC) and/or correctly limits surgery to lobectomy when appropriate.

Background: Either TT or lobectomy is often needed to diagnose differentiated thyroid cancer. Determining the correct extent of initial thyroidectomy is challenging.

Effects of testosterone and growth hormone on the structural and mechanical properties of bone by micro-MRI in the distal tibia of men with hypopituitarism.

Context: Severe deficiencies of testosterone (T) and GH are associated with low bone mineral density (BMD) and increased fracture risk. Replacement of T in hypogonadal men improves several bone parameters. Replacement of GH in GH-deficient men improves BMD.

Thyroid nodules (≥4 cm): can ultrasound and cytology reliably exclude cancer?

Background: Whether a threshold nodule size should prompt diagnostic thyroidectomy remains controversial. We examined a consecutive series of patients who all had thyroidectomy for a ≥4 cm nodule to determine (1) the incidence of thyroid cancer (TC) and (2) if malignant nodules could accurately be diagnosed preoperatively by ultrasound (US), fine needle aspiration biopsy (FNAB) cytology and molecular testing.

Methods: As a prospective management strategy, 361 patients with 382 nodules ≥4 cm by preoperative US had thyroidectomy from 1/07 to 3/12.

Nodule size is an independent predictor of malignancy in mutation-negative nodules with follicular lesion of undetermined significance cytology.

Background: In thyroid nodule fine-needle aspiration (FNA) cytology, the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) category has a 5-15% malignancy risk that increases to 85-99% when mutation testing for BRAF, RAS, RET/PTC, or PAX8/PPARγ is positive. However, negative testing does not exclude malignancy. The study objective was to identify clinical and imaging features that predict cancer in mutation-negative AUS/FLUS thyroid nodules.

"Colloid-rich" follicular neoplasm/suspicious for follicular neoplasm thyroid fine-needle aspiration specimens: cytologic, histologic, and molecular basis for considering an alternate view.

Background: Typically, thyroid follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cases show moderate to marked cellularity and scant or absent colloid. Recently, cases have been noted with microfollicular cellularity in the background of moderate to abundant amount of colloid. The purpose of this study was to compare these "colloid-rich" FN/SFN cases to the typical FN/SFN cases.

RAS mutations in thyroid FNA specimens are highly predictive of predominantly low-risk follicular-pattern cancers.

Introduction: RAS mutations are common in thyroid tumors and confer a high risk of cancer when detected in fine-needle aspiration (FNA) specimens. Specific characteristics of RAS-positive thyroid cancers are not well described.

Methods: From April 2007 to April 2009, 921 consecutive patients undergoing FNA were evaluated prospectively with a panel of molecular markers.

BRAF mutation detection in indeterminate thyroid cytology specimens: underlying cytologic, molecular, and pathologic characteristics of papillary thyroid carcinoma.

Background: BRAF mutations are highly specific for papillary thyroid carcinoma (PTC) and many cytology specimens with BRAF mutations are expected to demonstrate cytologic features typical of PTC. However, indeterminate thyroid cytology cases are inevitable and understanding the significance of the BRAF mutation within the context of the Bethesda System for Reporting Thyroid Cytopathology would be valuable.

Methods: Thyroid cytology cases submitted for conventional cytomorphologic evaluation and BRAF mutational analyses were selected from the authors' cytopathology files from April 2007 to October 2011.

A combined molecular-pathologic score improves risk stratification of thyroid papillary microcarcinoma.

Background: Thyroid papillary microcarcinoma (TPMC) is an incidentally discovered papillary carcinoma that measures ≤1.0 cm in size. Most TPMCs are indolent, whereas some behave aggressively.

Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples.

Context: Thyroid nodules are common in adults, but only a small fraction of them is malignant. Fine-needle aspiration (FNA) cytology provides a definitive diagnosis of benign or malignant disease in many cases, whereas about 25% of nodules are indeterminate, hindering most appropriate management.

Objective: The objective of the investigation was to study the clinical utility of molecular testing of thyroid FNA samples with indeterminate cytology.

Both BRAF V600E mutation and older age (≥ 65 years) are associated with recurrent papillary thyroid cancer.

Purpose: This study was designed to examine the aggressive features of BRAF-positive papillary thyroid cancer (PTC) and association with age.

Methods: We compared the clinicopathologic parameters and BRAF V600E mutation status of 121 elderly (age ≥65 years) PTC patients who underwent thyroidectomy from January 2007 to December 2009 to a consecutive cohort of 98 younger (age <65 years) PTC patients.

Results: Younger and elderly PTC patients had similar incidences of BRAF-positive tumors (41% vs.

Imaging surveillance of differentiated thyroid cancer.

Intensive imaging surveillance has resulted in the ability to detect small-volume, often clinically occult, residual or recurrent disease. For most patients with differentiated thyroid cancer (DTC), such findings are unlikely to have an impact on disease-specific survival but our ability to predict which patients are at greatest risk and should receive the most aggressive therapies is surpassed by our ability to detect recurrence. Thus, the optimal treatment and surveillance regimens will surely continue to evolve as our ability to predict tumor behavior and aggressiveness improves.

Diagnosis and treatment of differentiated thyroid carcinoma.

Thyroid cancer is the most common endocrine malignancy. Historically, the diagnosis has been made via fine-needle aspiration cytology; however, molecular marker analysis, particularly in indeterminate specimens, is beginning to play a more prominent role. Once the diagnosis of thyroid cancer is established, patients should undergo preoperative ultrasound evaluation followed by appropriate surgical resection, radioiodine ablation, and thyrotropin suppression.

Evaluation of a thyroid nodule.

The thyroid specialist frequently evaluates thyroid nodules because they may represent malignancy. Nodules are typically found on physical examination or incidentally when other imaging studies are performed. Malignant or symptomatic nodules that compress nearby structures warrant surgical excision.

Clinical usefulness of positron emission tomography-computed tomography in recurrent thyroid carcinoma.

Objectives: To determine the efficacy of combined positron emission tomography-computed tomography (PET-CT) in identifying recurrent thyroid cancer and to elucidate its role in the clinical management of thyroid carcinoma.

Design: Retrospective study.

Setting: Tertiary care referral academic center.

Contribution of molecular testing to thyroid fine-needle aspiration cytology of "follicular lesion of undetermined significance/atypia of undetermined significance".

Background: "Follicular lesion of undetermined significance/atypia of undetermined significance" is a heterogeneous category of cases that cannot be classified into 1 of the other established categories. The use of ancillary molecular studies has not been widely explored for this diagnosis.

Methods: All thyroid cytology cases diagnosed as follicular lesion of undetermined significance/atypia of undetermined significance were retrieved from April 2007 to December 2008.