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Considerations in the Management of Thyroid Malignancy
Symposium on Surgical Techniques
Considerations in the Management of Thyroid Malignancy
Cornelius E. Sedgwick, M.D .
The natural history of thyroid malignancy varies from a slowly growing tumor that may remain localized in the neck for many years to a rapidly growing tumor that may cause death a few months after it is discovered. In many instances it is difficult to assess the effective treatment or the final outcome, and thus thyroid malignancy presents a difficult problem to the physician and surgeon selecting a plan of management. Thyroid malignancy comprises only 1 per cent of all malignancies of the human being, and few physicians or clinics have a sufficient number of patients treated by a definite mode of therapy and followed long enough to draw definite conclusions as to the efficacy of treatment. In other tumors, 5 year and 10 year survival rates are significant. In thyroid malignancy, 20 to 30 year follow-up studies are necessary. Further difficulty in evaluating survival rates is the lack of any universally accepted histologic and clinical classification of thyroid tumors. One cannot compare the survival rate of a low-grade papillary carcinoma confined to a lobe with a higher grade of malignant follicular tumor with cervical gland metastases or the most highly malignant undifferentiated tumor. Furthermore, tumors of the thyroid may transform from a low to a high potential malignancy probably secondary to the influence of the thyroid-stimulating hormone CTSH) of the pituitary. What may be a papillary adenocarcinoma may become a follicular adenocarcinoma or even an undifferentiated malignancy after the removal of the initial primary tumor. For these reasons and from our experience, the best we can do is to propose a plan of management that at the moment seems most reasonable. Our plan of management depends upon the pathologic classification or degree of malignancy, the clinical stage or degree of invasion, the age and sex of the patient, and finally the location of the primary tumor within the gland. The pathologic classification (Table 1) grades the tumor according to its degree of malignancy. Papillary adenocarcinoma is the least malignant, follicular adenocarcinoma somewhat more malignant, medullary carcinoma even more malignant, and undifferentiated tumors Surgical Clinics of North America - Vol. 53, No.2, April 1973
307
308
CORNELIUS
E.
SEDGWICK
Table 1. Pathologic Classification of Thyroid Malignancies Predominantly papillary adenocarcinoma (Adenoma with capsular or blood vessel invasion) Predominantly follicular carcinoma (Adenoma with capsular or blood vessel invasion) Medullary carcinoma Undifferentiated carcinoma Small cell carcinoma Giant cell carcinoma
the most malignant. A subdivision of both the papillary and follicular adenocarcinomas is the exceedingly low-grade adenoma with minimal capsular, lymphatic, or blood vessel invasion. The clinical classification (Table 2) is based on the degree of invasion both at the time of clinical evaluation and as observed at the time of operation. The tumor confined to the gland itself is the least invasive, to the cervical lymphatics and adjacent structures more invasive, and those tumors which have spread beyond the confines of the neck are most invasive. Carcinoma of the thyroid appears to have a different growth potential in adults, particularly men, as compared with children. Differentiated tumors, although extensive, tend to remain stationary for a longer period of time, and the instances of transformation into higher degrees of malignancy occur less often in children. These features of the biologic behavior of thyroid tumors must be considered in choosing the appropriate therapy. The location of the primary tumor will influence the extent of surgery in some instances. If one is dealing with a primary tumor located in the inferior pole of the low-lying gland and a classical radical neck dissection is considered, one must realize that the chances of pretracheal lymphatic drainage subsequently invading the lymphatics of the mediastinum may be involved. If radical surgery is contemplated a mediastinal dissection is as important as the radical neck dissection. If the primary lesion is invading the posterior capsule with involvement of the retropharyngeallymphatics, radical surgery must be abandoned, as radical neck dissection will not accomplish the removal of all tumor. In the management of thyroid malignancy we have at our disposal several modalities of therapy that may be used alone or in combination: surgery, radioactive iodine (131 I), supervoltage radiation, and suppression of TSH with thyroid extract.
SURGERY Other than the excision of a cervical gland for a pathologic diagnosis, the initial operation usually involves removing a solitary nodule or suspected lesion from the thyroid gland. There is controversy relative to
309
THYROID MALIGNANCY
Table 2. Stage Stage Stage Stage
Clinical Staging of Thyroid Malignancies 1- Confined to thyroid gland 2-Cervicallymph node metastases 3 - Invasion of other structures in the neck 4-Distant metastases
whether one should initially excise the nodule or perform a subtotal lobectomy or a near total lobectomy. If a competent pathologist is available to obtain a frozen section, it makes little difference. Further surgery may easily be performed if indicated. However, if one must proceed without the help of the pathologist, a radical subtotal or near total thyroidectomy is the better procedure. If later permanent section reveals a benign tumor, then nothing is lost. If the tumor is a low-grade differentiated tumor confined to the gland, adequate surgery will have been performed, and nothing further is indicated. If the final pathologic classification reveals the tumor to be of a higher degree of malignancy than suspected and further surgery is indicated such as the removal of the isthmus and opposite lobe or even a radical neck dissection, Jhe secondary procedure may be somewhat easier if all or most of the gland on the side of the primary lesion has been removed and the recurrent nerve spared. In my experience, however, it has made little difference in technique whether more surgery is performed after either excision of the primary lesion or lobectomy. If the tumor proves to be a low-grade papillary adenoma, that is, an adenoma with minimal capsular, lymphatic, or blood vessel invasion, a radical subtotal or near total lobectomy will suffice. If the histologic examination reveals the tumor to be of a higher degree of differentiated malignancy, that is, papillary or follicular adenocarcinoma, but the clinical stage of invasion is stage 1, the isthmus and most of the opposite lobe must be removed. The chances of foci of tumor in the isthmus and opposite lobe is as high as 80 per cent even though the gland appears normal. Although evidence is not conclusive that these foci of malignancy will grow or metastasize, we believe the removal of this tissue does not add to mortality or morbidity. We do not perform a near total lobectomy on the opposite side because of the danger of removing all the parathyroid glands. We perform a radical subtotal lobectomy leaving a small remnant of posterior capsule with at least one parathyroid visualized and preserved. A second reason for removing as much normal thyroid tissue as possible is to be able to study and possibly to treat metastasis with 1311. The avidity of metastatic foci for 131 I depends upon the complete absence of all normal thyroid tissue. The question of proceeding with a radical neck dissection in differentiated tumors depends upon the stage of invasion. If lymphatic involvement is not visible or if the nodes are present and frozen section reveals they are not invaded (clinical stage 1), it is debatable whether or not radical neck dissection is indicated. In such instances, we would not proceed with radical neck dissection in children. In adults, particularly in men, because of our experience of finding 30 to 40 per cent positive nodes
310
C(}RNELIUS
E.
SEDGWICK
in unsuspected specimens, we would remove the jugular vein and adjacent lymphatics, preserving the sternocleidomastoid and the prethyroid muscles. In those patients with differentiated papillary or follicular adenocarcinoma with obvious but not massive nodal metastasis (clinical stage 2), we would proceed with classical radical neck dissection. Our goal would be a chance of cure by removing all tumor. We would abandon radical neck dissection if extensive nodal metastasis involves structures high in the neck (above the parotid), the retropharyngeal nodes, or the suprasternal nodes. If only pretracheal nodes were involved in low-lying regions, we would add mediastinal dissection to radical neck dissection. In many patients with small differentiated primary tumors, extensive massive cervical nodal involvement or invasion of surrounding neck structures makes radical neck dissection as a curative procedure unattainable. In this group we remove as much nodal involvement as we can more or less by the "berry-picking" technique. This allows for easier postoperative administration of t:Jl I or supervoltage radiation therapy. Medullary carcinoma is best treated by near total lobectomy on the side involved and radical subtotal lobectomy with the isthmus on the opposite side. Radical neck dissection should be performed on the side of the primary lesion. Undifferentiated carcinoma rarely lends itself to radical surgery. All macroscopic tumor is removed, frequently tracheostomy is performed, and supervoltage radiation is given postoperatively. The type of incision used for thyroid cancer is usually dictated by the pathology involved. If exploration of the neck is performed for removal of a solitary nodule through the usual low collar thyroidectomy incision and the tumor is found to be malignant, the ends of the incisions are carried upward (horse-shoe type), and adequate exposure is obtained for more extensive thyroid surgery or radical neck dissection. If a diagnosis has already been established by a previous cervical gland biopsy and radical neck dissection is contemplated, I prefer the usual radical neck incision extending from the mastoid to the sternum and then back along the clavicle. Wide flaps can then be developed and excellent exposure obtained.
131
I THERAPY
The avidity of 131 1 for metastasis depends upon the absence of all normal thyroid tissue. It is assumed that in all differentiated thyroid tumors bilateral near total or radical subtotal thyroidectomy has been performed. One month after operation, the neck is scanned with 131 I. Any remaining normal thyroid tissue is then ablated with the isotope. A 131 I urinary excretion test is then performed. If 90 per cent of the isotope is recovered in the urine 24 to 48 hours after administration, the presence of residual tumor is unlikely. If only 40 to 50 per cent is excreted in the urine, the neck, mediastinum, and chest are scanned for possible metastases. If metastatic disease is present, it is treated with t:lll. Follicular adenocarcinoma has more avidity for 1311. However, if TSH, 10 units a day for three
311
THYROID MALIGNANCY
days, is given before 131 1 is administered and if larger doses of 131 1 are used, some mixed papillary adenocarcinomas may also pick up the isotope. Those metastatic tumors or residual tumors showing an uptake of 131 1 are then treated with 131 1 usually in divided doses.
SUPERVOLTAGE RADIATION Supervoltage radiation is reserved for those unresectable differentiated tumors which will not pick up 131 1 and most undifferentiated tumors. A tracheostomy may be necessary during therapy because of radiation effect. Usually the tracheostomy tube can be removed after therapy.
THYROID SUPPRESSANT Thyroid tumors may be hormone dependent and their rate of growth depends upon increased pituitary output of TSH. Differentiated tumors show regression if TSH is suppressed with thyroid extract. Furthermore, TSH suppression may prevent transformation of a low-grade to a highgrade malignancy. All patients with thyroid malignancy regardless of previous treatment must be given thyroid extract permanently, usually 3 grains daily. Lahey Clinic Foundation 605 Commonwealth Avenue Boston, Massachusetts 02215
Considerations in the Management of Thyroid Malignancy
Cornelius E. Sedgwick, M.D .
The natural history of thyroid malignancy varies from a slowly growing tumor that may remain localized in the neck for many years to a rapidly growing tumor that may cause death a few months after it is discovered. In many instances it is difficult to assess the effective treatment or the final outcome, and thus thyroid malignancy presents a difficult problem to the physician and surgeon selecting a plan of management. Thyroid malignancy comprises only 1 per cent of all malignancies of the human being, and few physicians or clinics have a sufficient number of patients treated by a definite mode of therapy and followed long enough to draw definite conclusions as to the efficacy of treatment. In other tumors, 5 year and 10 year survival rates are significant. In thyroid malignancy, 20 to 30 year follow-up studies are necessary. Further difficulty in evaluating survival rates is the lack of any universally accepted histologic and clinical classification of thyroid tumors. One cannot compare the survival rate of a low-grade papillary carcinoma confined to a lobe with a higher grade of malignant follicular tumor with cervical gland metastases or the most highly malignant undifferentiated tumor. Furthermore, tumors of the thyroid may transform from a low to a high potential malignancy probably secondary to the influence of the thyroid-stimulating hormone CTSH) of the pituitary. What may be a papillary adenocarcinoma may become a follicular adenocarcinoma or even an undifferentiated malignancy after the removal of the initial primary tumor. For these reasons and from our experience, the best we can do is to propose a plan of management that at the moment seems most reasonable. Our plan of management depends upon the pathologic classification or degree of malignancy, the clinical stage or degree of invasion, the age and sex of the patient, and finally the location of the primary tumor within the gland. The pathologic classification (Table 1) grades the tumor according to its degree of malignancy. Papillary adenocarcinoma is the least malignant, follicular adenocarcinoma somewhat more malignant, medullary carcinoma even more malignant, and undifferentiated tumors Surgical Clinics of North America - Vol. 53, No.2, April 1973
307
308
CORNELIUS
E.
SEDGWICK
Table 1. Pathologic Classification of Thyroid Malignancies Predominantly papillary adenocarcinoma (Adenoma with capsular or blood vessel invasion) Predominantly follicular carcinoma (Adenoma with capsular or blood vessel invasion) Medullary carcinoma Undifferentiated carcinoma Small cell carcinoma Giant cell carcinoma
the most malignant. A subdivision of both the papillary and follicular adenocarcinomas is the exceedingly low-grade adenoma with minimal capsular, lymphatic, or blood vessel invasion. The clinical classification (Table 2) is based on the degree of invasion both at the time of clinical evaluation and as observed at the time of operation. The tumor confined to the gland itself is the least invasive, to the cervical lymphatics and adjacent structures more invasive, and those tumors which have spread beyond the confines of the neck are most invasive. Carcinoma of the thyroid appears to have a different growth potential in adults, particularly men, as compared with children. Differentiated tumors, although extensive, tend to remain stationary for a longer period of time, and the instances of transformation into higher degrees of malignancy occur less often in children. These features of the biologic behavior of thyroid tumors must be considered in choosing the appropriate therapy. The location of the primary tumor will influence the extent of surgery in some instances. If one is dealing with a primary tumor located in the inferior pole of the low-lying gland and a classical radical neck dissection is considered, one must realize that the chances of pretracheal lymphatic drainage subsequently invading the lymphatics of the mediastinum may be involved. If radical surgery is contemplated a mediastinal dissection is as important as the radical neck dissection. If the primary lesion is invading the posterior capsule with involvement of the retropharyngeallymphatics, radical surgery must be abandoned, as radical neck dissection will not accomplish the removal of all tumor. In the management of thyroid malignancy we have at our disposal several modalities of therapy that may be used alone or in combination: surgery, radioactive iodine (131 I), supervoltage radiation, and suppression of TSH with thyroid extract.
SURGERY Other than the excision of a cervical gland for a pathologic diagnosis, the initial operation usually involves removing a solitary nodule or suspected lesion from the thyroid gland. There is controversy relative to
309
THYROID MALIGNANCY
Table 2. Stage Stage Stage Stage
Clinical Staging of Thyroid Malignancies 1- Confined to thyroid gland 2-Cervicallymph node metastases 3 - Invasion of other structures in the neck 4-Distant metastases
whether one should initially excise the nodule or perform a subtotal lobectomy or a near total lobectomy. If a competent pathologist is available to obtain a frozen section, it makes little difference. Further surgery may easily be performed if indicated. However, if one must proceed without the help of the pathologist, a radical subtotal or near total thyroidectomy is the better procedure. If later permanent section reveals a benign tumor, then nothing is lost. If the tumor is a low-grade differentiated tumor confined to the gland, adequate surgery will have been performed, and nothing further is indicated. If the final pathologic classification reveals the tumor to be of a higher degree of malignancy than suspected and further surgery is indicated such as the removal of the isthmus and opposite lobe or even a radical neck dissection, Jhe secondary procedure may be somewhat easier if all or most of the gland on the side of the primary lesion has been removed and the recurrent nerve spared. In my experience, however, it has made little difference in technique whether more surgery is performed after either excision of the primary lesion or lobectomy. If the tumor proves to be a low-grade papillary adenoma, that is, an adenoma with minimal capsular, lymphatic, or blood vessel invasion, a radical subtotal or near total lobectomy will suffice. If the histologic examination reveals the tumor to be of a higher degree of differentiated malignancy, that is, papillary or follicular adenocarcinoma, but the clinical stage of invasion is stage 1, the isthmus and most of the opposite lobe must be removed. The chances of foci of tumor in the isthmus and opposite lobe is as high as 80 per cent even though the gland appears normal. Although evidence is not conclusive that these foci of malignancy will grow or metastasize, we believe the removal of this tissue does not add to mortality or morbidity. We do not perform a near total lobectomy on the opposite side because of the danger of removing all the parathyroid glands. We perform a radical subtotal lobectomy leaving a small remnant of posterior capsule with at least one parathyroid visualized and preserved. A second reason for removing as much normal thyroid tissue as possible is to be able to study and possibly to treat metastasis with 1311. The avidity of metastatic foci for 131 I depends upon the complete absence of all normal thyroid tissue. The question of proceeding with a radical neck dissection in differentiated tumors depends upon the stage of invasion. If lymphatic involvement is not visible or if the nodes are present and frozen section reveals they are not invaded (clinical stage 1), it is debatable whether or not radical neck dissection is indicated. In such instances, we would not proceed with radical neck dissection in children. In adults, particularly in men, because of our experience of finding 30 to 40 per cent positive nodes
310
C(}RNELIUS
E.
SEDGWICK
in unsuspected specimens, we would remove the jugular vein and adjacent lymphatics, preserving the sternocleidomastoid and the prethyroid muscles. In those patients with differentiated papillary or follicular adenocarcinoma with obvious but not massive nodal metastasis (clinical stage 2), we would proceed with classical radical neck dissection. Our goal would be a chance of cure by removing all tumor. We would abandon radical neck dissection if extensive nodal metastasis involves structures high in the neck (above the parotid), the retropharyngeal nodes, or the suprasternal nodes. If only pretracheal nodes were involved in low-lying regions, we would add mediastinal dissection to radical neck dissection. In many patients with small differentiated primary tumors, extensive massive cervical nodal involvement or invasion of surrounding neck structures makes radical neck dissection as a curative procedure unattainable. In this group we remove as much nodal involvement as we can more or less by the "berry-picking" technique. This allows for easier postoperative administration of t:Jl I or supervoltage radiation therapy. Medullary carcinoma is best treated by near total lobectomy on the side involved and radical subtotal lobectomy with the isthmus on the opposite side. Radical neck dissection should be performed on the side of the primary lesion. Undifferentiated carcinoma rarely lends itself to radical surgery. All macroscopic tumor is removed, frequently tracheostomy is performed, and supervoltage radiation is given postoperatively. The type of incision used for thyroid cancer is usually dictated by the pathology involved. If exploration of the neck is performed for removal of a solitary nodule through the usual low collar thyroidectomy incision and the tumor is found to be malignant, the ends of the incisions are carried upward (horse-shoe type), and adequate exposure is obtained for more extensive thyroid surgery or radical neck dissection. If a diagnosis has already been established by a previous cervical gland biopsy and radical neck dissection is contemplated, I prefer the usual radical neck incision extending from the mastoid to the sternum and then back along the clavicle. Wide flaps can then be developed and excellent exposure obtained.
131
I THERAPY
The avidity of 131 1 for metastasis depends upon the absence of all normal thyroid tissue. It is assumed that in all differentiated thyroid tumors bilateral near total or radical subtotal thyroidectomy has been performed. One month after operation, the neck is scanned with 131 I. Any remaining normal thyroid tissue is then ablated with the isotope. A 131 I urinary excretion test is then performed. If 90 per cent of the isotope is recovered in the urine 24 to 48 hours after administration, the presence of residual tumor is unlikely. If only 40 to 50 per cent is excreted in the urine, the neck, mediastinum, and chest are scanned for possible metastases. If metastatic disease is present, it is treated with t:lll. Follicular adenocarcinoma has more avidity for 1311. However, if TSH, 10 units a day for three
311
THYROID MALIGNANCY
days, is given before 131 1 is administered and if larger doses of 131 1 are used, some mixed papillary adenocarcinomas may also pick up the isotope. Those metastatic tumors or residual tumors showing an uptake of 131 1 are then treated with 131 1 usually in divided doses.
SUPERVOLTAGE RADIATION Supervoltage radiation is reserved for those unresectable differentiated tumors which will not pick up 131 1 and most undifferentiated tumors. A tracheostomy may be necessary during therapy because of radiation effect. Usually the tracheostomy tube can be removed after therapy.
THYROID SUPPRESSANT Thyroid tumors may be hormone dependent and their rate of growth depends upon increased pituitary output of TSH. Differentiated tumors show regression if TSH is suppressed with thyroid extract. Furthermore, TSH suppression may prevent transformation of a low-grade to a highgrade malignancy. All patients with thyroid malignancy regardless of previous treatment must be given thyroid extract permanently, usually 3 grains daily. Lahey Clinic Foundation 605 Commonwealth Avenue Boston, Massachusetts 02215