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.

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.