Well-differentiated Thyroid Cancer. Anton Sharapov, R4

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1 Well-differentiated Thyroid Cancer Anton Sharapov, R4

2 Outline Types of DTC Diagnosis of DTC Treatment options Extent of surgery Follow up cases

3 A bit of history Theodore Kocher, Bern, Switzerland 1872, first thyroidectomy 1901 performed 2000 th procedure 1901 overall mortality decreased from 50% to 4.5% 1909 Nobel Prize Mayo brothers, Rochester Bloodless thyroid surgery

4 Introductory Case 20 yof, G1P0 admitted for labor 1/12 hx of neck swelling Thought to be normal part of pregnancy Past several days noted SOB Difficult to swallow

5 Case cont d Dyspnea during labor PPD 2 increased swelling of neck R >> L Increased compressive sxs Noted to increase size 50% within 24 h What next?

6 Exam Lymph nodes felt in Zone 4, 5, R Firm mass anterior neck What next?

7 Case cont d CT scan carried out Vascular tissue & LN in neck LN in retroperitoneum noted LN in retrosternal area What next?

8 Biopsy carried out FNA vs tissue sample R lymph bx d Papillary carcinoma What next?

9 Thyroid Cancers 1.5% cancers in US MC endocrine malignancy In US 22,000 new cases/year 74% women

10 Pathology Differentiated (pap 75%, fol 10%, Hurtle 5%) Undifferentiated (anaplastic 5%) C-cell (parafollicular origin) (5%) Other (lymphoma<1%)

11 Pap Ca Pure Follicular Tall cell Columnar cell Oxyphilic these radioiodine resistant, more aggressive, poorer prognosis Diffuse sclerosing Encapsulated

12 Papillary Ca F:M= 2:1 Mean age at presentation Multicentric 30-50% Mets to mid/lower ant LN Unusual to invade adjacent structures

13 Papillary Ca Review of 1077 pts 24% multicentric 46% LN mets up to 90% if micromets are considered 2% lung+/- bone mets

14 Microcarcinomas papillary carcinomas smaller than 1.0 cm Most found incidentally at autopsy may be present in up to 35% of the population Usually clinically silent morbidity and mortality is minimal and near that of the normal population 1.3% mortality rate

15 Follicular cancer F:M=3:1 Mean age 50 Painless nodule or Rapidly growing nodule in a goiter setting Spread to lung/bones LN and Multicentricity less common 10% will have spread to LN

16 Minimally Invasive FC limited capsular invasion Grey area in pathology Not well defined criteria Practice susceptible to personal & legal bias Tend to be overcalled?? Driven by fear of missing Ca

17 Hurtle cell: 5% of all thyroid cancers subtype to follicular Need to have at least 75% hurtle cell component Have greater tendency to spread to LN, distant mets, 90% fail to concentrate radioiodine worse survival

18 Comparative survival Papillary 90% at 20 y Follicular 70% at 20 y Hurtle 70% at 10 Y, trails off then Higher recurrence

19 Diagnosis: Most present with palpable thyroid nodule Most asymptomatic Less common with cerv LN:

20 If sxs - suspect advanced ds Hoarseness Dysphagia Dyspnea/orthopnea Coughing/choking spells

21 Consider Genetics Inherited Ca (medullary) Ds d via genetic testing MEN II Gardiner syndrome Cowden disease Multiple hamartomas

22 Thyroid nodule 10% malignant ID which lesions are likely malignant

23 Risk Factor analysis Radiation (low and high level) FH Gender (men) Age (children, >60yoa)

24 Evaluation of Thyroid Nodule Hx PE Nodule size change Compressive sxs Consistency Fixation LN

25 Adjuncts Laryngoscopy if hoarse Paralyzed vocal cord is suggestive of Ca

26 Lab and Radiology H&PE non-specific Hence use of lab, US, Nuclear medicine nodule is likely malignant if shown to be metabolically active either through TSH or uptake studies

27 Role of Radiology US detects features suggestive of malignancy Irregular borders Microcalcifications Intranodal vascular markings Neither specific nor sensitive in clinical setting Radioisotope active vs inactive Most nodules are cold Cold tend to be malignant (4-24% chance) 13% of warm nodules, and 4% of hot nodules malignant

28 TSH in evaluation of nodules Generally not helpful... TSH level Normal or High I.e. lesion may be hypometabolic suspicious consider FNA to investigate the nodule TSH level Low Consider I 123 scan to ID level of thyroid activity If hyperfunctioning likely need f/u only If hypofunctioning likely need FNA

29 Limitations of Nucs and Labs At best, nuclear medicine and lab investigation provide a suggestion that there could be a malignancy

30 Definitive diagnosis Hence, proceed (start?) with FNA FNA & TSH plus clinical exam suffice in most cases

31 FNA bx Reliable Cost-effective Safe Halved number of people needing thyroidectomy Increased yield of thyroidectomy by two fold

32 FNA outcomes for nodules Benign 70% Malignant Med or Pap 5% Suspicious for pap Ca OR Follicular/Hurtle cell neoplasia 10% Indeterminate 15%

33 Management options in general Total Extracapsular Thyroidectomy f/u by thyroid remnant ablation and TSH suppression Lobectomy & Isthmusectomy f/u by TSH suppression

34 What to do if FNA is Indeterminate? US guidance may be useful repeat FNA is needed

35 What to do if FNA POSITIVE for Pap Ca or Med Ca? FNA is diagnostic False positive 1% No need to do frozen section do definitive surgery If Medullary basal calcitonin, screen for pheo and hyperparathyroidism

36 What constitutes definitive surgery? For high risk lesions - total thyroidectomy or near total thyroidectomy (<2 g thyroid remaining) f/u by ablation and TSH suppression for Low risk lesions Debated, particularly for 1-4 cm lesions depends on the center arguments for TT vs LI

37 Papillary Carcinoma: HIGH risk Mortality 48%, Recurrence 48% Women > 50 Men >40 Poorly diff, bad path (tall, oxy, columnar) Think silver skyscrapers >= 4 cm Local invasion Distal Mets

38 Pap Carcinoma: LOW risk, Mortality %, Rec 5-11% Women <50 Men <40 Well-mod differentiated <4 cm diameter Some say 1 cm confined to gland no distant mets

39 Different systems for risk assessment AGES age, grade, extent, size AMES age, mets, extent, size GAMEs, degroot, etc TNM

40 AJCC TNM Staging of WD thyroid tumor Unique Most important prognostic factor is age Also, extragland invasion, LN invasion

41 Staging < 45 yoa, Stage I - no distant mets Stage II - distant mets > 45 yoa, Stage I <2 cm intrathyroid Stage II -2-4 cm intrathyroid Stage III LN and local invasion, or >4 Stage IV distal mets

42 Problem in risk identification Able to stratify by post-op analysis only Available systems will underestimate risk in young Low mortality, significant recurrence Recurrences occur even in low risk group if recurred mortality 30-50% Should total procedures be preferred?

43 Papillary CA: when to do lobectomy & isthmusectomy <1.5 cm incidental pap ca (<1cm) NO risk factors Studies suggest <5% recurrence, <0.1% death 50% or recurrences are cured surgically

44 Papillary Ca: when to do Total thyroidectomy Any high risk pt Pts with previous irradiation - total thyroidectomy regardless of RF Presence of Risk factors Any low risk pt? controversial

45 Advantages of Total Thyroidectomy Can use ablative I-131 therapy BIGGY! Can use thyroglobulin and radioactive iodine to ID recurrence IMPORTANT! Prevents 1% risk of anaplastic transformation Avoids higher complication rate with reoperation in the hostile field

46 Advantages of Total thyroidectomy: Associated with lowest recurrence LR improved in TT for pap cancers >1.5 cm and follicular cancers.but not minimally invasive FC If recurs, ONLY 50% are salvageable Glass is half empty, might as well prevent cancer from the start with total procedure If carry out Lobectomy & Isthmusectomy alone 5-10% recurrence occur in opposite lobe 11% risk of subsequent pulmonary mets

47 Total Thyroidectomy vs LI For low risk (AGES <3.99) lesions At 20 years f/u L & I TT LR 14% 2% Pulmonary mets - 19% 6% But SAME SURVIVAL

48 Arguments against TT prognosis of low risk pt s same to TT What are we actually achieving here by total? Higher complications 1% Recurrent Laryngeal N. 1-5% parathyroid injury, some permanent Experienced <1%, in general 3-5% Transient hypo 10%, leads to eventual permanent failure down the line?

49 Arguments against Total 50 % of local rec rescued with surgery Glass is half full, will fix it if it breaks, why do extra stuff from the start? Less then 5% rec occur in thyroid bed Multicentricity?? has little clinical significance

50 Alternative to Total Thyroidectomy? Subtotal, leave 4-10 g tissue behind 54,000 thyroid Ca 20 year follow-up Compared total vs subtotal less morbidity, same survival

51 What to do if FNA is Suspicious for Papillary Ca? Initial Thyroid Lobectomy & Isthmusectomy If frozen confirms FNA choose definitive surgery LI for very low risk <1cm or TT (most likely option ) Allows ablation & scan follow up!

52 What to do if FNA shows follicular neoplasm? FNA won t distinguish btw Follicular/Hurtle cell adenoma vs Carcinoma Neither will frozen section Hence, do lobectomy & isthmusectomy, close and then await permanent H & E evaluation look for capsule/vascular invasion

53 Invasive Follicular Ca Completion thyroidectomy. Why? For follow-up reasons Can do ablation and NM scan follow up For contralateral 10% risk of synchronous tumor

54 Some split High risk into two subgroups (to allow for Follicular) Intermediate risk group Men >40 years and women > 50 years who have papillary carcinoma - recurrence rate - 29% -death rate -21% High risk group Men > 40 years and women > 50 years who have follicular carcinoma - recurrence rate - 40% - death rate - 36%

55 Minimally invasive FC Lobectomy & thyroidectomy for tumors that are minimally invasive TT if wish to follow up and have expert levels M&M controversial

56 Response to Dr. Pollett There are no double blind randomized studies and these are not feasible Economic and statistical considerations All comparisons based on retrospective analysis Mathematical models exist

57 Role of LN dissection: 30-40% incidence of lymphadenopathy Prophylactic not warranted Enlarged LN in central area should be removed, if positive in central central neck dissection is carried out. If positive in lateral - MRND

58 Modified radical neck dissection: aka functional neck dissection Levels 2-5 lymph nodes, i.e. anterior and posterolateral to internal jugular v. From mastoid to subclavian vein laterally as far as accessory n. Spare: Internal Jugular v., Accessory n., SCM muscle

59 Zones of the neck

60 In summary Total procedure Seems oncologically sound For all follicular/hurtle/all high risk & some low risk papillary Higher morbidity (for some surgeons) Facilitates ablation, f/u with thyroglobulin as a marker of recurrent disease detection, treatment of met disease

61 Summary of Lymph node dissection Lymph node dissection only for gross metastatic disease What constitutes -clinical exam? Digital through skin? Actually go looking during surgery? Run risk of Thoracic duct injury

62 Long term FU of differentiated Thyroid Cancer Recurs in 20-40% 10-15% mets to lungs/bones Greatest in first 2 years after thyroidectomy Risk remains for years Hence, long term FU, with PE, serum TG, and I-131 whole body scans

63 Follow up To improve survival to improve surveillance thyroglobulin and stimulated TG to improve diagnosis with iodine imaging.

64 Post op follow-up: Definition of terms Thyroid remnant ablation destruction of residual thyroid tissue after thyroidectomy. I-131 Radioiodine therapy larger doses I-131 to treat distant mets/ln

65 Post operative ablation is recommended for: Pap cancer >1.5 cm Pap cancer with LN involvement Invasive Follicular Ca Hurtle cell Ca Hence, for these Cancers, need to have TT...

66 Technique: T3 given (triiodothyronine) 25 mcg OD Short half-life of 24 h. Stop 2/52 before scanning Low iodine diet Measure TSH Should be > 30 mu/ml

67 Technique cont d 30 mci dose of I 131 as an output will ablate 80% of pts. Repeat dose can be given in 6-12/12. Then suppress TSH with thyroid hormones TSH encourages tumor growth

68 Thyroglobulin Glycoprotein Produced by normal and neoplastic thyroid tissue Reliable marker

69 Thyroglobulin Undetectable level with high TSH - excludes residual/metastatic cancer in 99% A high TG with low TSH indicates presence of abnormal thyroid tissue

70 Combine TG with whole body I-131 scan Different schedules available

71 Follow up: TG and Scan Annually until negative then annually for 5 years Each 5 years for 20 years In addition, combination of iodine scan with TG levels: Do scan when TG > 3 while on hormone replacement, or TG > 10 while in withdrawal from hormone.

72 Practical implications TG less then 3 will r/o cancer in 94 % of pts But Anti TG antibodies will alter TG level in 15% of pts with Cancer Hence, importance of TSH stimulated TG measurement

73 Utility of stimulated TG measurement Great diagnostic tool TSH induced TG >2 is 100% sensitive, has 100% NPV, FP 9%

74 Two ways to stimulate TSH: Induce hypothyroidism Administer rhtsh RhTSH is useful for pts intolerant of hypothyroidism CHF, pulmonary disease, pituitary/hypothalamic problems

75 Survival with mets 10 year survival with mets 25-45% Need to ID them before they occur New developments Redifferentiation therapy Suicide gene insertion

76 Quick review Endocrine cases

77 Case 1 65 yom with 3 cm thyroid lump FNA - pap carcinoma total vs lobectomy & isthmusectomy? TT, ablation, suppression LND?

78 Case 2 35 yom 1.5 cm thyroid node FNA Papillary Ca total vs lobectomy? If not RF - LI, otherwise TT Controversial Prefer TT if skilled high volume operator LND?

79 Case 3 40 yof 2 cm nodule FNA - follicular neoplasm total vs lobectomy? Total, ablation, suppression, followup Total for followup reasons only LND?

80 Case 4 45 yof with 2 cm lump FNA follicular neoplasm Path - minimally invasive Follicular Ca Tx? LI, some will consider TT, ablation, suppression for follow-up

81 Case 5 53 yom with goiter and solid 3 cm cold nodule in L lobe What next? Had L lobectomy on clinical spec Path: invasive follicular Ca 1 cm what next?

82 Case 6 postpartum lady with pap carcinoma TT, ablation, suppression, follow-up role of preop iodine? To settle vascularity

83 Case 7 35 yom goiter had lobectomy for cosmetic reasons small (1 cm) focus of Pap Ca what next? No need to do completion thyroidectomy incidental Pap Ca - lobectomy suffices

84 Conclusions Survival is good (pap>fol>hurtle) FNA is excellent tool TT, Ablation, Suppression of High Risk LI and suppression for very Low risk papillary carcinoma and Minimally Invasive Follicular Ca Be aware of pro s and con s of TT Life-long follow up

85 Reference Extent of surgery for differentiated thyroid cancer. A. Dackiw, M. Zeiger. Surgical Clinics of NA, vol. 84, #3, June 2004 Cameron, Current Surgical Therapy, 2004 Multiple internet web sites E.g. ThyroidCA-9810/ThyroidCA-9810.pps

THYROID CANCER IN CHILDREN. Humberto Lugo-Vicente MD FACS FAAP Professor Pediatric Surgery UPR School of Medicine

THYROID CANCER IN CHILDREN. Humberto Lugo-Vicente MD FACS FAAP Professor Pediatric Surgery UPR School of Medicine THYROID CANCER IN CHILDREN Humberto Lugo-Vicente MD FACS FAAP Professor Pediatric Surgery UPR School of Medicine Thyroid nodules Rare Female predominance 4-fold as likely to be malignant Hx Radiation exposure?