Management of Thyroid Nodules

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Management of Thyroid Nodules 38 y/o female with solid 1.5 cm right Thyroid nodule. TSH=0.68 Vincent J. Reid, MD., FACS Thyroid Cancer Incidence & Mortality 1974 to 2004 Overall Women Men Mortality 1

Cancer cases per year 100 Belarus Ukraine Russia 80 60 40 20 0 1986 1987 1988 1989 1990 1991 1992 1993 1994 Year Incidence of pediatric thyroid cancers in the countries receiving highest levels of radiation contamination after the Chernobyl nuclear accident in 1986. Note the major increase beginning in 1990. The southernmost region of Belarus, immediately north of Chernobyl, was the most affected. Issues in the Management of Thyroid Cancer Histologic subtype DiagnosPc work- up Management of RLN and parathyroids during surgery PrognosPc factors and risk groups RAI ablapon of thyroid remnant 1. Follow up - role of serial RAI uptake - role of suppressive therapy - role of thyroglobulin Intra- operapve decisions When a things ceases to be a subject of controversy, it ceases to be a subject of interest. William Hazlitt 2

Thyroid Nodule Investigations Routine Special Studies History/physical Thyroid scan Indirect laryngoscopy Sonogram TFTs CT scan CBC/SMAC/calcium MRI Thyroid anpbodies Needle aspirapon DiagnosPc Work- up What is Available? What is Necessary? Imaging Clinical Surgery Needle biopsy Thyroid Mass - Risk Factors House officer to prominent surgeon: Are you telling us that all thyroid nodules should be removed surgically? Looking down his nose at the young upstart, the surgeon replied: Certainly not, young man! Only those referred to me! Sex Age Hx of low dose radiapon to the neck Residence Rapid growth Sudden change in the size of a nodule 3

Thyroid Mass - Risk Factors Neck nodes Vocal cord paralysis Clinical characterispcs hard, fixed Pressure effects Recurrent cyspc mass Benign nodule Malignant psyche Needle Biopsy of Thyroid Malignant Suspicious Benign Inadequate Papillary Cellular smears Colloid goiter DegeneraPon nodule Medullary Follicular neoplasm Colloid cyst Technical problems AnaplasPc Hurthle lesions ThyroidiPs Hemorrhagic cyst 4

Solitary THYROID MASS Multinodular History & Physical Exam ( suspicious risk factors for malignancy) (Thyroid Function Tests - T4, TSH, antibodies) Risk Factors++ (Clinically Suspicious) No Risk Factors FNA Inconclusive, Repeat FNA FNA Thyroid Scan (hot or cold) Surgery Malignant or Suspicious Benign Extent of Surgery Based on Prognostic Factors and Risk Group Analysis Surgery Thyroxine (suppressive therapy) (6-9 months) Consider Repeat Needle Biopsy Regression or Unchanged Increase in Size Close Follow Up Surgery Thyroid Imaging - MRI Thyroid Cancer a Unique Human Neoplasm Clinically palpable Risk factors + Incidentalomas of the Thyroid Non- palpable No clinical concern Clinical concern FNA ObservaPon Ultrasound and ObservaPon Ultrasound needle biopsy (if difficult to follow) Age is most important prognospc factor No stage III and IV cancers in papents below 45 MulPcentricity of thyroid cancer is frequent No prognospc impact Microscopic tumor laboratory cancer Nodal Metastasis has no impact on outcome Impact of extrathyroidal spread Grade of the tumor and histologic poorly differenpated features 5

Differentiated Cancer of the Thyroid PrognosPc Factors Low Risk Thyroid Cancer Comparison of Risk Group Definitions Age Grade Extension Size AGES (Mayo Clinic) Age Metastasis Extension Size AMES (Lahey Clinic) Total Cases Dead of Disease Ages (1946 1970) Mayo Clinic Pap CA Low Risk 737 (86%) 2% High Risk 121 (14%) 46 % Ames (1961-1980) Lahey Clinic Pap & Fol Ca Low Risk 737 (86%) 2% High Risk 121 (14%) 46% Differentiated Thyroid Cancer Rx Expectations 80 Percent do well aner lobectomy alone 5% die regardless of Rx 15% require aggressive surgery and RAI 6

Differentiated Thyroid Cancer 1930-1985 Survival: Age Differentiated Thyroid Cancer 1930-1985 Survival: Tumor Size Differentiated Thyroid Cancer 1930-1985 Survival: Extrathyroidal Extension Differentiated Thyroid Cancer 1930-1985 Survival: Distant Metastases 7

Differentiated Thyroid Cancer 1930-1985 Survival: Nodal Status Differentiated Thyroid Cancer 1930-1985 Survival: Focality Differentiated Thyroid Cancer 1930-1985 Survival: Histology Differentiated Cancer of the Thyroid Risk Group Definitions Low Risk Intermediate Risk High Risk Age (years) <45 <45 >45 >45 Distant mets M0 M+ M0 M+ Tumor size T1/T2 T3/T4 T1/T2 T3/T4 (<4cm) (>4cm) (<4cm) (>4cm) Histology & Papillary Follicular Papillary Follicular Grade &/or &/or high grade high grade 8

Differentiated Thyroid Cancer 1980-1980 SURVIVAL: Risk Groups Differentiated Thyroid Cancer 1980-1980 SURVIVAL: Lobectomy vs. Total 1 0.8 Proportion Surviving 100% 99% 0.6 0.4 0.2 Lobectomy n = 276 Total n = 90 0 0 5 10 15 20 TIME (years) Differentiated Thyroid Cancer Prognostic Factors Mayo Clinic Lahey Clinic Swedish MSKCC Mayo 1987 group clinic 1993 Age Age Age DNA ploidy Grade Metastasis Grade Metastasis Ploidy Age Age Age (distant) Extra- Extra- Extra- Metastasis Mets Completeness capsular capsular capsular of resecpon tumor tumor tumor Extent Extra- Invasion capsular tumor Size Size Size Size Size Size Eur J Cancer 21(2):305-313, 1988. Thyroid Cancer: The Case for Total Thyroidectomy ORLO H. CLARK, KENNETH LEVIN, QI-HUA ZENG, FRANCIS S. GREENSPAN & ALLAN SIPERSTEIN Veterans AdministraPon Medical Center & The University of California, San Francisco, U.S.A. 9

Indications for Total Thyroidectomy The fact that total thyroidectomy can be performed safely does not necessarily mean that it is indicated in all papents with thyroid cancer... An operapon not worth doing is not worth doing well. Collin Thomas - 1987 Chapel Hill Grossly palpable disease in both lobes High risk papent with high risk tumor Radiated papent Young papent with large nodal metastasis to facilitate RAI PaPent with distant metastasis likely to require RAI Thyroid Surgery A conservapve approach is not to treat all tumors by a limited operapon, but to tailor the extent of the procedure to the biological characterispcs and extent of the disease in each case. 10

Complications of Thyroid Surgery Distribution of Thyroidectomies performed by Residents (1993-94) The complications of thyroid surgery are directly proportional to the extent of the thyroidectomy and inversely proportional to the experience of the operating surgeon! 11

Metastatic Cervical Nodes from Thyroid Lateral aberrant thyroid Modified neck dissec?on for palpable nodes Evaluate jugular and superior medias?nal nodes at the?me of surgery Modified neck dissec?on: Berry picking Preserve SCM, IJ, XI Submandibular gland Locally Aggressive Thyroid Cancer Thyroid carcinoma with Extrathyroid Extension Treatment Failure Clinical features Histological features Molecular and markers 50 40 30 Percent 47.9 41.3 P < 0.0001 37.4 20 10 0 9.2 15.7 10.7 Local Regional Distant No ETE ETE 12

Intraop Decisions Principles All gross tumor should be removed Preserve funcponing structures Preserve vital structures Balance between tumor control and best funcponal results Use adjuvant treatment RAI, External RT Histology Papillary Ca - Increased aggressiveness associated with: Solid/trabecular Diffuse, sclerosing type Tall cell Columnar cell (very aggressive) Areas of poorly differenpated Ca Extensive angioinvasion Extensive capsular invasion 13

Tall Cell Thyroid Cancer Biological Markers Ploidy EGF receptor status Presence of oncogenes and tumor suppressor gene mutapon Adenylate Cyclase response to TSH (The rapo of TSH spmulated to basal adenylate cyclase acpvity in thyroid cancers diminishes with advancing stage) P53 Morphologic Progression Histological Correlates RAI Positive FDG PET Positive Percent Positive Scans 100 80 80 60 60 40 40 20 20 0 0 Well Moderate Poorly Undiff Degree of Tumor Differentiation 14

FDG Uptake versus Survival Genetic Progression of Thyroid Cancer Exploiting Biology for Management Prognostication in Thyroid Cancer 15

Paradigm Shift in Detection of Recurrent Thyroid Cancer RAI Scan CT, MRI Thyroglobulin Ultrasound and Ultrasound- guided FNA FDG - PET Thyroid Nodule Lobectomy Frozen Benign Permanent Malignant? Follicuilar Tumors Intraoperative Decision Making During Thyroid Surgery Follicular adenoma Atypical follicular adenoma Encapsulated, well- differenpated follicular neoplasm of low malignant potenpal Follicular neoplasm without capsular invasion Follicular neoplasm with minimal capsular invasion Follicular neoplasm with major capsular invasion Follicular neoplasm with vascular invasion minor/major Follicular carcinoma Poorly differenpated follicular carcinomal AnaplasPc carcinoma 16

Good judgment comes from experience; and experience comes from bad judgment. Thyroid Cancer Thyroid Cancer Thyrogen Recombinant TSH No need to make papent hypothyroid Can be done post- op- follow- up Low iodine diet Ease of treapng with RAI 17

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