Sonographic Evaluation of Intrathyroid Metastases.

OBJECTIVES: Intrathyroid metastases from extrathyroid primary tumors are rare. Clinical findings may be subtle, but detection of intrathyroid metastases has improved with sonography. The objective of this study was to evaluate the sonographic appearance of intrathyroid metastases. METHODS: Patients with thyroid masses with cytopathologic features matching those of an extrathyroid primary tumor were retrospectively identified. The appearances of intrathyroid metastases on sonography were reviewed for the following features: size, margin regularity, echogenicity, echotexture, vascularity on power or color Doppler ultrasonography, and the presence or absence of any associated cervical adenopathy. RESULTS: The study included 52 patients. The most frequent primary tumor sites were lung, head and neck, and breast. Intrathyroid metastases presented as a discrete nodule in 34 patients and as diffuse infiltration of the gland in 18 patients. The discrete nodules ranged in size from 1.1 to 5.6 cm (mean ± SD, 2.5 ± 1.2 cm). Thirty-three lesions (63%) had irregular margins, and 19 (37%) had well-defined margins. Most of the lesions were heterogeneously hypoechoic (n = 50, 96%). Vascularity was present in 32 of 50 measured lesions (64%) that were evaluated with Doppler sonography. Cervical adenopathy was present in 37 patients (71%). CONCLUSIONS: Intrathyroid metastases have sonographic characteristics similar to those described for both benign and malignant thyroid diseases. In patients with a previous or current extrathyroid malignancy, thyroid nodules or diffuse infiltration of the thyroid gland on sonography should be viewed as a potential intrathyroid metastasis and evaluated via ultrasound-guided fine-needle aspiration regardless of the site of the primary tumor.

Use of transoral sonography with an endocavitary transducer in diagnosis, fine-needle aspiration biopsy, and intraoperative localization of retropharyngeal masses.

OBJECTIVE: The purpose of this article is to describe the use of transoral sonography in the diagnosis, fine-needle aspiration (FNA) biopsy, and intraoperative localization of retropharyngeal masses. MATERIALS AND METHODS: We reviewed images and data for eight patients with a retropharyngeal mass identified on CT, MRI, or PET/CT as being suspicious for a metastatic Rouviere node. Transoral ultrasound was performed using a commercially available endorectal or endovaginal transducer. Transoral ultrasound-guided FNA biopsy was performed using a needle guide attached to the transducer shaft. Color and power Doppler imaging were used to identify the internal carotid artery and jugular vein and to plan the safest path to the targeted mass. The mass was intraoperatively localized by marking the mucosa with a permanent marker or by injecting methylene blue. RESULTS: There were six patients with a history of thyroid cancer (five papillary cancers and one medullary cancer), one patient with a history of esthesioneuroblastoma, and one patient with no history of cancer. Transoral ultrasound imaging was successful in all eight patients. Transoral ultrasound-guided FNA biopsy was performed in four patients, and a satisfactory cytologic diagnosis was obtained in all cases, although in one of those four cases, an additional core biopsy with an 18-gauge needle was performed to completely rule out lymphoma. Six patients underwent a transoral resection of the lesion. In three of them, the lesion was localized intraoperatively by making a mark on the mucosa and in one case by adding transoral ultrasound-guided injection of methylene blue. CONCLUSION: Transoral ultrasound can be used to visualize, sample, and localize abnormal masses in the retropharyngeal space, such as metastatic Rouviere nodes in patients with a history of head and neck cancer.

Phosphoproteomic analysis of signaling pathways in head and neck squamous cell carcinoma patient samples.

Molecular targeted therapy represents a promising new strategy for treating cancers because many small-molecule inhibitors targeting protein kinases have recently become available. Reverse-phase protein microarrays (RPPAs) are a useful platform for identifying dysregulated signaling pathways in tumors and can provide insight into patient-specific differences. In the present study, RPPAs were used to examine 60 protein end points (predominantly phosphoproteins) in matched tumor and nonmalignant biopsy specimens from 23 patients with head and neck squamous cell carcinoma to characterize the cancer phosphoproteome. RPPA identified 18 of 60 analytes globally elevated in tumors versus healthy tissue and 17 of 60 analytes that were decreased. The most significantly elevated analytes in tumor were checkpoint kinase (Chk) 1 serine 345 (S345), Chk 2 S33/35, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) S65, protein kinase C (PKC) ζ/ι threonine 410/412 (T410/T412), LKB1 S334, inhibitor of kappaB alpha (IκB-α) S32, eukaryotic translation initiation factor 4E (eIF4E) S209, Smad2 S465/67, insulin receptor substrate 1 (IRS-1) S612, mitogen-activated ERK kinase 1/2 (MEK1/2) S217/221, and total PKC ι. To our knowledge, this is the first report of elevated PKC ι in head and neck squamous cell carcinoma that may have significance because PKC ι is an oncogene in several other tumor types, including lung cancer. The feasibility of using RPPA for developing theranostic tests to guide personalized therapy is discussed in the context of these data.

Human Amnion/Chorion Membrane May Reduce Transient Recurrent Laryngeal Nerve Injury During Thyroid Surgery.

Recurrent laryngeal nerve (RLN) damage is a significant and prevalent complication of thyroid surgery. Based on the beneficial role of a human amnion/chorion membrane (HACM) allograft in wound management and nerve regeneration, we investigated whether placement of a commercially available HACM allograft on dissected RLN could reduce the occurrence and/or duration of RLN injury during thyroidectomy. Among 67 patients undergoing thyroidectomy, 100 at-risk nerves (exposure of at least 3 cm of RLN) received intraoperative placement of HACM; 205 at-risk RLNs without HACM in 134 matched patients served as controls. Patient-reported vocal analysis, physician-assessed vocal analysis, and laryngoscopic assessment of vocal-fold dysfunction were performed before and after surgery. At 24 h after surgery, 17 patients in the control group (12.5%) had documented voice changes; these changes persisted for at least 3 weeks in seven patients (5%). Only one patient (1.5%) in the HACM group had vocal changes at 24 h after surgery, which resolved within 1 week (P < 0.01). Intraoperative placement of the HACM allograft over at-risk RLNs during thyroidectomy may reduce the incidence, severity, and/or duration of intraoperative RLN injury, which could address a significant complication of head and neck surgery. A larger prospectively designed clinical study is warranted to further investigate a possible benefit of the HACM allograft in thyroid surgery and to begin to understand the mechanisms through which a clinical benefit might be mediated.

New role for LEKTI in skin barrier formation: label-free quantitative proteomic identification of caspase 14 as a novel target for the protease inhibitor LEKTI.

Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is recognized as a serine protease inhibitor and is thought to play a key role in skin barrier function through the inhibition of kallikrein (KLK) activities and regulation of skin desquamation. LEKTI has a total of 15 potential inhibitory domains, and we hypothesize that it has other potential targets in the skin. To identify candidate protease targets of LEKTI, a label-free quantitative proteomic approach was employed. This work describes a novel, rapid, and noninvasive method for the identification and quantitation of the major proteins present in the uppermost layers of the skin. By using cells scraped from the elbow, we were able to rapidly identify and quantitate 79 proteins. Caspase 14 and bleomycin hydrolase were identified as the proteases of highest abundance. Despite the fact that caspase 14 is a cysteine protease and LEKTI is described as a serine protease inhibitor, we demonstrate that caspase 14 is inhibited by full-length LEKTI and 5 recombinant fragments of LEKTI to varied extents. Details of the development of the methods used for the creation of the skin proteome and the inhibition of caspase 14 by LEKTI and implications for LEKTI as a multifunctional protease inhibitor are discussed.

High rate of BRAF and RET/PTC dual mutations associated with recurrent papillary thyroid carcinoma.

PURPOSE: Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, usually possesses BRAF mutation or rearranged in translation (RET)/PTC rearrangements. PTC usually possesses BRAF mutation or RET/PTC rearrangements. The mutation status of patients with recurrent PTC has never been characterized in a large population. EXPERIMENTAL DESIGN: Mutation status was determined in a cohort of 54 patients with recurrent PTC and analyzed for clinicopathologic relationships. BRAF and ras mutations were determined by PCR and sequencing of genomic DNA. RET/PTC rearrangements were analyzed by reverse transcription-PCR. RESULTS: BRAF mutation in exon 15 (V600E) was found in 42/54 (77.8%) recurrent PTC patients. The RET/PTC rearrangements were detected in 9 of 54 (16.7%) patients. In addition, 5 of 54 (9.3%) recurrent PTC patients had both a BRAF mutation and a RET/PTC rearrangement. The prevalence of tumors with dual mutations found in the recurrent population far exceeds the frequency historically reported for patients with primary PTC. Patients with dual mutations were significantly older (80% older than 45 years) than patients with a BRAF mutation alone (38% older than 45 years). CONCLUSIONS: Recurrent PTC is significantly associated with a predominant BRAF mutation. RET/PTC rearrangements, although commonly associated with primary PTCs in younger patients, are uncommonly found in recurrent PTC patients. In addition, the incidence of dual mutations was higher in patients with recurrent PTC than in those primary PTC, as reported by others.

Clinical significance of distinguishing between follicular lesion and follicular neoplasm in thyroid fine-needle aspiration biopsy.

BACKGROUND: Subclassifying indeterminate thyroid fine-needle aspiration (FNA) biopsy findings as follicular lesion or follicular neoplasm has been suggested as useful in triaging patients to observation or surgery, respectively. However, terminology and therefore the probability of malignancy vary between pathologists and institutions. The purpose of this study was to evaluate a single institution's experience with indeterminate thyroid FNA results to determine if subclassification (neoplasm versus lesion) aids in identifying patients at higher risk for malignancy. METHODS: From 1990 to 2006, all patients with indeterminate thyroid FNA results (follicular lesion or neoplasm) at The University of Texas M.D. Anderson Cancer Center were evaluated for FNA correlation with the surgical specimen diagnosis. Patients with FNAs suspicious for papillary thyroid carcinoma or with definitive malignant disease (i.e., metastases) were excluded. RESULTS: Indeterminate FNA results were present in 540 patients, including 410 as follicular lesion and 130 as follicular neoplasm. Two hundred ninety-seven (55.0%) patients underwent surgical resection: 199 (48.5%) follicular lesions and 98 (75.4%) follicular neoplasms. Incidence of malignancy was higher in thyroid nodules classified as neoplasm compared with lesion (21.4% versus 7.0%, respectively; P=0.0005) and increased in follicular neoplasms with nodule size (37.5% malignant if nodule was [4 cm, P=0.03). CONCLUSIONS: Subclassification of indeterminate thyroid FNA biopsy results into neoplasm and lesion successfully defines high- and low-risk nodules, respectively. These findings support surgical resection for follicular neoplasms, selective use of surgical intervention for follicular lesions at our institution, and continued efforts to define unified terminology between institutions.

Phosphorylated insulin like growth factor-I receptor expression and its clinico-pathological significance in histologic subtypes of human thyroid cancer.

Overexpression of insulin-like growth factor-I receptor (IGF-IR) is seen in a multitude of human thyroid cancers and correlates with poor prognosis. However, recent studies suggest that low phospho-IGF-IR (pIGF-IR) expression rather than its overexpression may be an indicator of poorly differentiated disease. No previous study has evaluated the expression of pIGF-IR to determine if activation or loss of expression of this receptor is associated with thyroid tumor progression. Accordingly, a quantitative immunohistochemical (IHC) method was used to evaluate the clinico-pathological significance of pIGF-IR expression in archival samples of human thyroid carcinomas. Quantitative analysis of pIGF-IR levels revealed a significant difference in the median index of pIGF-IR between different histological subtypes of thyroid cancer (P < 0.001). Specifically, the median pIGF-IR index of differentiated thyroid cancers was significantly higher than the median index of other poorly differentiated thyroid cancer (P < 0.001). This was further confirmed in individual tumor sections of thyroid carcinoma where anaplastic and differentiated components co-existed. No significant difference was noted in the pIGF-IR index of tumors grouped by size or stage but a trend towards lower mean pIGF-IR index was noted in older patients. Our data indicates that pIGF-IR is upregulated in a majority of follicular thyroid carcinomas, suggesting it may be a potential target for therapy for patients with this disease. In addition, since low pIGF-IR expression was found to correlate with aggressive human thyroid carcinoma, it also suggests that IGF-IR may not be needed for progression of anaplastic thyroid carcinoma possibly because other cell signaling pathways are activated, obviating the need for IGF-IR signaling. However, more mechanistic studies would be necessary to substantiate the possibility that pIGF-IR may be important for differentiation of thyroid tissues and is lost with disease progression.

Sorafenib potently inhibits papillary thyroid carcinomas harboring RET/PTC1 rearrangement.

PURPOSE: Papillary thyroid carcinomas (PTC) are the most common type of thyroid malignancy with one of the two mutations, RET/PTC rearrangement or BRAF mutation. Both mutations are able to activate the MEK/ERK signaling transduction pathway and result in the activation of transcription factors that regulate cellular proliferation, differentiation, and apoptosis. Sorafenib (Nexavar, BAY 43-9006) is a multikinase inhibitor, and in this study, we tested its effects on PTC cells carrying either mutation. EXPERIMENTAL DESIGN: The effects of sorafenib on cell proliferation and signaling were evaluated in vitro on PTC cells using growth curves, cell cycle analysis, and immunoblotting. Using an orthotopic mouse model, we determined the antitumor effects of sorafenib in vivo. RESULTS: The concentration needed for 50% growth inhibition (GI(50)) by sorafenib was 0.14 mumol/L for the PTC cells with the RET/PTC1 rearrangement, and 2.5 mumol/L for PTC cells with a BRAF mutation, both readily achievable serum concentrations. After 3 weeks of oral administration of sorafenib (80 mg/kg/d) in mice, small (94% reduction compared with controls) or no tumor growth was detected in mice inoculated with PTC cells bearing the RET/PTC1 rearrangement, whereas the tumor volume of the orthotopic tumor implants of PTC cells with a BRAF mutation was reduced 53% to 54% (as compared with controls). CONCLUSIONS: PTC cells carrying the RET/PTC1 rearrangement were more sensitive to sorafenib than PTC cells carrying a BRAF mutation. Because RET/PTC rearrangements are unique to thyroid carcinomas, our findings support the clinical evaluation of sorafenib for patients with PTC and the identification of patients most likely to respond to sorafenib treatment.

Comprehensive Genetic Characterization of Human Thyroid Cancer Cell Lines: A Validated Panel for Preclinical Studies.

PURPOSE: Thyroid cancer cell lines are valuable models but have been neglected in pancancer genomic studies. Moreover, their misidentification has been a significant problem. We aim to provide a validated dataset for thyroid cancer researchers. EXPERIMENTAL DESIGN: We performed next-generation sequencing (NGS) and analyzed the transcriptome of 60 authenticated thyroid cell lines and compared our findings with the known genomic defects in human thyroid cancers. RESULTS: Unsupervised transcriptomic analysis showed that 94% of thyroid cell lines clustered distinctly from other lineages. Thyroid cancer cell line mutations recapitulate those found in primary tumors (e.g., BRAF, RAS, or gene fusions). Mutations in the TERT promoter (83%) and TP53 (71%) were highly prevalent. There were frequent alterations in PTEN, PIK3CA, and of members of the SWI/SNF chromatin remodeling complex, mismatch repair, cell-cycle checkpoint, and histone methyl- and acetyltransferase functional groups. Copy number alterations (CNA) were more prevalent in cell lines derived from advanced versus differentiated cancers, as reported in primary tumors, although the precise CNAs were only partially recapitulated. Transcriptomic analysis showed that all cell lines were profoundly dedifferentiated, regardless of their derivation, making them good models for advanced disease. However, they maintained the BRAFV600E versus RAS-dependent consequences on MAPK transcriptional output, which correlated with differential sensitivity to MEK inhibitors. Paired primary tumor-cell line samples showed high concordance of mutations. Complete loss of p53 function in TP53 heterozygous tumors was the most prominent event selected during in vitro immortalization. CONCLUSIONS: This cell line resource will help inform future preclinical studies exploring tumor-specific dependencies.

Growth factor receptors expression in anaplastic thyroid carcinoma: potential markers for therapeutic stratification.

Anaplastic thyroid carcinoma is a rare and universally fatal disease. Therefore, novel biomarkers are needed as surrogate end points in triaging patients for novel and selective biologic treatments. Up-regulation of several growth factor receptors has been shown to be associated with the biologic progression and response to targeted therapy of several malignancies. To determine the role of growth factor receptors in the biologic stratification of anaplastic thyroid carcinoma, we studied the expression of epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor beta, and HER-2 receptor in a large cohort of anaplastic thyroid carcinomas by immunohistochemical techniques. The percentage of positive cells, staining intensity and localization of staining in the anaplastic component, and coexisting well-differentiated thyroid carcinoma and adjacent nonneoplastic thyroid were evaluated for these markers. EGFR, platelet-derived growth factor receptor beta, and HER-2 were overexpressed in 58%, 16%, and 16% of anaplastic carcinomas, respectively. In tumors with adjacent normal thyroid parenchyma and/or differentiated carcinoma components, overexpression of all 3 markers was noted exclusively in the anaplastic component. Mutational analysis of exons 18, 19, and 21 of the EGFR gene showed no mutations in all anaplastic carcinomas. We conclude that the expression of these markers (1) may play a role in a subset of thyroid tumorigenesis and anaplastic transformation and (2) can be validated for potential use in the stratification of patients for targeted therapy.

LBP-1b, LBP-9, and LBP-32/MGR detected in syncytiotrophoblasts from first-trimester human placental tissue and their transcriptional regulation.

LBP-1b, LBP-9, and LBP-32/MGR (LBP proteins) are transcriptional factors that regulate the expression of the P450 side-chain cleavage enzyme (P450scc) in the human placenta. Placenta contains at least two types of trophoblasts: cytotrophoblasts and syncytiotrophoblasts. P450scc has been detected in syncytiotrophoblasts through all stages of pregnancy. The expression of LBP proteins in different placental stages is unknown. We isolated total RNA from cytotrophoblasts and syncytiotrophoblasts of both first-trimester and full-term human placenta. The mRNA expressions of LBP proteins were detected only in the syncytiotrophoblasts from both first-trimester and full-term placenta. To determine the regulation among LBP proteins, we isolated the 5'-flanking region of one of the LBP proteins (LBP-32/MGR). After determining the transcriptional initiation site by a primer extension assay, we isolated and tested the activity of different lengths of the LBP-32/MGR promoter. A core promoter region for LBP-32/MGR extending from -639 to -184 bp was used to determine the interaction among LBP proteins. We cotransfected LBP-1b and LBP-9 with the LBP-32/MGR promoter and found that both stimulated LBP-32/MGR promoter activity. Our data suggested that an interaction exists among these transcriptional factors at the transcriptional level and provided us with information in our basic understanding of P450scc regulation.

Repair capacity for UV light induced DNA damage associated with risk of nonmelanoma skin cancer and tumor progression.

PURPOSE: To examine the role of suboptimal DNA repair capacity (DRC) for UV light-induced DNA damage in the development of nonmelanoma skin cancer (NMSC) and tumor progression. EXPERIMENTAL DESIGN: We conducted a hospital-based case-control study of 255 patients with newly diagnosed NMSC [146 with basal cell carcinoma (BCC) and 109 with squamous cell carcinoma (SCC)] and 333 cancer-free controls. We collected information on demographic variables and risk factors from questionnaires, tumor characteristics from medical records, and lymphocytic DRC phenotype by the host-cell reactivation assay. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Overall, there was a relative 16% reduction in DRC in NMSC patients compared with controls (P < 0.001 for BCC and for SCC, respectively). DRC below the controls' median value was associated with increased risk significantly for BCC (OR, 1.62; 95% CI, 1.07-2.45) but borderline for SCC (OR, 1.63; 95% CI, 0.95-2.79) after adjustment for age, sex, and other assay-related covariates. When the highest tertile of controls' DRC was used as the reference, the intermediate and low DRC were associated with a statistically significant trend for increasing risk for both BCC (P(trend) = 0.007) and SCC (P(trend) = 0.020). However, patients with aggressive or multiple SCC tended to have a higher DRC than those with nonaggressive or single SCC. CONCLUSIONS: Reduced DRC is an independent risk factor for BCC and single or nonaggressive SCC but not for multiple primaries, local aggressiveness, or recurrence of NMSC.

An orthotopic model of papillary thyroid carcinoma in athymic nude mice.

OBJECTIVE: To develop a reproducible orthotopic model of papillary thyroid carcinoma for the BRAF(V600E) mutation (GenBank NM004333) and an RET/PTC rearrangement (GenBank M31213) that recapitulates the clinical picture in humans. DESIGN: In vitro and in vivo study. SETTING: Department of Head and Neck Surgery, M. D. Anderson Cancer Center. SUBJECTS: Eight- to 12-week-old athymic female nude mice. INTERVENTIONS: Either BRAF-mutated or RET/PTC1-rearranged papillary thyroid carcinoma cells were injected into the thyroid glands of athymic female nude mice. The mice were euthanized when the tumor burden exceeded 1.0 cm or when they exhibited significant morbidity. MAIN OUTCOME MEASURES: Tumorigenicity, extent of tumor invasion and metastasis, cell invasion and migration, and median survival. RESULTS: All the BRAF-mutated cell lines and 1 selected RET/PTC1-rearranged cell line were 100% tumorigenic in mice. These mouse tumor models exhibited a wide range of biological potential, including laryngeal invasion, lymph node metastasis, and pulmonary metastasis, thus reflecting the clinical spectrum of papillary carcinoma. CONCLUSIONS: An orthotopic model of papillary thyroid carcinoma was successfully established in nude mice using BRAF-mutated and RET/PTC1-rearranged cell lines. These models mimic the human disease and will thus be useful for evaluating the clinical potential of novel targeted therapies.

Surgical management of recurrent thyroid cancer.

While well-differentiated thyroid cancer is generally thought to be a treatable cancer with excellent outcomes, some patients suffer from recurrent disease. Risk factors for recurrent disease include primary disease greater than 4 cm, incomplete resection, multiple positive lymph nodes in the central compartment, and lateral neck disease with multiple positive lymph nodes in multiple levels or pathologic extracapsular extension. These factors can help stratify the thyroid cancer population in to low-, medium-, and high-risk patients. Low-risk patients can generally be followed with thyroglogulin levels and routine ultrasounds to the head and neck. High-risk patients are best monitored with stimulated thyroglobulin, ultrasound of the head and neck, and low-dose iodine 131 uptake scans at the 6- to 12-month mark. The treatment of locoregional recurrent thyroid cancer is surgical resection with the overall goal of complete tumor removal while maintaining function and decreasing risks. The use of adjuvant therapy is dependent on the presence / absence of high risk pathologic features.

Management of the central compartment in differentiated thyroid carcinoma.

Management of differentiated thyroid carcinoma (DTC) is gradually evolving with considerations of de-escalation of treatment and/or active surveillance in a significant proportion of patients on the basis of an improved understanding of the long-term disease and functional outcomes from both surgical and non-surgical approaches. This is fueled by improved risk stratification using clinicopathologic prognostic factors as determined through high resolution ultrasound and fine needle aspiration cytology. This paper discusses general recommendations for preoperative decision-making in the management of the central compartment in DTC with particular reference to micropapillary thyroid carcinoma and encapsulated follicular variant papillary thyroid carcinoma. Given the multitude of specific factors that must be considered for each patient, therapeutic decisions should occur in a multidisciplinary setting weighing the risks of treatment morbidity against the risks of disease progression or recurrence. Recurrent/persistent disease merits special attention with regard to pre-operative planning and surgical risk, and should be managed by high-volume thyroid surgeons.

Management of the lateral neck compartment in patients with sporadic medullary thyroid cancer.

BACKGROUND: The purpose of this retrospective analysis was to evaluate the benefits of an elective lateral neck dissection (ELND) in patients with medullary thyroid cancer (MTC) without radiographically apparent lateral neck metastases. METHODS: Patients with sporadic MTC without radiographic evidence of lateral neck metastasis who underwent definitive surgery were divided into 2 groups based on surgical approach: no ELND (the observation group) and ipsilateral or bilateral ELND (the ELND group). Primary outcomes were biochemical cure, locoregional recurrence, distant metastasis, and overall survival (OS). RESULTS: Sixty-six patients met inclusion criteria: 44 patients (67%) in the observation group and 22 patients (33%) in the ELND group. Two of 44 patients (5%) in the observation group developed subsequent (ipsilateral) lateral neck disease. At last follow-up, locoregional disease control rates among the observation and ELND groups were 98% and 100% (P > .999), respectively, whereas biochemical cure rates were 82% and 85% (P > .999), respectively, and 5-year OSs were 84% and 100% (P = .156), respectively. CONCLUSION: Patients with MTC without lateral neck metastasis have similar biochemical cure rates with observation or elective dissection of lateral neck compartments.