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Context.—: Thyroid nodules are a common clinical problem. Cytologic evaluation via fine-needle aspiration is often employed in the diagnostic workup, and rapid on-site assessment of adequacy can help ensure an adequate sample is obtained. However, rapid on-site assessment of adequacy only examines part of the sample, a part that may not then be available for ancillary testing. Moreover, the procedure is time-consuming and poorly reimbursed., Objective.—: To develop an automatable fluorescence-based image analysis system for assessing the adequacy of thyroid fine-needle aspirations that uses the entire aspirated sample., Design.—: There were 12 previously diagnosed cases that served as a training set, and 11 cases were used for validation of an image analysis algorithm. The samples were fluorescently stained and imaged using a fluorescent microscope. The images were assessed for adequacy by an image analysis algorithm. Following image analysis, a ThinPrep slide was prepared and blindly scored by a cytopathologist. The standard and computer-derived results were then compared., Results.—: The algorithm was optimized using the 12 cases in the training set and then applied to the 11 test cases. A total of 8 of 8 adequate samples in the test group were correctly scored as adequate, and 2 of 3 cases that were inadequate were correctly scored as inadequate by the algorithm. One case was erroneously designated as not adequate by the algorithm., Conclusions.—: Our results demonstrate the feasibility of automating thyroid adequacy assessment using a fluorescent labeling technique followed by computer image analysis.

Context: Controversy exists about whether thyroid fine-needle aspirates (FNAs) should be processed with conventional smears or liquid-based preparations (LBPs)., Objective: To compare the performance of conventional smears to LBPs for thyroid FNA slides circulated in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology., Design: Participant responses for thyroid FNA slides were compared with the reference diagnosis at the level of 3 general diagnostic categories: negative, suspicious (which included only follicular and Hürthle cell neoplasm), and malignant. For specific reference diagnoses of benign/goiter and papillary thyroid carcinoma, the participants' specific diagnoses were analyzed and poorly performing slides were rereviewed., Results: The 47, 076 thyroid FNA slide responses, between 2001 and 2009, included 44, 478 responses (94%) for conventional smears and 2598 responses (6%) for LBPs. For the general reference category negative, participant responses were discrepant in 14.9% of conventional smears compared with 5.9% for LBPs (P < .001). The specific reference diagnosis of benign/goiter was misdiagnosed as a follicular neoplasm in 7.8% of conventional smears, compared with 1.3% of LBP. For the general reference category of malignant, participant responses were discrepant in 7.3% of conventional smears compared with 14.7% of LBPs (P < .001). The specific reference diagnosis of papillary thyroid carcinoma was misdiagnosed as benign/goiter in 7.2% of LBPs, compared with 4.8% of conventional smears (p <.001)., Conclusions: LBPs performed worse than conventional smears for cases with a reference diagnosis of papillary thyroid carcinoma. However, LBPs performed better than conventional smears for cases with a benign reference diagnosis. Specific features in thyroid FNAs that may improve the diagnostic accuracy of LBPs and conventional smears are described.

Background: Although thyroid fine-needle aspiration (TFNA) is an excellent test in evaluating thyroid nodules, there are occasionally false negatives (FN). The clinical impact and pathologic features of FN TFNA is understudied in the peer-reviewed literature., Methods: A cohort of patients with thyroid cancer was separated into those with referring FN TFNA and those with referring true positive (TP) TFNA. Preoperative characteristics, pathologic finding, and clinical outcomes were compared within the 2 groups., Results: A total of 192 patients with TP TFNA (n = 162) and FN TFNA (n = 30) were included in the study. There were no significant differences in the demographics or length of follow-up of the 2 groups. The FN TFNA group was more likely to have a larger clinical nodule size and experienced a significant delay from initial TFNA to surgery. The FN TFNA group was more likely to be diagnosed with the follicular variant of papillary thyroid cancer (73.3% vs 25.9%, P < .001), less likely to have positive lymph nodes at surgery (6.7% vs 35.8%, P = .001), and more likely to undergo 2-step surgery (30% vs 9.9%, P = .007). Despite the delay in diagnosis, persistent/recurrent or metastatic disease, incidence of aggressive histologic variants, and pT4 disease was not different in the 2 groups., Conclusions: The clinical impact of FN TFNA at our high-volume center is minimal. Cancers in this setting are low grade, and outcomes are not adversely affected despite the delay in diagnosis., (Copyright © 2012 American Cancer Society.)

Background: ThinPrep (TP) liquid-based preparations are increasingly being used in nongynecologic specimens. Few studies have evaluated TP as a sole diagnostic modality in the setting of thyroid fine-needle aspiration (T-FNA). Herein, the authors evaluate the usefulness of TP as a sole diagnostic modality in a nonsplit sample., Methods: Consecutive T-FNAs were identified at 2 tertiary care institutions; 1 institution processed thyroid FNA entirely with TP, and the other used a combination of TP and conventional preparations (CP). Cytodiagnoses, surgical pathology, and/or clinical follow-up were recorded. Performance parameters for the 2 settings were compared., Results: A cytologic diagnosis of positive for malignancy was correct in 98.8% of TP + CP cases and in 100% of TP cases. Papillary thyroid carcinoma cases were definitively diagnosed in 53.1% of T-FNAs prepared by TP + CP compared with 34.4% of T-FNAs prepared with TP alone (P = .0015 by Fisher 2-tailed exact test). Of patients ultimately diagnosed with papillary thyroid carcinoma, 89% were initially treated by total thyroidectomy in the TP + CP group compared with 79.5% in the TP-only group (P = .027 by Fisher exact test)., Conclusions: TP as a sole preparatory technique does not improve the usefulness of T-FNA as a screening test. However, combining CP and TP increases the rate of definitive cytologic diagnosis of malignancy in papillary thyroid carcinoma. Thus, combining TP and CP enhances the diagnostic component of T-FNA., (Copyright © 2010 American Cancer Society.)

Objective: To determine whether or not significant differences in the risk of malignancy exist between subgroups of atypical follicular cells in The Bethesda System for Reporting Thyroid Cytology (TBSRTC) in patients who underwent surgical resection., Study Design: Between 2004 and 2009, consecutive thyroid fine-needle aspirates at our institutions with a cytologic diagnosis of 'atypical follicular cells' were retrieved and subclassified using the diagnosis and diagnostic comment as: (1) atypical follicular cells with equivocal features of papillary carcinoma [cannot exclude papillary thyroid carcinoma (PTC)] and (2) atypical follicular cells, other patterns. The risks of malignancy for excised nodules were calculated and comparisons were made between these subgroups. Categorical analysis was performed using a 2-tailed Fisher's exact test, and p < 0.05 was considered statistically significant., Results: A total of 7,072 thyroid fine-needle aspiration cases were retrieved, with 1,542 (21.8%) having a histologic follow-up. There were 222 (3.1%) cases of 'atypical follicular cells', with 127 (57.2%) having a histologic correlation and 33 having confirmed malignancies. Atypical follicular cells, cannot exclude PTC, have a significantly higher risk of malignancy than atypical follicular cells, other patterns (45.8 vs. 13.9%, p < 0.01)., Conclusions: Atypical follicular cells with equivocal features of papillary carcinoma is not a low-risk cytologic diagnosis., (Copyright © 2011 S. Karger AG, Basel.)

Radioiodide uptake activity mediated by the human Na(+)/I(-) symporter (hNIS) in thyroid follicular cells is the basis for effective (131)I therapy in thyroid cancer. However, radioiodide therapy is not effective in patients with thyroid cancer displaying low or absent hNIS expression. This study assessed the Cre/loxP system for enhancing thyroid-targeted hNIS expression driven by the thyroglobulin (Tg) promoter. The following three recombinant adenoviruses (rAd) were constructed: rAd-Tg-hNIS drives hNIS expression by the Tg promoter; rAd-Tg-Cre drives Cre expression by the Tg promoter; and rAd-CMV-loxP-hNIS drives hNIS expression by the cytomegalovirus (CMV) promoter after Cre-mediated excision of an intervening loxP-GFP-Zeo-loxP. Immortalized normal and malignant rat thyroid cell lines and primary cultures of normal human thyroid and human follicular adenoma cells were investigated. We found that the relative promoter activity of Tg vs. CMV is critical for the efficacy of the Cre/loxP system. In cells with weak Tg promoter activity, coinfection of rAd-Tg-Cre and rAd-CMV-loxP-hNIS induced higher hNIS expression than single infection of rAd-Tg-hNIS. Finally, Tg promoter activity was partially restored in malignant thyroid cells by forced expression of the paired domain-containing transcription factor (Pax-8), allowing the Cre/loxP system to mildly enhance radioiodide uptake.

The human Na+/I- symporter (hNIS) is the plasma membrane protein that mediates active iodide uptake into several tissues, such as the thyroid and salivary glands. To study the distribution and cellular localization of the hNIS protein, we have generated a polyclonal antibody that could detect the hNIS protein by immunohistochemical staining on tissue sections. In normal thyroids, hNIS expression is heterogeneous, and it is only detected in sporadic thyrocytes of a given follicle. The hNIS protein was not detected in thyroid carcinomas, yet it was detected in the majority of thyrocytes in Graves' thyroids. In salivary glands, hNIS protein was not detected in acinar cells, but it was detected in ductal cells. The hNIS proteins are clustered in the basal and lateral membranes in cells stained positive for hNIS.