Faculty Bibliography

OBJECTIVE:To analyze clinical outcomes in a series of indeterminate thyroid nodules (ITNs) with repeat fine-needle aspiration (FNA) biopsy and results of genomic classifier. STUDY DESIGN/METHODS:Historical chart review. SETTING/METHODS:Tertiary care center. METHODS:We reviewed FNA samples from subjects with Bethesda III or IV diagnoses from January 2015 to December 2018 at a single institution and selected those with repeat FNA and ThyroSeq testing of the same nodule. Patient demographics, Bethesda classifications, ThyroSeq results, treatment detail, and surgical pathology, when available, were analyzed. RESULTS:< .0001). In excised nodules, the prevalence of malignancy and noninvasive follicular thyroid neoplasm with papillary-like nuclear features was 28% (n = 10) and 22% (n = 8), respectively, and all malignancies were low risk. CONCLUSION/CONCLUSIONS:In this case series, repeat FNA helped patients with ITNs avoid diagnostic surgery through reclassification to benign cytology. The risk of high-risk malignancy in ThyroSeq-positive nodules with repeat indeterminate cytology was low.

OBJECTIVE:The objective of this disease state clinical review is to provide clinicians with a summary of the nonsurgical, minimally invasive approaches to managing thyroid nodules/malignancy, including their indications, efficacy, side effects, and outcomes. METHODS:A literature search was conducted using PubMed and appropriate key words. Relevant publications on minimally invasive thyroid techniques were used to create this clinical review. RESULTS:Minimally invasive thyroid techniques are effective and safe when performed by experienced centers. To date, percutaneous ethanol injection therapy is recommended for recurrent benign thyroid cysts. Both ultrasound-guided laser and radiofrequency ablation can be safely used for symptomatic solid nodules, both toxic and nontoxic. Microwave ablation and high-intensity focused ultrasound are newer approaches that need further clinical evaluation. Despite limited data, encouraging results suggest that minimally invasive techniques can also be used in small-size primary and locally recurrent thyroid cancer. CONCLUSION/CONCLUSIONS:Surgery and radioiodine treatment remain the conventional and established treatments for nodular goiters. However, the new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses.

Thyroidectomy remains the gold standard treatment for benign, symptomatic, or enlarging thyroid nodules, malignant nodules, and metastatic lymph node disease. However, in the past 2 decades, image-guided interventional techniques have emerged as promising alternative treatments for these conditions. Percutaneous ethanol ablation is now an accepted first-line treatment for recurring cystic thyroid nodules. Thermal ablation techniques such as high-intensity focused ultrasound, laser ablation, radiofrequency ablation, and microwave ablation have shown efficacy in producing a nodular volume reduction of greater than 50% that is maintained for several years with resolution of local compressive symptoms. There is also increasing evidence that these techniques can effectively treat papillary thyroid microcarcinomas and recurrent metastatic lymph node disease. Because these interventional ablation techniques are performed safely in an outpatient setting, are well tolerated, and the risk for needing thyroid hormone supplementation is negligible, they are becoming a popular alternative treatment to surgical resection. In this comprehensive review, we discuss each of these percutaneous interventions: the devices and techniques, the advantages and disadvantages of each energy, and summarize the outcomes published in the literature.

Importance/UNASSIGNED:Genomic classifiers were developed to better guide clinicians in the treatment of indeterminate thyroid nodules (ITNs). To our knowledge, whether there is variation in the diagnostic accuracy of these tests depending on ITN size has not been previously studied. Objective/UNASSIGNED:To analyze the diagnostic performance of a genomic classifier in relation to ITN size. Design, Setting, and Participants/UNASSIGNED:A case series study with medical records review was conducted including all patients with a cytologic diagnosis of ITN managed with genomic classifier testing and surgery from January 2015 to December 2018 at NYU Langone Health. Demographics, ITN characteristics, genomic profiles, treatment, and final pathologic findings were recorded. Data analysis was conducted from March to April 2021. Main Outcomes and Measures/UNASSIGNED:The primary aim was to assess the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of a genomic classifier test (ThyroSeq) in relation to ITN size (<2, 2-4, and >4 cm). The secondary aim was to investigate the risk of cancer associated with genetic signatures. Results/UNASSIGNED:Of the 212 patients with 218 ITNs, 158 (74.5%) were women; median (SD) age was 49 (15.6) years. Genomic classifier results were positive in 173 ITNs (79.4%) treated with surgery. In this group of 173 positive ITNs, 46 (26.6%) were malignant on final pathologic testing. Overall, the observed cancer prevalence in the population was 23.9% (52 ITNs). In 45 ITNs that underwent surgery despite a negative genomic classifier interpretation, 6 (13.3%) were malignant. The PPV of a positive test was 27% and the NPV was 87%. The PPV and NPV findings improved as the ITN size increased (<2 cm [n = 98]: PPV, 25%; NPV, 79% vs >4 cm [n = 33]: PPV, 50%; NPV, 89%). Test specificity was higher in larger ITNs (<2 cm: 15% vs >4 cm: 40%; P = .01). Isolated RAS sequence variations were the most common variant identified in malignant nodules (11 [21.1%] of all ITNs), followed by BRAF variants (7 [13.5%] of all ITNs). Conclusions and Relevance/UNASSIGNED:In this case series, the performance of the ThyroSeq test improved for larger ITNs. The risk of cancer in large ITNs with negative test results was low. These data suggest that, in genomic classifier-negative ITNs larger than 4 cm, initial management of thyroid lobectomy may be sufficient.

BACKGROUND:Nephrolithiasis is a sequela of primary hyperparathyroidism and an indication for parathyroidectomy. The prevalence of primary hyperparathyroidism in patients with nephrolithiasis is 3% to 5%; however, recent studies suggest that many hypercalcemic patients with nephrolithiasis never undergo workup for primary hyperparathyroidism. Our goal is to evaluate primary hyperparathyroidism screening rates at a tertiary academic health institution and identify opportunities to increase referral rates in patients presenting with nephrolithiasis. METHODS:We retrospectively reviewed 15,725 patients across an academic health system who presented with nephrolithiasis between 2012 and 2020. Calcium levels measured within 6 months of presentation were identified, and those with hypercalcemia (≥10.3 mg/dL) were reviewed if parathyroid hormone levels were measured. Patients with primary hyperparathyroidism were evaluated to see if they were referred to a specialist for treatment. RESULTS:Of 15,725 patients presenting with nephrolithiasis, 12,420 (79%) had calcium levels measured; 630 patients (4.0%) were hypercalcemic, and 207 (33%) had parathyroid hormone levels measured. Patients were more likely to have parathyroid hormone levels sent if they were older, had higher calcium levels, or presented to an outpatient clinic (P = .028, P = .002, P < .001). We identified 89 patients (0.6%) with primary hyperparathyroidism, of which only 35 (39%) were referred for treatment. CONCLUSION/CONCLUSIONS:The proportion of patients presenting with nephrolithiasis ultimately diagnosed with primary hyperparathyroidism was significantly lower than others have reported. Additionally, a substantial number of patients with nephrolithiasis did not have calcium and/or parathyroid hormone levels measured. These missed opportunities for diagnosis are critical as early definitive management of primary hyperparathyroidism can prevent recurrent nephrolithiasis and other primary hyperparathyroidism-related end organ effects.

Introduction: Molecular tests such as ThyroSeq are recommended in the workup of cytologically indeterminate thyroid nodules (ITN). While repeat molecular testing is often performed after repeat fine needle aspiration (FNA) yields persistently indeterminate cytology, ThyroSeq's inter-test reliability is unclear. We assessed consistency of initial and repeat ThyroSeq analyses performed on samples from the same thyroid nodules.
Method(s): All thyroid nodules diagnosed as ITN on consecutive FNAs that received ThyroSeq with both biopsies from 2014-2018 at our institution, were reviewed. Initial analysis was ThyroSeq v2 while repeat was v2 or v3. Nodules with gene mutations, fusions, or copy number alterations (CNA) were considered ThyroSeq-positive.
Result(s): During the study period, 30 patients underwent ThyroSeq analysis on initial and repeat FNA samples (median interval=21 months). On initial testing, 27 (90%) nodules were ThyroSeq-negative and 3 (10%) low-risk mutations (RAS, EIF1AX, TSHR) were identified. Repeat ThyroSeq re-identified these 3 nodules and also interpreted 9 initially ThyroSeq-negative nodules as positive (kappa=0.286). All 9 molecular alterations were low-risk, most were identified on v3 (7, 77.8%), and CNA was the most common change (6, 66.7%). Of 12 patients with ThyroSeq-positive nodules, 8 underwent lobectomy. Final pathology identified low-risk malignancy in 3 nodules; the remainder were benign.
Conclusion(s): New findings on repeat ThyroSeq are possible. Whether these findings were detected by expanded panel or are the result of de-novo changes is unknown. The risk of missing high-risk changes appears to be low. More studies are needed to characterize the concordance of ThyroSeq analyses and natural evolution of ITNs.
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Introduction: The prognostic significance of a singular RAS mutation in cytologically indeterminate thyroid nodules (ITN) is unclear. This study aimed to analyze the incidence of malignancy and clinical outcomes of ITNs diagnosed on fine needle aspiration (FNA) cytology with RAS mutations.
Method(s): All FNA ITNs that underwent ThyroSeq testing and thyroidectomy from 2014-2018 were reviewed. ITNs with RAS (N-, H-, or K-RAS) mutations identified on ThyroSeq testing were selected. Demographics, Bethesda classifications, genomic profiles, treatment, final pathology, and clinical outcomes were recorded.
Result(s): During the study period, 93 patients with cytologic diagnosis of ITN and RAS mutations were identified. The mean nodule size was 2.2 cm (range: 0.5-6.6 cm). Most nodules were classified as Bethesda III (77, 82.8%). NRAS mutations were the most common (53, 57%), followed by HRAS (24, 25.8%), and KRAS (16, 17.2%). The majority of patients were treated with thyroid lobectomy (67, 72%). On final pathology, 9 (10%) were diagnosed as malignant (follicular variant of papillary thyroid carcinoma [FVPTC]) and were distributed among all 3 RAS variants (NRAS: 4 [7.5%]; HRAS: 4 [16.7%]; KRAS: 1 [6.3%]; p=0.4). Most FVPTCs were encapsulated (8, 88.9%). With a median follow up of 19 months (interquartile range = 8-35), no recurrences or progression was seen.
Conclusion(s): The risk of malignancy in ITNs with singular RAS mutations is low. All malignancies were low-risk. Our findings demonstrate a low incidence of high-risk malignancy in ITNs with RAS mutations, suggesting that initial management with conservative approaches such as thyroid lobectomy may be justified.
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BACKGROUND:Unlike medullary thyroid carcinoma in adults, the vast majority of pediatric medullary thyroid carcinoma is hereditary. Pediatric medullary thyroid carcinoma is known to have different genetic alterations driving tumorigenesis, but it is not known if pediatric medullary thyroid carcinoma has different clinicopathologic features. This study aims to identify which pediatric medullary thyroid carcinoma patients might warrant elective neck dissection. METHODS:We selected all patients ages 0 to 19 diagnosed with clinically evident medullary thyroid carcinoma in the National Cancer Database between 2004 to 2016. Clinicopathologic factors, treatments, and outcomes were analyzed and compared between this cohort and adults (ages ≥20) with medullary thyroid carcinoma. RESULTS:One hundred twenty-five pediatric medullary thyroid carcinoma (median age: 13) and 5,086 adult medullary thyroid carcinoma (median age: 57) patients were identified. Pediatric patients had smaller tumors (median diameter: 1.2 cm vs 2.0 cm; P < .001), lower rates of nodal metastases (n = 31, 36.9% vs 1,689, 50.4%; P = .02) but double the incidence of multifocal tumors (n = 70, 59.3%, vs 1,412, 29.9%; P < .001) compared with adults. Multifocal tumors conferred a significantly increased risk of nodal metastases in adult medullary thyroid carcinoma (64.4% vs 43.2%; P < .001) but not pediatric medullary thyroid carcinoma (37.7% vs 35.7%; P = .85). Nodal metastases were more frequent among older children (0-5 years: 0.0%, 6-12: 40.7%, 13-19: 41.7%; P = .04). However, rates of occult nodal metastases were similar between older children (6-19 years: n = 12, 21.4%) and adults (557, 25.8% P = .56). CONCLUSION/CONCLUSIONS:Pediatric medullary thyroid carcinoma has lower rates of lymph node metastases compared with adults. The risk of nodal disease was low among the youngest children, but older children ages 6 to 19 were at considerable risk for occult metastases. These findings could guide clinicians in selecting pediatric patients considered for elective lymph node dissection.