Challenges in Risk Stratification of Solid Atypical Mixed Echogenicity Thyroid Nodules.

Background: To determine the prevalence and risk of malignancy (ROM) in solid atypical mixed echogenicity thyroid nodules (SAMENs) with sonographic patterns not classifiable by the 2015 American Thyroid Association Ultrasound Risk Stratification System (NC ATA). Methods: We searched our prospectively collected endocrine surgery thyroid nodule (TN) database, with particular attention to those solid nodules that were NC ATA. An algorithm assigned each into one of the five ATA risk groups per the 2015 American Thyroid Association Ultrasound Risk Stratification System (ATA USRSS). TNs that the algorithm could not assign to a risk group were deemed NC ATA and were subsequently analyzed. Additionally, we categorized this group using an algorithm based on the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). We were specifically interested in the characteristics that resulted in non-classification by the 2015 ATA USRSS and the fine needle aspiration biopsy (FNAB) cytology and surgical pathology results from the group. Results: We evaluated data from 5,040 nodules, of which 1,772 had surgical pathology. There were 150 solid nodules not classified by 2015 ATA USRSS, all of which demonstrated atypical features along with iso-, hetero-, hyper-and mixed echogenicity (solid atypical mixed echogenicity nodules-SAMENs). Sixty of these nodules were excised and sent for surgical pathology, while 90 were followed without surgical excision. Out of the 90 that did not undergo surgery, 82 underwent FNAB with cytologic evaluation. Of our 150 SAMENs, 40 were malignant by surgical histology and six were likely malignant by cytology (total SAMEN ROM without noninvasive follicular thyroid neoplasm with papillary-l ike nuclear features 31%). The most common sonographic pattern present in our SAMEN group consisted of an isoechoic solid component with microcalcifications (28/40-70% of all excised malignant nodules). In our excised malignant SAMENs, 50% demonstrated follicular-patterned neoplastic architecture while 48% displayed papillary architecture. Conclusion: Our study demonstrates that SAMENs with at least one suspicious sonographic feature: including (1) microcalcifications; (2) irregular or other suspicious margins,;opulation, and a higher ROM (31%) than the intermediate-risk group of the 2015 ATA USRSS (10-20%).

NEOADJUVANT LENVATINIB IN ADVANCED UNRESECTABLE MEDULLARY THYROID CARCINOMA: A CASE REPORT.

OBJECTIVE: Medullary thyroid carcinoma, a rare form of thyroid cancer, is typically managed with surgical excision. However, in patients with locally-invasive tumors, an aggressive surgical attempt may result in unnecessary morbidity. Neoadjuvant tyrosine kinase inhibition has been utilized to downstage tumors prior to surgical excision but its role in thyroid cancer treatment is not well-established. We describe the potential role that lenvatinib, a tyrosine kinase inhibitor, may have as a neoadjuvant agent in advanced locoregional medullary thyroid carcinoma. METHODS: Our patient presented with a large left thyroid mass and bulky left lateral neck lymphadenopathy. Imaging studies revealed a hypervascular and locally-invasive tumor with metastatic central and left lateral lymphadenopathy. A lymph node biopsy cytologic evaluation and plasma calcitonin concentration of 32,926 pg/mL were consistent with medullary thyroid carcinoma. Rearranged during transfection germline mutation testing was negative. A multidisciplinary team of physicians deemed the patient a poor surgical candidate and recommended 4 months of neoadjuvant lenvatinib therapy to reduce tumor burden with a subsequent reassessment of resectability. Given the tumor's hypervascularity, lenvatinib was chosen due its potent vascular endothelial growth factor receptor inhibition, as well as its availability at our institution. RESULTS: Lenvatinib therapy resulted in rapid regression of tumor volume (approximately 70% reduction) as documented by computed tomography and ultrasound. Surgery after 4 months of treatment resulted in a 99% reduction in serum calcitonin and imaging studies 6 months later showed no residual disease. CONCLUSION: Lenvatinib has potential as a neoadjuvant agent in advanced medullary thyroid carcinoma, and permitted tumor resection in this previously inoperable patient.

STATISTICAL COMPARISON OF AFIRMA GSC AND AFIRMA GEC OUTCOMES IN A COMMUNITY ENDOCRINE SURGICAL PRACTICE: EARLY FINDINGS.

OBJECTIVE: The Veracyte Afirma Gene Expression Classifier (GEC) has been the most widely used negative predictive value molecular classifier for indeterminate cytology thyroid nodules since January 2011. To improve the specificity and further reduce unnecessary thyroid surgeries, a second-generation assay (Afirma Genetic Sequence Classifier [GSC]) was released for clinical use in August 2017. We report 11 months of clinical outcomes experience with the GSC and compare them to our 6.5-year experience with the GEC. METHODS: We searched our practice registry for FNAB nodules with Afirma results from January 2011through June 2018. GEC versus GSC results were compared overall, in oncocytic and nononcocytic aspirates and by pathologic outcomes. RESULTS: GSC identified less indeterminate cytology nodules as suspicious (38.8%; 54/139) when compared to GEC (58.4%; 281/481). There was a decrease of in the percentage of oncocytic fine-needle aspiration thyroid biopsy (FNAB) subjects classified as suspicious in the GSC group, with 86 of 104 oncocytic indeterminates (82.7%) classified as suspicious by GEC and 12 of 34 (35.3%) classified as suspicious by GSC. The surgery rate in patients with oncocytic aspirates fell from 56% in the GEC group to 31% in the GSC-evaluated group (45%). Pathology analysis demonstrated a false-negative percentage for an incomplete surgical group of 9.5% for GEC and 1.2% for GSC. CONCLUSION: Our GSC data suggest that the GSC further reduces surgery in indeterminate thyroid nodules by improving the specificity of Afirma technology without compromising sensitivity. A primary determinant for this change is a significant improvement in the specificity of the Afirma GSC test in oncocytic FNAB aspirates. ABBREVIATIONS: FNAB = fine-needle aspiration biopsy; GEC = Gene Expression Classifier; GSC = Genetic Sequence Classifier.

COMMUNITY ENDOCRINE SURGICAL EXPERIENCE WITH FALSE-NEGATIVE AFIRMA GEC® RESULTS: 2011-2017.

OBJECTIVE: Afirma Gene Expression Classifier® (Afirma GEC) molecular analysis (Veracyte, Inc, San Francisco, CA) is a negative predictive value test developed to reduce the number of thyroidectomies in thyroid nodule patients with indeterminate cytology. GEC technology has reportedly reduced unnecessary thyroid surgery, but few studies have examined Afirma GEC false-negative rates, since usually patients with GEC benign nodules do not undergo surgery for definitive diagnosis. Occasionally, Afirma GEC benign patients require removal of their thyroid nodules for other reasons; this work describes the incidence of malignancy and noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) in this population. METHODS: We reviewed our community endocrine surgical practice database for patients who had undergone thyroid surgery from January 2011 through April 2017 despite benign Afirma GEC results. RESULTS: Afirma GEC testing was completed for 475 patients during the study period. Surgery was clinically indicated for other reasons in 42 of the 193 patients (22%) with Afirma GEC benign results. Malignancy or NIFTP in the targeted nodule was found in the final histologic evaluation of 14 of the 42 Afirma GEC benign surgical patients. The Afirma GEC false-negative percentage for our incomplete surgical group (FNP-ISG), defined as the surgically proven false negatives divided by the total Afirma GEC benign patients, was 7.3%. CONCLUSION: Our high surgical rate in Afirma GEC benign nodules reveals an FNP-ISG of 7.3% in our community endocrine surgical patient population; this value exceeds the 5.7% reported in the multicenter 2012 Afirma GEC validation study. ABBREVIATIONS: Afirma GEC = Afirma Gene Expression Classifier; FNA = fine-needle aspiration; FNP = false-negative percentage; FNP-ISG = false-negative percentage for an incomplete surgical group; NIFTP = noninvasive follicular thyroid neoplasms with papillary-like nuclear features.

Pharyngoesophageal diverticula simulating thyroid nodules: An unusual occurrence with unique features.

Pharyngoesophageal diverticula (PED) of the Zenker's and Killian-Jamieson types arise in close proximity to the thyroid gland, and may rarely be confused with a thyroid nodule on ultrasonography. In this brief report, we detail the cytologic, clinical, and radiologic findings of three PED that were thought to be thyroid nodules, and were subjected to fine-needle aspiration (FNA). The patients were females with an age range of 51-64 years. All three patients had multiple thyroid nodules, and two patients reported symptoms attributable to the diverticulum. Nodule sizes ranged from 1.0 to 2.7 cm, and either the right or left thyroid lobe could be involved. Microcalcifications were present by ultrasonography in all three cases. FNA of these thyroid nodule mimics showed squamous cells with granular or amorphous debris, bacterial and/or fungal colonies, inflammation, and food particles. These cytologic features, particularly the presence of vegetable or meat fragments, are characteristic, and have also been reported in the few previous reports of PED. The presence of a diverticulum was confirmed with imaging studies in all our patients. Although a rare occurrence, the inadvertent FNA of a PED masquerading as a thyroid nodule is important to recognize, as a recommendation for appropriate radiologic studies could potentially avoid inappropriate therapy for thyroid disease.

Noninvasive Encapsulated Follicular Variant of Papillary Thyroid Cancer: Clinical Lessons from a Community-Based Endocrine Surgical Practice.

Objective. Retrospective studies have found that noninvasive encapsulated follicular variant of papillary thyroid cancer (EFVPTC) exhibits highly indolent clinical behavior. We studied the clinical features of our patients with noninvasive EFVPTC tumors culled from a community endocrine surgical practice registry over the past four years. Methods. We interrogated the Memorial Center for Integrative Endocrine Surgery (MCIES) Registry for all recorded encapsulated follicular variant of papillary cancer pathologic diagnoses. We identified a subgroup of patients without capsular or vascular invasion and studied their clinical characteristics. Results. Thirty-seven patients met inclusion and exclusion criteria. The typical patient was young and female. Nodules averaged 3.1 cm in greatest dimension by ultrasound evaluation. Thirteen patients were found to have synchronous malignancies elsewhere in the thyroid (35%). At the time of this writing, we have not seen a clinical recurrence in any of our 37 noninvasive EFVPTC patients. Conclusions. Early clinical follow-up data suggests that the majority of noninvasive EFVPTC tumors exhibit indolent behavior, but clinical decision-making with regard to completion thyroidectomy, central lymph node dissection, and adjunctive radioiodine therapy often depends on the amount and type of synchronous thyroid cancer detected elsewhere in the thyroid gland and the central neck.

Unusual manifestation of parathyroid carcinoma in the setting of papillary thyroid cancer.

OBJECTIVE: To describe a rare manifestation of parathyroid carcinoma in association with papillary thyroid carcinoma. METHODS: We describe the clinical history, findings on physical examination, results of laboratory studies, imaging findings, and histopathologic features of a woman with 2 previously palpable thyroid nodules and mild hypercalcemia. RESULTS: A 79-year-old woman presented to our endocrinology clinic for reevaluation of 2 thyroid nodules and long-standing hyperparathyroidism. She initially had undergone assessment 6 years previously, at which time an intact parathyroid hormone level was 89 pg/mL (reference range, 10 to 69) and the serum calcium concentration was 10.4 mg/dL (reference range, 8.2 to 10.2) in conjunction with normal alkaline phosphatase, creatinine, and 25-hydroxyvitamin D levels. Subsequently, she was found to have multifocal papillary thyroid cancer in the right thyroid lobe and a 5-cm parathyroid carcinoma in the left side. CONCLUSION: Synchronous parathyroid and thyroid carcinomas are extremely rare. To our knowledge, our current case is the first documented patient with parathyroid carcinoma who had a clinical presentation consistent with longstanding mild adenoma in addition to synchronous papillary thyroid carcinoma.

Unusual recurrence of hypercalcemia due to concurrent parathyroid adenoma and parathyroid sarcoidosis with lymph node involvement.

OBJECTIVE: To describe a patient presenting with the rare findings of synchronous parathyroid adenoma and parathyroid sarcoidosis. METHODS: We describe the clinical history, physical examination findings, laboratory values, imaging findings, and pathologic data of a man who developed recurrent severe hypercalcemia after successful parathyroidectomy. RESULTS: A 67-year-old man had the following initial blood test results: calcium, 11.1 mg/dL (reference range, 8.5-10.6 mg/dL); albumin 4.0 g/dL (reference range, 3.2- 5.2 g/dL); intact parathyroid hormone, 166 pg/mL (reference range, 10-69 pg/mL); creatinine, 1.9 mg/dL; 25-hydroxyvitamin D, 15 ng/mL (reference range, 30-80 ng/mL); and 1,25-dihydroxyvitamin D, 44 pg/mL (reference range, 16-72 pg/mL). Chest x-ray was normal, and delayed images from a technetium Tc 99m sestamibi scan showed increased activity in the right lower pole of the thyroid. Two months after successful parathyroidectomy, the patient was admitted to the hospital with a serum calcium concentration of 17 mg/dL. Pathologic examination of the resected gland confirmed the diagnosis of parathyroid adenoma, and subsequent review disclosed the presence of noncaseating granulomas within the adenoma. CONCLUSIONS: Sarcoidosis with parathyroid involvement causing severe hypercalcemia is unique to this case. Recurrent hypercalcemia after successful resection of a parathyroid adenoma may require consideration of potential causes other than the initial diagnosis.

Quality improvement by standardization of procurement and processing of thyroid fine-needle aspirates in the absence of on-site cytological evaluation.

BACKGROUND: Thyroid nodules are relatively common and are routinely evaluated by fine-needle aspiration cytology, usually performed by clinicians. We noticed qualitative and/or quantitative variability in samples submitted to the cytopathology laboratory from clinicians, for example, the number of glass slides submitted (2-25) and air-dried smears versus alcohol-fixed slides, with variability in specimen adequacy and interpretability. The objective of this study was to standardize the preanalytic variables to determine if there is an improvement in the specimen quality. METHODS: We standardized the method of collection (ultrasound-guided, 25-gauge needle, four passes) and preparation of samples (four total smears: two air-dried, two fixed, with liquid-based preparation and/or cell block) and personnel involved. RESULTS: Standardization of thyroid nodule fine-needle aspiration and sample preparation by clinical staff resulted in an overall improvement in the quality of sample (odds ratio = 3.82, 95% confidence interval 2.02-7.24, p < 0.0001) with an increased proportion of satisfactory samples from 67% prestandardization to 89% poststandardization. CONCLUSIONS: Standardization resulted in a significant improvement in specimen interpretability.

Graves' disease in the cervical thyroid and thyroglossal duct remnant: case report and review of literature.

OBJECTIVE: To describe a patient with a rare presentation of Graves' disease in the cervical thyroid and thyroglossal duct remnant. METHODS: We present a detailed case report, including initial manifestations, laboratory findings, and radiologic evaluation of a patient with Graves' disease. A review of the relevant medical literature is included. A search for articles in the MEDLINE database from 1966 to November 2003 was performed with use of the following key words: thyroglossal duct remnant, thyroglossal duct cyst, thyrotoxicosis, Graves' disease, hyperthyroidism, and ectopic thyroid tissue. The reference lists from the articles obtained from the MEDLINE database were then reviewed for other pertinent articles. English abstracts of non-English articles were also reviewed. RESULTS: A 63-year-old woman presented with thyrotoxicosis. Examination of her neck was notable for a 3.5-cm soft, mobile midline mass overlying the thyroid cartilage. She had no extrathyroidal manifestations of Graves' disease. The rest of the physical examination was unremarkable. Laboratory studies revealed a thyrotropin (thyroid-stimulating hormone) level of 0.01 microIU/mL (normal range, 0.3 to 6.6) and free thyroxine level of 4.7 ng/dL (normal range, 0.6 to 1.5). An ultrasound study showed a normal-appearing thyroid and an infrahyoidal neck mass (3.0 by 1.7 cm). A radioiodine (123I) thyroid scan demonstrated diffuse homogeneous uptake throughout the gland in conjunction with 66.6% uptake at 24 hours. In addition, a large rounded area of increased activity slightly left of the midline was noted. The left anterior oblique image showed that this area was not continuous with the left upper pole. We thought that this finding represented a hyperfunctioning thyroglossal duct cyst or remnant tissue. Our patient subsequently underwent radioiodine therapy with 15.56 mCi of 131I. A review of the English-language literature revealed only rare case reports of thyrotoxicosis in ectopic thyroid tissue. CONCLUSION: Although the occurrence of thyrotoxicosis is common, to the best of our knowledge this is only the second case of Graves' disease involving the thyroglossal duct remnant reported in the English literature.