PRACTICE GUIDELINES: Thyroid Nodules and Cancer 2017 ESEO Alexandria

PRACTICE GUIDELINES: Thyroid Nodules and Cancer 2017 ESEO Alexandria James V. Hennessey MD Associate Professor of Medicine Harvard Medical School

Case 1 28 year old woman sees OB for routine visit ROS: Negative except for occasional dysphonia PE: BP 122/78, HR 72 BPM, 5 5, 120 lbs. Thyroid Exam: 2.5 cm smooth nodule left Moves easily with swallowing 1 cm left SCM lymph node palpable

Questions to be answered: How frequently are thyroid nodules and thyroid cancer encountered?

8X 5X CT MRI Scanners first introduced (35) Morris LGT et al. 2013 Thyroid 23(7):885-891

THYROID NODULES PREVALENCE: 30-50% Risk of nodule (U/S or Autopsy) 4-8% risk palpable nodule THYROID CANCER 64,300 cases in U.S. 2016 (Estimate) 0.005% of U.S. population < 5% fatal (1980 deaths in 2016 estimated) Cancer Facts and Figures 2016 American Cancer Society

Risk of malignancy per nodule High Risk malignancy / nodule Kwong N et al. 2015 JCEM 100:4434-4440

DIAGNOSIS: Hx favors benign diagnosis? FHx Hashimoto s Probably NOT FHx of MNG Probably NOT FHx Benign nodule Probably NOT helpful Sx of Hyperthyroidism

Adjusted Odds Ratio TSH & Risk of Malignancy 12 10 * 11.8 *=P< 0.05 8 6 4 2 0 1 < 0.4 mu/l * 2.72 1.31 3.88 0.4-0.9 1.0-1.7 1.8-5.5 >5.5 * TSH Boelaert et al. 2006 JCEM 91(110:4295-301

Percent TSH and Malignancy Risk 843 Surgical patients with pre-op TSH 60 50 40 30 20 10 * * * P < 0.002 Malignancy 0 TSH <0.06 0.4-1.39 1.4-4.99 > 5.0 Haymart MR et al. 2008 JCEM 93:809-14

Mean TSH 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 TSH and Malignancy Risk 843 Surgical patients with pre-op TSH * * p=0.002 Stage I/II Stage III/IV Haymart MR et al. 2008 JCEM 93:809-14 TSH

Solitary vs. MNG Photos courtesy of Marla Barkoff M.D.

Thyroid Cancer Risk: Multinodular (MNG) versus Single Nodule (SN) Goiter Squares/horizontal lines: Odds ratio/95%ci; diamonds: pooled odds ratio Brito JP et al. Thyroid. 2013 Apr;23(4):449-55

Summary of High Risk History 1. Family Hx Thyroid Cancer 1 relative 2. Hx XRT/Ionizing Irradiation as child (Adolescent) 3. Surgical Dx Thyroid Cancer in contralateral lobe 4. 18 FDG-PET positive nodule 5. MEN2/FMTC RET proto-oncogene positive 6. Calcitonin > 100 pg/ml 7. MEN 2 (MCT, Hyperpara., Pheochromocytoma 8. Familial Medullary Thyroid Cancer Haugen BR et al. 2016 Thyroid 26(1):1-133

Case 2 63 year old woman seen in the ER for dizziness. PE: Stable VS, Thyroid nl, Heart RRR Labs: Routine chemistry nl, TSH 2.3 IU/L Carotid Ultrasound: No vascular lesion Three 0.8-1.1 cm hypoechoic nodules left thyroid lobe Ultrasonographic features described Doppler flow study performed

Incidentaloma Facts Frequency: 19-67% in prospective studies Thyroid Cancer found in 4% of FNAs the # of nodule FNAs will Cancer rates Incidental thyroid cancer characteristics: Capsule invasion 20% or Extra thyroidal 17-21% Positive cervical lymph nodes 12-25% Tumor multifocality 32-39% Distant metastases 1.6-2.5% Thyroid cancer specific mortality 1% Mazzaferri, E. 2006 JAMA 295:2179-2182

Ultrasound Pattern = Risk High Suspicion = 70-90% Cancer Risk Hypoechoic, microcalcs, irregular border Hypoechoic, microlobulated margin Hypoechoic, irreg margin, Taller than wide Hypoechoic, irreg margin, X-thyroid Extension Irregular margins, suspicious Lymph nodes Haugen BR et al. 2016 Thyroid 26(1):1-133

High Suspicion Images

Ultrasound Pattern = Risk High Suspicion = 70-90% Cancer Risk Hypoechoic, microcalcs, irregular border Hypoechoic, microlobulated margin Hypoechoic, irreg margin, Taller than wide Hypoechoic, irreg margin, X-thyroid Extension Irregular margins, suspicious Lymph nodes Intermediate suspicion = 10-20% Risk Hypoechoic with regular margins Haugen BR et al. 2016 Thyroid 26(1):1-133

Intermediate Suspicion

Ultrasound Pattern = Risk Low Suspicion = 5-10% Risk of cancer Hyperechoic, solid, regular margins Isoechoic, solid, regular margins Partially Cystic, eccentric solid area Haugen BR et al. 2016 Thyroid 26(1):1-133

Low Suspicion

Ultrasound Pattern = Risk Low Suspicion = 5-10% Risk of cancer Hyperechoic, solid, regular margins Isoechoic, solid, regular margins Partially Cystic, eccentric solid area Very Low suspicion = <3% Risk of cancer Spongiform, partially cystic no suspicions features Haugen BR et al. 2016 Thyroid 26(1):1-133

Very Low Suspicion

Ultrasound Pattern = Risk Low Suspicion = 5-10% Risk of cancer Hyperechoic, solid, regular margins Isoechoic, solid, regular margins Partially Cystic, eccentric solid area Very Low suspicion = <3% Risk of cancer Spongiform, partially cystic no suspicions features Benign Purely cystic Haugen BR et al. 2016 Thyroid 26(1):1-133

Benign

Fine Needle Aspiration FNA is the procedure of choice in Rec. 7 the evaluation of thyroid nodules when clinically indicated. Strong Recommendation, High-quality evidence Haugen BR et al. 2016 Thyroid 26(1):1-133

Who to Biopsy? R8 Sonographic Risk Pattern Estimated Malignancy Risk Consider Biopsy Strength of Recommenda tion Quality of Evidence High Suspicion >70-90% > 1 cm Strong Moderate Intermediate Suspicion 10-20% > 1 cm Strong Low Low Suspicion 5-10% > 1.5 cm Weak Low Very Low suspicion < 3% > 2 cm Weak Moderate Benign < 1% No Strong Low FNA NOT recommended for nodules not meeting above criteria, including ALL nodules < 1cm Strong Moderate Haugen BR et al. 2016 Thyroid 26(1):1-133

Indeterminate FNA Malignancy Prediction with Bethesda System Category Risk of Malig What next? Non-Dx 1-4+% Re-do (U/S) Benign 0-3% Clinical F/U Atypical 5-15% Re-do (U/S) Foll Neoplas. 15-30% Lobectomy Suspicious 60-75% Total Tx Malignant 97-99% Total Tx Ali SZ & Cibas E 2009 The Bethesda system for Reporting Thyroid Cytopathology. New York: Springer

Indeterminate: What Next? Mutation Panel BRAF, RET, RAS, RET/PTC, PAX8/PPARγ, etc. Modest Positive Predictive value (50-60%) Higher Negative Predictive value (85-90+%) Gene Expression Classifier: id benign nodules High Negative predictive value (94-95%) mirna +/- Mutation panel in FNA or circulation Modest Positive Predictive value (50-60%) Higher Negative Predictive value (85-90+%)

FNA Disposition Inadequate Malignant Indeterminate Benign Repeat FNA US guidance Surgery Repeat FNA Cytogenetics? Inadequate Mutation Mut. Neg. B9 Close F/U Surgery? Surgery T-Tx? Surgery Hemi or Follow

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