Thyroid Cancer by Christopher Muller PowerPoint Presentation

Slide 1 -

Thyroid Cancerby Christopher Muller (MS4) UTMB Grand Rounds October 7, 1998 Faculty disscussants: Dr. Byron J. Bailey and Dr. Anna M. Pou

Slide 2 -

Intoduction Consistent techniques of thyroid surgery date back approximately 100 years Theodor Kocher of Bern, Switzerland made major contibutions to thyroid the understanding of thyroid disease and thyroid surgery 1872 - performed his first thyroidectomy 1901 - had performed 2,000 thyroid procedure 1901 - overall operative mortality had decreased from 50% to 4.5% 1909 - won the nobel prize for his work (Cady, 1991, Soh,1996)

Slide 3 -

Statistics of Thyroid Cancer 1.0%-1.5% of all new cancer cases in the United States (Sessions, 1993, Silverberg, 1989) ten fold less than that of lung, breast, or colorectal cancer 8,000-14,000 new cases diagnosed each year (Sessions, 1993, Geopfert, 1998) 3% of patients who die of other causes have occult thyroid cancer and 10% have microscopic cancers (Robbins, 1991) 35% of thyroid gland at autopsy in some studies have papillary carcinomas (<1.0cm) (Mazzaferri, 1993) 1,000-1,200 patients in the U.S. die each year of thyroid cancer (Goldman, 1996)

Slide 4 -

Statistics of Thyroid Cancer(continued…) 4%-7% of adults in North America have palpable thyroid nodules (Mazzaferri, 1993, Vander, 1968) 4:1 women to men (Mazzaferri, 1993) Overall, fewer than 5% of nodules are malignant (Mazzaferri, 1988)

Slide 5 -

History Symptoms The most common presentation of a thyroid nodule, benign or malignant, is a painless mass in the region of the thyroid gland (Goldman, 1996). Symptoms consistent with malignancy Pain dysphagia Stridor hemoptysis rapid enlargement hoarseness

Slide 6 -

History (continued...) Risk factors Thyroid exposure to irradiation low or high dose external irradiation (40-50 Gy [4000-5000 rad]) especially in childhood for: large thymus, acne, enlarged tonsils, cervical adenitis, sinusitis, and malignancies 30%-50% chance of a thyroid nodule to be malignant (Goldman, 1996) Schneider and co-workers (1986) studied, with long term F/U, 3000 patients who underwent childhood irradiation. 1145 had thyroid nodules 318/1145 had thyroid cancer (mostly papillary)

Slide 7 -

History (continued...) Risk factors (continued…) Age and Sex Benign nodules occur most frequently in women 20-40 years (Campbell, 1989) 5%-10% of these are malignant (Campbell, 1989) Men have a higher risk of a nodule being malignant Belfiore and co-workers found that: the odds of cancer in men quadrupled by the age of 64 a thyroid nodule in a man older than 70 years had a 50% chance of being malignant

Slide 8 -

History (continued…) Family History History of family member with medullary thyroid carcinoma History of family member with other endocrine abnormalities (parathyroid, adrenals) History of familial polyposis (Gardner’s syndrome)

Slide 9 -

Evaluation of the thyroid Nodule(Physical Exam) Examination of the thyroid nodule: consistency - hard vs. soft size - < 4.0 cm Multinodular vs. solitary nodule multi nodular - 3% chance of malignancy (Goldman, 1996) solitary nodule - 5%-12% chance of malignancy (Goldman, 1996) Mobility with swallowing Mobility with respect to surrounding tissues Well circumscribed vs. ill defined borders

Slide 10 -

Physical Exam (continued…) Examine for ectopic thyroid tissue Indirect or fiberoptic laryngoscopy vocal cord mobility evaluate airway preoperative documentation of any unrelated abnormalities Systematic palpation of the neck Metastatic adenopathy commonly found: in the central compartment (level VI) along middle and lower portion of the jugular vein (regions III and IV) and Attempt to elicit Chvostek’s sign

Slide 11 -

Evaluation of the Thyroid Nodule(Blood Tests) Thyroid function tests thyroxine (T4) triiodothyronin (T3) thyroid stimulating hormone (TSH) Serum Calcium Thyroglobulin (TG) Calcitonin

Slide 12 -

Evaluation of the Thyroid Nodule(Radioimaging) Radioimaging usually not used in initial work-up of a thyroid nodule Chest radiograph Computed tomography Magnetic resonance imaging

Slide 13 -

Evaluation of the Thyroid Nodule(Ultrasonography) Advantages Most sensitive procedure or identifying lesions in the thyroid (2-3mm) 90% accuracy in categorizing nodules as solid, cystic, or mixed (Rojeski, 1985) Best method of determining the volume of a nodule (Rojeski, 1985) Can detect the presence of lymph node enlargement and calcifications Noninvasive and inexpensive

Slide 14 -

Ultrasonography (Continued…) When to use Ultrasonography: Long term follow-up for the following: to evaluate the involution of a multinodular gland or a solitary benign nodule under suppression therapy monitor for reaccumulation of a benign cystic lesion follow thyroid nodules enlargement during pregnancy Evaluation of a thyroid nodule: help localize a lesion and direct a needle biopsy when a nodule is difficult to palpate or is deep-seated Determine if a benign lesion is solid or cystic

Slide 15 -

Ultrasonography (Continued…) Disadvantages Unable to reliably diagnose true cystic lesions Cannot accurately distinguish benign from malignant nodules

Slide 16 -

Evaluation of the Thyroid Nodule(Radioisotope Scanning) Prior to FNA, was the initial diagnostic procedure of choice Performed with: technetium 99m pertechnetate or radioactive iodine Technetium 99m pertechnetate cost-effective readily available short half-life trapped but not organified by the thyroid - cannot determine functionality of a nodule

Slide 17 -

Radioisotope Scanning (Continued…) Radioactive iodine radioactive iodine (I-131, I-125, I-123) is trapped and organified can determine functionality of a thyroid nodule

Slide 18 -

Radioisotope Scanning (continued...) Limitations Not as sensitive or specific as fine needle aspiration in distinguishing benign from malignant nodule 90%-95% of thyroid nodules are hypofunctioning, with 10%-20% being malignant (Geopfert, 1994, Sessions, 1993) Campbell and Pillsbury (1989) performed a meta-analysis of 10 studies correlating the results of radionuclide scans in patients with solitary thyroid nodules with the pathology reports following surgery and found: 17% of cold nodules, 13% of warm or cool nodules, and 4% of hot nodules to be malignant

Slide 19 -

Radioisotope Scanning (continued…) Specific uses of thyroid scanning: Preoperative evaluation When patients have benign (by FNA), solid (by U/S) lesions When patients have nonoxyphilic follicular neoplasms Postoperative evaluation immediately postop for localization of residual cancer or thyroid tissue follow-up for tumor recurrence or metastasis (Geopfert, 1994)

Slide 20 -

Evaluation of the Thyroid Nodule(Fine-Needle Aspiration) Currently considered to be the best first-line diagnostic procedure in the evaluation of the thyroid nodule: Advantages: Safe Cost-effective Minimally invasive Leads to better selection of patients for surgery than any other test (Rojeski, 1985)

Slide 21 -

Fine-Needle Aspiration (continued…) FNA halved the number of patients requiring thyroidectomy (Mazzaferri, 1993) FNA has double the yield of cancer in those who do undergo thyroidectomy (Mazzaferri, 1993)

Slide 22 -

Fine-Needle Aspiration (continued…) Pathologic results are categorized as: positive, negative, or indeterminate Hossein and Goellner (1993) use four categories. They pooled data from seven series and came up with the following rates: benign - 69% suspicious -10% malignant - 4% nondiagnostic - 17%

Slide 23 -

Fine-Needle Aspiration (continued…) Limitations skill of the aspirator Sampling error in lesions <1cm, >4cm, multinodular lesions, and hemorrhagic lesions Error can be diminished using ultrasound guidance expertise of the cytologist difficulty in distinguishing some benign cellular adenomas from their malignant counterparts (follicular and Hurthle cell) False negative results = 1%-6% (Mazzeferri, 1993) False positive results = 3%-6% (Rojeski, 1985, Mazzeferri, 1993, Hall, 1989)

Slide 24 -

Evaluation of the Thyroid Nodule(Thyroid-Stimulating Hormone Suppression) Mechanism/Rationale Exogenous thyroid hormone feeds back to the pituitary to decrease the production of TSH Cancer is autonomous and does not require TSH for growth whereas benign processes do Thyroid masses that shrink with suppression therapy are more likely to be benign Thyroid masses that continue to enlarge are likely to be malignant

Slide 25 -

Thyroid Suppression (continued…) Limitations: 16% of malignant nodules are suppressible Only 21% of benign nodules are suppressible Provides little use in distinguishing benign from malignant nodules (Geopfert, 1998)

Slide 26 -

Thyroid Suppression (continued…) Uses: Preoperative patients with nonoxyphilic follicular neoplasms patients with solitary benign nodules that are nontoxic (particularly men and premenopausal women) women with repeated nondiagnostic tests Postoperative Use in follicular, papillary and Hurthle cell carcinomas (Geopfert, 1998, Mazzaferri, 1993)

Slide 27 -

Thyroid Suppression (continued…) How to use thyroid suppression administer levothyroxine maintain TSH levels at <0.1 mIU/L use ultrasound to monitor size of nodule if the nodule shrinks, continue L-thyroxine maintaining TSH at low-normal levels if the nodule has remained the same size after 3 months, reaspirate if the nodule has increased in size, excise it (Geopfert, 1998,)

Slide 28 -

Classification of Malignant Thyroid Neoplasms Papillary carcinoma Follicular variant Tall cell Diffuse sclerosing Encapsulated Follicular carcinoma Overtly invasive Minimally invasive Hurthle cell carcinoma Anaplastic carcinoma Giant cell Small cell Medullary Carcinoma Miscellaneous Sarcoma Lymphoma Squamous cell carcinoma Mucoepidermoid carcinoma Clear cell tumors Pasma cell tumors Metastatic Direct extention Kidney Colon Melanoma

Slide 29 -

Well-Differentiated Thyroid Carcinomas (WDTC) - Papillary, Follicular, and Hurthle cell Pathogenesis - unknown Papillary has been associated with the RET proto-oncogene but no definitive link has been proven (Geopfert, 1998) Certain clinical factors increase the likelihood of developing thyroid cancer Irradiation - papillary carcinoma Prolonged elevation of TSH (iodine deficiency) - follicular carcinoma (Goldman, 1996) relationship not seen with papillary carcinoma mechanism is not known

Slide 30 -

WDTC - Papillary Carcinoma 60%-80% of all thyroid cancers (Geopfert, 1998, Merino, 1991) Histologic subtypes Follicular variant Tall cell Columnar cell Diffuse sclerosing Encapsulated Prognosis is 80% survival at 10 years (Goldman, 1996) Females > Males Mean age of 35 years (Mazzaferri, 1994)

Slide 31 -

WDTC - Papillary Carcinoma(continued…) Lymph node involvement is common Major route of metastasis is lymphatic 46%-90% of patients have lymph node involvement (Goepfert, 1998, Scheumann, 1984, De Jong, 1993) Clinically undetectable lymph node involvement does not worsen prognosis (Harwood, 1978)

Slide 32 -

WDTC - Papillary Carcinoma (Continued…) Microcarcinomas - a manifestation of papillary carcinoma Definition - papillary carcinoms smaller than 1.0 cm Most are found incidentally at autopsy Autopsy reports indicate that these may be present in up to 35% of the population (Mazzaferri, 1993) Usually clinically silent Most agree that the morbidity and mortality from microcarcinoma is minimal and near that of the normal population One study showed a 1.3% mortality rate (Hay, 1990)

Slide 33 -

WDTC - Papillary Carcinoma(continued…) Pathology Gross - vary considerably in size - often multi-focal - unencapsulated but often have a pseudocapsule Histology - closely packed papillae with little colloid - psammoma bodies - nuclei are oval or elongated, pale staining with ground glass appearanc - Orphan Annie cells

Slide 34 -

WDTC - Follicular Carcinoma 20% of all thyroid malignancies Women > Men (2:1 - 4:1) (Davis, 1992, De Souza, 1993) Mean age of 39 years (Mazzaferri, 1994) Prognosis - 60% survive to 10 years (Geopfert, 1994) Metastasis - angioinvasion and hematogenous spread 15% present with distant metastases to bone and lung Lymphatic involvement is seen in 13% (Goldman, 1996)

Slide 35 -

WDTC - Follicular Carcinoma(Continued…) Pathology Gross - encapsulated, solitary Histology - very well-differentiated (distinction between follicular adenoma and carcinomaid difficult) - Definitive diagnosis - evidence of vascular and capsular invasion FNA and frozen section cannot accurately distinquish between benign and malignant lesions

Slide 36 -

WDTC - Hurthle Cell Carcinoma Variant of follicular carcinoma First described by Askanazy “Large, polygonal, eosinophilic thyroid follicular cells with abundant granular cytoplasm and numerous mitochondria” (Goldman, 1996) Definition (Hurthle cell neoplasm) - an encapsulated group of follicular cells with at least a 75% Hurthle cell component Carcinoma requires evidence of vascular and capsular invasion 4%-10% of all thyroid malignancies (Sessions, 1993)

Slide 37 -

WDTC - Hurthle Cell Carcinoma(Continued…) Women > Men Lymphatic spread seen in 30% of patients (Goldman, 1996) Distant metastases to bone and lung is seen in 15% at the time of presentation

Slide 38 -

WDTC - Prognosis Based on age, sex, and findings at the time of surgery (Geopfert, 1998) Several prognostic schemes represented by acronyms have been developed by different groups: AMES (Lahey Clinic, Burlington, MA) GAMES (Memorial Sloan-Kettering Cancer Center, New York, NT) AGES (Mayo Clinic, Rochester, MN)

Slide 39 -

WDTC - Prognosis (Continued…) Depending on variables, patients are categorized in to one of the following three groups: 1) Low risk group - men younger than 40 years and women younger than 50 years regardless of histologic type - recurrence rate -11% - death rate - 4% (Cady and Rossi, 1988)

Slide 40 -

WDTC - Prognosis (Continued…) 1) Intermediate risk group - Men older than 40 years and women older than 50 years who have papillary carcinoma - recurrence rate - 29% - death rate - 21% 2) High risk group - Men older than 40 years and women older than 50 years who have follicular carcinoma - recurrence rate - 40% - death rate - 36%

Slide 41 -

Medullary Thyroid Carcinoma 10% of all thyroid malignancies 1000 new cases in the U.S. each year Arises from the parafollicular cell or C-cells of the thyroid gland derivatives of neural crest cells of the branchial arches secrete calcitonin which plays a role in calcium metabolism

Slide 42 -

Medullary Thyroid Carcinoma (Continued…) Developes in 4 clinical settings: Sporadic MTC (SMTC) Familial MTC (FMTC) Multiple endocrine neoplasia IIa (MEN IIa) Multiple endocrine neoplasia IIb (MEN IIb)

Slide 43 -

Medullary Thyroid Carcinoma (continued…) Sporadic MTC: 70%-80% of all MTCs (Colson, 1993, Marzano, 1995) Mean age of 50 years (Russell, 1983) 75% 15 year survival (Alexander, 1991) Unilateral and Unifocal (70%) Slightly more aggressive than FMTC and MEN IIa 74% have extrathyroid involvement at presentation (Russell, 1983)

Slide 44 -

Medullary Thyroid Carcinoma (Continued…) Familial MTC: Autosomal dominant transmission Not associated with any other endocrinopathies Mean age of 43 Multifocal and bilateral Has the best prognosis of all types of MTC 100% 15 year survival (Farndon, 1986)

Slide 45 -

Medullary Thyroid Carcinoma (continued…) Multiple endocrine neoplasia IIa (Sipple’s Syndrome): MTC, Pheochromocytoma, parathyroid hyperplasia Autosomal dominant transmission Mean age of 27 100% develop MTC (Cance, 1985) 85%-90% survival at 15 years (Alexander, 1991, Brunt, 1987)

Slide 46 -

Medullary Thyroid Carcinoma (continued…) Multiple endocrine neoplasia IIb (Wermer’s Syndrome, MEN III, mucosal syndrome): Pheochromocytoma, multiple mucosal neuromas, marfanoid body habitus 90% develop MTC by the age of 20 Most aggressive type of MTC 15 year survival is <40%-50% (Carney, 1979)

Slide 47 -

Medullary Thyroid Carcinoma (continued…) Diagnosis Labs: 1) basal and pentagastrin stimulated serum calcitonin levels (>300 pg/ml) 2) serum calcium 3) 24 hour urinary catecholamines (metanephrines, VMA, nor-metanephrines) 4) carcinoembryonic antigen (CEA) Fine-needle aspiration Genetic testing of all first degree relatives RET proto-oncogene

Slide 48 -

Anaplastic Carcinoma of the Thyroid Highly lethal form of thyroid cancer Median survival <8 months (Jereb, 1975, Junor, 1992) 1%-10% of all thyroid cancers (Leeper, 1985, LiVolsi, 1987) Affects the elderly (30% of thyroid cancers in patients >70 years) (Sou, 1996) Mean age of 60 years (Junor, 1992) 53% have previous benign thyroid disease (Demeter, 1991) 47% have previous history of WDTC (Demeter, 1991)

Slide 49 -

Anaplastic Carcinoma of the Thyroid Pathology Classified as large cell or small cell Large cell is more common and has a worse prognosis Histology - sheets of very poorly differentiated cells little cytoplasm numerous mitoses necrosis extrathyroidal invasion

Slide 50 -

Management Surgery is the definitive management of thyroid cancer, excluding most cases of ATC and lymphoma Types of operations: lobectomy with isthmusectomy - minimal operation required for a potentially malignant thyroid nodule total thyroidectomy - removal of all thyroid tissue - preservation of the contralateral parathyroid glands subtotal thyroidectomy - anything less than a total thyroidectomy

Slide 51 -

Management (WDTC) - Papillary and Follicular Subtotal vs. total thyroidectomy

Slide 52 -

Management (WDTC)- Papillary and Follicular (continued…) Rationale for total thyroidectomy 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 iodine (Soh, 1996) 5) Residual WDTC has the potential to dedifferentiate to ATC

Slide 53 -

Management (WDTC) - Papillary and Follicular (Continued…) 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)

Slide 54 -

Management (WDTC) - Papillary and Follicular (continued) 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

Slide 55 -

Management (WDTC) - Papillary and Follicular (continued) Managing lymphatic involvement pericapsular and tracheoesophageal nodes should be dissected and removed in all patients undergoing thyroidectomy for malignancy Overt nodal involvement requires exploration of mediastinal and lateral neck if any cervical nodes are clinically palpable or identified by MR or CT imaging as being suspicious a neck dissection should be done (Goldman, 1996) Prophylactic neck dissections are not done (Gluckman)

Slide 56 -

Management (WDTC) - Papillary and Follicular (continued) Postoperative therapy/follow-up Radioactive iodine (administration) Scan at 4-6 weeks postop repeat scan at 6-12 months after ablation repeat scan at 1 year then... every 2 years thereafter

Slide 57 -

Management (WDTC) - Papillary and Follicular (continued) Postoperative therapy/follow-up Thyroglobulin (TG) (Gluckman) measure serum levels every 6 months Level >30 ng/ml are abnormal Thyroid hormone suppression (control TSH dependent cancer) (Goldman, 1996) should be done in - 1) all total thyroidectomy patients 2) all patients who have had radioactive ablation of any remaining thyroid tissue

Slide 58 -

Management (WDTC) - Hurthle Cell Carcinoma (continued) Total thyroidectomy is recommended because: 1) Lesions are often Multifocal 2) They are more aggressive than WDTCs 3) Most do not concentrate iodine

Slide 59 -

Management (WDTC) - Hurthle Cell Carcinoma (continued) Postoperative management Thyroid suppression Measure serum thyroglobulin every 6 months Postoperative radioactive iodine is usually not effective (10% concentrate iodine) (Clark, 1994)

Slide 60 -

Medullary Thyroid Carcinoma (Management) Recommended surgical management total thyroidectomy central lymph node dissection lateral jugular sampling if suspicious nodes - modified radical neck dissection If patient has MEN syndrome remove pheochromocytoma before thyroid surgery

Slide 61 -

Medullary Thyroid Carcinoma (Management) Postoperative management disease surveillance serial calcitonin and CEA 2 weeks postop 3/month for one year, then… biannually If calcitonin rises metastatic work-up surgical excision if metastases - external beam radiation

Slide 62 -

Anaplastic Carcinoma (Management) Most have extensive extrathyroidal involvement at the time of diagnosis surgery is limited to biopsy and tracheostomy Current standard of care is: maximum surgical debulking, possible adjuvant radiotherapy and chemotherapy (Jereb and Sweeney, 1996)