5/18/2013 Most thyroid nodules are benign • Incidence • Etiology • Risk factors • Diagnosis Thyroid nodules: new – Gene classification system techniques in • Treatment evaluation Postgraduate Course in General Surgery Jessica E. Gosnell MD (Tuttle and Lehoeuf, Endo Metab N Am) May 18, 2013 (ATA revised guidelines for Thyroid Nodules , Thyroid 2009) 2 2 Thyroid cancer is now the most Most thyroid nodules are benign rapidly increasing cancer in women • thyroid nodules occur in 77% of the world ’ s population • Approximately 37,200 new • palpable thyroid nodules cases of thyroid cancer were occur in about 5% of women diagnosed in 2009 and 1% of men in the US • Yearly incidence 3.6 per • more common in women, advancing age, iodine 100,000 in 1973 --> 8.7 per deficiency, family history and 100,000 in 2002 radiation exposure • Most of the change is • high resolution ultrasound can attributed to increases in detect nodules in 19-67%, with papillary thyroid cancer, increasing rates in women and which comprises 90% of all the elderly thyroid cancers • Almost have of the rising incidence consisted of (Tuttle and Lehoeuf, Endo Metab N Am) tumors <1cm (ATA revised guidelines for Thyroid Nodules , Thyroid 2009) 4 3 3 4 1
5/18/2013 Thyroid nodules: differential Thyroid nodules: diagnosis History • Symptoms of hypo, hyperthryoidism • Local symptoms in the neck – dysphagia, dyspnea, dysphonia – neck pain • family history of thyroid or other cancers • exposure to ionizing radiation to the head and neck (Gosnell and Clark, Management of thyroid nodules, in Cameron ’ s Current Surgical Therapy, 10th ed, 2010) 5 5 6 6 Physical exam • vitals • eye signs – stare, lid lag, exophthalmos • visible, palpable nodules – fixed mass, tenderness • deviation of midline Pemberton’s sign structures • cervical lymphadenopathy • cardiac • extremities – pretibial myxedema – -tremor • skin – rash, cutaneous lichen amyloidosis obstruction of vena cava 7 7 8 2
5/18/2013 Thyroid nodules Most thyroid cancers are Thyroid nodules: imaging biochemically “ silent ” • Ultrasound – better than palpation and scintigraphy for thyroid • TSH is the signal best test to assess for thyroid nodules and cervical lymph nodes dysfunction – inexpensive, non-invasive • T3, T4 as indicated – provides valuable characteristics of the nodule • thyroglobulin (calcifications, vascularity, borders) – Suh et al., Serum thyroglobulin is a poor diagnostic – cannot distinguish between benign and malignant biomarker of malignancy in follicular and Hurthle-cell lesions neoplasms of the thyroid. • 366 pts with follicular/Hurthle cell lesions • Tg levels>500mug/L had positive predictive value of 0.75 (Suh et al., Am J Surg 2010Jul;200:41) Ultrasound for the Endocrine Surgeon , Surgery 2005, 138(6):1193 1010 9 9 Thyroid nodules: ultrasound guided Value of preoperative ultrasound FNA Unsuspected disease was found by ultrasonography in 52 patients (34%) and altered the operative approach to include dissection of the central lymph nodes in 32 patients, ipsilateral nodes in 21 patients and contralateral nodes in 9 patients (Kouvaraki et al, Surgery 134:946, 2003) (J Mechanick, Endocrine Surgery, 2004) 11 11 12 12 3
5/18/2013 Thyroid scintigraphy= Limited role! Other imaging modalities • Historically, used to characterize thyroid • Useful to evaluate for retrosternal extension, nodules by their ability to take up isotope, as a tracheal deviation/compression way to distinguishing benign from malignant – CT scan – up to 80% of thyroid nodules are “cold”, only 20% of • avoid iodinated contrast in patients that may need RAI these are malignant treatment • Now, useful in patients with biochemical – MRI hyperthyroidism – distinguish between Graves’ disease, toxic adenoma and Plummer’s disease (toxic MNG) toxic MNG toxic adenoma in the left superior pole 13 13 14 14 FNA biopsy for thyroid nodules: FNA biopsy for thyroid nodule when is it indicated?? 10 – 50% risk > 90% • Most do not advocate biopsy of all thyroid of cancer accurate nodules FNA biopsy – >1cm, worrisome ultrasound findings, rapid enlargement, family history or radiation exposure Indeterminate/suspicious (5-50%) Benign (70%) Nondiagnostic (<10%) Malignant (<10%) 10 – 50% risk of cancer Total thyroidectomy (lobectomy) "Diagnostic" thyroidectomy Need for more accurate diagnostic tests than FNA cytology! (Gharib and Burguera, Thyroid incidentalomas. Prevalence, diagnosis, significance and management. Endocrin Metab Clin North Am 20002 Mar;29(1):187) (Cooper et al. Revised ATA guidelines 2009) 15 15 16 16 4
5/18/2013 FNA: typical papillary thyroid Indeterminate FNA cytology cancer follicular cell lesion Hurthle cell lesion “ Orphan Annie eyes ” 17 17 18 18 Gene Expression Classifier Gene Expression Classifier - Measures the expression of 142 genes on a microarray chip Indeterminate FNA* - Expression levels then used to classify nodules as benign or malignant Ultrasound Gene expression Surgical - Useful for: surveillance classifier consult -“follicular lesion of undetermined significance” (FLUS) -“atypia of undetermined suspicious significance” (AUS) Benign -“suspicious for Hurthle/follicular >95% NPV neoplasm” - FNA done. Cytology done “follicular lesion of undetermined significance” (FLUS), first, if still non-diagnostic, goes “atypia of undetermined significance” (AUS), for gene expression “suspicious for Hurthle/follicular neoplasm” - If insurance does not cover, out of pocket cost $300 or less 19 19 20 20 5
5/18/2013 Indications for thyroidectomy in Preoperative diagnosis of benign thyroid nodules with indeterminate cytology patients with thyroid nodules • FNA/gene-classifier suspicious/ malignant - New England Journal of Medicine findings 2012 August 23;367(8):705-15 • worrisome nodules despite benign FNA/gene- Alexander EK et al classifier findings – >4cm, growing • 19 month, prospective multicenter validation study • local compression • 4812 fine-needle aspirates • retrosternal extension • 265 cytologically indeterminate aspirates • family history of thyroid cancer and exposure to • Gene-expression classifier correctly identified 78 of the 85 ionizing radiation nodules as suspicious • selected cases of hyperthyroidism (toxic MNG, • Negative predictive values for “atypia (or follicular lesion of Graves ’ disease) undetermined significance”, “follicular neoplasm or suspicious for follicular neoplasm” or “suspicious findings” • cosmesis were 95%, 94% and 85%, respectively 21 21 22 22 The role of diagnostic surgery • Indicated for follicular or Hurthle cell neoplasms, possibly if suspicious on gene- classifier • Indicated for patients with worrisome clinical findings – growing nodules, risk factors for thyroid cancer • Should be considered for nodules > 4cm The role of intraoperative frozen section • useful for nodules suspicious for papillary thyroid cancer but not follicular or Hurthle cell nodules • useful for cervical lymph nodes, parathyroid glands Gosnell and Clark. Management of Thyroid Nodules. In Cameron, Current (Livolsi, Surgical Pathology of the Thyroid, 2nd ed, 2007) Surgical Therapy, 10th ed, 2011 23 23 24 6
5/18/2013 Thank you 7
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