5/3/2017. Ahn et al N Engl J Med 2014; 371

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1 Alan Failor, M.D. Clinical Professor of Medicine Division of Metabolism, Endocrinology and Nutrition University of Washington April 20, 2017 No disclosures to report 1. Appropriately evaluate s in adult patients 2. Interpret initial evaluation results to help guide further treatment or surveillance 3. Understand the options for molecular testing in s and the indications for testing. 1

2 Ahn et al N Engl J Med 2014; 371 2

3 Initiation of national screening program US incidence 2011 Ahn et al N Engl J Med 2014; 371 ~5% have palpable nodules in iodine replete areas up to 2/3 have nodules by ultrasound screening >50 % of people over age 50 have nodules by autopsy 6 30 % rate of thyroid cancer in autopsy studies ~5 8 % of s are malignant 41 yo man with detected on CT 28 yo female nursing student with a on exam 3

4 41 yo man with detected on CT Suffered a neck injury while working as a security guard. CT scan detected a No hoarseness, trouble, history of radiation exposure. No family history of thyroid disease. 28 yo female nursing student with a on exam 41 yo man with detected on CT Suffered a neck injury while working as a security guard. CT scan detected a No hoarseness, trouble, history of radiation exposure. No family history of thyroid disease. Healthy, mother of month history of chronic cough, sense of having to clear her throat, occasional trouble dry foods Barium swallow identified external compression from a mass at the level of the thyroid. 28 yo female nursing student with a on exam 41 yo man with detected on CT Suffered a neck injury while working as a security guard. CT scan detected a No hoarseness, trouble, history of radiation exposure. No family history of thyroid disease. Healthy, mother of month history of chronic cough, sense of having to clear her throat, occasional trouble dry foods Barium swallow identified external compression from a mass at the level of the thyroid. 28 yo female nursing student with a on exam Otherwise healthy young woman with a history of hypothyroidism in her mother. Nodule was detected by a co student when learning to do thyroid exams. No hoarseness, trouble, history of radiation exposure. 4

5 Check the thyroid stimulating hormone (TSH) Kondo et al Nat Rev Cancer 41 yo man with detected on CT TSH 1.4 IU/L (normal) Free T4 1.0 ng/dl (normal) TSH 0.02 IU/L (low) Free T4 2.0 ng/dl (high) 28 yo female nursing student with a on exam TSH 5.8 IU/L (high) Free T4 0.4 ng/dl (low) TSH reference range IU/L Free T4 reference range ng/dl Ultrasound: Right 4.2 cm solid and cystic nodule with coarse calcifications. Left 2.4 cm solid, hyperechoic nodule without calcifications. Muscle Carotid Trachea TSH reference range IU/L Free T4 reference range ng/dl 5

6 Ultrasound: Right 4.2 cm solid and cystic nodule with coarse calcifications. Left 2.4 cm solid, hyperechoic nodule without calcifications. Trachea Muscle Carotid Right 4.2 cm Left 2.4 cm Which nodule needs a fine needle aspiration? Haugen et al Thyroid; 26(1) 6

7 Haugen et al Thyroid; 26(1) Low TSH History, Physical Check TSH Radio iodine Uptake and Scan RAO Right 4.2 cm, low suspicion No FNA indicated for a hot nodule Left 2.4 cm, low suspicion FNA indicated Which nodule needs a fine needle aspiration? 7

8 Left nodule FNA shows bland follicular cells, abundant colloid, consistent with a benign I Diagnostic Category Nondiagnostic/ Unsatisfactory Description Must have a least 6 groups of follicle cells, at least 10 cells per group II Benign Bland follicular cells in follicles, abundant colloid, macrophages ok III IV Atypia of undetermined significance (AUS)/ Follicular lesion of undetermined significance (FLUS) Suspicious for follicular neoplasm AUS not clearly benign, nor suspicious; may be poor fixation FLUS highly cellular, overcrowding, nuclear overlap, scant colloid FNA cytology cannot distinguish adenoma from carcinoma capsular or vascular invasion needed V Suspicious for malignancy Nuclear features of carcinoma, but not enough cells for diagnosis VI Malignant Enlarged and elongated nuclei, pseudoinclusions, nuclear grooves, powdery chromatin, psammomatous calcifications Cibas and Ali 2009 Am J Clin Pathol;132 Diagnostic Category Risk of Malignancy I Nondiagnostic/Unsatisfactory 1 4% II Benign 0 3% III Atypia of undetermined significance / Follicular lesion of undetermined significance (FLUS) AUS 5 15% FLUS 15 30% IV Suspicious for follicular neoplasm 15 50% V Suspicious for malignancy 60 75% VI Malignant 97 99% Cibas and Ali 2009 Am J Clin Pathol;132 8

9 Right with benign FNA Treated with I131 therapy for a toxic nodule Cough and dysphagia resolved over 6 months Labs on follow up: 3 mo post I131: TSH 0.03 (low), free T4 1.2 (nl) 6 mo post I131: TSH 3.4 (nl), free T4 0.8 (nl) 9 mo post I131: TSH 2.5 (nl), free T4 0.9 (nl) 1 yr ultrasound Rt decreased in size, lt nodule unchanged Remains off thyroid hormone 41 yo man with detected on CT TSH 1.4 IU/L (normal) Free T4 1.0 ng/dl (normal) TSH 0.02 IU/L (low) Free T4 2.0 ng/dl (high) 28 yo female nursing student with a on exam TSH 5.8 IU/L (high) Free T4 0.4 ng/dl (low) TSH reference range IU/L Free T4 reference range ng/dl Low TSH Radio iodine Uptake and Scan History, Physical Check TSH Normal TSH Hot nodule? If no If yes Treat for hyperthyroidism Neck ultrasound Nodule on US Do FNA if indicated 9

10 41 yo man with detected on CT Ultrasound: Left 1.5 cm solid, illdefined, hypoechoic with calcifications and posterior shadowing. No other nodules No abnormal lymph nodes Normal thyroid tissue Muscle Trachea Nodule Acoustic shadowing Carotid Does this nodule need an FNA? Haugen et al Thyroid; 26(1) FNA shows few follicular cells and blood Impression: Bethesda I, Non diagnostic I Diagnostic Category Nondiagnostic/ Unsatisfactory Description Must have a least 6 groups of follicle cells, at least 10 cells per group What should be done next for a non diagnostic, 1.5 cm, high suspicion? A. Repeat an ultrasound in 6 12 months. B. Repeat FNA. C. Refer for diagnostic lobectomy? 10

11 Overall risk of malignancy low, 1 4% Guidelines recommend repeating an FNA If repeat FNA non diagnostic, 6 12 month surveillance by ultrasound Repeat FNA if change in size or characteristics Consider diagnostic lobectomy in high suspicion nodules Initial FNA non diagnostic Repeat FNA consistent with papillary thyroid cancer Initial FNA non diagnostic Repeat FNA consistent with papillary thyroid cancer Total thyroidectomy with ipsilateral central neck dissection 1.6 cm papillary thyroid cancer, no extrathyoidal extension or vascular invasion 6/9 lymph nodes contained foci of thyroid cancer Stage 1, T1bN1a Treated with radioactive iodine (I131) Excellent response to treatment Undetectable tumor marker (thyroglobulin) and normal ultrasound at 1 year 11

12 After surgery levothyroxine mcg/kg Initial goal is TSH below normal range Goal will change based on response to therapy Haugen et al Thyroid; 26(1) 41 yo man with detected on CT TSH 1.4 IU/L (normal) Free T4 1.0 ng/dl (normal) TSH 0.02 IU/L (low) Free T4 2.0 ng/dl (high) 28 yo female nursing student with a on exam TSH 5.8 IU/L (high) Free T4 0.4 ng/dl (low) TSH reference range IU/L Free T4 reference range ng/dl 12

13 Low TSH Radio iodine Uptake and Scan History, Physical Check TSH Normal TSH High TSH Evaluate and treat hypothyroidism Hot nodule? If no If yes Treat for hyperthyroidism Neck ultrasound Nodule on US Do FNA if indicated 28 yo female nursing student with a on exam Ultrasound: Left 1.8 cm complex nodule, primarily cystic with central vascularity. No other nodules Mildly prominent cervical lymph nodes but symmetric bilaterally and without increased vascularity. No suspicious lymphadenopathy. Muscle Trachea Carotid Low suspicion nodule FNA recommended if > 1.5 cm Benign follicular cells Malignant follicular cells Atypical follicular cells 13

14 Diagnostic Category Risk of Malignancy I Nondiagnostic/Unsatisfactory 1 4% II Benign 0 3% III Atypia of undetermined significance / Follicular lesion of undetermined significance (FLUS) AUS 5 15% FLUS 15 30% IV Suspicious for follicular neoplasm 15 50% V Suspicious for malignancy 60 75% VI Malignant 97 99% Cibas and Ali 2009 Am J Clin Pathol;132 What should be done next for a low suspicion with an indeterminate FNA result? A. Repeat an ultrasound in 6 12 months. B. Repeat FNA. C. Refer for diagnostic lobectomy? D. All of the above are reasonable options! 1. Repeat FNA can yield benign results in up to 50% of cases 2. Diagnostic lobectomy for definitive diagnosis High clinical suspicion Symptomatic nodule Patient preference 14

15 DNA/RNA mutation analysis ThyroSeq ThyGenX Con: Low sensitivity (you can t identify EVERY mutation) Pro: High specificity (mutation present = cancer) RNA gene expression Afirma GEC Con: Cost effectiveness variable based on underlying risk of cancer and experience of cytology Pro: Pattern recognition to rule out cancer MicroRNA analysis ThyraMir Rosetta Reveal Con: Accuracy of diagnosis still in early testing Pro: Combination of pattern recognition and specific mutations identified Nishino 2016 Cancer Cytopathology FNA shows a follicular lesion of undetermined significance (FLUS) (risk of malignancy 15 30%) Repeat FNA 2 months later shows FLUS again Afirma Gene Expression Classifier (GEC) sent on repeat FNA suspicious Is this likely to be cancer? No risk of cancer is still 15 30% 15

16 FNA shows a follicular lesion of undetermined significance (FLUS) (risk of malignancy 15 30%) Repeat FNA 2 months later shows FLUS again Afirma Gene Expression Classifier (GEC) sent on repeat FNA suspicious Patient underwent hemithyroidectomy Pathology showed follicular adenoma 1 month post operatively, TSH 12 (high) Levothyroxine initiated What is the long term follow up for a thyroid nodule with a benign FNA result? A. Begin levothyroxine therapy to suppress nodule growth. No role for thyroid suppression of nodules and increases risk of osteoporosis and atrial fibrillation B. Repeat a neck ultrasound in 12 months for surveillance. YES! Even benign nodules need to be followed at 1 year, then every 2 5 years, for growth, symptoms or change in ultrasound characteristics C. Begin Thyroid Support Supplement Adequate iodine intake (150 mcg/day) is important in deficient regions, but many supplements actually contain undocumented thyroid hormone In a multinodular goiter, which nodule should undergo evaluation by fine needle aspiration? A. Every nodule greater than 1 cm should have an FNA. FNA size criteria varies by ultrasound risk stratification, so not every nodule >1cm requires FNA B. Only the largest nodule on each side should undergo FNA. This is correct only if all nodules have similar risk based on ultrasound characteristics C. The highest risk nodules by ultrasound should undergo FNA, regardless of size. YES! FNA should be performed preferentially based on ultrasound risk pattern and respective size cut offs 16

17 Questions? 17