Thyroid tumors Dr. Gehan Mohamed

Classification of thyroid tumors A- benign tumors: more common than malignant thyroid neoplasm. e.g follicular thyroid adenoma B- Malignant thyroid tumors.

Criteria for diagnosis of follicular adenoma 1- solitary nodule 2- encapsulated 3- presence of compressed thyroid tissue outside capsule of thyroid adenoma.

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 Plasma cell tumors Metastatic Direct extention Kidney Colon Melanoma

Normal Thyroid colloid Thyroid epithelial cells T4 90% T3 10% TSH

Types of Thyroid Cancer Papillary (80%-85%): develops from thyroid follicle cells in 1 or both lobes; grows slowly but can spread Follicular (5%-10%): common in countries with insufficient iodine consumption; lymph node metastases are uncommon Medullary: develops from C-cells, can spread quickly; sporadic . Anaplastic: develops from existing papillary or follicular cancers; aggressive, usually fatal Lymphoma: develops from lymphocytes; uncommon Types of Thyroid Cancer. Thyroid cancer is more common in women than in men, and occurs most frequently in individuals between 35 and 45 years of age. There are several types of thyroid cancer.1 Papillary thyroid cancer (PTC) is the most common form, comprising 80% to 85% of thyroid cancers. Papillary thyroid cancer and follicular thyroid cancer (FTC) arise from thyroid follicle cells. Papillary thyroid cancer is frequently a multifocal and bilateral disease while follicular thyroid cancer tends to present as a single focus within the thyroid gland.2 Papillary cancers grow slowly, but often spread to regional cervical lymph nodes. Follicular thyroid cancer accounts for approximately 5% to 10% of thyroid cancers.1 It is more common in countries where the population does not have sufficient iodine intake.1 Follicular cancer infrequently spreads to regional cervical nodes, but can spread to the lungs and bones.1 Medullary thyroid cancer (MTC) develops from the C-cells and can spread quickly to the lymph nodes, lungs, or liver before a thyroid nodule is detected.1 Medullary cancer can either be sporadic or can arise as a part of a number of genetic syndromes associated with endocrine abnormalities, including hyperparathyroidism and pheochromocytoma (such as multiple endocrine neoplasia [MEN] 2 syndrome).1 Anaplastic thyroid cancer (ATC) is uncommon, and is believed to develop from existing papillary or follicular carcinomas.1 Anaplastic thyroid cancer is one of the most aggressive and lethal of all solid malignancies. In most series, 3-year survival rates were less than 10%.3 Thyroid lymphoma is a rare disease that usually arises in the setting of pre-existing chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis).2 References 1. Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003. 2. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000. 3. Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at: http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003.

Risk Factors for development of thyroid carcinoma Radiation High dose x-rays of the neck or face during infancy or teenage years is a risk factor specially for papillary carcinoma Family History Goiters and prolonged TSH stimulation is a risk for follicular carcinoma. Mutated RET oncogene Gender males

When suspect malignancy in thyroid mass 1-Male sex 2- Solitary thyroid nodules in patients >60 or <30 years of age 3-Large Nodules (>3 or 4 cm) with rapid Growth 4-Symptoms especially a change in voice,Pain,dysphagia,Stridor,hemoptysis

Molecular Level Medullary Carcinoma Papillary Carcinoma Mutation in RET gene Papillary Carcinoma Mutated RET, RAS, or BRAF gene

Typical Presentation of Thyroid Cancer Painless lump Normal thyroid function tests Found on routine examination or by the patient Typical Presentation of Thyroid Cancer. Most thyroid cancers present in clinically euthyroid patients who have normal thyroid function tests. These tests, including those measuring thyroid stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3), are measurements of the functional status of the thyroid and provide no information on the presence or absence of structural disease of the thyroid (eg, nodules).1 A mass in the thyroid may be found during a routine examination by a health care provider or may be noted by the patient.1 Often thyroid cancer is present in a nodule for months or years with only minimal growth.2 Thus, lack of consistent nodule size over long periods of time does not rule out the presence of thyroid cancer.3 References 1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33. 2. Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003. 3. Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.

Lymph node involvement is common Papillary Carcinoma Most common type Females outnumber males 3:1 Highest incidence in women in midlife. Lymph node involvement is common Major route of metastasis is lymphatic

Papillary Thyroid Cancer Characteristics Unencapsulated tumor nodule with ill-defined margins Tumor typically firm and solid First presentation of the patient may be lymph node enlargment. Commonly metastasizes to neck and mediastinal lymph nodes 40% to 60% in adults and 90% in children <5% of patients have distant metastases at time of diagnosis Lung is most common site Papillary Thyroid Cancer. Characteristics. Approximately 80% to 90% of PTC cases are comprised of unencapsulated or partially encapsulated tumor nodules with poorly defined margins.1 Papillary thyroid tumors are typically firm and solid. They may be associated with a loss of differentiation that suggests an aggressive neoplasm in middle-aged or elderly patients.1 The tall cell variant is a more aggressive form of PTC compared with the standard PTC variety.1,2 It comprises approximately 10% of total cases2 and some of the tumors are composed of cells with oncocytic cytoplasm.1 Papillary thyroid cancer may present as a nodal enlargement and usually metastasizes in the neck and mediastinal lymph nodes.2 Fewer than 5% of patients have distant metastases at the time of diagnosis, and metastases most often appear in the lungs.2 References 1. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000. 2. Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.

Thyroid carcinoma

Micropapillary thyroid carcinomas Definition - papillary carcinoma smaller than 1.0 cm Most are found incidentally at autopsy Usually clinically silent

Papillary Carcinoma (continued…) Pathology Gross - vary considerably in size - often multi-focal - unencapsulated but often have a pseudocapsule which is normal thyroid tissue compressed by the tumor mass. Histopathology - closely packed papillae which have fibrovascular core. - psammoma bodies which is a laminated calcification - nuclei are oval or elongated, pale staining with ground glass appearance .

Papillary carcinoma of thyroid

Papillary Thyroid Cancer: nuclei are oval or elongated, pale staining with ground glass appearance Papillary thyroid cancer is the most common type of thyroid cancer and accounts for approximately 80% to 85% of all diagnosed thyroid cancers in the United States.1 Papillary thyroid cancer has a 3-fold higher incidence in women than in men, and has a peak incidence in the third and fourth decades of life.2 Approximately two thirds of PTC is found to have follicular elements and is often classified histologically as a follicular variant of papillary thyroid carcinoma.2 References 1. Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003. 2. Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.

Follicular variant of papillary carcinoma

2- Follicular Thyroid Carcinoma Second most common type of thyroid cancer Solid invasive tumors, usually solitary and encapsulated Usually stays in the thyroid gland, but can spread to the bones, lungs, and central nervous system. Usually does not spread to the lymph nodes Follicular Thyroid Cancer. Follicular thyroid cancer is the second most common type of thyroid cancer, accounting for approximately 15% of all thyroid cancers.1 Its peak incidence is in the fifth decade of life in patients living in the United States and it occurs more frequently in women.1 Follicular thyroid cancer usually presents as a fleshy, solid, encapsulated mass that is sometimes focally fibrotic and calcified.2 These tend to be slow-growing tumors and are usually recognized prior to metastasis as a nodule in the thyroid gland.2 Follicular thyroid cancers with only minimal capsular invasion (minimally invasive FTCs) rarely spread to distant sites and are often cured with surgical resection. However, follicular cancers with widespread capsular invasion and/or vascular invasion are more likely to spread to the skeleton, lungs, brain, and other tissues.2 These neoplasms rarely spread to cervical lymph nodes.3 References 1. Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical Information – Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003. 2. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000. 3. Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.

Follicular Carcinoma Pathology Gross - encapsulated, solitary Histology - very well-differentiated. (distinction between follicular adenoma and follicular carcinoma is so difficult so we depend on presence of vascular and capsular invasion to diagnose follicular carcinoma.

Invasive follicular carcinoma:malignant follicles invade pink fibrous capsule

Follicular thyroid carcinoma

Hürthle Cell Carcinoma A variant of follicular cancer that tends to be aggressive Microscope : there are Large, polygonal, eosinophilic thyroid follicular cells with abundant granular cytoplasm and numerous mitochondria Hürthle Cell Tumor Hürthle Cell Cancer. Hürthle cell cancer is a rare type of thyroid cancer that accounts for 3% to 10% of all thyroid cancers.1 It is an aggressive cancer that tends to poorly concentrate RAI.1,2 Scattered benign Hürthle cells are frequently seen in chronic lymphocytic thyroiditis, multinodular goiter, and subacute thyroiditis.1 However, Hürthle cell neoplasms are hypercellular nodules, with a predominance of Hürthle cells (greater than 75%), few or no lymphocytes, and scanty or absent colloid.1 The presence of an invasion of blood vessels or of the tumor capsule differentiates a malignant Hürthle carcinoma from a benign Hürthle cell adenoma.1 References 1. Aytug S, et al. Hürthle cell carcinoma. eMedicine Web site. Available at: http://www.emedicine.com/med/topic1045.htm. Accessed December 10, 2003. 2. Kloos RT, Mazzaferri E. Thyroid carcinoma. In: Cooper DS, ed. Medical Management of Thyroid Disease. Monticello, NY:Marcel Dekker, Inc.; 2001:239-241. High power magnification

Hürthle Cell tumor May be benign or malignant, based on demonstration of vascular or capsular invasion Malignancies tend to have a worse prognosis than other follicular tumors Tend to be locally invasive Hürthle Cell Cancer. Prognosis. Hürthle cell carcinomas can metastasize to regional lymph nodes as well as spread hematogenously.1 In addition, they are invasive and the capsule and blood vessels should be assessed for invasion.1,2 Patients with malignant Hürthle cell carcinomas have a decreased survival prognosis compared with patients who have other follicular tumors.2 Hürthle cell carcinomas rarely respond to RAI therapy, so the discovery of a Hürthle cell cytology should lead to surgical resection of the lesion; however, there is a strong likelihood of recurrence following surgery.1,2 Caplan et al3 found that 4.4% of Hürthle cell cancers were hot on scan and 8.9% were warm. References 1. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000. 2. Mazzaferri EL. Thyroid carcinoma: papillary and follicular. In: Mazzaferri, EL, Samaan N, eds. Endocrine Tumors. Cambridge, MA: Blackwell; 1993:278-333. 3. Caplan RH, et al. Thyroid. 1994;4:243-248.

3- Anaplastic Thyroid Cancer Often occurs in the elderly population (mean age: 65 years) Three fold greater risk in iodine-deficient areas Tumor is typically hard, poorly circumscribed, and fixed to surrounding structures. Extremely aggressive and exceptionally virulent Anaplastic Thyroid Cancer. Fewer than 10% of thyroid carcinomas are classified as anaplastic.1 These tumors are commonly of the spindle cell and giant cell types.1 They are aggressive neoplasms that usually occur in the elderly and in women.1 They are composed wholly or in part of undifferentiated cells and demonstrate a high incidence of remnants of well-differentiated FTC or PTC.1,2 Anaplastic thyroid cancer does not concentrate RAI and is often treated primarily with external beam irradiation and chemotherapy.2,3 Despite an initial response to external beam irradiation, local recurrence is expected in most patients.2,3 This local recurrence usually results in the death of the patient in less than 1 year from the time of diagnosis.3 References 1. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000. 2. Sherman SI. Lancet. 2003;361:501-511. 3. Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical Information – Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.

Anaplastic Carcinoma of the Thyroid Pathology Classified as Composed wholly or in part of undifferentiated cells which may be 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

Medullary Thyroid Carcinoma Tumor arising from the calcitonin-secreting C-cells of the thyroid gland. Developes in 3 clinical settings: Sporadic MTC (SMTC) Familial MTC (FMTC) Multiple endocrine neoplasia.

Medullary Thyroid Carcinoma characterized by presence of pink amyloid in between malignant cells. Medullary Thyroid Cancer. Medullary thyroid cancer is associated with C-cell proliferation, causing tumors that appear from the calcitonin-secreting C-cells of the thyroid gland.1,2 Medullary thyroid cancer constitutes approximately 5% of thyroid cancers and has a mortality rate of 10% to 20% at 10 years.1-3 References 1. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000. 2. Sherman SI. Lancet. 2003;361:501-511. 3. Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at: http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003.

Medullary Thyroid Cancer Metastases Cervical lymph node metastases occur early Tumors >1.5 cm are likely to metastasize, often to bone, lungs, liver, and the central nervous system Metastases usually contain calcitonin and stain for amyloid Medullary Thyroid Cancer. Metastases. In MTC, cervical lymph node metastases occur early and tumors larger than 1.5 cm are likely to metastasize and spread.1,2 Medullary thyroid cancer can also spread to the skeleton, lungs, liver, and the central nervous system.1 The metastases that occur with MTC usually contain calcitonin, which is found in the C-cell, or carcinoembryonic antigen (CEA).3 Both calcitonin and CEA are released into the blood and can be detected with a blood test.3 References 1. Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at: http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003. 2. Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical Information – Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003. 3. Thyroid Cancer Detailed Guide. American Cancer Society Web site. Available at: http://documents.cancer.org/196.00/196.00.pdf. Accessed December 10, 2003.

Evaluation of any thyroid Nodule (Physical Exam) Examination of the thyroid nodule: consistency - hard vs. soft size – more than 4.0 cm Multinodular vs. solitary nodule multi nodular : 3% chance of malignancy solitary nodule : 5%-12% chance of malignancy

Physical Exam (continued…) Examine for ectopic thyroid tissue Indirect or fiberoptic laryngoscopy vocal cord mobility evaluate airway

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

Ultrasonography (Continued…) Disadvantages Cannot accurately distinguish benign from malignant nodules