Text of + Thyroid Nodules and Cancer Netee Papneja, PGY5
+ Thyroid Nodules and Cancer Netee Papneja, PGY5
+ Objectives Review Epidemiology of thyroid nodules/cancers Approach to thyroid nodules Newer evidence re: indications for biopsy Molecular characterization of FNA results Thyroid cancer guidelines
+ Epidemiology Thyroid nodules are very common Palpable nodules 5% of women 1% of men Ultrasound series 19-67% Autopsy series 37-57% The prevalence of nodules increases with age Prevalence in women 1.5-1.7 times higher than men ATA guidelines 2009
+ Etiology of Benign Nodules Focal thyroiditis Benign adenomas follicular and hurthle cell Thyroid, parathyroid, thyroglossal cysts Post surgical/radiation remnant hyperplasia Rare: teratoma, lipoma, hemangioma
+ Thyroid Nodules Thyroid cancer which occurs in 515% of nodules TypeFrequencyPrognosis PTC80%30-year survival 95% Follicular (including Hurthle cell) 10%30-year survival 85% Medullary5%10-year survival 65% Anaplastic3%5-year survival 5% Miscellaneous (lymphoma, fibrosarcoma, SCC, teratomas, metastatic carcinomas) 1%
+ Thyroid Cancer Incidence Incidence of thyroid cancer is increasing 1973: 3.6 per 100,000 2009: 8.7 per 100,000 However, mortality rates have stayed the same ? due to actual increase in incidence or increased detection Socioeconomic status and increased access to healthcare resources are associated with higher rates of papillary thyroid cancer (US, Canada)
+ Thyroid Cancer - Incidence Aim: examined whether the density of endocrinologists and general surgeons use of US were factors associated with increased incidence of thyroid cancer Methods: compared incidence data from SEER database (National Cancer Institute's Surveillance Epidemiology and End Results) from 1999 to 2009 with the density of endocrinologists and general surgeons Udelsman,R.&Zhang,Y.Theepidemicof thyroid cancer in the United States: the role of endocrinologists and ultrasounds. Thyroid http://dx.doi.org/10.1089/thy.2013.
+ Results: The incidence rates were significantly correlated with the density of endocrinologists (r=0.58, p
+ Thyroid Cancer Risk Factors Extremes of Age Thyroid nodules in children are twice as likely to be malignant In adults, higher rate of malignancy if age > 60 Sex Malignancy rate 2x higher in men compared to women (8% vs 4%) Family history FHx of a thyroid cancer syndrome (eg, familial polyposis, Carney Complex, MEN type 2) 10-fold increased risk of thyroid cancer in first degree relatives of thyroid cancer patients Uptodate: Overview of thyroid nodule formation
+ Thyroid Cancer Risk Factors Clinical signs rapid growth, fixation of the nodule to surrounding tissues, new onset hoarseness or vocal cord paralysis, or the presence of ipsilateral cervical lymphadenopathy Radiation Explosure most important RF = radiation exposure during childhood ~25% have thyroid nodules ~33% have malignant nodules No evidence that radiation-associated thyroid cancers are more aggressive than other thyroid cancers
+ Thyroid cancer risk factors Radiation exposure - potential sources: medical uses of radiation (eg, childhood malignancies) atomic weapons (eg, Nagasaki/Hiroshima, Japan 1945), or nuclear power plant accidents (eg, Chernobyl 1986, Fukushima Daiichi nuclear disaster 2011) ionizing radiation to treat benign conditions of the head and neck in 1950s
+ Laboratory tests Serum TSH If low radionuclide thyroid scan Either 123 I or 99m Tc pertechnetate Otherwise Further evaluation for possible FNA TSH level correlates to risk of thyroid cancer
+ Thyroid Cancer and TSH TSH (mU/L)Prevalence of thyroid cancer (%) < 0.42.8% 0.4 0.93.7% 1.0 1.78.4% 1.8 5.512.3% > 5.529.7% Boelaert K, Horacek J, Holder RL, et al. Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab 2006; 91:4295.
+ Investigations Laboratory tests Serum thyroglobulin (Tg) Can be elevated in most thyroid diseases Insensitive and nonspecific test for thyroid cancer Not recommended as part of the initial evaluation
+ Investigations Serum calcitonin Screening with calcitonin may detect MTC at an earlier stage (likely present if level > 100 pg/mL) But also detects C-cell hyperplasia and micromedullary carcinoma (clinical significance uncertain) ATA: Cannot recommend either for or against routine measurement False-positive results: hypercalcemia, hypergastrinemia, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, goiter, and chronic autoimmune thyroiditis prolonged treatment with omeprazole (greater than two to four months), beta-blockers, and glucocorticoids
+ Ultrasound Hypoechoic Increased central vascularity Incomplete halo Microcalcifications Irregular borders Taller than wide (transverse view) Suspicious lymph nodes Hyperechoic Peripheral vascularity Complete Halo Comet-tail Large, coarse calcifications High Risk FeaturesLow Risk Features
+ Central Vascularity
+ Irregular Borders
+ Taller Than Wide
+ Comet-tail Artifact
+ Investigations Fine-needle aspiration (FNA) Most accurate and cost effective Sensitivity 76-98%, specificity 71-100% Prior to FNA, only 15% of resected nodules were malignant With FNA, malignancy rate of resected nodules > 50% False positive and non-diagnostic cytology rates lowered with US guidance
+ ATA FNA Indications High-risk history: History of thyroid cancer in first degree relatives; external beam radiation as a child; exposure to ionizing radiation in childhood or adolescence; prior hemithyroidectomy with discovery of thyroid cancer, 18FDG avidity on PET scanning; MEN2=FMTC-associated RET protooncogene mutation, calcitonin >100 pg=mL. Suspicious features: microcalcifications; hypoechoic; increased nodular vascularity; infiltrative margins; taller than wide on transverse view.
+ Diagnostic Accuracy of the Ultrasonographic Features for Subcentimeter Thyroid Nodules Suggested by the Revised ATA Guidelines KIM ET AL, THYROID, Volume 23, Number 12, September 2013 Purpose: To analyze the diagnostic performance of the ATA guidelines and compared it to that of other modified guidelines. Methods: 713 nodules 6-10mm (Yonsei University, Korea) Frequencies of US features in benign and malignant nodules were compared Seven modified guidelines were made based on the revised ATA guidelines and from multi- variate analysis results
+ Modified guidelines 1. excluded increased nodular vascularity 2. included composition criteria and only solid nodules were considered 3. excluded the increased nodular vascularity and included solid 4. included macrocalcification 5. included macrocalcification and excluded increased nodular vascularity 6. included macrocalcification and only solids 7. Included macrocalcifications and excluded increased nodular vascularity
+ Results Solid composition and macrocalcification were significantly associated with malignancy (p=0.001 and 0.003). Increased vascularity was not significantly associated with malignant nodules (odds ratio 0.729, p = 0.212). Among the eight guidelines, the ATA guidelines showed the lowest diagnostic performance (Az = 0.616). Excluding increased vascuarity and including solid composition +/- macrocalcification to the suspicious US features of the ATA guidelines improved sensitivity (96.6% vs. 97.0%), specificity (26.6% vs. 42.9%), PPV (48.3% vs. 54.7%), and NPV (91.7% vs. 95.2%), thereby resulting in the highest Az value (diagnostic performance) (Az = 0.699, p < 0.001)
+ Conclusions: This study suggests that excluding increased vascularity and adding solid composition to the suspicious ultrasonographic features of the ATA guidelines would significantly improve the diagnostic performance in subcentimeter nodules for the identification of malignant lesions.
+ Risk of Thyroid Cancer Based on Thyroid Ultrasound Imaging Characteristics Results of a Population-Based Study Rebecca Smith-Bindman, MD; Paulette Lebda, MD; Vickie A. Feldstein, MD; Dorra Sellami, MD; Ruth B. Goldstein, MD; Natasha Brasic, MD; Chengshi Jin, PhD; John Kornak, PhD JAMA Intern Med. Published online August 26, 2013
+ Risk of Thyroid Cancer Based on Thyroid Ultrasound Imaging Characteristics Retrospective case control study 8,806 patients with 11,618 thyroid US at a UCSF facility from January 2000 - March 2005. patients did not have a diagnosis of thyroid cancer at the time of US They linked the patients with the California Cancer Registry and identified 105 who were diagnosed with thyroid cancer The cancer patients were matched with a group of cancer-free control subjects from the same cohort, based on factors such as gender, age and the year of the ultrasound exam