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6.15 Thyroid Malignancies

Updated: 15 September 2004

Any disease of the thyroid gland can manifest as an apparent solitary nodule and as such become a clinical problem for the physician. While carcinomas of the thyroid are uncommon and account for only 1% of all malignancies, an adequate initial pathological diagnosis is essential for the successful eradication of the disease.

Although surgery is the basic treatment for cancer of the thyroid, the initial assessment, treatment planning and subsequent follow-up requires the active involvement of pathologists, internists and oncologists.

Prognostic Factors

The size of the primary tumour and the lymph node involvement (staging) are important prognostic factors but less significant than the age at diagnosis, sex, pathological differentiation of the tumour, and the completeness of the surgical excision. Most cancers are derived from the epithelial cells of the thyroid follicles and are well-differentiated papillary, follicular or mixed adenocarcinomas (75%). Cancer of the thyroid in the young (under 40 years of age) is usually well-differentiated and the overall prognosis is excellent. On the other hand, anaplastic carcinomas (l5%), particularly in older patients, have a significantly poorer prognosis and are rarely cured.

The pathological assessment of the thyroid tumours is of paramount importance as it will not only give the degree of differentiation of the tumour but will assess multicentricity, the extent and site of nodal involvement and the completeness of the surgical resection.

1. Surgery

Appropriate thyroidectomy and surgical removal of lymph nodes containing metastatic cancer remains the basic treatment for patients with thyroid malignancy. The surgeon undertaking surgical treatment in such patients should be prepared to perform total or near total thyroidectomy when indicated and be competent to deal appropriately with lymph node involvement. The first surgical procedure is unquestionably the key to cure and when incomplete removal necessitates further procedures, the morbidity increases significantly.

In the majority of patients, the diagnosis of malignancy should have been made or been strongly suspected prior to the surgical procedure. The methods of diagnosis have been outlined. Open biopsy for diagnosis is rarely indicated. It is probably to the patient's benefit if the surgeon has immediate rush diagnosis by a pathologist available at the time of thyroid surgery but it is not essential.

Types of Thyroidectomy

The minimal procedure for a solitary lesion confined to one lobe is a total lobectomy which includes the isthmus and anterior aspect of the contralateral lobe. This necessitates early identification of the recurrent laryngeal nerve with careful preservation. The superior pole vessels should be ligated well above the upper pole margin to ensure complete removal of thyroid tissue. If significant removal of the contralateral lobe will also be necessary, the parathyroid glands should be identified and protected. Careful evaluation by palpation of the thyroid is mandatory. Careful search for lymph nodes in the area must be made and all obvious nodes removed, (see paragraph on lymph nodes). In most cases more extensive thyroidectomy is needed. The type of thyroidectomy will depend upon the histological type of the malignancy, the size of the primary, and lymph node involvement. If strap muscles are adherent to the thyroid gland, they should be widely removed and left attached to the tumour. If the surgeon, on dissecting the malignant thyroid gland from the trachea, suspects there may be further tumour which is non-removable, a biopsy of the paratracheal tissue beyond the resection line should be taken and appropriately labeled. This can assist any decision for adjuvant therapy.

Conventional Radical Neck Dissection

Patients are still seen with metastatic lymph node involvement invading the jugular vein, sternomastoid muscle, etc. These patients require a classical radical neck dissection with the sacrifice of muscle and vein. Morbidity, however, is low. If the surgeon encounters areas where he suspects incomplete removal deeply, appropriate marking of the area will assist the radiation oncologist in postoperative therapy. Patients with lymph node involvement in medullary carcinoma should have a radical neck dissection.

Well Differentiated Papillary and Mixed Papillary-folllicular Carcinoma

In patients with a solitary nodule, confined to one lobe and with no lymph node metastases evident, surgical treatment as described above will be sufficient. If there is evidence of multifocal disease, even in one lobe, a near total thyroid lobectomy should be performed on the contralateral side, leaving only a small rim of tissue posteriorly for added protection of the parathyroids. If at the time of diagnosis there is clinical and pathological involvement of lymph nodes, even from an apparent solitary nodule in one lobe, the more extended surgery with near total thyroidectomy is indicated. This will facilitate and reduce the morbidity of subsequent radioactive iodine therapy which is indicated in this situation. Both recurrent laryngeal nerves must be carefully dissected and every effort made to preserve some parathyroid tissue.

Pure Follicular Carcinoma

As these lesions are the most likely to benefit from radioactive iodine treatment of metastases, a near total thyroidectomy is indicated in all patients with planned radioactive iodine ablation of any residual thyroid tissue post-operatively. The patient with a well-differentiated lesion in which the pathologist has difficulty in differentiating between benign and malignant, can be treated by total lobectomy alone.

Poorly Differentiated Carcinoma

These frequently occur in older patients. If, on clinical assessment, the surgeon believes that thyroidectomy is possible, exploration should be carried out and thyroidectomy performed, but in the majority of patients resection is not possible. There is an occasional patient with papillary carcinoma and associated thyroiditis which masquerades as a poorly differentiated carcinoma. When possible, these patients should be identified and appropriate surgery performed.

Medullary Carcinoma

Total or near total thyroidectomy is the operation recommended for such patients.

Carcinoma Developing in Multinodular Goiter

The surgeon must remember that patients with large multinodular goiters may develop malignancy as well. Usually, palpation at the time of surgery will lead the surgeon to suspect a malignancy in certain areas of the goiter. Rush diagnosis can confirm this. A near total thyroidectomy is indicated.

Cervical Lymph Node Metastases in Thyroid Cancer

A significant number of patients with thyroid cancer present with metastatic lymph nodes in the neck and no palpable thyroid lesion. These patients have a so-called occult cancer. In many patients, preoperative ultrasound can confirm the presence of the primary lesion. All such patients require a near total thyroidectomy and appropriate node dissection.

Whenever patients have a thyroidectomy for malignancy, the surgeon should carefully search for potentially involved lymph nodes in the perithyroid area, even when no nodes have been clinically detected preoperatively. In such cases the most common sites for lymph node involvement are along the recurrent nerves and in the paratracheal space below the isthmus. It is worthwhile exploring the lower jugular area as well. All obvious nodes and especially enlarged ones should be removed and appropriately labeled as to site.

Lymph Node Involvement Other Than Perithyroid

The jugular lymph nodes are the next most likely site of lymph node involvement in the neck, followed by involvement of supraclavicular and posterior triangle nodes. The submandibular triangle is not frequently involved but if there is upper jugular involvement, submandibular triangle involvement is quite possible. Clinical evaluation of lymph nodes in the neck containing metastatic thyroid cancer is not accurate and the experienced surgeon is often amazed at the degree of involvement found at the time of node dissections. The type of node dissection will depend on the site involved and the character of the nodal involvement.

Picking Procedure

This localized removal of involved lymph nodes is justified if only perithyroid and lower jugular nodes are involved. It is not commonly indicated.

Functional and Radical Lymph Node Dissection

If nodal involvement clinically extends to the midjugular level, a more complete lymph node dissection of the neck is indicated. In patients who have mobile nodes not adherent to or involving the jugular vein, and not invading adjacent muscle, a functional type of neck dissection is indicated. In this, the sternomastoid muscle is skeletonized but preserved and the jugular vein and accessory nerve left intact. With experience, extensive removal of lymph nodes is possible. In patients who have lymph node metastases at the time of initial diagnosis, the lymph node dissection should be done in association and in continuity with the thyroidectomy. Some patients, of course, develop their lymph node metastases at varying times following initial surgical treatment of the primary.​

2. Radioactive Iodine

Radioactive iodine is recommended in the post-surgical treatment of well-differentiated thyroid carcinomas in the following circumstances:

  1. To ablate the remaining normal thyroid gland after sub-total thyroidectomy.
  2. To treat patients with metastatic or recurrent cancer which take up 131 I.
  3. To scan for and determine radioiodine uptake characteristics of metastases.

The indication for radioactive iodine ablation after subtotal thyroidectomy is related to the fact that the potential for recurrent disease is increased if: 1) the initial mass is greater than 2.5 cm; 2) the disease is multifocal; 3) the tumour is follicular; 4) the tumour has penetrated the thyroid capsule; 5) there is metastatic node disease; 6) the patient is older than 40 years of age.

Patients having any of these high-risk parameters should be recommended to have have radioactive iodine ablation. The recommended dose of radioactive iodine should be enough to reduce the uptake to 1%. This can be usually accomplished with 50 millicuries which could be repeated if required.

Another indication for radioactive iodine is to treat metastatic, well-differentiated carcinoma of the thyroid. In these patients, radioactive iodine initially is prescribed to destroy the normal thyroid tissue. This will induce hypothyroidism. It is hoped that a high TSH will promote uptake in the tumour tissue and allow use of the radioactive iodine as therapy. When metastatic disease is present, larger doses of radioactive iodine are employed (100 to 200 millicuries). After the initial dose a body scan is done to determine if the metastatic tumour concentrates the 131 I. Thyroid replacement therapy is prescribed for three months and a repeat body scan is done using 5 millicuries 131Iodine with uptake measurements at 48 and 72 hours. If there is uptake in the tumour, a further l50 millicuries is given. If uptake does occur then the dose is repeated every three to four months until there is no further uptake in the tumour. Thyroid therapy is prescribed after each therapy dose of radioactive iodine.

When T4 is to be discontinued for scanning, T3 (liothyronine 50 mcg per day) should be prescribed for one month. It will then be discontinued for two weeks prior to the scan to achieve high endogenous TSH levels.

Recombinant TSH (Thyrogen) is an effective, though costly, alternative to thyroxine withdrawal for iodine scanning. It can be funded for appropriate patients via an Undesignated Drug Application to the Sytemic Therapy Program.

3. Hormonal Treatment

Treatment with thyroxine is an important part of the management of patients with thyroid carcinomas. The aim of such treatment is to suppress TSH stimulation of the thyroid. This can be achieved by maintaining the serum T4 at the upper limit of normal. The starting dose of thyroxine is 1 mcg/lb/day. The level will equilibrate in one month and then the T4 and TSH can be checked. The dosage can then be altered to achieve the desired level.

4. External Irradiation

While surgical resection is the main treatment for cancer of the thyroid gland, external irradiation has a definite role as an adjuvant to surgery or as treatment in the following circumstances:

  1. As an adjuvant treatment following surgery and radioactive iodine ablation when the surgical resection has been incomplete and residual microscopic or macroscopic disease is left behind which does not take up the radioisotope.
  2. As a palliative treatment for inoperable unresected tumours or anaplastic carcinomas.
  3. As a palliative treatment of symptomatic metastases.

5. Chemotherapy

Metastatic thyroid carcinoma may be an indolent disease, especially if the primary tumour was well differentiated. Treatment is palliative and cytotoxic chemotherapy should be reserved for patients whose symptomatic disease cannot be controlled by localized irradiation. Anaplastic thyroid carcinoma is often locally or systemically aggressive and may require chemotherapy early to manage disease which cannot be managed with irradiation because of local recurrence or extensive metastases. Medullary carcinoma, when metastatic, may pursue either an indolent or aggressive course.

When cytotoxic chemotherapy is used for thyroid carcinoma, the intent is palliative and potential benefits must be weighed against known toxicity. Combinations containing doxorubicin and cisplatin are the most active with 30-60% response rate. A reasonable starting regimen of doxorubicin 50-60 mg per m² and cisplatin 40-50 mg per m² intravenously every 3-4 weeks may be tried then adjusted appropriately based on patient tolerance and tumour response. Second line chemotherapy is of no proven value.

SOURCE: 6.15 Thyroid Malignancies ( )
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