Ultrasound-guided fine-needle aspiration of thyroid nodules: does size matter?

PURPOSE: Some authors have questioned the benefit of fine-needle aspiration (FNA) of thyroid nodules ≥ 4 cm. They report that the results of the FNA are not as reliable when compared to nodules <4 cm. The aims of this study are to evaluate the accuracy and predictive values of ultrasound-guided FNA (USFNA) of thyroid nodules ≥ 4 cm and compare these findings to nodules <4 cm. METHODS: A retrospective study of 998 patients who underwent thyroid surgery between 2006 and 2012 at the McGill University Thyroid Cancer Center was performed. USFNA and post-operative pathology diagnoses of nodules ≥ 4 cm versus those <4 cm were compared. Pre-operative USFNA results were divided into three groups: benign, indeterminate, and malignant/suspicious for malignancy subgroups. Post-operative results were separated into benign and malignant groups. RESULTS: There were 225 patients with nodules ≥ 4 cm and 773 patients with nodules <4 cm. The sensitivity, specificity, positive predictive value and negative predictive value for USFNA of nodules ≥ 4 cm were 84.62% (CI 71.91-93.10), 91.49% (CI 79.6-97.58), 91.67% (CI 80.0-97.63) and 84.31% (CI 71.4-92.95), respectively. The sensitivity, specificity, positive predictive value and negative predictive value for USFNA of nodules <4 cm were 90.48% (CI 86.1-93.8), 85.92% (CI 75.6-93.02), 95.8% (CI 92.41-97.96) and 71.76% (CI 60.95-81.0), respectively. The difference in diagnostic accuracy of USFNA between both groups was not statistically significant (p>0.05). CONCLUSION: This study shows that the sensitivity, specificity, positive predictive value and negative predictive value for USFNA of nodules ≥ 4 cm are similar to that of smaller nodules. It is therefore suggested that these nodules undergo USFNA.

Fine-needle aspiration biopsies in the management of indeterminate follicular and Hurthle cell thyroid lesions.

OBJECTIVES: To determine the value of fine-needle aspiration biopsies (FNABs) of the thyroid and stratify the risk of malignancy within the indeterminate FNAB diagnostic category at our institution. STUDY DESIGN: Case series with chart review of preoperative FNABs of consecutive patients who underwent total thyroidectomy between 2005 and 2007. SUBJECTS AND METHODS: A total of 115 cases were reviewed, and FNABs were categorized into four groups: benign, positive or suspicious for malignancy, indeterminate (follicular or Hurthle cell lesions), and nondiagnostic. Cytohistologic correlation was then established. RESULTS: The accuracy of FNAB in detecting thyroid malignancy was 88 percent with false-negative and false-positive rates of 13 percent and 7 percent, respectively. Overall, 52 percent of the indeterminate cases were carcinomas (48 percent of follicular lesions and 62 percent of Hurthle cell lesions). In the presence of cytologic atypia, the rate of malignancy increased to 75 percent and 83 percent for the follicular and Hurthle cell lesions, respectively. CONCLUSIONS: FNAB is an accurate and helpful method for the evaluation of thyroid nodules with results directly correlating with management. Surgery should be considered for FNABs categorized as indeterminate, especially in the presence of cytologic atypia. Because of the high false-negative rate, benign FNABs require close follow-up with ultrasound examination and periodic biopsies.

Spinal hamartoma with severe kyphoscoliosis--a rare case of spinal mass in a fetus.

Spinal hamartomas are rare lesions consisting of disorganized ecto- and mesodermal tissues of the spinal region. While postnatal identification of spinal hamartomas has been reported, a literature search did not reveal any published reports of prenatal identification of spinal hamartomas. Here we report a 46,XX fetus who presented at 20 weeks' gestation with a lower thoracic and lumbar kyphoscoliosis, suspected spina bifida, and amniotic fluid alpha-fetoprotein (AFP) levels within the normal range. Interestingly, autopsy at 22 weeks revealed a lumbosacral spinal hamartoma with kyphoscoliosis. We discuss the differential diagnosis for such spinal masses which includes congenital tumors and spinal dysraphism. This case illustrates that spinal hamartomas should be considered as part of the prenatal differential diagnosis of spinal dysraphisms, especially in the presence of normal AFP levels.

Incidence and histopathological behavior of papillary microcarcinomas: study of 429 cases.

OBJECTIVE: We aim to present papillary microcarcinoma (PMC) incidence at a university teaching hospital, to compare characteristics of PMC in relation to size, and to assess for significant difference in PMC incidence among patients with non-PMC thyroid malignancies. MATERIALS AND METHODS: Pathology results were reviewed for consecutive total thyroidectomies between 2002 and 2007 (n = 860). Statistical significance was calculated using chi(2) or, when unavailable, Fisher exact test. RESULTS: PMC was found in 429 cases, which is 49.9 percent of all total thyroidectomies. In PMC > or =5 mm, 25.1 percent had extrathyroidal extension vs 9.1 percent for <5 mm (P < 0.001). When 4 mm is used as a threshold, P value was 300-fold smaller. Incidence in patients with any non-PMC thyroid malignancy was 51.6 percent against 47.2 percent in all other patients (P = 0.203). CONCLUSIONS: In this study, PMC was found in 49.9 percent of patients, which, to our knowledge, is higher than any other reported incidence. A threshold of > or =4 mm was more significant than 5 mm for carrying increased risk for extrathyroidal spread. There was no significant difference in PMC incidence in patients with malignant vs benign disease.

Long-Term Outcomes of Patients with Papillary Thyroid Cancer Undergoing Remnant Ablation with 30 milliCuries Radioiodine.

BACKGROUND: The study considered the long-term outcome of patients with papillary thyroid carcinoma treated with 30 mCi radioiodine. OBJECTIVE: The aims of this study were to define and compare the remission rates of papillary thyroid carcinoma ablated with 30 mCi (131)I prepared by either thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH; Thyrogen(®)), and to identify variables predictive of a favorable prognosis. METHOD: An observational study was conducted at an academic medical center and a comparative summary of six studies is presented. Three hundred and seventy patients (THW group, n = 203; rhTSH group, n = 167) were recruited from a prospectively managed registry. The mean follow-up was 9.3 years (range 5.1-15.8 years) in the THW group and 7.1 years (range 5.0-9.7 years) in the rhTSH group. The primary endpoint was the long-term remission rates (no evidence of disease) in the THW group compared with the rhTH group. RESULTS: The response at 12-18 months after 30 mCi remnant ablation was excellent in 79.3% and 76.0% of patients in the THW group and the rhTSH group, respectively (p > 0.05). The long-term remission rates also did not significantly differ between both groups at 95.6% and 97.0%. Although the surveillance period for the THW group exceeded that of the rhTSH group, no significant difference in recurrence-free survival was discerned by the Kaplan-Meier curves. In a multivariate analysis, an excellent response to therapy at 12-18 months correlated significantly with long-term remission rates in the THW group (p = 0.031, odds ratio [OR] = 2.6 [confidence interval (CI) 1.1-6.0]), the rhTSH group (p = 0.03, OR = 5.3 [CI 1.2-23.8]), and the pooled groups (p = 0.001, OR = 3.43 [CI 1.63-7.2]). The pre-ablation thyroglobulin level significantly correlated with remission rates only in the THW group (p = 0.035, OR = 5.5 [CI 1.1-27.1]). CONCLUSIONS: The response to remnant ablation with 30 mCi radioiodine is often excellent, and the long-term remission rates can be expected to be high, independent of the method of delivery (i.e., THW or rhTSH).

The McGill Thyroid Nodule Score's (MTNS+) role in the investigation of thyroid nodules with benign ultrasound guided fine needle aspiration biopsies: a retrospective review.

BACKGROUND: Ultrasound guided fine needle aspiration (USFNA) biopsies of thyroid nodules sometimes create a decision-making dilemma for surgeons as they may yield falsely benign results. The McGill Thyroid Nodule Score + (MTNS+) was developed to aid in clinical guidance regarding the management of patients with these USFNA results. The aim of this study was to assess the MTNS+ as a clinical tool in patients with benign preoperative thyroid nodule USFNAs and to analyze the relationship between nodule size and malignancy in these patients. METHODS: We conducted a retrospective chart review of 1312 patients who underwent thyroidectomies between 2010 and 2015 at the McGill University Teaching Hospitals. Patients with Bethesda II (benign) USFNA results, calculated MTNS+, and nodule size evaluated on ultrasound were included in the study. The false-negative rate was calculated, and MTNS+ and nodule size were each compared to final pathology results. Binary logistic regression was used for statistical analysis. RESULTS: Of the 1312 patients, 101 met the inclusion criteria and together had an average MTNS+ score of 6.83, which corresponds to a predicted malignancy rate between 25 and 33 %. Final pathology revealed malignancy in 16 (15.8 %) subjects. The average MTNS+ of patients with malignant nodules on surgical pathology was 8.25, while that of patients with benign nodules was 6.56. Patients with nodule size 1-1.9 cm (a) and 2-2.9 cm (b) each had an equal rate of malignancy of 2.97 % (n = 3), nodule size 3-3.9 cm (c) had a rate of 1.98 % (n = 2), and nodule size ≥4 cm (d) a rate of 7.92 % (n = 8). CONCLUSION: The rate of malignancy (15.8 %) is higher than expected when reviewing the risk of malignancy in nodules considered as Bethesda class 2. On the other hand, the rate is lower than the 25-33 % predicted by the MTNS+. We also found a higher malignancy rate for nodules above 4 cm in size, but size was a poor predictor of malignancy when used alone. Therefore, while the MTNS+ may be helpful at helping to identify USFNAs that are incorrectly classified as benign, the percentage risk of malignancy is lower than expected.

The role of repeat fine needle aspiration in the management of indeterminate thyroid nodules.

BACKGROUND: Management decisions are not straightforward when the Ultrasound Guided Fine Needle Aspiration (USFNA) demonstrates a Bethesda score of either category III or IV, and a diagnostic hemi-thyroidectomy or a repeat USFNA (r-USFNA) could be performed. The aim of this study is to assess the effectiveness of r-USFNA in the management of indeterminate thyroid nodules by evaluating the likelihood of obtaining a definite diagnosis. METHODS: We reviewed the medical records of all patients with thyroid nodules between 2011 and 2015 at the Jewish General Hospital (Montreal, Canada). Three hundred fifty-one patients who had undergone a surgical procedure (hemi or total thyroidectomy) and a diagnosis of B3 or B4 on the primary USFNA (p-USFNA) were included in the study. Ninety-six of the included patients also had a repeat USFNA prior to the surgery. Demographic data, type of procedure, and McGill Thyroid Nodule Score (MTNS) were obtained from the medical records. Malignancy rates were calculated based on the final surgical histopathology report. RESULTS: Upon r-USFNA, an average 76 % of patients did not change Bethesda categories, 7.4 % downgraded to a benign category. The results showed that, on an average 17.3 % of patients with p-USFNA of B3 and 20 % of patients with p-USFNA of B4, upgraded to a malignant or suspicious for malignancy category, thus changing the clinical management to total thyroidectomy. Our data demonstrates that r-USFNA facilitates choosing the correct surgery of total thyroidectomy in about 20 % of nodules that have upgraded from B3/B4 to a more definite malignant category. CONCLUSIONS: r-USFNA in patients with indeterminate diagnoses (B3 or B4) increases categorization into more definite categories. Approximately 20 % of patients are found to have malignant thyroid nodules and suspicious for malignancy thyroid nodules upon repeating the biopsy, hence a diagnostic hemi-thyroidectomy was avoided and a more definitive surgery could be performed. Furthermore, repeat USFNA results in a fewer number of hemi-thyroidectomy and completion thyroidectomy procedures.

The Mcgill thyroid nodule score - does it help with indeterminate thyroid nodules?

BACKGROUND: Ultrasound guided fine-needle aspiration (USFNA) biopsy of thyroid nodules often gives a result of indeterminate pathology, placing thyroid specialists in difficult management situations. The aim of this study is to evaluate the incidence of malignancy in patients undergoing surgery and to correlate these results with the McGill Thyroid Nodule Score (MTNS). METHODS: We performed a retrospective study comparing USFNA results, MTNS and histopathology of patients undergoing thyroid surgery between 2010 and 2012. Pre-operative USFNA results were divided into three subgroups: benign, indeterminate and suspicious for/malignant. The indeterminate USFNA subgroup comprised of Bethesda type III (atypia of undetermined significance) and Bethesda type IV (follicular neoplasms, including Hurthle cell neoplasms) lesions. Post-operative histopathology was divided into benign or malignant groups. RESULTS: Of the 437 patient charts reviewed, 57.0% had an indeterminate USFNA biopsy. Within the indeterminate group, the malignancy rate was 39.8%. For indeterminate USFNA, the median MTNS was 7 (32% risk of malignancy) for benign nodules and 9 (63% risk of malignancy) for malignant nodules on post-operative histopathology (p < 0.05). CONCLUSION: The rate of malignancy in operated patients with an indeterminate USFNA result was 39.8%. The MTNS can be of value to thyroid specialists in pre-operative decision-making when dealing with an indeterminate result of a thyroid nodule on USFNA.

Coexistence of malignant struma ovarii and cervical papillary thyroid carcinoma.

CONTEXT: Struma ovarii is an uncommon monodermal teratoma in which thyroid tissue is the predominant element. Malignant transformation of struma ovarii is an even rarer occurrence. CASE PRESENTATION: We describe a 42-year-old woman who underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a symptomatic left pelvic mass. Histology revealed malignant struma ovarii with classical papillary thyroid carcinoma expression. Ultrasonography of the cervical neck showed thyroid micronodules and a dominant 1-cm nodule in the left thyroid lobe. As the ovarian tumor was large, the patient underwent a total thyroidectomy with the intention of administering ¹³¹I therapy in an adjuvant setting. Histology of the cervical thyroid gland revealed bilateral multifocal papillary thyroid carcinoma with extrathyroidal extension and perithyroidal lymph node metastasis. METHODS: Morphological (microscopy), immunohistochemical (Hector Battifora mesothelial cell 1, cytokeratin-19, galectin-3), and molecular (BRAF V600E, RAS, RET-PTC) characteristics and clonality analysis of the cervical thyroid and ovarian tumors were explored to distinguish them as separate malignancies. RESULTS: The thyroid-type tumors from the cervical gland and ovary were discordant in terms of tissue histology and level of cytokeratin-19 expression. The clinical features and tumor profile results supported the independent existence of these two embryologically related, although topographically distinct, malignancies. CONCLUSION: Our findings provided support for synchronous, albeit distinct, primary tumors in the ovary and cervical thyroid. "Field cancerization" and early genomic instability may explain multifocality in all thyroid-type tissue. In this regard, patients with malignant struma ovarii should undergo imaging of their thyroid gland for coexisting disease and thyroidectomy recommended for suspected malignancy or in preparation for radioiodine therapy.

Intraoperative parathyroid hormone level in parathyroidectomy: which patients benefit from it?

BACKGROUND: Intraoperative parathyroid hormone level (IOPTH) is withdrawn during parathyroidectomy to confirm the success of the procedure. Recently, the importance of IOPTH has been put to question. The purpose of this study is to determine whether IOPTH is necessary for all patients undergoing parathyroidectomy in the presence of frozen section. MATERIALS AND METHODS: A cohort study of parathyroidectomies was performed in three university affiliated hospitals during 2007-2012. The patients were divided into two groups. Group 1: Patients with two preoperative concordant imaging localizing a hyperactive gland. Group 2: Patients without two concordant imaging. A comparison of benefit of IOPTH was carried out. Frozen section results were also analyzed to determine sensitivity and predictability of a parathyroid adenoma. RESULTS: The study considered 221 patients having parathyroidectomies for primary hyperparathyroidism (PHPT). Of them, 10 were excluded due to incomplete data. Among the remaining, 186 had 2 concordant imaging preoperatively localizing an adenoma. 93.5% of whom were found intraoperatively in that location. IOPTH was not found to be of importance in 98.92% of the preoperative localized adenomas in the presence of frozen section. IOPTH added an estimate of 30.9 minutes on average to the surgery time. CONCLUSION: This study demonstrates that the added operating time associated with IOPTH may not be justified for patients undergoing parathyroidectomy who have 2 concordant imaging preoperatively in the presence of frozen section. This study suggests a simple algorithm, The McGill Parathyroid Protocol (MPP), to help in approaching PHPT patients undergoing parathyroidectomy.

Serum thyroglobulin predicts thyroid remnant ablation failure with 30 mCi iodine-131 treatment in patients with papillary thyroid carcinoma.

BACKGROUND: Most patients with differentiated thyroid cancer are treated with radioiodine (131-I) after thyroidectomy. The characteristics predictive of successful remnant ablation with low activities of 131-I are ill defined and could help stratify patients into those who should receive higher activities. METHODS: In a case series of 193 consecutive patients with papillary thyroid cancer who underwent total thyroidectomy and received 30 mCi (1110 MBq) of 131-I, we assessed the percentage of successful radioremnant ablation as defined by a composite of scintigraphic and biochemical endpoints. Clinical, histological, scintigraphic, and biochemical covariables were analyzed to identify associations with treatment failure. RESULTS: Successful radioremnant ablation with low-activity 131-I was obtained in 78% of the entire cohort of patients. The presence of limited microscopic extrathyroidal extension, nodal micrometastases, or an elevated stimulated ablation was associated with failure to ablate the remnant. While accounting for other factors in a multivariable analysis, patients with an ablation thyroglobulin of at least 6 µg/l were at a more than five times greater risk (P<0.001) to fail 30 mCi 131-I remnant ablation. CONCLUSION: The majority of patients with papillary thyroid carcinoma experienced successful ablation. However, elevated-stimulated ablation thyroglobulin levels were strongly predictive of ablation failure, suggesting that this biochemical marker correlates with a more aggressive tumor profile and identifies those patients who might benefit from additional therapy.

McGill Thyroid Nodule Score (MTNS): "rating the risk," a novel predictive scheme for cancer risk determination.

OBJECTIVE: There are presently a great number of publications pertaining to the clinical risk factors associated with thyroid cancer. These studies deal mostly with a single feature from either patient demographics, physical examination, laboratory values, imaging, or cytology. We sought to create a novel scoring system that integrates the diagnostic indices of each of these clinical features for carcinoma. METHODS: A retrospective analysis of 1047 consecutive thyroidectomy patients was performed. Each patient was assigned a cancer risk score according to a newly devised 22-variable scoring scheme termed the McGill Thyroid Nodule Score (MTNS). The MTNS was developed by a multidisciplinary team of endocrinologists, thyroid surgeons, and pathologists using already established evidence-based risk factors for thyroid cancer. RESULTS: The exact incidence of malignancy was calculated for each MTNS score based on final pathology. The incidence for scores of 1 to 3 was 27%, of 4 to 7 was 32%, of 8 was 39%, of 9 to 11 was 63%, of 12 to 13 was 88%, and of 14 to 18 was 93%. All (130 of 130) patients with a score ≥ 19 had carcinoma. A score ≤ 8 correlated with a 32% (115 of 357) risk of thyroid cancer, whereas a score > 8 implied an 86% (417 of 487) risk. CONCLUSION: Our data suggest that a combined scoring system, the MTNS, can serve as an accurate predictor of the risk for thyroid cancer in a specific thyroid nodule. This will help physicians better formulate management decisions accordingly.

Bilateral papillary thyroid cancer and associated histopathologic findings.

OBJECTIVE: To determine the incidence of bilateral papillary thyroid cancer (PTC) at total thyroidectomy (TT) and compare demographic risk factors (gender and age) and histopathologic findings (tumour size, extrathyroidal extension [ETE], T staging, and multifocality) between patients with PTC in both thyroid lobes and those with PTC limited to the ipsilateral lobe and/or isthmus. DESIGN: Retrospective study. SETTING: University teaching hospital. METHODS: The pathology results of 1047 consecutive patients who underwent TT between 2002 and 2008 were reviewed. Statistical significance was obtained using the chi-square test. MAIN OUTCOME MEASURES: Incidence of bilateral PTC and its association with demographic risk factors and histopathologic findings. RESULTS: Among 592 patients with PTC, 13.2% had bilateral PTC and 86.8% had unilateral and/or isthmian PTC. Bilaterality was present in 12.4% of women and 16.7% of men (p = .24) and in 12.9% of patients aged > or = 45 years and 13.5% < 45 years (p = .83). Bilateral PTC was found in 12.6% of patients with a primary tumour < or = 2 cm and 13.5% > 2 cm (p = .75); 23.6% of tumours with ETE demonstrated bilaterality compared to 9.7% without (p < .0001), and 8.7% of pT1 (p = .08), 9.2% of pT2 (p = .02), 23.0% of pT3 (p < .0001), and 12.5% of pT4 (p = .87) tumours were bilateral, respectively. Among bilateral PTC patients, 43.2% had multifoci in at least one lobe compared to 6.4% when nonbilateral (p < .0001). CONCLUSIONS: After TT, 13.2% of patients had bilateral PTC. No significant correlation was established between bilaterality and gender, age, and tumour size. Bilaterality was more commonly found in patients with ETE, advanced T stage, and at least one multifocal lobe.

Fine-needle aspiration biopsy of the thyroid: review of cytopathologic features predictive of malignancy.

OBJECTIVE: To determine the value of specific cytopathologic features on fine-needle aspiration biopsies (FNABs) at predicting thyroid malignancy. DESIGN: Retrospective review of consecutive patients undergoing thyroidectomy between 2005 and 2007 following FNAB of thyroid nodules. SETTING: Two McGill University teaching hospitals in Montreal. METHODS: One hundred forty-seven patients were reviewed and further categorized into two groups (benign vs malignant) based on the final histopathologic diagnosis. The frequency of specific cytopathologic features from the preoperative FNAB samples was recorded for 106 patients from the first hospital and 41 patients from the second. RESULTS: The presence of atypical cells (30% vs 72%; p = 3.23 x 10(-7)), nuclear grooves (5% vs 23%; p = .002), anisonucleosis (8% vs 36%; p = .00011), variable chromatin staining (10% vs 28%; p = .007), hypochromasia (11% vs 47%; p = 7.19 x 10(-6)), nuclear overlapping/crowding (8% vs 29%; p = .0019), irregular nuclear membranes (15% vs 52%, p = 3.22 x 10(-6)), micronucleoli (15% vs 60%, p = .003), and powdery chromatin (8% vs 47%, p = .004) correlates with an increased risk of malignancy. Alternatively, siderophages (44% vs 23%; p = .007) and honeycomb arrangements (92% vs 60%; p = .012) were more associated with benign processes. HBME-1 staining (n = 53) was positive or focally positive on 61% of the malignant cases (p = .0002), with a specificity of 100%. All biopsies demonstrating intranuclear inclusions, papillary fragments, or atypical architecture were malignant. CONCLUSION: Some cytopathologic features are more significantly associated with thyroid malignancy. The cytopathologic features listed in FNAB reports and HBME-1 immunoreactivity are, alone or in combination, additional tools available to the physician to guide management of thyroid nodules.

Predictors of malignancy in preoperative nondiagnostic biopsies of the thyroid.

OBJECTIVE: To determine whether preoperative variables can be used to predict malignancy for thyroid nodules with follicular, Hürthle, or nondiagnostic cytology on fine-needle aspiration biopsy (FNAB). MATERIALS AND METHODS: Retrospective analysis of 77 consecutive patients selected for total or subtotal thyroidectomy for follicular, Hürthle, or nondiagnostic lesions of the thyroid in two university hospitals. Eleven clinical variables, as well as nodule size, multiplicity, and ultrasound calcifications, were correlated with final histopathologic diagnosis of benign or malignant disease. Analysis was preformed using the Pearson chi-square test. RESULTS: The overall rate of malignancy in our series was 61% (n = 47). FNABs classified as follicular or Hürthle lesions without cellular atypia had a significantly lower risk of malignancy (49% vs 71%; p = .05). Patients who presented with a solitary nodule and FNAB cellular atypia displayed an increased risk of malignancy (92% vs 55%; p = .011). The rate of malignancy was higher for patients with a positive family history (100% vs 59%), a solitary nodule (73% vs 53%), cellular atypia (76% vs 54%), or intrathyroidal calcifications on ultrasonography (71% vs 57%), although none were found to be statistically significant (p > .05). Male gender, age > 45 years, nodule size > 3 cm, mass effect symptoms, and radiation exposure to the neck were not associated with malignancy in our series. CONCLUSION: When presented with follicular, Hürthle, or nondiagnostic biopsies for thyroid nodules, thyroid surgeons should rely systematically on sonographic findings and cytopathologic features to guide their management approach.

Body mass index in the evaluation of thyroid cancer risk.

BACKGROUND: Obesity has been linked to numerous diseases including thyroid cancer, but the exact nature of the relationship, especially with respect to patients with thyroid nodules, remains unclear. The objective of this study was to evaluate the impact of body mass index (BMI) on thyroid cancer risk in a population of patients with indeterminate cytology on fine-needle aspiration biopsy (FNAB). METHODS: A total of 253 consecutive patients with indeterminate thyroid nodule FNABs who underwent total thyroidectomy in a tertiary care teaching hospital between 2002 and 2007 were reviewed. Height and weight reported on the anesthesia summary were recorded for each patient. Malignancy rates were calculated for the underweight, normal, overweight, and obese groups stratified according to their BMI. Subanalyses according to age and sex were also performed. RESULTS: The risk of malignancy tended to be lower in obese patients compared to patients with BMIs in the underweight, normal, and overweight ranges (52% vs. 61%, p = 0.195). In men, a BMI classified as obese was associated with a significantly lower rate of malignancy (36% vs. 72%, p = 0.003). Women older than 45 years were a subgroup in which higher malignancy rates were associated with obesity (65% vs. 54%, p = 0.293). Conversely, in men over the age of 45 years and women under 45 years, a BMI in the obesity range was linked to a lower incidence of malignancy (20% vs. 68% p = 0.009 and 36% vs. 68% p = 0.043, respectively). When older women were excluded from the population studied, the rate of malignancy in obese patients was 36% versus 70% in nonobese patients (p = 0.002) with an associated reduction of 5% in the risk of malignancy per increased unit of BMI. CONCLUSIONS: For patients with FNAB results of indeterminate significance, a higher BMI correlates with lower rates of thyroid malignancy for all patients except women over the age of 45 years.

The role of sentinel lymph node biopsy in differentiated thyroid carcinoma.

OBJECTIVE: To determine whether sentinel lymph node (SLN) biopsy can accurately predict central compartment metastasis in patients with differentiated thyroid carcinoma. DESIGN: Prospective clinical study. SETTING: Academic tertiary care center. PATIENTS: Ninety-eight patients (82 women and 16 men; mean age, 48.3 years) underwent a total thyroidectomy and central compartment dissection. INTERVENTION: Peritumoral injection of methylene blue dye, 1%, followed by SLN biopsy. MAIN OUTCOME MEASURES: The final pathology report established the presence of metastasis among SLNs and lymph nodes that did not stain blue (non-SLNs [NSLNs]). RESULTS: Differentiated thyroid carcinoma was found in 75 of 98 patients (77%). Seventy of 75 patients with differentiated thyroid carcinoma presented with SLNs and/or NSLNs within the central compartment. Fifteen of 70 patients had metastasis-positive SLNs, while 55 had metastasis-negative SLNs. Six of 15 patients with positive SLNs also had positive NSLNs. No patients with negative SLNs were found to have positive NSLNs. Sentinal lymph node status was a highly significant predictor of NSLN result (Fisher exact test, P < .001). The accuracy, sensitivity, specificity, and positive and negative predictive values of SLN biopsy were 87%, 100%, 86%, 40%, and 100%, respectively. CONCLUSIONS: To our knowledge, this is the largest series of SLN biopsy in patients with differentiated thyroid carcinoma. Our experience suggests that this is an accurate and noninvasive means to identify subclinical lymph node metastasis. Because negative SLNs correlate strongly with a negative central compartment (100% in this study, P < .001), this technique can be used as an intraoperative guide when determining the extent of surgery necessary in cervical level VI.

Clinically relevant oral cancer model for serum proteomic eavesdropping on the tumour microenvironment.

BACKGROUND: Serum proteomics has enormous potential in the identification of biomarkers and the development of new therapies for oral cancer. Current efforts are limited by the lack of a control subject. The human-mouse chimeric model offers a solution. OBJECTIVES: To develop and test two orthotopic xenograft mouse models of human oral squamous cell carcinoma for research in serum proteomics. METHODS: Advanced human oral cancer from three patients was implanted orthotopically into the tongues of 19 SCID and 4 RAG2/gamma(c) knockout (KO) mice. Adjacent normal tissue from each patient was also implanted into nine SCID and 4 RAG2/gamma(c) KO mice. The models were compared for tissue take, the presence of metastasis, and histologic invasiveness. Mouse serum was preserved for studies in serum proteomics. RESULTS: Tumour tissue was successfully implanted into SCID and RAG2/gamma(c) mice, and the invasiveness was confirmed pathologically. Three of the control mice demonstrated the persistence of normal tissue more than 1 month after implantation. This is the first time that this has been reported. The larger size of the RAG2/gamma(c) KO mouse facilitated serum collection for serum proteomics. CONCLUSIONS: Both RAG2/gamma(c) KO and SCID mouse are able to reliably engraft human oral cancer. Engraftment of normal oral tissue was less reliable. This is the first in vivo model allowing identification of proteins released from the tumour microenvironment.

HER2/neu and Ki-67 as prognostic indicators in mucoepidermoid carcinoma of salivary glands.

INTRODUCTION: Mucoepidermoid carcinoma is the most common salivary gland malignancy, representing up to 30% of all cases. Despite attempts to correlate histopathologic grades to clinical outcomes, some histologically "low"-grade lesions continue to behave aggressively despite appropriate treatment. OBJECTIVE: This preliminary study will attempt to evaluate the use of immunohistochemical markers HER2/neu and Ki-67 as prognostic markers of biologic aggressiveness for mucoepidermoid carcinoma of the salivary glands. DESIGN AND METHODS: A retrospective chart review of 42 patients with mucoepidermoid carcinoma of major and minor salivary glands treated between 1970 and 1995 was conducted. A combination of primary resection with or without postoperative irradiation was used. Histologic grading and correlation with outcome analyses are provided. RESULTS: In the current study, positive HER2/neu staining and strong Ki-67 staining occurred in patients with high-grade mucoepidermoid carcinoma, whereas low-grade carcinoma was correlated with negative or weak staining. CONCLUSION: These preliminary results indicate that, overall, the overexpression of both the HER2/neu and the Ki-67 oncoproteins may serve as prognostic markers for poor outcome in salivary gland mucoepidermoid carcinoma.