Distinguishing follicular variant of papillary carcinoma (FVPC) from follicular adenoma and follicular carcinoma can be difficult if nuclear features of papillary carcinoma are not well developed or only focally present. We assessed interobserver and intraobserver agreement among 6 thyroid experts by using 15 cases in which original pathologists suspected FVPC. There was unanimous expert agreement in diagnosing FVPC in only 2 cases (13%) and majority agreement in 6 cases (40%). Unanimous agreement on benign and malignant diagnoses was seen in 4 cases (27%) and majority agreement on malignancy in 8 cases (53%). Intraobserver agreement ranged from 17% to 100%. Histologic features considered most helpful in diagnosing FVPC were nuclear clearing, nuclear grooves, nuclear overlapping and crowding, nuclear membrane irregularity, and nuclear enlargement. This considerable interobserver and intraobserver variability in the diagnosis of FVPC seems to result from lack of agreement on the minimal criteria needed to diagnose FVPC, even among experts.

The National Cancer Institute (NCI) sponsored the NCI Thyroid fine-needle aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters addressing manual and ultrasound guided FNA technique and related issues. Specific topics covered include details regarding aspiration needles, devices, and methods, including the use of core needle biopsy; the pros and cons of anesthesia; the influence of thyroid lesion location, size, and characteristics on technique; the role of ultrasound in the FNA of a palpable thyroid nodule; the advantages and disadvantages of various specialists performing a biopsy; the optimal number of passes and tissue preparation methods; sample adequacy criteria for solid and cystic nodules, and management of adverse reactions from the procedure. (http://thyroidfna.cancer.gov/pages/info/agenda/)

The scheme recommends statements on specimen adequacy followed by the major classification category and then a subclassification and/or comments section. Each of the six main diagnostic categories is associated with an estimated risk of malignancy. Subsequent documents will propose ancillary testing recommendations, techniques for cytologic sampling, indications for cytologic study and postcytologic diagnosis management and follow-up recommendations.

Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) diagnosed in core needle biopsy (CNB) are generally regarded as risk indicators for developing invasive ductal or lobular carcinoma in either breast. Currently, there are no well-established guidelines for management of these patients. The most common management options are careful observation and endocrine chemoprophylaxis for high-risk patients. Previous studies had contradicting recommendations regarding follow-up surgical excision (FSE) of CNB yielding ALH or LCIS. These studies, unfortunately, have been limited by their retrospective nature, small number of patients examined, and association with other high-risk lesions. Only CNB diagnosed as pure LCIS or ALH (not associated with other high-risk lesions such as ADH, radial scar, or papilloma) were included in the study. We reviewed 33 CNB (20 ALH and 13 LCIS) with subsequent FSE from 33 patients (age range, 30-83 years; mean, 58 years). Eighteen of these patients were prospectively analyzed, where FSE was performed in an unselected fashion. All CNBs were obtained by mammotome (11-gauge, 30 cases; and 14-gauge, 3 cases). Mammography identified calcifications in 29 cases (88%) and a mass in 4 cases (12%). FSE revealed infiltrating ductal and/or lobular carcinoma in 4 of 13 LCIS (31%). FSE of 20 ALH revealed cancer in 5 cases (25%), including 4 ductal carcinoma in situ (DCIS) and 1 invasive lobular carcinoma. Seven of these nine cancers were associated with calcifications, and two presented as masses. Sampling error and underestimation of cancer (DCIS or invasive carcinoma) was associated with CNB diagnosis of LCIS or ALH in 27% of all cases. Underestimation of cancer was seen in 28% of prospectively examined patients, including 20% of ALH and 38% of LCIS. CNB associated with mass lesions or that showed histologic features of pleomorphic LCIS or extensive classic LCIS had a higher rate of cancer underestimation. Despite removal of all abnormal mammographic calcifications by CNB in 6 patients, one cancer was detected on FSE. To the best of our knowledge, this is the largest study reported to date, and the only one to include prospectively examined patients with no pre-selection bias. Our data strongly suggests that subsequent FSE is warranted in all patients with CNB diagnoses of LCIS or ALH, to exclude the presence of cancer.

Context Molecular tests have improved the accuracy of preoperative diagnosis of indeterminate thyroid nodules. The Afirma Gene Sequencing Classifier (GSC) was developed to improve the specificity of the Gene Expression Classifier (GEC). Independent studies are needed to assess the performance of GSC. Objective The aim was to compare the performance of GEC and GSC in the assessment of indeterminate nodules. Design, Settings, and Participants Retrospective analysis of Bethesda III and IV nodules tested with GEC or GSC in an academic center between December 2011 and September 2018. Benign call rates (BCRs) and surgical outcomes were compared. Histopathologic data were collected on nodules that were surgically resected to calculate measures of test performance. Results The BCR was 41% (73/178) for GEC and 67.8% (82/121) for GSC (P < .001). Among specimens with dominant Hürthle cell cytology, the BCR was 22% (6/27) for GEC and 63.2% (12/19) for GSC (P = .005). The overall surgery rate decreased from 47.8% in the GEC group to 34.7% in the GSC group (P = .025). One GEC-benign and 3 GSC-benign nodules proved to be malignant on surgical excision. GSC had a statistically significant higher specificity (94% vs 60%, P < .001) and positive predictive value (PPV) (85.3% vs 40%, P < .001) than GEC. While sensitivity and negative predictive value (NPV) dropped with GSC (97.0% vs 90.6% and 98.6% vs 96.3%, respectively), these differences were not significant. Conclusions GSC reclassified more indeterminate nodules as benign and improved the specificity and PPV of the test. These enhancements appear to be resulting in fewer diagnostic surgeries.