THYROID CANCER

Thyroid Cancer Type and Incidence Papillary ~ 60-75% Follicular ~20-30% Medullary ~ 5-10% Anaplastic ~ 3%

Thyroid cancer is the most common malignancy of the endocrine glands. KEY POINTS Thyroid cancer is the most common malignancy of the endocrine glands. The great majority of cancers of the follicular thyroid epithelium are well-differentiated (papillary and follicular) and have a good prognosis, particularly in young patients.

Thyroid Ca is one of the most curable cancers. KEY POINTS Thyroid Ca is one of the most curable cancers. The incidence of thyroid Ca in thyroid nodules ranges from 0.5% to 10%.

gene rearrangements RET/PTC (papillary Ca) ETIOPATHOGENESIS ONCOGENES: gene rearrangements RET/PTC (papillary Ca) mutations of the ras gene family (an early event in thyroid tumorigenesis) inactivating mutations of the p53 tumor-suppressor gene (undiffereniated thyroid Ca)

ETIOPATHOGENESIS External irradiation of the neck (the latency period is at least 5 years) Iodine deficiency (Follicular Ca)

PAPILLARY CANCER The Most Common Thyroid Cancer Peak onset ages 30 through 50 Females more common than males by 3 to 1 ratio Prognosis directly related to tumor size [less than 1.0 cm - good prognosis] Accounts for 85% of thyroid cancers due to radiation exposure

PAPILLARY CANCER Spread to lymph nodes of the neck present in more than 50% of cases Distant spread (to lungs or bones) is very uncommon Overall cure rate very high (near 100% for small lesions in young patients)

MANAGEMENT OF PAPILLARY THYROID CANCER Papillary carcinomas that are well circumscribed, isolated, and less than 1cm in a young patient (20-40) without a history of radiation exposure may be treated with hemithyroidectomy and isthmusthectomy.

MANAGEMENT OF PAPILLARY THYROID CANCER All others should be treated with total thyroidectomy and removal of any enlarged lymph nodes in the central or lateral neck areas.

MANAGEMENT OF PAPILLARY THYROID CANCER AFTER SURGERY Since papillary cancer may respond to TSH, thyroid hormone is given in doses large enough to suppress secretion of TSH and help prevent a recurrence.

MANAGEMENT OF PAPILLARY THYROID CANCER AFTER SURGERY Serum FT3 i FT4 should be in the normal range to avoid iatrogenic thyrotoxicosis Serum Tg, a marker of cell function, increases dramatically during hypothyroidism, while it returns to low levels during hormone therapy

MANAGEMENT OF PAPILLARY THYROID CANCER AFTER SURGERY Papillary cancer cells absorb iodine and therefore they can be targeted for death by giving the toxic isotope (I-131).

MANAGEMENT OF PAPILLARY THYROID CANCER AFTER SURGERY In patients with larger tumors, spread to lymph nodes or other areas, tumors which appear aggressive microscopically, radioactive iodine is often given in expectation that any remaining thyroid tissue or cancer that has spread away from the thyroid will take it up and be destroyed.

PAPILLARY THYROID CANCER LONG-TERM FOLLOW UP A yearly chest X-ray Thyroglobulin levels a high serum thyroglobulin level that had previously been low following total thyroidectomy especially if gradually increased with TSH stimulation is virtually indicative of recurrence. A value of greater than 10 ng/ml is often associated with recurrence even if an iodine scan is negative.

FOLLICULAR CANCER THE SECOND MOST COMMON THYROID CANCER Peak onset ages 40 through 60 Females more common than males by 3 to 1 ratio Prognosis directly related to tumor size [less than 1.0 cm - good prognosis] Rarely associated with radiation exposure Spread to lymph nodes is uncommon (~10%)

FOLLICULAR CANCER Invasion into vascular structures (veins and arteries) within the thyroid gland is common. Distant spread (to lungs or bones) is uncommon, but more common than with papillary cancer. Overall cure rate high (near 95% for small lesions in young patients), decreases with advanced age.

FOLLICULAR THYROID CANCER Many cases of follicular thyroid cancer are subclinical. Most common presentation of thyroid cancer is an asymptomatic thyroid mass, or a nodule, that can be felt in the neck. Some patients have persistent cough, difficulty breathing, or difficulty swallowing. Pain seldom is an early warning sign of thyroid cancer.

FOLLICULAR THYROID CANCER Other symptoms (rare): pain, stridor, vocal cord paralysis, hemoptysis, rapid enlargement. These symptoms can be caused by less serious problems.

FOLLICULAR THYROID CANCER At diagnosis, 10-15% of patients have distant metastases to bone and lung and initially are evaluated for pulmonary or osteoarticular symptoms (eg, pathologic fracture, spontaneous fracture).

MANAGEMENT OF FOLLICULAR THYROID CANCER Follicular carcinoma should always be treated with total thyreoidectomy. A completion thyreoidectomy should always be performed in patients who have undergone a lobectomy for a presumed benign tumor that proved to be follicular carcinoma at definitive histology.

MANAGEMENT OF FOLLICULAR THYROID CANCER AFTER SURGERY Perform postoperative scintiscan of the neck after 4-6 weeks.  If thyroid tissue is present, a dose of radioactive iodine is administrated to destroy residual tissue.

MANAGEMENT OF FOLLICULAR THYROID CANCER AFTER SURGERY Repeat scintiscan 6-12 months after ablation and, thereafter, every 2 years. Radioactive iodine may ablate the metastatic tissue in the lungs and bone.

MANAGEMENT OF FOLLICULAR THYROID CANCER AFTER SURGERY Perform thyroid hormone suppression in all patients with total thyroidectomies and in all patients who have had radioactive ablation of any remaining thyroid tissue.

MANAGEMENT OF FOLLICULAR THYROID CANCER AFTER SURGERY A patient who has had a thyroidectomy without parathyroid preservation will require vitamin D and calcium for the rest of their life. Evaluate thyroglobulin serum levels every 6-12 months for at least 5 years.

FOLLICULAR ADENOMA It is benign neoplasm. No differentiation is possible between adenoma and carcinoma by cytology or in most cases even by frozen section. Capsular and vascular invasion are key features that distinguish between benign and malignant follicular proliferation.

HÜRTHLE CELL CARCINOMA WHO 1988: oxyphilic variant of follicular carcinoma. It may be also Hürthle cell variant of papillary thyroid Ca. Some authors classify it separately as Hürthle cell carcinomas.

HÜRTHLE CELL CARCINOMA Although preferentially classified among follicular tumors, Hüthle cell carcinomas are usually more aggresive and metastasizing, and they are less prone to take up radioiodine and produce thyroglobulin than well-differentiated thyroid carcinomas.

ANAPLASTIC CANCER Peak onset age 65 and older. Very rare in young patients. Males more common than females by 2 to 1 ratio. Can occur many years after radiation exposure. Typically presents as rapidly growing neck mass.

Spread to lymph nodes of the neck present in more than 90% of cases. ANAPLASTIC CANCER Spread to lymph nodes of the neck present in more than 90% of cases. Distant spread (to lungs or bones) is very common even when first diagnosed. Overall 5-year survival rate is reportedly less than 10%, and most patients do not live longer than a few months after diagnosis.

ANAPLASTIC CANCER SYMPTOMS A rapidly growing neck mass Dysphagia Cough Neck pain Dyspnea Patients with metastases also may note bone pain, weakness, and cough Neurologic deficits may be observed with brain metastases.

ANAPLASTIC CANCER SURGICAL CARE Perform surgery in conjunction with radiation and chemotherapy. Use surgery to obtain a definitive diagnosis when fine needle aspiration is unsuccessful.

ANAPLASTIC CANCER Despite the typically large size of these tumors, extent of resection is limited when diagnosis is made.

ANAPLASTIC CANCER Rather than performing complete thyroidectomy, resect as much thyroid tissue as possible without attempting resection of all adjacent structures because of the high incidence of postoperative morbidity (eg, vocal cord paralysis, esophageal fistula).

ANAPLASTIC CANCER FURTHER INPATIENT CARE Radiotherapy: Despite the fact that ATC is largely radioresistant, use external beam radiotherapy for local control.

Doxorubicin and cisplatin are the two most common agents used. ANAPLASTIC CANCER Chemotherapy: Currently, no available chemotherapeutic agent or combination of chemotherapeutic agents shows sufficient antineoplastic activity to prevent death; yet in rare instances, chemotherapy may prolong life by a few weeks or perhaps months. Doxorubicin and cisplatin are the two most common agents used.

MEDULLARY THYROID CANCER A distinct thyroid carcinoma that originates in the parafollicular C cells of the thyroid gland. These C cells produce calcitonin. Females more common than males (except for inherited cancers).

MEDULLARY THYROID CANCER Regional metastases (spread to neck lymph nodes) occurs early in the course of the disease. Spread to distant organs (metastasis) occurs late and can be to the liver, bone, brain, and adrenal medulla.

MEDULLARY THYROID CANCER Not associated with radiation exposure. Usually originates in the upper central lobe of the thyroid.

MEDULLARY THYROID CANCER Poor prognostic factors include age >50, male, distant spread (metastases), and MEN II-B. Residual disease (following surgery) or recurrence can be detected by measuring calcitonin.

MEDULLARY THYROID CANCER FOUR CLINICAL SETTINGS SPORADIC Accounts for 80% of all cases of medullary thyroid cancer MEN II-A (SIPPLE SYNDROME) bilateral medullary carcinoma or C cell hyperplasia, pheochromocytoma hyperparathyroidism

MEDULLARY THYROID CANCER FOUR CLINICAL SETTINGS MEN II-B medullary carcinoma pheochromocytoma an unusual appearance which is characterized by mucosal ganglioneuromas (tumors in the mouth) and a Marfanoid habitus. hyperparathyroidism (uncommon) INHERITED MEDULLARY CARCINOMA WITHOUT ASSOCIATED ENDOCRINOPATHIES.

Endocrine diseases occuring together in different endocrine glands are due to multiple, mostly hereditary benign and malignant neoplasms or hyperplasia with excessive function (MEN=MEA), or develop in response to an autoimmune reaction affecting different endocrine and perhaps other glands (autoimmune polyglandular syndromes =APS)

AUTOIMMUNE POLYGLANDULAR SYNDROMES TYPE 1 = Blizzard’s syndrome Major components: Chronic mucocutaneous candidiasis Hypoparathyroidism Addison’s disease + other endocrinopathies and features TYPE 2 = Schmidt’s syndrome Major components: Autoimmune thyroid disease Type 1 diabetes melltus Addison’s disease Premature ovarian failure + other endocrinopathies and features

MEDULLARY THYROID CANCER SYMPTOMS a lump at the base of the neck, especially during swallowing; hoarseness, dysphagia, and respiratory difficulty;

MEDULLARY THYROID CANCER SYMPTOMS various paraneoplastic syndromes, including Cushing or carcinoid syndrome (uncommon). Diarrhea secondary to high plasma calcitonin levels. Distant metastases.

MEDULLARY THYROID CANCER WORKUP Serum calcitonin levels. Pentagastrin-stimulated calcitonin levels. DNA testing for RET (it may replace the diagnostic method mentioned above). 24-hour urinalysis for catecholamine metabolites.

MEDULLARY THYROID CANCER WORKUP Screening for the development of familial MCT in family members of patients with history of MCT or MEN 2A or 2B. Screen all family members for missense mutation in RET in leukocytes.

MEDULLARY THYROID CANCER WORKUP A cervical ultrasound (to detect LN metastases). CT scan, MRI, and bone scans. Fine needle aspiration.

MEDULLARY THYROID CANCER MANAGEMENT All patients should receive total thyroidectomy, a complete central neck dissection (removal of all lymph nodes and fatty tissues in the central area of the neck), and removal of all lymph nodes and surrounding fatty tissues within the side of the neck which harbored the tumor. Radioactive iodine therapy is not useful.

MEDULLARY THYROID CANCER MANAGEMENT Long-Term Follow A yearly chest x-ray as well as calcitonin levels.