1. What work ups are needed, if any?

2. MALIGNANT VS. BENIGN History taking Physical examination Fine-needle aspiration biopsy (FNAB) Other imaging and laboratory evaluation

3. Evaluation of a Thyroid Nodule History – Risk factors for thyroid cancer History of thyroid irradiation, especially in infancy or childhood Age < 20 yr Male sex Family history of thyroid cancer or multiple endocrine neoplasia A solitary nodule Dysphagia Dysphonia Increasing size (particularly rapid growth or growth while receiving thyroid suppression treatment) Physical Examination – Signs that suggest thyroid cancer stony hard consistency or fixation to surrounding structures cervical lymphadenopathy hoarseness due to recurrent laryngeal nerve paralysis

4. Testing

5. Fine-Needle Aspiration Biopsy (FNAB) – Cornerstone in the evaluation of solitary thyroid nodules and also dominant nodules within multinodular goiters – Currently considered to be the best first-line diagnostic procedure in the evaluation of the thyroid nodule

6. Fine-Needle Aspiration Biopsy Advantages: – Safe – Cost-effective – Minimally invasive – Leads to better selection of patients for surgery than any other test (Rojeski, 1985) – Halved the number of patients requiring thyroidectomy (Mazzaferri, 1993) – Double the yield of cancer in those who do undergo thyroidectomy (Mazzaferri, 1993)

7. Fine-Needle Aspiration Biopsy Limitations – Skill of the aspirator – Expertise of the cytologist – Difficulty in distinguishing some benign cellular adenomas from their malignant counterparts (follicular and Hurthle cell) Sensitivity: 65 – 98% (avg. 83%) Specificity: 72 – 100% (avg. 92%) Positive Predictive Value: 50 – 96% (avg. 75%) False-negative Rates: 1.5 – 11.5% (avg. < 5%) False-positive Rates: 0 – 8% (avg. 3%) Reference: Gharib, H. (2008). Fine-Needle Aspiration Biopsy of the Thyroid Gland. Thyroid Disease Manager.

9. Fine-Needle Aspiration Biopsy Four Categories of Cytologic Diagnosis – Benign (Negative) – 69% Benign – Suspicious (Indeterminate) – 10% Suspicious – Malignant (Positive) – 4% Malignant – Unsatisfactory (Nondiagnostic) – 17% Unsatisfactory Reference: Gharib, H. (2008). Fine-Needle Aspiration Biopsy of the Thyroid Gland. Thyroid Disease Manager.

10. Benign Cytology Aspirates obtained from multinodular goiters, benign microfollicular adenoma, or normal thyroid are referred to as “colloid nodules” and show loosely cohesive sheaths of follicular epithelium, colloid, blood, and rare macrophages Colloid nodules are the most common cytology and contain an abundance of colloid with sparse follicular cells There is considerable variation in the number of cells as well as the type and amount of colloid present

11. Benign Cytology Hashimoto’s Thyroiditis – It has a fairly characteristic pattern on FNA smears, showing hypercellularity with lymphocytes, Hürthle cells, and minimal or no colloid Subacute(granulomatous) Thyroiditis – Smear shows multinucleated giant cells, epithelioid histiocytes, and scattered inflammatory cells A)Group of Hürthle cells, with large cytoplasm and prominent nuclei, surrounded by a teratogeneous population of lymphocytes B)Hypercellular aspirate with lymphocytes and Hürthle cells Large multinucleated giant cells in a mixed inflammatory background. Absence of colloid is noticeable. Reference: Gharib, H. (2008). Fine-Needle Aspiration Biopsy of the Thyroid Gland. Thyroid Disease Manager.

12. Malignant Cytology Papillary carcinoma – the most common thyroid malignancy – readily diagnosed by FNAB Typically, cytology shows a papillary configuration, large irregular nuclei, and nuclear grooves. Psammoma bodies may or may not be present, but if present, they are highly suggestive of papillary thyroid carcinoma Medullary thyroid carcinoma – accounts for 5% to 10% of thyroid cancers and may present as a thyroid nodule or neck mass – Typically, aspirates from a medullary thyroid carcinoma are hypercellular, composed of large, poorly cohesive cells, and are predominantly spindle ‑ shaped. – Amyloid is often, but not invariably, present, and there is no colloid High-grade carcinoma – Can be diagnosed cytologically, but distinguishing between primary and metastatic cancer is not easy A)Cellular specimen staining positively for calcitonin with immunoperoxidase B)Loosely cohesive fragments of spindle-shaped cells. Amyloid is present as amorphous blue material intimately associated with neoplastic cells. A)Follicular cells with large irregular nuclei, nuclear grooving, and pale chromatin. B)Histologic preparation showing typical papillary configurations. Reference: Gharib, H. (2008). Fine-Needle Aspiration Biopsy of the Thyroid Gland. Thyroid Disease Manager.

13. Suspicious Cytology Cytologic features neither confirm nor rule out malignancy Hypercellular specimens from follicular or Hürthle cell lesions may have features suggestive of, but not diagnostic for, malignancy – Histologic examination is necessary for definitive diagnosis Hypercellularity may be seen with nonneoplastic lesions, and Hürthle cell changes may be seen in patients with lymphocytic thyroiditis. The diagnosis of follicular neoplasm is indicative of an underlying malignancy in 14% of cases and Hürthle cell neoplasm in 15%. Many pathologists maintain that benign and malignant follicular or Hürthle cell tumors cannot be distinguished on the basis of aspirated cells only and the lesion must be removed for histopathologic examination. However, follicular adenomas and follicular carcinomas usually can be differentiated on the basis of nuclear size but Hürthle cell lesions are difficult to diagnose cytologically (Kini, 1993). A)Cytology shows hypercellularity, dispersed microfollicular pattern, and absent colloid. B)Thyroidectomy showed benign follicular adenoma Reference: Gharib, H. (2008). Fine-Needle Aspiration Biopsy of the Thyroid Gland. Thyroid Disease Manager.

14. Nondiagnostic Cytology Factors that influence nondiagnostic rates for FNAB results: – skill of the operator – vascularity of the nodule – criteria used to judge adequacy of the specimen – cystic component of the nodule Overall, a satisfactory smear contains at least 6 clusters of well ‑ preserved cells, with each group consisting of at least 10 to 15 cells. Reaspiration yields satisfactory specimens in at least 50% of cases that are considered nondiagnostic on initial FNA

15. CT/MRI

16. THYROID STIMULATING HORMONE (TSH) A sensitive TSH assay is useful in the evaluation of solitary thyroid nodules – Benign = low serum TSH – Malignant = cannot be determined

17. SERUM THYROGLOBULIN Not helpful diagnostically Elevated in most benign thyroid conditions Other thyroid function tests are usually not necessary in the initial workup

18. SERUM CALCITONIN Elevated levels are highly suggestive of medullary thyroid carcinoma (MTC) Once the mainstay in the diagnosis of FMTC Replaced by sensitive polymerase chain reaction (PCR) assays for germline mutations in the RET proto- oncogene Currently used as tumor markers to monitor patients who have been treated for MTC

19. Staging and Prognosis AGES and AMES scoring systems – AAge of patient – G Tumour Grade – MDistant metastasis – EExtent of tumour – SSize of tumour Both scoring systems have identified 2 distinct subgroups; – Low-risk group; Men 40years or younger, women 50 or younger, without distant metastasis (bone & lungs) – Older patients with intrathyroid follicullar/papillary carcinoma, with minor capsular involvement with tumours < 5cms in diameter – High –risk group; All patients with distant metastasis – All older patients with extrathyroid papillary/follicular carcinoma & tumours >5 cms regardless of extent of disease

20. MAICS

21. AMES

22. Treatment Options

23. Surgical Treatment: Papillary CA High risk or bilateral tumors: Total or near - total thyroidectomy Minimal Papillary Thyroid Tumor Unilateral lobectomy and isthmusectomy

24. Enables the use of RAI for detecting and treating residual thyroid tissue and metastatic disease. Makes serum Tg level a more sensitive marker of recurrent or persistent disease Eliminates contralateral occult cancer as sites of recurrence Reduces risk of recurrence Increases survival Decreases 1% risk of progression to ATC Reduces need for reoperative surgery Total Thyroidectomy Lower complication rate Recurrence is unusual (5%) Excellent prognosis Unilateral Lobectomy

25. Why Thyroidectomy? Recurrence rates are lowered and survival is improved when a patient underwent thyroidectomy Diminished survival was noted in patients with low-risk disease

26. Total Thyroidectomy Enables the use of RAI for detecting and treating residual thyroid tissue and metastatic disease. Makes serum Tg level a more sensitive marker of recurrent or persistent disease Eliminates contralateral occult cancer as sites of recurrence Reduces risk of recurrence Increases survival Decreases 1% risk of progression to ATC Reduces need for reoperative surgery

27. 1) 30%-87.5% of papillary carcinomas involve opposite lobe (Hirabayashi, 1961, Russell, 1983) 2) 7%-10% develop recurrence in the contralateral lobe (Soh, 1996) 3) Lower recurrence rates, some studies show increased survival (Mazzaferri, 1991) 4) Facilitates earlier detection and tx for recurrent or metastatic carcinoma with RAI (Soh, 1996) 5) Residual WDTC has the potential to dedifferentiate to ATC Rationale for total thyroidectomy

28. Indications for total thyroidectomy 1) Patients older than 40 years with papillary or follicular carcinoma 2) Anyone with a thyroid nodule with a history of irradiation 3) Patients with bilateral disease

29. Rationale for subtotal thyroidectomy 1) Lower incidence of complications  Hypoparathyroidism (1%-29%) (Schroder, 1993)  Recurrent laryngeal nerve injury (1%-2%) (Schroder, 1993)  Superior laryngeal nerve injury 2) Long term prognosis is not improved by total thyroidectomy (Grant, 1988)

30. Non- Surgical approach External Beam Radiotherapy and Chemotherapy Radioiodine Therapy TSH Suppresion Therapy