Molecular Testing Has Limited Utility in the Surgical Evaluation of Bethesda III Thyroid Nodules.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology has 6 diagnostic categories, each with an implied cancer risk of malignancy (ROM). Bethesda III, defined as atypia or follicular lesions of undetermined significance (AUS/FLUS) on fine needle aspiration (FNA), has an indeterminate ROM. This study investigates the utility of Afirma Gene Expression Classifier (GEC) and Thyroid Sequencing (ThyroSeq) molecular testing to predict malignancy in AUS/FLUS thyroid nodules. METHODS: A retrospective review of prospectively collected data of 1457 patients with index thyroid nodules who underwent FNA and thyroidectomy at a single academic institution was performed. Use of GEC or ThyroSeq for AUS/FLUS thyroid nodules was examined. GEC testing was reported benign or suspicious for malignancy whereas ThyroSeq testing was reported on a spectrum of low, intermediate or high ROM. Descriptive statistics were utilized to compare the ROM among AUS/FLUS thyroid nodules. RESULTS: Of 1457 patients with FNA thyroid cytology, 359 (25%) corresponded to AUS/FLUS results. There were 132 (37%) patients with GEC testing and 88 (24%) had ThyroSeq testing. ROM without GEC or ThyroSeq testing was 49%, whereas ROM with suspicious GEC was 55%. ROM with positive ThyroSeq was 73%. Among ThyroSeq patients, 43 had intermediate-risk mutations with 60% malignancy, and 23 had high-risk mutations with 96% malignancy (P < 0.01). CONCLUSION: Surgical patients with AUS/FLUS thyroid nodules have a high ROM. High-risk ThyroSeq testing may have some utility in predicting malignancy, but GEC and intermediate-risk TGC results have limited value. Surgeons should carefully consider the utility of molecular tests to determine surgical resection.

Fine needle aspiration and the Bethesda system: Correlation with histopathology in 1,228 surgical patients.

BACKGROUND: Fine-needle aspiration combined with the Bethesda System for Reporting Thyroid Cytopathology is indispensable in the diagnostic evaluation of thyroid nodules. Their increased detection over the last few decades mandates the determination of which thyroid nodules require surgical management for malignancy. This study examines the correlation of fine-needle aspiration to final histopathology of dominant thyroid nodules in a large series of surgical patients undergoing thyroidectomy at a single academic institution. METHODS: A retrospective review of prospectively collected data of 1,228 patients who underwent fine-needle aspiration for a dominant thyroid nodule and thyroidectomy from a single institution between 2010 and 2019 was performed. The cases were stratified into all 6 Bethesda categories. Fine-needle aspiration results were compared to index thyroid nodule malignancy on final histopathology. RESULTS: Of 1,228 patients who underwent thyroidectomy, the overall malignancy rate was 53%. When fine-needle aspiration was stratified by the Bethesda System for Reporting Thyroid Cytopathology, malignancy rate was 29% for nondiagnostic; 11% for benign; 51% for atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); 47% for follicular neoplasm/suspicious for follicular neoplasm (FN/SFN); 84% for suspicious for malignancy (SFM); and 98% for malignant results on final histopathology. There was a false positive rate of 1% and false negative rate ranging from 7 to 11%. CONCLUSION: Fine-needle aspiration of a dominant thyroid nodule in patients who underwent thyroidectomy had an overall malignancy rate of 53%. False negative and false positive rates are within the reported range in surgical patient populations. The majority of patients with AUS/FLUS, FN/SFN and SFM results with underlying malignancy received the appropriate surgical resection.

High Rates of Underlying Thyroid Cancer in Patients Undergoing Thyroidectomy for Hyperthyroidism.

BACKGROUND: The rate of thyroid cancer in patients with hyperthyroidism is reported to be rare, and patients with toxic thyroid nodules do not routinely undergo fine-needle aspiration (FNA) to evaluate for malignancy. However, higher rates of malignancy in hyperthyroid patients may exist than previously reported. This study examines the rate of malignancy in patients with hyperthyroidism who have undergone thyroidectomy. METHODS: A retrospective review of prospectively collected data of 138 patients with hyperthyroidism who underwent thyroidectomy at a single institution was performed. Patients were divided into three groups: Graves' disease (n = 80), toxic multinodular goiter (n = 46), and toxic solitary nodule (n = 12). Patients with previous thyroid surgery were excluded from the study. All patients had biochemical confirmation of hyperthyroidism with thyroid-stimulating hormone <0.1 mIU/L and clinical diagnosis by a referring physician. RESULTS: Of 138 patients, 22% (31/138) were found to have malignancy on final pathology. The breakdown of malignancy by hyperthyroid condition was as follows: 16% in Graves' disease, 24% in toxic multinodular goiter patients, and 50% in toxic solitary nodule patients. CONCLUSIONS: There is a clinically significant rate of malignancy seen in patients who undergo thyroidectomy for hyperthyroidism. Patients with distinct thyroid nodules in the presence of hyperthyroidism may have the highest rates of malignancy and should undergo appropriate workup with ultrasound and FNA to exclude underlying malignancy. In cases with suspicious ultrasound features and/or FNA cytopathology, surgical treatment should be considered as initial management.

Increased Incidental Thyroid Cancer in Patients With Subclinical Chronic Lymphocytic Thyroiditis.

BACKGROUND: The autoimmune process and increased TSH associated with chronic lymphocytic thyroiditis (CLT) are factors that may promote development of thyroid cancer. When surgically removed, the cellular changes of CLT are commonly seen surrounding thyroid cancers. This study investigates the malignancy rate in CLT patients when compared with non-CLT patients after thyroidectomy. METHODS: A retrospective review of prospectively collected data for 1268 patients with index thyroid nodules who underwent thyroidectomy at a single institution was performed. Patients were excluded if they had previous thyroid surgery, known thyroid cancer, Graves' disease, family history of thyroid cancer, and history of radiation exposure. Patients were subdivided into CLT and non-CLT groups by final pathology. Final pathology was reviewed and grouped into cancer in the index thyroid nodule and incidental thyroid cancers. Chi-squared analyses were performed using SAS. RESULTS: Of 359 patients that met study criteria, 52 had CLT. Overall, the malignancy rate was 37% in both CLT patients (19/52) and non-CLT patients (114/307) (P = 0.86). However, incidental thyroid cancer was found in 15% (8/52) of CLT patients and 10% (31/307) of non-CLT patients (relative risk = 1.52) who had no index nodule cancer. The breakdown of incidental cancer subtype in CLT patients was classic variant papillary thyroid carcinoma (PTC), n = 3; follicular variant PTC, n = 5. CONCLUSIONS: Patients with CLT have a 1.5-fold increased risk of incidental PTC. CLT should be considered a risk factor for incidental thyroid cancer, and patients with this thyroid condition should be counseled and monitored periodically for underlying thyroid malignancy.

Inverse Relationship of BMI to TSH and Risk of Papillary Thyroid Cancer in Surgical Patients.

BACKGROUND: Obesity and thyroid cancer has increased in recent decades. Thyroid malignancy is linked with elevated thyroid-stimulating hormone (TSH) levels, which may have a positive association with body mass index (BMI). This study examines obesity and TSH level effect on papillary thyroid cancer (PTC) risk in a surgical population. METHODS: A retrospective review of prospectively collected data for 991 patients who underwent thyroidectomy at a single institution was performed. Patients were stratified according to BMI into three groups: nonobese (18.5-29.9 kg/m2), obese (30-39.9 kg/m2), and morbidly obese (≥40 kg/m2). Further subdivisions into benign and malignant outcomes based on final pathology were compared with preoperative TSH levels. Subanalyses according to sex were also performed. RESULTS: Of 517 patients with PTC, rate of malignancy (ROM) decreased (55% versus 48% versus 41%, P < 0.05) as BMI increased with a concomitant decrease in average TSH levels (1.75 versus 1.69 versus 1.41 mU/L), respectively. According to sex, decreased ROM (53% versus 44% versus 42%, P < 0.05) and TSH (1.79 versus 1.70 versus 1.33 mU/L), respectively, with increased BMI was identified in women. However, decrease of ROM was not significant in men with increasing TSH levels as BMI increased. Male sex was associated with increased PTC risk (OR, 1.916; 95% CI, 1.331-2.759), whereas obesity with reduced PTC risk (OR, 0.736; 95% CI, 0.555-0.976). CONCLUSIONS: Higher BMI correlates with decreased PTC rates and lower TSH levels and suggests other factors may be involved in thyroid tumorigenesis. Obese patients with thyroid cancer should not be managed differently compared with nonobese patients.