Oncogenic mutations are common in thyroid cancers. While the frequently detected RAS-oncogene mutations have been studied for diagnostic use in cytologically indeterminate thyroid nodules, no ...investigation has studied such mutations in an unselected population of thyroid nodules. No long-term study of RAS-positive thyroid nodules has been performed.
We performed a prospective, blinded cohort study in 362 consecutive patients presenting with clinically relevant (>1 cm) thyroid nodules. Fine needle aspiration cytology and mutational testing were obtained for all nodules. Post-operative histopathology was obtained for malignant or indeterminate nodules, and benign nodules were sonographically followed. Histopathological features were compared between RAS- and BRAF-positive malignancies. RAS-positive benign nodules were analyzed for growth or cellular change from prior aspirations.
Overall, 17 of 362 nodules were RAS-positive. Nine separate nodules were BRAF-positive, of which eight underwent surgery and all proved malignant (100%). Out of the 17 RAS-positive nodules, ten underwent surgery, of which eight proved malignant (47%). All RAS-positive malignancies were low risk - all follicular variants of papillary carcinoma, without extrathyroidal extension, metastases, or lymphovascular invasion. RAS-positivity was associated with malignancy in younger patients (P = 0.028). Of the nine RAS-positive benign nodules, five had long-term prospective sonographic follow-up (mean 8.3 years) showing no growth or signs of malignancy. Four of these nodules also had previous aspirations (mean 5.8 years prior), all with similar benign results.
While RAS-oncogene mutations increase malignancy risk, these data demonstrate a low-risk phenotype for most RAS-positive cancers. Furthermore, cytologically benign, yet RAS-positive nodules behave in an indolent fashion over years. RAS-positivity alone should therefore not dictate clinical decisions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose To determine the relationship between demographic and sonographic characteristics of thyroid nodules and malignancy in a pediatric population. Materials and Methods All thyroid nodules in ...patients younger than 19 years that underwent ultrasound (US)-guided fine-needle aspiration biopsy between January 2004 and July 2017 were retrospectively identified. Age, sex, and background appearance of the thyroid gland were recorded for each patient, and sonographic characteristics and pathologic diagnosis were recorded for each nodule. Demographic and sonographic characteristics were assessed to determine which were associated with malignancy. Categorical and continuous variables and interobserver variability were assessed. Results A total of 404 nodules in 314 patients (82.8% female) (age range, 2-18 years; mean age, 14.9 years) were analyzed. A total of 77 nodules (19.1%) were malignant, the majority of which were papillary thyroid carcinoma (n = 68 88.3%). The likelihood of malignancy did not differ between boys and girls (27.8% vs 22.7%, P = .64), nor did it differ between prepubertal and pubertal patients (18.8% vs 19.1%, P > .99). The cancer rate in patients with a solitary nodule was higher than that in patients with multiple nodules (29.4% vs 14.2%, P = .003). Sonographic characteristics associated with malignant nodules included larger size, solid parenchyma, taller-than-wide shape, presence of speckled calcifications, lack of a smooth margin, and presence of abnormal lymph nodes. Interobserver variability for assessment of sonographic characteristics ranged from moderate to very strong. Conclusion In children with thyroid nodules, solitary nodules, larger nodule size, solid parenchyma, taller-than-wide shape, speckled calcifications, irregular margins, and abnormal lymph nodes raise concern for malignancy.
Objective Surgical resection is recommended for cytologically indeterminate pediatric thyroid nodules due to their intermediate malignancy risk. We evaluated the utility of ultrasound characteristics ...for refining malignancy risk to inform the management of these nodules. Design Retrospective cohort study (2004–2019). Methods We analyzed consecutive thyroid nodules with indeterminate fine-needle aspiration cytology (Bethesda category III, IV, or V) in pediatric patients (<19 years). We assessed the association of demographic and sonographic characteristics with malignancy risk among all indeterminate nodules and within each Bethesda category. Results Eighty-seven cytologically indeterminate nodules were identified in 78 patients. Bethesda category was III in 56 nodules (64%), IV in 12 (14%), and V in 19 (22%). The malignancy rate was 46/87 (53%) overall, and 23/56 (41%), 8/12 (75%), and 15/19 (79%) in Bethesda III, IV, and V nodules, respectively. Malignancy rate was higher in solitary nodules (67% vs 37%, P = 0.004) and nodules with irregular margins (100% vs 44%, P < 0.001) or calcifications (82% vs 43%, P = 0.002). American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) risk level TR5 was associated with a higher rate of malignancy than lower TI-RADS risk levels (80% vs 42%, P = 0.002). Within individual Bethesda categories, TI-RADS risk level was not associated with malignancy. No sonographic feature had a negative predictive value for malignancy greater than 80%. Conclusions In pediatric thyroid nodules with indeterminate cytology, some sonographic features – including higher ACR TI-RADS risk level – are associated with malignancy, but these associations are unlikely to alter clinical management in most cases.
Context: Controversy remains as to the optimal management of patients with multiple thyroid nodules.
Objective: The objective of this study was to determine the prevalence, distribution, and ...sonographic features of thyroid cancer in patients with solitary and multiple thyroid nodules.
Design: We describe a retrospective observational cohort study that was carried out from 1995 to 2003.
Setting: The study was conducted in a tertiary care hospital.
Patients: Patients with one or more thyroid nodules larger than 10 mm in diameter who had ultrasound-guided fine needle aspiration (FNA) were included in the study.
Main Outcome Measures: The main outcome measures were prevalence and distribution of thyroid cancer and the predictive value of demographic and sonographic features.
Results: A total of 1985 patients underwent FNA of 3483 nodules. The prevalence of thyroid cancer was similar between patients with a solitary nodule (175 of 1181 patients, 14.8%) and patients with multiple nodules (120 of 804, 14.9%) (P = 0.95, χ2). A solitary nodule had a higher likelihood of malignancy than a nonsolitary nodule (P < 0.01). In patients with multiple nodules larger than 10 mm, cancer was multifocal in 46%, and 72% of cancers occurred in the largest nodule. Multiple logistic regression analysis of statistically significant features demonstrates that the combination of patient gender (P < 0.02), whether a nodule is solitary vs. one of multiple (P < 0.002), nodule composition (P < 0.01), and presence of calcifications (P < 0.001) can be used to assign risk of cancer to each individual nodule. Risk ranges from a 48% likelihood of malignancy in a solitary solid nodule with punctate calcifications in a man to less than 3% in a noncalcified predominantly cystic nodule in a woman.
Conclusions: In a patient with one or more thyroid nodules larger than 10 mm in diameter, the likelihood of thyroid cancer per patient is independent of the number of nodules, whereas the likelihood per nodule decreases as the number of nodules increases. For exclusion of cancer in a thyroid with multiple nodules larger than 10 mm, up to four nodules should be considered for FNA. Sonographic characteristics can be used to prioritize nodules for FNA based on their individual risk of cancer.
Assessing thyroid nodules for malignancy is complex. The impact of patient and nodule factors on cancer evaluation is uncertain.
To determine precise estimates of cancer risk associated with clinical ...and sonographic variables obtained during thyroid nodule assessment.
Analysis of consecutive adult patients evaluated with ultrasound-guided fine-needle aspiration for a thyroid nodule ≥1 cm between 1995 and 2017. Demographics, nodule sonographic appearance, and pathologic findings were collected.
Estimated risk for thyroid nodule malignancy for patient and sonographic variables using mixed-effect logistic regression.
In 9967 patients 84% women, median age 53 years (range 18 to 95), thyroid cancer was confirmed in 1974 of 20,001 thyroid nodules (9.9%). Significant ORs for malignancy were demonstrated for patient age <52 years OR: 1.82, 95% CI (1.63 to 2.05), P < 0.0001, male sex OR: 1.68 (1.45 to 1.93), P < 0.0001, nodule size OR: 1.30 (1.14 to 1.49) for 20 to 19 mm, OR: 1.59 (1.34 to 1.88) for 30 to 39 mm, and OR: 1.71 (1.43 to 2.04) for ≥40 mm compared with 10 to 19 mm, P < 0.0001 for all, cystic content OR: 0.43 (0.37 to 0.50) for 25% to 75% cystic and OR: 0.21 (0.15 to 0.28) for >75% compared with predominantly solid, P < 0.0001 for both, and the presence of additional nodules ≥1 cm OR: 0.69 (0.60 to 0.79) for two nodules, OR: 0.41 (0.34 to 0.49) for three nodules, and OR: 0.19 (0.16 to 0.22) for greater than or equal to four nodules compared with one nodule, P < 0.0001 for all. A free online calculator was constructed to provide malignancy-risk estimates based on these variables.
Patient and nodule characteristics enable more precise thyroid nodule risk assessment. These variables are obtained during routine initial thyroid nodule evaluation and provide new insights into individualized thyroid nodule care.
Total thyroidectomy is recommended for children with papillary thyroid carcinoma, partly because of a high prevalence of bilateral disease. Identifying characteristics that predict bilateral disease ...might identify candidates for more limited surgery.
Investigate associations of preoperative or histopathological characteristics with bilateral disease in children with differentiated thyroid cancer.
Retrospective cohort study (1998-2020) at 2 academic hospitals. Patients <19 years who underwent total thyroidectomy for differentiated thyroid cancer were included. Clinical, sonographic, and histopathological characteristics were evaluated. The presence of bilateral disease on histopathology was assessed by univariable analysis and multivariable logistic regression.
One hundred and fifteen subjects were analyzed (90% with papillary carcinoma). Median (range) age at diagnosis was 15.0 (8.1-18.9) years. Bilateral disease was present in 47/115 subjects (41%). Bilateral disease was associated with solid parenchyma, calcifications, irregular margins, and abnormal lymph nodes detected by ultrasound, Bethesda class V/VI cytology, papillary histology, tumor multifocality in the primary lobe, extrathyroidal extension, lymphovascular invasion, and nodal metastases. In multivariable analysis, only multifocality in the primary lobe was independently associated with bilateral disease (OR 7.61, 95% CI 2.44-23.8, P < .001). Among clinically node-negative subjects with papillary carcinoma who did not have tumor multifocality in the primary lobe, bilateral disease was present in 5/32 (16%).
In children with differentiated thyroid cancer, tumor multifocality in the primary lobe is associated with bilateral disease and should prompt consideration of completion thyroidectomy after initial lobectomy. Clinically node-negative children with tumors that are unifocal in the primary lobe have a low likelihood of contralateral disease.
Predictive models of thyroid nodule cancer risk are presently based upon nodule composition, echogenicity, margins, and the presence of microcalcifications. Nodule shape has shown promise to be an ...additive factor helping determine the need for nodule biopsy.
We sought to determine if calculation of a nodule's spherical shape independently associates with cancer risk.
This prospective cohort study, conducted at a single large academic healthcare system in the United States, included patients with 1 or 2 clinically relevant thyroid nodules (predominantly solid and over 1 cm) presenting for diagnostic evaluation. Thyroid ultrasound, cytological evaluation with fine-needle biopsy, and/or histopathological examination on occasion of thyroid surgery were performed. We calculated the nodule's long to short ratio (spherical shape), and its association with tissue proven benign or malignant endpoints.
The long to short nodule ratio was significantly lower in malignant compared to benign nodules indicating greater risk of malignancy in more spherical nodules (1.63 ± 0.38 for malignant nodules vs 1.74 ± 0.47 for benign, P < 0.0001). The risk of malignancy continually increased as the long to short ratio approached a purely spherical ratio of 1.0 (ratio > 2.00, 14.6% cancer; ratio 1.51-2.00, 19.7%; ratio 1.00-1.50, 25.5%, P < 0.0001). In multiple regression analysis, younger age, male sex, and nodule's spherical shape were each independently associated with cancer risk.
The more a thyroid nodule is spherically shaped, as indicated by a long to short ratio approaching 1.0, the greater its risk of malignancy. This was independent of age, sex, and nodule size. Incorporating a nodule's sphericity in the risk stratification systems may improve individualized clinical decision making.
Thyroid nodules are common. Evaluation of patients with thyroid nodules typically includes fine needle aspiration biopsy (FNA), an approach that has proven to be accurate for the detection of thyroid ...cancer. Although the majority of biopsies are adequate for a cytological diagnosis, up to 20% will be insufficient or nondiagnostic. Current opinion suggests that such aspirates should be repeated, although no systematic study has investigated the usefulness of this approach, especially when ultrasound guidance is used to direct the initial FNA. We sought to define the predictors and optimal follow-up strategy for initial nondiagnostic ultrasound-guided FNAs of thyroid nodules.
Data were collected for all patients at the Brigham and Women’s Hospital Thyroid Nodule Clinic between 1995–2000 who underwent ultrasound-guided FNA of a thyroid nodule. All patients with nondiagnostic cytology were advised to return for a repeat ultrasound-guided FNA. Patient age, gender, nodule size, cystic content, solitary vs. multinodular thyroid, and nodule location were documented and evaluated as possible predictors of a nondiagnostic biopsy in a multivariable model. The rate of diagnostic cytology obtained on repeat ultrasound-guided FNA was calculated.
A total of 1128 patients with 1458 nodules were biopsied over a 6-yr period. A total of 1269 aspirations (950 patients) were diagnostic, and 189 (178 patients) were nondiagnostic. The cystic content of each nodule was the only significant independent predictor of nondiagnostic cytology (P < 0.001). The fraction of specimens with initial nondiagnostic cytology increased with greater cystic content (P < 0.001 for trend). A diagnostic ultrasound-guided FNA was obtained on the first repeat biopsy in 63% of nodules and was inversely related to increasing cystic content of each nodule (P = 0.03). One hundred and nineteen patients with 127 nodules returned for follow-up as advised, and malignancy was documented in 5%.
Despite ultrasound-guided FNA, there remains a significant risk of initial nondiagnostic cytology, largely predicted by the cystic content of each nodule. Repeat aspiration is often successful and should be the standard approach to such nodules, given their risk of malignancy.
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