Aarti Mathur

Malignancy risk and reproducibility associated with atypia of undetermined significance on thyroid cytology

BACKGROUND The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) describes several subcategories within atypia of undetermined significance (AUS), including (1) presence of focal nuclear atypia (AUS-N), (2) focal microfollicular proliferation (AUS-F), (3) focal Hürthle cell proliferation (AUS-HC), and (4) other (AUS-O). Several publications suggest that 5-15% is an underestimate of the malignancy risk for AUS, and that the underestimation is owing to the similarity between AUS-N and suspicious for malignancy (SFM). Thus, we investigated the AUS subcategories during morphologic re-review at a tertiary care center and their associated malignancy risk. METHODS Of 4,827 fine-needle aspiration specimens were sent between January 2009 and August 2013 for morphologic re-review, 806 were categorized as AUS. Comparison of AUS subcategory diagnoses were made between outside and re-review results. The malignancy risk was also determined for 255 nodules with available surgical pathology. RESULT The outside diagnoses of the 806 cases read as AUS on second review were as follows: 5 insufficient (0.1%), 149 benign (19%), 463 AUS (57%), 124 SFN or suspicious for follicular or Hürthle cell neoplasm (15%), 56 SFM (7%), and 9 malignant (1%). Of the 463 cases in which both the outside and re-review diagnosis was AUS, the distribution of the subcategories in order of increasing frequency was 53 AUS-HC (11%), 74 AUS-O (16%), 79 AUS-F (17%), and 257 AUS-N (56%). Of the 255 resected nodules, 99 (39%) were malignant. Subcategory malignancy rates were: AUS-HC, 19% (9/47); AUS-O, 26% (14/54); AUS-F, 39% (19/49); and AUS-N, 54% (57/105). Cases in which both the referring institution and re-review agreed about the AUS-N subcategory had an even greater risk of malignancy (68%; 17/25). CONCLUSION Disagreement about the diagnosis of AUS between institutions is frequent. The malignancy risk for AUS is higher than originally proposed by TBSRTC and attributable to the high risk of AUS-N. Furthermore, agreement on AUS-N after re-review portends a malignancy risk that borders on that of SFM. This suggests that AUS-N may have discrete features that can provide specific morphologic predictors and enable the consolidation of AUS-N into SFM.

Evaluation of the Effect of Diagnostic Molecular Testing on the Surgical Decision-Making Process for Patients With Thyroid Nodules

IMPORTANCE Diagnostic molecular testing is used in the workup of thyroid nodules. While these tests appear to be promising in more definitively assigning a risk of malignancy, their effect on surgical decision making has yet to be demonstrated. OBJECTIVE To investigate the effect of diagnostic molecular profiling of thyroid nodules on the surgical decision-making process. DESIGN, SETTING, AND PARTICIPANTS A surgical management algorithm was developed and published after peer review that incorporated individual Bethesda System for Reporting Thyroid Cytopathology classifications with clinical, laboratory, and radiological results. This algorithm was created to formalize the decision-making process selected herein in managing patients with thyroid nodules. Between April 1, 2014, and March 31, 2015, a prospective study of patients who had undergone diagnostic molecular testing of a thyroid nodule before being seen for surgical consultation was performed. The recommended management undertaken by the surgeon was then prospectively compared with the corresponding one in the algorithm. Patients with thyroid nodules who did not undergo molecular testing and were seen for surgical consultation during the same period served as a control group. MAIN OUTCOMES AND MEASURES All pertinent treatment options were presented to each patient, and any deviation from the algorithm was recorded prospectively. To evaluate the appropriateness of any change (deviation) in management, the surgical histopathology diagnosis was correlated with the surgery performed. RESULTS The study cohort comprised 140 patients who underwent molecular testing. Their mean (SD) age was 50.3 (14.6) years, and 75.0% (105 of 140) were female. Over a 1-year period, 20.3% (140 of 688) had undergone diagnostic molecular testing before surgical consultation, and 79.7% (548 of 688) had not undergone molecular testing. The surgical management deviated from the treatment algorithm in 12.9% (18 of 140) with molecular testing and in 10.2% (56 of 548) without molecular testing (P = .37). In the group with molecular testing, the surgical management plan of only 7.9% (11 of 140) was altered as a result of the molecular test. All but 1 of those patients were found to be overtreated relative to the surgical histopathology analysis. CONCLUSIONS AND RELEVANCE Molecular testing did not significantly affect the surgical decision-making process in this study. Among patients whose treatment was altered based on these markers, there was evidence of overtreatment.

Follicular Lesions of the Thyroid

Follicular lesions of the thyroid encompass a wide spectrum of diseases with clinicopathologic overlap, including benign follicular adenoma, malignant follicular carcinoma, and follicular variant of papillary cancer. This review addresses the clinical presentation, preoperative diagnosis in the era of molecular markers, pathologic diagnosis, treatment, and prognosis of follicular lesions, taking into account the frequent controversy about definitive histologic diagnoses.

Are preoperative sestamibi scans useful for identifying ectopic parathyroid glands in patients with expected multigland parathyroid disease

Background. The role of preoperative localization studies in patients with hyperparathyroidism and expected multigland disease remains poorly defined. Our study investigates the usefulness of obtaining preoperative sestamibi scans and ultrasonography of the neck in identifying ectopic glands in this group of patients. Methods. Under Institutional Review Board approval, we performed a retrospective review of patients who underwent operation for secondary hyperparathyroidism, tertiary hyperparathyroidism, lithium‐induced hyperparathyroidism, and multiple endocrine neoplasia syndrome at a tertiary institution between 2004 and 2015. We reviewed patient demographics, laboratory, radiology, pathology, and operative reports. Results. Of 2,975 parathyroidectomies performed during this period, 154 operations were performed in 149 patients who met the criteria. Of the 149 patients, 82 (55.0%) had secondary, 31 (20.8%) had tertiary, 23 (15.4%) had lithium‐induced HPT, and 13 (10.1%) had multiple endocrine neoplasia syndrome; 86 ectopic glands were identified in 64 patients (43.0%). Sensitivity for identification of ectopic glands was 29% for sestamibi scan and 7% for ultrasonography, while 89% of mediastinal glands were localized by sestamibi scans and thoracotomy, thoracoscopy, or sternotomy occurred in 4.7% of patients. Conclusion. We found a greater rate of preoperative localization of ectopic glands than reported previously. Because the sensitivity of sestamibi for identification of ectopic glands is 23.0%, the implication of missing mediastinal glands warrants preoperative imaging.

Association of Parathyroid Hormone Level With Postthyroidectomy Hypocalcemia: A Systematic Review

Importance There has been an increased interest in measuring parathyroid hormone (PTH) levels as an early predictive marker for the development of hypocalcemia after total thyroidectomy. However, significant variation exists in the timing, type of assay, and thresholds of PTH in the literature. Objective We performed a systematic review to examine the utility of PTH levels in predicting temporary postthyroidectomy hypocalcemia. Evidence Review A systematic literature review of studies published prior to May 25, 2016 was performed within PubMed, EMBASE, SCOPUS, and Cochrane databases using the following terms and keywords: “thyroidectomy,” “parathyroid hormone,” and “hypocalcaemia,” “calcium,” or “calcitriol.” Each candidate full-text publication was reviewed by 2 independent reviewers and selected for data extraction if the study examined the prognostic significance of PTH obtained within 24 hours after thyroidectomy to predict hypocalcaemia. Studies were excluded if calcium supplementation was used routinely or based on a PTH level. Study characteristics, PTH parameters used to predict hypocalcemia, and their respective accuracies were summarized. Findings The initial search yielded 2417 abstracts. Sixty-nine studies, comprising 9163 patients, were included. Overall, for an absolute PTH threshold, the median accuracy, sensitivity, and specificity were 86%, 85%, and 86%, respectively. For a percentage change over time the median accuracy, sensitivity, and specificity were 89%, 88%, and 90%, respectively. Conclusions and Relevance The existing literature regarding PTH levels to predict postthyroidectomy hypocalcemia is extremely heterogeneous. A single PTH threshold is not a reliable measure of hypocalcemia. Additional prospective studies controlled for timing of laboratory draws and a priori defined PTH thresholds need to be performed to ascertain the true prognostic significance of PTH in predicting postthyroidectomy hypocalcaemia.

Genomic medicine for cancer prognosis

There is a heavy research emphasis on prognostic and predictive approaches based on genomic data, which has in turn challenged standard paradigms for the management of patients with malignant disease. This review will highlight the recent advances made in genomic medicine, specifically with regard to prognosis associated with thyroid cancer, cutaneous melanoma, and pancreatic adenocarcinoma. Although none of the markers reviewed have been incorporated into routine clinical practice, this review covers the most promising ones. J. Surg. Oncol. 2015 111:31–37.

Is there an increased risk of second primary malignancy after diagnosis of thyroid cancer

In this issue of Cancer, through a nationwide, population-based cancer registry, Cho et al have provided an excellent review of the incidences and types of second primary malignancies (SPM) in a Korean population treated for thyroid cancer. Recent reports on the risk of developing an SPM have raised concern about whether enhanced surveillance is warranted in this patient population. The study is well conceived, well presented, and describes a 6% increase in the risk of developing an SPM. Cho and colleagues used a central cancer registry to identify 178,844 patients with thyroid cancer, 92% of whom had papillary thyroid cancer, between 1993 and 2010. The authors excluded 628 patients who developed another malignancy within the first 2 months of their thyroid cancer diagnosis. Standardized incidence ratios (SIRs) for each site of second malignancy were then calculated by determining the ratio of observed cancers to expected cancers. The expected number of incident malignancies in the Korean general population without a history of thyroid cancer was determined separately for men and women in 5-year time intervals. The increased risk was then derived from the magnitude of increase in SIRs from 1.00. Patients were followed from 3 to 20 years to determine the rate of SPM. It is noteworthy that the authors report a dramatic increase in the incidence of thyroid cancer, with only 1642 diagnoses reported in 1993 compared with 35,993 diagnoses in 2010, corresponding to an average annual increase of 24% since 1999. Overall, 2895 of 178,844 patients (1.6%) developed an SPM and accounted for 2960 metachronous events. Because of the dramatic rise in the incidence of thyroid cancer, almost half (47.6%) of the patients in this study were registered between 2008 and 2010. The highest incidence of SPM occurred in the salivary gland (SIR, 3.34; 95% confidence interval [CI], 2.12-5.01) followed, in decreasing incidence, by cancers of the kidney (SIR, 2.12; 95% CI, 1.74-2.57), hematopoietic system (SIR, 2.00; 95% CI, 1.59-2.49), brain and central nervous system (SIR, 1.6; 95% CI, 1.16-2.16), prostate (SIR, 1.47; 95% CI, 1.12-1.90), lung (SIR, 1.35; 95% CI, 1.22-1.50), and breast(SIR, 1.2; 95% CI, 1.11-1.30). It is noteworthy that there was a decrease in the rates of both stomach cancer and cervical cancer. This latter phenomenon affected the overall rates of SPM, and the overall patterns persisted across all 5-year time intervals. Statistical significance for the development of an SPM was highest between 6 and 10 years after a diagnosis of thyroid cancer. The largest proportion of patients who developed an SPM were diagnosed with thyroid cancer between 2003 and 2007, probably because the majority of patients were diagnosed during the latter half of the study, and this group was followed for at least 6 years. The authors conclude that there was a 6% increased risk for developing an SPM overall at any site after a diagnosis of thyroid cancer and that this risk was most evident within the first 10 years. In addition to being the first study of its kind to evaluate a Korean population with thyroid cancer, the study by Cho et al also includes the largest series to date of patients with thyroid cancer who were evaluated for their risk of developing an SPM. The second largest series used the Surveillance, Epidemiology, and End Results (SEER) database and only included 52,103 patients. Since its creation in 1999, the Korean population-based registry has been systematically updated; therefore, it reflects much more complete and accurate data compared with the hospital-based registry used in the earlier part of the study. Furthermore, the authors performed a detailed and thorough statistical analysis calculating

Computed Tomography in the Management of Adrenal Tumors: Does Size Still Matter?

Objective We sought to evaluate computed tomography (CT) imaging as a predictor of adrenal tumor pathology. Methods A retrospective review was conducted of patients who underwent unilateral adrenalectomy for an adrenal mass between January 2005 and July 2015. Tumors were classified as benign, indeterminate, or malignant based on preoperative CT findings. Results Of 697 patients who underwent unilateral adrenalectomy, 216 met the inclusion criteria. Pathology was benign in 88.4%, indeterminate in 2.3%, and malignant in 9.3%, with a median tumor diameter of 2.7 cm (interquartile range, 1.7–4.1 cm) and 9.5 cm (interquartile range, 7.1–12 cm) in the benign and malignant groups, respectively (P < 0.001). Of the tumors with benign features on CT, 100% (143/143) had benign final pathology. Conclusions Imaging characteristics of adrenal tumors on CT scan predict benign pathology 100% of the time. Regardless of size, when interpreted as benign on CT scan, laparoscopic adrenalectomy, if technically feasible, should be the technique used when surgery is offered, or close surveillance may be a safe alternative.

Molecular Profiles and the “Indeterminate” Thyroid Nodule

Although fine-needle aspiration (FNA) biopsy is the most accurate and reliable diagnostic test available for the evaluation of a thyroid nodule, 20–30 % of FNA results are indeterminate or suspicious. In order to improve upon the diagnostic accuracy of FNA, several ancillary molecular tests have emerged to further refine the diagnostic role of FNA biopsy and improve the accuracy of preoperative diagnosis of indeterminate thyroid lesions. Over the past decade, significant progress has been made in the investigation of these molecular markers, and promising findings have been reported. However, because of the complexity of surgical decision-making processes, the clinical usefulness and impact of these markers remain unclear. This chapter will review the efficacy and potential clinical utility of these molecular markers in preoperative diagnosis of an indeterminate thyroid nodule.

Association Between Age and Patient-Reported Changes in Voice and Swallowing After Thyroidectomy: Voice and Swallowing Changes after Thyroidectomy

Despite intact recurrent laryngeal nerves, patient‐reported voice and swallowing changes are common after thyroidectomy. The association between patient age or frailty status and these changes is unknown. The aim of this study was to evaluate the impact of age and frailty on the incidence of voice and swallowing alterations after thyroidectomy.