Thyroid Malignancies In Children Bhaskar N. Rao, M.D. St. Jude Children’s Research Hospital 10/03

THYROID CANCER Staging T0 No evidence of tumor T1 tumor <1 cm T2 tumor 1-4 cm T3 tumor >4 cm T4 tumor any size beyond capsule N0 No nodal mets N1 regional nodes N1a ipsilateral cervical nodes N1b bilateral or mediastinal M0 N0 distant mets M1 distant mets

THYROID CANCER Staging (Pap/follicular) Age <45 Stage 1 Any T Any N M0 Age >45 Stage 1 T1 N0 M0 Stage 2 T2/T3 N0 M0 Stage 3 T4 or N0 M0 T1-4 N1 M0 Stage 4 T1-4 Any N M1 Anaplastic All cases are stage IV Staging (Medullary) Stage 1 T1 N0 M0 2 T2-4 N0 M0 3 Any T N1 M0 4 Any T Any N M1

Thyroid Cancer Epidemiology 20,000 new cases/year in the US more often in women and whites Peak incidence: 40 (women), 60 (men) Lifetime risk: 1% Histology: Papillary - 80% Follicular - 11% Hurthle cell - 3% Medullary - 4% Anaplastic - 2%

Thyroid Cancer Epidemiology - Children Low incidence in childhood 1.5% of all tumors < 15 years peak 7-12 years 10% of all head and neck cancer 10% are diagnosed in childhood 2/3 in girls Indolent course, even with metastases Survival > 90% Up to 8% of secondary pediatric cancers

Thyroid Cancer Epidemiology - Children Low dose RT used for Thymus, Hemang, Acne Average dose 600cgy. One million people at risk One fourth will develop nodules Most (75%) Benign Hyperplasia, Adenoma, Fibrosis Treatment Lobectomy – Post-op Hormones

Thyroid Cancer Epidemiology - Children Increased risk of Carcinoma Most are Papillary Carcinomas (20-50%) Latency median 20 years Most are multicentric, with lymph nodes Other tumors – Salivary Gland, Parathyroid, Bone, Soft tissue Sarcomas, Thyroid lymphomas

Thyroid Cancer Histology Papillary 80% incidence increases with younger age High incidence of bilaterality, regional nodes Follicular Rare in children Distinguished from adenoma by vascular or capsular invasion Medullary arise from calcitonin-secreting c-cells Anaplastic Extremely aggressive, high mortality Tumor Variable Affecting Prognosis Histology Size Local invasion Lymph node Distant metastases

Thyroid Cancer Epidemiology - Children Thyroid cancer has proven to be a common SNM Between 1980 & 1987 58 centers in Europe reported 239 SMN’s 18 of 239 (7.5%) were thyroid cancers 6 / 18 primary was Hodgkins all received chemo + RT (25-42gy) 7 / 18 primary was ALL all had CS RT (18-24gy) 2 Ewings, 1 Wilms, 1 NB and 1 NPC

Thyroid Cancer Pediatric vs. Adult Thyroid nodules By far most thyroid nodules are benign and are either colloid nodules, adenomas or manifestations of thyroiditis They may be cystic or solid Most cystic are generally benign (degenerated colloid) They may be toxic or non toxic Thyroid Cancer Pediatric vs. Adult Thyroid masses more likely to be cancer 50% of solitary nodules are malignant More often larger, multicentric Higher rate of metastasis at diagnosis regional lymph nodes: 65% (35% adult [papillary]) distant: 20% (10% adult [follicular]) Higher rate of recurrence 40% <20y (also >60y); 20% adults 80% locoregional, 20% distant (similar)

Thyroid Cancer Diagnostic Imaging Traditionally I131 Now I123 or Technitium scans Nodules hyperfunctional (hot) with increased avidity Functional cold same as rest of gland Minimum 1 cm diameter for cold nodules Hot functional nodules practically benign Cold – incidence of malignancy higher

Thyroid Cancer Diagnostic Imaging USG – differentiate multinodular vs solitary CT or MRI – invasive lesion or sub-sternal location Specific / sensitive is F.N.A. Malignant, suspicious, benign or inadequate If it is suspicious I123 , hot, rarely malignant cold 20% or higher

Thyroid Cancer Pediatric vs. Adult Better overall survival >95% for children 75-90% for adults Better survival with metastases 86% of children 32% of adults Thyroid Cancer Pediatric vs. Adult Thyroid malignancies in pediatric population – how is it different? Papillary ca. constitutes 85-90% of all malignant lesions with medullary second, forming 5% Unlike adults follicular not as common and when present it is usually in the adolescent population Thyroid lymphomas and metastasis are hardly ever seen in pediatric population In familial medullary ca. prophylactic thyroidectomy is done in kids before they attain age 5yr PARADOX: often presents with extensive disease and progression or recurrence in a significant number of patients is rarely fatal Suggests biologic rather than treatment factors have a greater effect on outcome

Approach to a malignant thyroid nodule Clinically suspicious nodule >1cm Increased suspicion Male Nodule > 4cm Age < 15 yr H/O XRT exposure H/O Pheochromocytoma Hyperparathyroidism Gardner’s FAP Carney’s complex Cowden’s syndrome Highly suspicious Rapid nodule growth Fixation Family history V.C paralysis Lymph nodes Neck invasion TSH FNA of nodule/ lymph nodes If insufficient FNA → repeat FNA (imparts 50% extra chance) US solid or cystic and assist in FNA and determining the size of the nodule Cystic nodules may be followed

Thyroid Carcinoma Fine needle aspiration important Distinguishing benign/malignant follicular difficult Thyroid nodules containing follicular cytopathologic features have 20-30% malignancy Thyroid malignancy rate is 6.8% without atypia and 44-50% with atypia Allows for conservative approach in selected patients

Thyroid Cancer Surgical Options Total Thyroidectomy in patients with invasive or metastatic or bilateral or previous RT For others – controversy varies with surgery and complication rates Unilateral P.C. or F.C. < 1.5 cm lobectomy + isthmus If > 1.5 cm opposite lobe 30-80% recurrence rate is 10% Recurrence associated with 30% mortality with 50% desease found in central neck Total Thyroidectomy recurrence less than 5%

sup. parathyroid recurrent laryngeal n.

Thyroid Cancer Surgery Risk vs. Benefit Total Thyroidectomy High risk groups: radiation, MTC, Anaplastic Simplifies use of radioiodine Follow thyroglobulin levels Increased risk without increased survival benefit 15% each-recurrent laryngeal nerve injury, hypoparathyroidism 30% higher than lobectomy

Thyroid Cancer in Childhood sup. parathyroid Challenges of Thyroid Cancer Management recurrent laryngeal n. No prospective randomized trials of treatment The prognosis is generally excellent

Thyroid Carcinoma Minimally Invasive Surgery Criteria by Niccoli et al. (Am J Surg, 2001) Nodules less than 3.5 cm Total thyroid volume less than 15ml No previous neck surgery or irradiation Absence of thyroiditis/invasion Total 336 pts. One-third total thyroidectomy Conversion 4.5% Yamashita et al. 25-30 mm transverse upper lateral neck Total 39 pts. Recurrent nerve injury one Tumor size 1.9 – 5.5 cm Surgery 56 mm (36-90 minutes) Other approaches described Axillary Approach

Approach to a thyroid nodule (Papillary on FNA-high risk) Papillary ca. (dx. By FNA) and high risk Total thyroidectomy If L.N positive Central neck disec Lateral neck disec.(level II-IV, sparing spinal accessory nerve, int. jugular, SCM)

Management post lobectomy for papillary (<1cm- low risk) Their recurrence and cancer specific mortality rates are almost zero Supress TSH with thyroxine Tg and whole body I scan are insensitive Physical exam with local neck US seem to be the best suggested follow up

Follow up papillary P/E q 3-6 mo for 2yrs with periodic US Tg @ 6 & 12mo then annually RI scans q 12mo Periodic CXR/ CT chest For locoregional recurrences → surgery followed by RI Tg rise >10ng/ml → RI therapy with 100-150mCi

Thyroid Carcinoma Follicular lesion Follicular carcinoma represent 10-20% Prognostic factors include size, age, metastasis Witte et al., report L.N., size, stage, mets, sex Advised total thyroidectomy + L.N. dissection and ipsilateral or bilateral L.N. dissection for T3, T4 Follicular lesion TSH high → Thyroxine/Surg Follicular TSH normal → Surgery TSH low → Thyroid scan hot cold

Approach to thyroid nodule (Follicular on lobectomy) Invasive Follicular carcinoma on lobectomy Further local and metastatic work up < 1cm → observe/ re-resect > 1 cm → completion thyroidectomy followed by I 131

Approach to a thyroid nodule Medullary carcinoma Medullary on FNA Calcitonin levels CEA Pheo screening Serum calcium Screen for RET proto-oncogene Neck US