1. Endocrine Conference 2004. 6. 22 Department of Surgery R2. Heung Kwon Oh M.D.

2. Case 1 박 O O F/49 C.C) Thyroid nodule detected by routine check P.I) #1. Known HBsAg carrier #2. 2004 년 1 월 인근병원에서 시행한 건강검진 상 좌측 갑상선 결절 발견되어 Fine needle aspiration cytology 검사결과 thyroid cancer 진 단 하에 수술 위해 의뢰되어 본원외과 외래 통 해 입원함

3. #3. Outside neck sono (2004.1.19) 4.4x5.7x5.9mm sized ill defined hypoechoic nodule in Lt thyroid gland -> r/o malignancy #4. Outside FNAC (2004.2.5) smear and cell block reveal a few papillary clusters of typical follicle cells having frequent nuclear grooves and inclusion -> compatible with PTC

4. PMHx) DM/HT/Tbc/Liver Ds ( - / - / - / + ) Op Hx ( - ) Allergic Ds ( - ) Neck irradiation Hx ( - ) FHx) No Hx of thyroid ds. S/R) E/F ( - ), G/W ( - ), Wt loss ( - ) A/N/V/D/C ( - / - / - / - / - ), H/M/H ( - / - / - ) chest pain/palpitation/dyspnea ( - / - / - ) voice change ( - ), C/S/R ( - / - / -) Urinary Sx ( - )

5. Physical Examination V/S 121/64 – 76 – 18-36.9 G/A not so ill-looking, alert and intact HEENT not anemic, anicteric not dehydrated tongue PI ( - ), PTH ( - / - ) Neck no definite palpable mass LNE ( - / - ) Chest CBS without rale RHB without murmur Abdomen soft, flat no palpable mass normoactive BS, T/RT ( - / - ) Back and Ext. CVAT(-/-), P/C/C(-/-/-)

6. Laboratory study TFT) T3 96 (87 ~184) fT4 0.90 (0.7~1.8) TSH 0.22 (0.4~4.1) Tg 17.2 (0 ~52) Tg-Ab 38 (0 ~100) Routine lab) WNL

7. Neck CT(2004.3.16) 1) A small nodule at Lt thyroid gland posterior aspect. 2) No significant nodal enlargement

8. 2004.3.26 Total thyroidectomy Op finding) Lt lobe 0.6cm sized, solid, poorly encapsulated mass Capsular invasion ( + ), Adjacent structure invasion ( - ), Lt lobectomy -> frozen ; PTC -> total thyroidectomy LNE ( - ) Parathyroid gl. & recurrent laryngeal n. : saved

9. Hospital course 2004.3.29 Discharge without immediate postop complication

10. Pathology Thyroid, bilateral, total thyroidectomy: 1. Papillary microcarcinoma, left lobe with 1) size: 0.3 x 0.3 x 0.2cm 2) confinement to thyroid 3) clear resection margin 2. Adenomatous goiter, right lobe

11. Case 2 최 O O (F/26) C.C) Neck mass(onset : 3MA) P I) #1. Prev. healthy #2. 3MA 우연히 Rt neck mass (not tender, firm) 발 견하여 인근병원 방문후 큰병원 권유받고 r/o thyroid cancer 로 FNAC 시행후 highly suggestive PTC 소견 보여 수술 권유받았으나 환자, 보호자 원하여 본원 외과 외래 방문 후 수술 위해 입원함.

12. PMHx) DM/HT/Tbc/Liver Ds ( - / - / - / - ) op Hx ( - ) Allergic ds (-) Neck irradiation Hx ( - ) FHx) No Hx of thyroid ds. S/R) E/F ( - ), G/W ( - ), Wt loss ( - ) A/N/V/D/C ( - / - / - / - / - ), H/M/H ( - / - / - ) chest pain/palpitation/dyspnea ( - / - / - ) voice change ( - ), C/S/R ( - / - / -) Urinary Sx ( - )

13. Physical Examination V/S 110/70 – 70 – 20 – 36.5 G/A Not so ill-looking, alert and intact HEENT not anemic, anicteric PI(-), PTH(-/-) Neck 3x2cm sized, firm, fixed, ill - defined mass in Rt thyroid gland LNE ( + / - ) level lll 1cm firm Chest CBS without rale RHB without murmur Abdomen Soft, flat normoactive BS T/RT(-/-) Back and Ext. CVAT(-/-), P/C/C(-/-/-)

14. Laboratory Study TFT) T3 112 (87 ~184) fT4 1.27 (0.7~1.8) TSH 3.01 (0.4~4.1) Tg 61.4 (0 ~52) Tg-Ab 491 (0 ~100) Routine lab) WNL

15. Neck CT(2004.3.16) 1) 2cm sized nodule at Rt thyroid gland 2) LNE in right level III, space 1) 2cm sized nodule at Rt thyroid gland 2) LNE in right level III, submental space

16. 2004.4.6 Total Thyroidectomy, Rt MRND Op finding) Rt lobe 3x4cm sized, solid, poor encapsulated mass Capsular invasion ( + ), Adjacent structure invasion ( - ), Rt lobectomy -> frozen; PTC -> Total thyroidectomy multiple Rt cervical LNE ( + ) -> Rt MRND Parathyroid gl. & recurrent laryngeal n. : saved

17. Hospital course 2004.4.9 Discharge without immediate postop complication

18. Pathology Thyroid, bilateral, total thyroidectomy, Rt MRND: 1. Papillary carcinomas (x2), right lobe 1) tumor size; 1.5 x 1.5 x 1cm and 2 x 1 x 1cm 2) confinement to thyroid parenchyme 3) no endolymphatic tumor emboli 4) clear soft tissue resection margin 5) metastasis in four out of eight regional lymph nodes 2. Chronic lymphocytic thyroiditis, left lobe

19. Papillary thyroid cancer Randolph et al ; Surgery of the thyroid and parathyroid glands - chapter 15, papillary carcinoma of the thyroid

20. Thyroid Neoplasm Solitary nodule in the thyroid gland prevalence : increased with age averaging 6.4% of women, 1.5% of men autopsy study : as many as 50 % of necropsies Overall incidence of malignancy : 20% ~ 30% in surgical series

21. Evaluation of Patients with thyroid nodules History taking 1) Radiation 2) Time of onset 3) Age and sex 4) Preexisting thyroid disease 5) Voice change, dysphagia, dyspnea 6) Pharmaceutical agents and toxins lithium, phenobarbital : TSH↑ 7) Familial Hx : MTC, Gardner’s syn. Cowden’s disease

22. Physical Examination solitary or multinodular hard, firm, ill-defined margin hoarsness, unilateral vocal cord paralysis cervical adenopathy Evaluation of Patients with thyroid nodules

23. Diagnostic tests 1. Fine-needle aspiration biopsy malignant intermediate ; 10 ~ 30 % cancer benign Evaluation of Patients with thyroid nodules

24. 2.Ultrasound noninvasive, inexpensive, objectively follow the size 3.Thyroid scan cold nodule vs hot nodule 4.Chest radiograph 5.CT and MRI useful in evaluating with suspected aggressive carcinomas Evluation of Patients with thyroid nodules

25. FNA biopsy

26. Characteristics of Benign and Malignant Thyroid Nodules Benign Family Hx of benign goiter Diffuse or multinodular goiter Constant size Benign by FNA Simple cyst by USG Hyperfuctioning nodule by radioiodine scan Decreasing size with thyroid hormone replacement Malignant Solitary nodule Hard, fixed Rapidly enlarging Hoarseness with vocal cord paralysis Development of nodule at age 60 years Suspicious or malignant by FNA Cyst > 4cm or complex cyst Hypofuctioning by scan Hx of ionizing radiation Ipsilateral lymphadenopathy

27. Thyroid cancer Well differentiated cancer in the USA Papillary carcinoma 79.25% Follicular carcinoma 12.55% Hurthle cell carcinoma 2.94% Poorly differentiated cancer Medullary carcinoma 3.57% Anaplastic cancer 1.65% Lymphoma Sarcoma Metastastic cancer (Hundahl SA et al : Cancer 83:2638, 1988)

28. Thyroid cancer

29. Papillary thyroid cancer Pathologic feature Predisposing factor Typical presentation Diagnosis Extent of initial surgery Risk factor evaluation for prognosis Adjuvant therapy Follow up

30. Introduction Follicular cell-derived W/D cancer After treatment, cure or die from other causes 85 % of thyroid ca Children and young women (mean age 44) Prior exposure to ionizing radiation Hx Familial PTC (5~10%) Gene rearragement; ret/PTC, NTRK1

31. Pathologic feature A malignant epithelial tumor showing follicular cell differentiation and the formation of papillae and/or nuclear changes Orphan Annie eye; empty nucleaoplasm Psammoma body Papillary thyroid microcarcinoma (PMC) Multicentric involvement (30%) Extrathyroidal involvement (14%) Metastasis to cervical LN (35%)

32. Pathologic feature FNA from normal thyroid: sheets of follicular cells with uniform round evenly spaced nuclei and some macrofollicles filled with colloid. FNA from PTC: sheets of follicular cells with overlapping and crowded oval nuclei which show longitudinal nuclear grooves..

33. Diagnosis Hx and P/E Thyroid function test Thyroglobulin (Tg) Radioisotope scan; little useful USG (Power doppler tech); nodule CT, MRI; invasion FNA; primary test PCR; oncofetal fibronectin mRNA

34. Extent of surgery Complete resection of primary tumor and any locoregional extension is essential Bilateral lobar resection > lobectomy Local recurrence, survival rate Adjuvant therapy, postop f/u Multicentricity, anaplastic transformation Total thyroidectomy = Near total thyroidectomy Complication rate But experienced surgeon Central LND ± MRND ?

35. Prognosis

36. Poor prognostic factors Incomplete resection Extrathyroidal invasion Intrathyroidal microvascular invasion Male sex, old age ( > 50 yr) Tumor size Distant metastasis at presentation LN meta, local recurrence ; no impact

37. TNM staging (AJCC) T ; primary tumor T0 No evidence of primary tumor T1 Tumor ≤ 1cm T2 1cm < Tumor < 4cm T3 Tumor > 4cm T4 Tumor of any size extending beyond the thyroid capsule N ; regional LN N0 ( - ) regional LN metastasis / N1 (+) M ; distant metastasis M0 ( - ) distant metastasis / M1 ( + )

38. TNM staging (AJCC) Age < 45Age ≥ 45 Stage IAny T, Any N, M 0T1 N0 M0 Stage IIAny T, Any N, M1T2 or T3, N0, M0 Stage IIIT4, N0, M0 or any T, N1, M0 Stage IVAny T, Any N, M1

39. Survival rate by TNM staging

40. Risk stratification

42. AMES catergory

43. AMES catergory ; 박 O O F/49 Thyroid, bilateral, total thyroidectomy: 1. Papillary microcarcinoma, left lobe with 1) size: 0.3 x 0.3 x 0.2cm 2) confinement to thyroid 3) clear resection margin 2. Adenomatous goiter, right lobe Low risk patient

44. AMES catergory ; 최 O O F/29 Thyroid, bilateral, total thyroidectomy, Rt MRND: 1. Papillary carcinomas (x2), right lobe 1) tumor size; 1.5 x 1.5 x 1cm and 2 x 1 x 1cm 2) confinement to thyroid parenchyme 3) no endolymphatic tumor emboli 4) clear soft tissue resection margin 5) metastasis in four out of eight regional lymph nodes 2. Chronic lymphocytic thyroiditis, left lobe Low risk patient

45. Adjuvant therapy Thyroxine therapy 2.2 ~ 2.8 μg / kg / day TSH suppression -> significant reduction in progression -> TSH 0.1 < TSH < 0.4 (low risk group) Radioiodine remnant ablation Local or distant residual disease (+) More selective approach is needed

46. Follow-up and risk group Tg ; useful tumor marker TgAb, TSH USG Chest PA CT, Bone scan Radioiodine whole body scan TSH defendent PET