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Thyroid Canada Newsletter
- Issue 5
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JANUARY 2002 SURGICAL TREATMENT OF THYROID CANCER Irving B. Rosen, MD, FRCS (C), FACS
PRESENTATION (1) Thyroid cancer generally presents as an asymptomatic thyroid nodule discovered by patient or physician which may conform to the stereotypical description of cancer, - namely hard and fixed, - but that is not necessarily or even usually so. Micronodular (<1 cm.) cancer may be found incidentally following thyroidectomy or may be found inadvertently by ultrasound. Cervical nodes in the presence of a thyroid nodule suggests malignancy. Metastatic cervical lymphadenopathy may be the first sign of microcancer. Infrequently, patients may present with visceral metastases in lung and bone where the primary lesion may not be clinically appreciated, but this is highly unusual.
PATHOLOGY (2) Papillary and follicular carcinoma make up about 85% of thyroid cancer with papillary types being most common (about 80%). They have a characteristic microscopic appearance, but the follicular variant of papillary carcinoma demands the need for cytological examination since the characteristic histological pattern may be absent while the cellular changes associated with cancer are present. Well-differentiated cancer may infrequently show more aggressive forms such as tall cell, insular, trabecular or columnar cell variations. Medullary cancer makes up 5% of malignancies and has a variable but characteristic appearance and is distinguished on histology by its amyloid content. It may be familial or multinodular and associated with other endocrine neoplasia. Lymphoma occurs in 1-5% of malignancies and is usually a non-Hodgkin's B-cell phenotype associated on occasion with intestinal lymphoma. Anaplastic cancer occurs in 5-10% of malignancies and represents a highly undifferentiated tumor that often comes from neglected papillary cancer. Hurthle cell cancer has reputedly a poor outlook. It is viewed as a form of papillary or follicular cancer, but its natural history presents special concern since there have been reports associating this cancer type with aggressive behaviour.
DIAGNOSIS The diagnosis of malignancy is made by fine needle biopsy (FNAB) which has a 2% false positive rate but a 30% false negative rate and should be utilized in the sequential conservative management of thyroid nodules. It is done as an office procedure using local anesthetic and is important in the preoperative assessment of patients. Cytology reported as "cellular atypia" and "follicular" may show a 30% cancer rate and therefore also require surgical treatment. Frequency of cancer is low (<5%) in "benign" cytology and may be accountable by geographic misses or the multivaried state of thyroid cancer. Ultrasonography is useful for the detection of multinodular disease, response of nodules to thyroid suppression, delineation of cyst from solid lesion, but is limited as a screening method although frequently used for diagnosis by physicians. Thyroid scintiscanning using technetium 99M can provide functional activity of the gland and can map out the nature of nodular disease. "Cold" nodules do have a greater tendency towards being neoplastic than do "hot", but a scan is not specific. Computerized tomography or MRI is unnecessary as a rule. Where nodular disease is extensive and large, these procedures are used to delineate tracheal compression which is of particular interest to the attending anesthetist. Thyroid function testing in no way detects thyroid carcinoma but is an essential before contemplating any surgery to exclude correctable thyroid dysfunction. Other clinical factors suggestive of malignancy include exposure to radiation where lesions may show 30% to 60% malignant change. Familial papillary cancer is infrequent, but where present is a factor in patient selection. Familial syndromes to be considered include familial polyposis colon (Gardner's syndrome), Cowden's disease, Pendred's disease. Other factors that deserve attention include longstanding nodularity undergoing growth, parity, ethnicity, pediatric age group, and postoperative recurrent nodularity. Cystic lesions that recur or do not fully respond to aspiration require surgery to exclude a 30% underlying cancer rate. (3)
RISK ANALYSIS Determination of prognostic factors that influence outcome with the possibilty of influencing treatment are extensive. The Mayo Clinic group has had priority in the development of AGES (age, tumor grade, extent, and size), and MACIS (metastasis, age, completeness of surgery, invasion of extrathyroidal tissue, and size). Multivariant analysis have indicated that age, histological type and tumor extent have independent prognostic importance. Hay has demonstrated that a bilateral procedure offers the patient the best chance of avoiding recurrence, and in certain situations, lethality. These schema provide a guide for retrospective analysis rather than individual patient management. (4)
MOLECULAR BIOLOGY Remarkable progress has been made in the delineation of genetic factors described elsewhere in this series. There is no standard molecular genetic test that is of any assistance in patient management with the exception of medullary carcinoma. While of great interest, results of molecular biology lack relevance for clinical control. (5)
PRIMARY TREATMENT Surgical excision is the basic method of management. There has been an ongoing conflict regarding the extent of surgery, namely total or near-total as compared to a partial for the lateralized lesion. "Totalists" support their approach by citing the ability to use RAI adjuvant therapy, monitor recurrence, improved survival, avoidance of recurrence, and frequency of multinodularity. "Partialists" describe a decreased morbidity as far as parathyroid and recurrent nerve dysfunction is concerned with a similar frequency of cure. The current trend favours total to near-total thyroidectomy. Surgeons educated or seriously interested in thyroid cancer surgery will provide optimal results. Operative demonstration of the recurrent nerve is essential. Inferior parathyroid glands may elude conservation, requiring free transplantation to enhance eucalcemia which is supported by the current widespread use of prophylactic calcium intake for osteoporosis. Invasion of overlying strap muscle requires en bloc resection. Total resection of cancer is of paramount importance as is the preservation of recurrent nerve and at least one intact parathyroid gland. Node sampling of the central and mediastinal nodes and jugular nodes is helpful in prognostic implications and perhaps in prevention of gross clinical disease. In clinical metastatic nodal disease seen in about 15% of patients, modified neck dissection preserving spinal accessory nerve, carotid sheath, and the sternocleidomastoid muscle is carried out in preference to "node picking". Patients are considered postoperatively for ablative radioactive iodine therapy (RAI) which is only feasible after a total or near-total procedure. Thyrogen (recombinant TSH) may be utilized where TSH elevation is unsatisfactory to enhance RAI uptake. External radiation may be indicated for residual disease, recurrence extrathyroidal invasion or unusual pathology. The patient's postoperative course as a rule is quiescent. After one night in hospital, the patient is discharged on Cytomel and appropriate calcium support. Followup examination every three to four months in the first year is carried out and reduced to every six months after the first year with annual chest x-ray and cervical ultrasonography. Thyroglobulin is a marker for recurrent disease (6, 7, 8), and an undetectable serum thyroglobulin generally reflects a good prognosis.
SPECIAL CASE CONSIDERATION: A. WELL-DIFFERENTIATED CARCINOMA
B. POORLY-DIFFERENTIATED CANCER a) Anaplastic carcinoma arises 50% of the time from pre-existing thyroid nodularity. It may present with a bulky progressive lesion causing dysphonia and dysphagia. It is highly aggressive and efforts should be made to exclude systemic metastases which would support palliation only. Currently an attempt at complete resection and radiation +/- chemotherapy is indicated for a disease that has a five year survival rate of about 5% and usually has a six month survival. (13) b) Lymphoma of the thyroid is infrequent, about 1-5% of malignancy, and arises from cases of Hashimoto's thyroiditis which should be considered for surgery where needle biopsies are suspect, the lesion progresses in size, or produces obstructive symptoms. Surgery in lymphoma is primarily for diagnosis and may be carried out under local anesthesia. Management is by external radiation and chemotherapy using Adriamycin with a five year survival of about 50% depending on stage of disease. (14) c) Medullary carcinoma of the thyroid occurs in 5% of thyroid malignancy and may be random, or familial giving rise to MEA-2 syndrome. Treatment usually consists of near-total thyroidectomy because of the multicentricity, and node sampling, and exclusion of systemic spread. For clinically positive nodes, neck dissection is done. It is important to obtain genetic testing in patient and relatives to detect ret gene mutation that give rise to hereditary forms of MTC. This permits treatment for affected individuals, - even children, - before the emergence of disease (15) which has only a 50% five year survival. d) Secondary cancer (to thyroid): Patients dying of systemic cancer demonstrate in 30% of cases metastatic cancer to thyroid. It is infrequent that a patient will present clinically with metastatic cancer to the thyroid. Most originate from kidney or breast cancer but any site is possible. Operative management is in order depending on the state of the original primary. (16)
CONCLUSION While thyroid cancer is still uncommon, it is increasing in frequency more rapidly than any other malignancy. (17) Its common well-differentiated form has an excellent outlook. Fine needle biopsy is the most important diagnostic test that permits proper selection. Surgery by near-total thyroidectomy, node sampling and RAI ablation is preferred. In over 1000 cases of TCA, the author has recorded a cure rate of 97%, CA mortality of <3%, recurrence of 3%, O.R. morbidity of <1%. Thyroid cancer provides a wonderful opportunity to effect significant surgery with minor morbidity, maximal cure and optimal gratification.
******* BIBLIOGRAPHY
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EDITORIAL COMMENT: At the present time, the management of thyroid carcinoma usually consists of a near-total thyroidectomy followed where appropriate by radioactive iodine ablation and subsequent thyroxine therapy. Fortunately, as Dr. Rosen has stated in the vast majority of patients with papillary carcinoma of the thyroid, the outlook is very good and recurrences are uncommon. There is little that is new regarding the management, but there will be an increased use of recombinant human TSH in the pre-operative investigation of patients with thyroid carcinoma and we will look forward to the ultimate place for this agent in the overall management of such patients. Dr. Rosen has amply summarized the current status of surgical management for thyroid carcinoma. What is currently unclear is the cause of the apparent increase in the prevalence of thyroid carcinoma, which has been observed in recent years. Certainly, radiation is a well-known cause but does not seem to account for this increase. Improved means of pathological diagnosis may be an added factor. Despite the excellent prognosis in most cases, follow-up must be long-term, particularly with respect to serum thyroglobulin measurements (an undetectable serum thyroglobulin usually reflects an excellent prognosis). Another important element of follow-up management is that of TSH suppression by the thyroxine therapy; suppression slightly below the normal range appears to be sufficient, and thus complete suppression seems to be unnecessary. Robert Volpé, MD, FRCP (C) , MACP ******* IN CASE YOU MISSED IT”SOURCES OF INFORMATION FOR THYROID CANCER PATIENTS Cancer Connection, Canadian Cancer Society Thyroid Foundation of Canada Thyroid CancerSurvivor’s Association,
Inc. The Head & Neck Cancer Foundation
The Light of Life Foundation *******
If you would like to see an upcoming thyroid event published in the next issue of Thyroid Canada, please fax the information to Theramed Corporation at (905) 564-4776 as soon as possible. Published with a grant from Theramed Corporation.
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