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Thyroid and Parathyroid Glands
Palpable nodularity in the thyroid gland is common, especially in women and older persons. The incidence of palpable nodularity in the thyroid gland in the United States is reported to be 4% to 7% of the adult population. However, sonographic or other imaging studies indicate that thyroid nodules may be present in as many as 50% of the adult population. The vast majority of clinically detectable thyroid nodules are benign. The incidence of occult cancer in the thyroid gland ranges from 4% to 35% in adults based on autopsy studies and increases significantly with advancing age.
During the past two decades, a steep rise in the incidence of differentiated carcinoma of the thyroid gland has been observed worldwide. According to the American Cancer Society, the annual estimate for thyroid cancer has risen from 18,400 new cases in the year 2000 to 56,000 new cases in 2017 ( Fig. 12.1 ). Similar trends are reported in Europe and elsewhere in the world. However, the number of deaths attributed to thyroid cancer has not changed much during this time period, with an estimate of approximately 2000 deaths annually in the United States in the past few years. Moreover, most (nearly 90%) of the thyroid cancers that account for the observed increase in incidence are less than 2 cm, and in approximately 50% of patients they are less than 1 cm. These findings suggest that the apparent increase in the incidence of thyroid cancer likely represents detection of clinically occult, micropapillary carcinomas. Often, these tumors are detected on routine imaging studies done for other reasons, such as computed tomography (CT) scan; magnetic resonance imaging (MRI); positron emission tomography (PET) scan; or, more commonly, ultrasound of the neck done for study of the carotid arteries, breast examination, and sometimes as a simple screening test. Routine use of ultrasound as a cancer screening test, commonly practiced in South Korea, has resulted in a 15-fold rise in the detection of clinically occult micropapillary carcinomas.
The rising incidence of cancer of the thyroid in the United States (1997–2017).
Most of these tumors are well differentiated and indolent in behavior. The histologic distribution of primary carcinomas in the thyroid gland is shown in Fig. 12.2 . Most thyroid cancers are of follicular cell origin, but they also may arise from parafollicular cells (C cells). Follicular cell–derived thyroid cancers represent a spectrum of diseases, ranging from the indolent papillary and follicular carcinoma to the more aggressive variants such as tall cell and insular carcinomas, poorly differentiated carcinomas, and anaplastic carcinoma, which is almost universally fatal. Well-differentiated thyroid carcinomas can transform into more aggressive variants in a small proportion of patients, especially those with multiple recurrences. However, this transition occurs over decades in most instances. Evidence for such transition is the presence of focal areas of differentiated carcinoma in patients with poorly differentiated/undifferentiated or anaplastic carcinomas. A review of serial pathologic specimens in patients with multiple recurrences of papillary carcinoma often shows progression to an undifferentiated carcinoma. Thus, tumor heterogeneity at initial presentation and progressive anaplasia with multiple recurrences are in direct evidence that a tumor progression model exists in thyroid cancer. This tumor progression model is depicted in Fig. 12.3 .
The histologic distribution of primary carcinomas in the thyroid gland.
Tumor progression of thyroid cancer from differentiated to anaplastic carcinoma, incidence, and 5-year survival.
Benign Thyroid Nodules
A nodular goiter is one of the most common structural abnormalities of the thyroid gland. Goiters may present as a diffuse enlargement of the thyroid gland, as a single nodule, or as multiple nodules. The most common cause of goiters is dietary iodine deficiency. Thus goiters are more common in some parts of the world, where common salt used in dietary preparations is not routinely iodized. The other common cause for a diffuse goiter is an autoimmune disease such as Hashimoto thyroiditis or Graves’ disease, which can be identified through clinical features or laboratory studies. Lithium, used in the treatment of some psychiatric disorders, also promotes the development of goiters. Goiters can get quite large but rarely become symptomatic unless the airway is compressed by the mass. Benign neoplasms of the thyroid gland primarily include follicular and Hürthle cell adenomas, and they must be differentiated from their malignant counterparts.
Neoplasms of Follicular Cell Origin
Collectively grouped as differentiated thyroid cancers, papillary and follicular carcinomas constitute more than 90% of all malignant neoplasms of the thyroid gland. These tumors are most common in young adults, with a 2 : 1 predilection for women compared with men ( Fig. 12.4 ). In the last two decades, there has been a shift in age distribution in newly diagnosed patients with papillary carcinoma. The peak incidence in the past was in the fourth decade of life. However, in the past 20 years, the peak incidence is now in the fifth decade of life. Epidemiologic evidence suggests that papillary thyroid cancer may be inherited in up to 5% of patients. Although the precise genes involved have yet to be identified, the mode of transmission is thought to be autosomal dominant, with incomplete penetrance and variable expression. Several susceptibility loci have been identified, including those at 19p13.2, 14q, 1p13.2-1q22, and 2q21. A germline mutation in the TTF1 gene is suggested to account for at least a subset of these patients. None of these genetic mutations, however, are in routine clinical use since their role in the genesis of carcinoma is not uniformly reproducible. Nevertheless, the risk of thyroid cancer in affected families is more than five times higher than in the general population. These patients have a predilection for multifocal disease and a more aggressive clinical course. Thyroid cancers also can occur as part of established genetic syndromes including Cowden disease, familial adenomatous polyposis (cribriform-morular variant), and Carney complex.
Childhood exposure to radiation increases the risk for thyroid cancer by up to twentyfold. The highest incidence is observed in children exposed to radiation fallout from the Chernobyl nuclear accident and the atomic bomb explosions in Japan. Increased incidence of thyroid cancer is observed in adults who were exposed to low-dose radiation during childhood for the treatment of acne, a common practice until the 1960s. Similarly, increased incidence of thyroid cancer is observed in adults who were treated for lymphoma in childhood with mantle port radiation. Although the development of thyroid malignancy appeared to have a latency period of 20 years or more in patients treated with radiation during childhood, it is considerably shorter for children exposed to nuclear fallout. This, however, may be a reflection of the huge number of children exposed to the fallout showing the early age of the latency curve and increased awareness about the carcinogenic effect on the thyroid gland. Thyroid cancer rates also are reported to be higher in iodine-deficient areas, which suggests that iodine deficiency may be a predisposing factor. The presence of autoimmune thyroiditis may increase the risk for the development of lymphoma in the thyroid but does not appear to affect the incidence of thyroid carcinoma.
As stated previously, thyroid cancer presents a spectrum of histologic entities with diverse clinical behavior. A great majority of follicular cell–derived carcinomas have an indolent behavior and are curable. A small percentage of thyroid cancers of follicular cell origin (~10%–15%) have a more aggressive behavior and can be a threat to life.
Medullary Thyroid Carcinoma
Medullary carcinoma of the thyroid (MTC) accounts for approximately 4% of all malignant tumors of the thyroid gland. MTC can occur sporadically (in 75%–80% of all cases) or as part of an inherited cancer syndrome (in 20%–25% of cases). Inherited MTC results from mutation in the RET protooncogene; however, this gene also is mutated in up to 50% of sporadic cases. This is a somatic mutation and is only present within the tumor. On the other hand, RAS mutations are found in a significant number of patients without RET somatic mutation. MTC can occur as part of multiple endocrine neoplasia (MEN) syndromes (MEN 2A and 2B) as well as familial MTC (FMTC). MEN 2A is the most common inherited MTC, accounting for 80% of cases, whereas MEN 2B accounts for 5% to 10%, and FMTC accounts for the remainder of cases. MTC typically presents in the third to fourth decade of life in patients with MEN 2A, and these patients also are prone to the development of pheochromocytoma and primary hyperparathyroidism. According to 2015 American Thyroid Association (ATA) guidelines, MEN2A has been categorized into four categories: (1) classic MEN2A, of which 95% of patients have RET mutations; (2) MEN2A with cutaneous lichenoid amyloidosis (CLA); (3) MEN2A and Hirschsprung's disease (HD); and (4) familial medullary thyroid carcinoma (FMTC). FMTC is thought to be a variant of MEN 2A in which only MTC develops. MTC becomes manifest later in life (in the fourth decade) in patients with FMTC and tends to have a less aggressive course relative to patients with MEN 2A.
The onset of MTC is earlier in patients with MEN 2B (<30 years), and the disease typically is more aggressive in these patients. The characteristic features of MEN 2B include musculoskeletal abnormalities (i.e., marfanoid habitus), mucosal neuromas (on the lips, tongue, and conjunctiva), and urinary and intestinal ganglioneuromatosis. Although patients with MEN 2B are at risk for the development of pheochromocytoma, in contrast to patients with MEN 2A, hyperparathyroidism does not develop in these patients.
Each inherited MTC syndrome is associated with specific mutations in the RET gene ( Fig. 12.5 ). The location of the mutation affects the oncogenic potency of the RET gene. Mutations in the tyrosine kinase domain result in higher oncogenic potential and are associated with MEN 2B (912, 918, and 922), whereas those in the extracellular domain are less frequent, have lower virulence, and are associated with FMTC or MEN 2A.
Evaluation: Work Up and Staging
Neoplasms of Follicular Cell Origin
Tumors of the thyroid gland most frequently present as asymptomatic nodules. With more widespread use of ultrasound, MRI, CT, and 18F-fluorodeoxyglucose (FDG) PET scanning, small, subclinical thyroid nodules are increasingly being detected. Fortunately, the vast majority of thyroid nodules are benign, but 5% to 10% of nodules prove to be primary thyroid cancer.
Initial evaluation of any thyroid nodule begins with a complete history and physical examination that focuses on the thyroid gland and surrounding cervical lymph nodes. Clinical features such as a history of childhood radiation, a family history of thyroid cancer, a genetic syndrome that could include thyroid cancer (e.g., Cowden syndrome, familial adenomatosis polyposis, Carney complex, multiple endocrine neoplasia syndrome, or Werner syndrome), rapid nodule growth, palpable cervical lymphadenopathy, or hoarseness of voice due to vocal cord paralysis all increase the likelihood of thyroid malignancy.
Following a complete history and physical examination, the next step in evaluation of a thyroid nodule is measurement of the serum thyroid-stimulating hormone (TSH) level. Even though thyroid function tests, including TSH, are almost always normal in the setting of primary thyroid cancers, a suppressed TSH would raise the possibility of an autonomously functioning nodule. Such nodules can be identified by radionuclide scanning and carry an extremely low risk of malignancy; therefore they do not require further workup, such as fine-needle aspiration biopsy. Depending on the degree of hyperthyroidism, observation or therapy may be indicated to treat the autonomous hyperfunctioning thyroid nodule. While not a clinically useful discriminator, several studies have shown that the risk of thyroid malignancy is positively correlated with the degree of TSH elevation, even if within the normal reference range; that is, the higher the TSH at presentation, the greater the chance that a nodule harbors malignancy.
Serum thyroglobulin values are not helpful in the evaluation of thyroid nodules, as benign nodules can also produce thyroglobulin values significantly above the normal range. There continues to be controversy about whether serum calcitonin values should be measured in all patients with clinically significant thyroid nodules. Based on the available evidence, the ATA guidelines do not have a specific recommendation for or against measurement of serum calcitonin in the workup of thyroid nodules. Since many patients with benign disease have mildly elevated calcitonin values, the concern is that these false-positive calcitonin values would lead to more surgeries than necessary. Conversely, several studies have shown that routine use of calcitonin in the evaluation of thyroid nodules does increase the sensitivity for detecting medullary thyroid cancer. Therefore further studies are needed to address this issue.
The ATA 2015 guidelines provide a rational and risk-adapted approach to the evaluation and management of thyroid nodules. After a complete history and physical, and confirmation of a nonsuppressed TSH, the next step in evaluation of a thyroid nodule is neck ultrasonography. Neck ultrasounds should routinely provide a description of the sonographic features of the nodule(s) to enable malignancy risk stratification (as discussed below) and evaluate cervical lymph nodes in the central and lateral neck ( Fig. 12.6 ).
If very suspicious cervical lymph nodes are seen, then fine-needle aspiration of those lymph nodes can establish a diagnosis and lead to appropriate additional workup and treatment. If there are no suspicious lymph nodes identified, then the management algorithm for thyroid nodules relies on (1) sonographic features that define the risk of malignancy within the nodule and (2) the size of the nodule. This differs from previous approaches, where the size of the nodule was the primary factor influencing the decision to perform fine-needle aspiration biopsy ( Table 12.1 ).
Table 12.1
Sonographic Patterns and Risk of Malignancy in Thyroid Nodules
| SONOGRAPHIC PATTERN | ULTRASOUND FEATURES | ESTIMATED RISK OF MALIGNANCY, % | FINE-NEEDLE ASPIRATION SIZE CUTOFF (LARGEST DIMENSION) |
|---|---|---|---|
| High suspicion | Solid hypoechoic nodule or solid hypoechoic component of a partially cystic nodule with one or more of the following features: irregular margins (infiltrative, microlobulated), microcalcifications, taller than wide shape, rim calcifications with small extrusive soft-tissue component, evidence of ETE | >70-90a | Recommend FNA at ≥1 cm |
| Intermediate suspicion | Hypoechoic solid nodule with smoother margins without microcalcifications, ETE, or taller than wide shape | 10-20 | Recommend FNA at ≥1 cm |
| Low suspicion | Isoechoic or hyperechoic solid nodule or partially cystic nodule with eccentric solid areas, without microcalcification, irregular margin or ETE, or taller than wide shape | 5-10 | Recommend FNA at ≥1.5 cm |
| Very low suspicion | Spongiform or partially cystic nodules without any of the sonographic features described in low-, intermediate-, or high-suspicion patterns. | <3 | Consider FNA at ≥2 cm. Observation without FNA is also a reasonable option. |
| Benign | Purely cystic nodules (no solid component) | <1 | No biopsy |
ETE, Extrathyroidal extension; FNA, fine-needle aspiration. (2015 American Thyroid Association guidelines.)
As shown in Table 12.1 , nodules with sonographic patterns showing high suspicion features carry a risk of malignancy in over 70% to 90% of patients, while nodules with intermediate suspicious features carry a risk of malignancy of 10% to 20%, low suspicion features have a risk of 5% to 10%, and very low suspicion characteristics have a risk of malignancy in less than 3% of patients. Once these nodules have been risk stratified based on sonographic pattern, then the size of the nodule is used to recommend cutoff points for routine use of fine-needle aspiration biopsy ( Fig. 12.6 ). When multiple nodules are present, fine-needle aspiration should be preferentially directed toward the nodule with the highest risk of malignancy based on sonographic pattern and nodule size. In previous iterations of the ATA guidelines, essentially every nodule greater than 5 mm was considered for biopsy. However, in the 2015 edition of the ATA guidelines, nodules with low or very low suspicion are candidates for biopsy only if they are larger than 1.5 to 2 cm. Moreover, it is recommended that nodules with an intermediate- or high-suspicion pattern are considered for biopsy only if they are greater than 1 cm in size. This risk-stratified approach results in a significant number of sonographically detected thyroid nodules where routine use of fine-needle aspiration biopsy is not recommended. Using the same risk-stratified approach, thyroid nodules with a high suspicion pattern that are less than 1 cm can be followed with observation with repeat neck ultrasound in 6 to 12 months. Nodules with low to intermediate suspicion can be followed with repeat neck ultrasound in 12 to 24 months. Nodules greater than 2 cm with very low suspicion should have follow-up ultrasound no sooner than 24 months. Finally, nodules less than 1 cm with very-low-suspicion ultrasound pattern do not require routine sonographic follow-up.
These recommendations allow for observation rather than immediate fine-needle aspiration and surgery for highly suspicious subcentimeter nodules. This approach indirectly endorses an active surveillance management of such potentially malignant low-risk microcarcinomas. As noted in the ATA 2015 guidelines, while thyroid surgery is usually recommended for primary papillary thyroid cancer, active surveillance is now a reasonable alternative to immediate surgery, based largely on the experience published by Drs. Ito and Miyauchi from Kuma Clinic in Kobe Japan. Since cytologic confirmation of disease is not required for active surveillance, both the observation of biopsy-proven papillary thyroid cancer and observation of subcentimeter nodules that are highly suspicious for papillary thyroid cancer are appropriate within an active surveillance paradigm. Therefore an active surveillance option can be offered to patients with subcentimeter thyroid nodules, which are suspicious for or proven to be papillary thyroid carcinoma. However, this approach is recommended in a systematic active surveillance program with well-defined criteria and follow-up strategies. The usual observational approach includes a detailed neck ultrasound every 6 months for the first 2 years. The change in tumor size and volume during the first 2 years is used to establish the doubling time of the tumor. This doubling time is then used to plan the frequency of follow-up ultrasounds and the need for intervention. It is important to recognize that not every subcentimeter suspicious nodule is appropriate for observation. If the suspicious nodule has documented rapid growth, if there is evidence of metastatic disease outside the thyroid, if there is evidence of extrathyroidal extension, or if the tumor is sitting in a location where even minor extrathyroidal extension would be associated with neurovascular or tracheal compromise, then cytologic confirmation followed by surgery is usually recommended.
When fine-needle aspiration is indicated, the Bethesda classification system for cytology is very valuable in helping to risk stratify the various cytologic patterns into a risk of malignancy ( Box 12.1 ). If the cytology is nondiagnostic, a repeat fine-needle aspiration is usually warranted. For benign cytology, in the absence of other worrisome clinical features, a follow-up ultrasound done at an interval consistent with the overall suspicion of the nodule is appropriate. When appropriate nodules are biopsied, a malignant cytology (i.e., Bethesda VI) almost always leads to surgery. Likewise, cytologically suspicious nodules (i.e., Bethesda V lesions) usually require surgical resection for definitive diagnosis and therapy.
Box 12.1
Bethesda Classification of Fine-Needle Aspiration Cytology of Thyroid Nodules
- I
Nondiagnostic or unsatisfactory
- II
Benign
- III
Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS)
- IV
Follicular neoplasm or suspicious for a follicular neoplasm
- V
Suspicious for malignancy
- VI
Malignant
Despite many advances in the molecular biology of thyroid nodules, the cytologic classification of AUS/FLUS (atypia of undetermined significance or follicular lesion of undetermined significance) and FN/FSN (follicular neoplasm or suspicious for follicular neoplasm), Bethesda category III and IV, remain problematic and carry a risk of malignancy that approximates 5% to 15% and 15% to 30%, respectively. Multiple molecular markers have been developed for clinical use to further delineate the risk of malignancy of an indeterminate lesion. Therefore, depending on the clinical risk factors, sonographic features, availability of molecular testing, and patient preference, these molecular profiles may be useful in clinical decision-making.
Following the recommendations of the ATA 2015 guidelines, the interval for repeat ultrasonography following establishment of benign cytology is based on the sonographic pattern of the nodule. Even after a benign fine-needle aspiration, nodules that have a high-suspicion pattern on the ultrasound should probably have a repeat neck ultrasound and fine-needle aspiration within 12 months. However, nodules with low to intermediate suspicion can have a repeat neck ultrasound at 12 to 24 months, reserving a repeat biopsy for those nodules that exhibit evidence of growth of at least 2 to 3 mm, or more than 50% change in volume, or the development of new suspicious sonographic features. Overall, appropriate risk stratification for the management and follow up of thyroid nodules requires accurate initial characterization of the sonographic features of the nodule, proper selection of nodules to undergo fine-needle aspiration versus observation, and standardized communication of cytology results using Bethesda classification.
With regards to medical therapy for benign nodules, routine TSH suppressive therapy is not recommended. Although TSH suppression may lead to a modest deceleration of nodule growth, the potential adverse effects of long-term TSH suppression are thought to outweigh this minor treatment benefit. Iodine status should be assessed, and iodine deficiency should be treated with 150 µg of supplemental iodine daily.
Medullary Thyroid Cancer
Patients with MTC may present with a palpable mass in the thyroid or with cervical lymphadenopathy. In some patients, thyroid workup is undertaken because of the family history of medullary carcinoma, and in that setting, a clinically occult primary tumor may be identified. FNAC is usually sufficient to establish tissue diagnosis, but immunocytochemistry to determine the presence of calcitonin or serum calcitonin level may be helpful if the diagnosis is unclear. In addition to serum calcitonin, serum CEA is also a necessary part of the workup. All patients with a diagnosis of MTC should be counseled and tested for the presence of RET mutation, because absence of a family history is not sufficient to rule out inherited disease. Up to 7% of patients with apparently sporadic MTC harbor a germline mutation. This finding is especially true in persons with MEN 2B, for whom de novo germline RET mutation is seen in 50% of cases. Germline mutations are seen more commonly in younger patients or in those with multifocal disease, but they also may occur in older patients or in patients who present with a single thyroid nodule. Testing of all first-degree relative family members is recommended if the patient has a germline RET mutation. Additional workup includes contrast-enhanced CT scan of the neck and mediastinum to assess the presence and extent of regional lymph node metastasis to facilitate surgical planning. A whole-body FDG PET scan may be used to rule out distant metastases.
Staging
The American Joint Committee on Cancer (AJCC) and International Union Against Cancer (UICC), have jointly developed a uniform staging system, published in the eighth edition of the AJCC staging manual in 2016. For full details on the staging for all thyroid cancers, one should review the eighth edition staging manual published by the AJCC. However, the major changes in the recent revision mentioned here incorporate the biological behavior of differentiated thyroid cancer. In this revised staging system, patient's age is an important criterion distinguishing between high- and low-risk groups. This age cutoff is now advanced to 55 from the previous 45 years. In addition, other important changes include removal of microscopic extrathyroid extension to upstage a tumor to T3. For a tumor to be staged as T3, it should have gross minor (anterior) extrathyroid extension to strap muscles or perithyroid soft tissues. All gross major (posterior) extrathyroid extension would upstage the tumor to T4a. Further, lymph nodes at level VI and VII are now combined and included under the category N1a, and all lateral neck nodes are staged as N1b.
Radiographic Evaluation
Currently used imaging techniques for the thyroid gland include ultrasonography, a CT scan, an MRI scan, a Technetium-99 or iodine-131 thyroid scan, and FDG-PET scanning. Ultrasonography is the most widely used imaging modality for initial evaluation of the thyroid gland and regional lymph nodes as has been described in detail previously. In most instances, no other specific radiographic studies are required when planning a surgical procedure on the thyroid gland. A CT scan of the neck is necessary when planning surgical treatment for patients whose primary tumors have extrathyroid extension to involve the central compartment structures like larynx or trachea. It is essential that the CT scan be performed with contrast enhancement for accurate assessment of the primary tumor as well as regional lymph nodes. CT and MRI scans also are useful in evaluating the retropharyngeal lymph nodes, which are not accessible for ultrasound examination. A thyroid scan provides functional evaluation of the thyroid gland, but this information generally is not useful in treatment planning. FDG-PET scanning is useful in selected patients, especially older patients with poorly differentiated tumors that are not expected to concentrate radioactive iodine.
Ultrasound is the first and often the only radiologic study required. It is more accurate than any other imaging study for small nodules and low-volume nodal metastases, particularly in the central compartment of the neck. It clearly differentiates between a solid, cystic, or a mixed echostructure nodule. Several sonographic features of the nodule increase the index of suspicion for malignancy. These are extrathyroid extension, irregular margins, microcalcification in the nodule, internal hypervascularity, and hypoechoic pattern. In addition, intracystic solid lesions particularly with microcalcifications within the nodule raise the suspicion for cancer. An example of a small intracystic papillary carcinoma suspected on an ultrasound and confirmed by surgical resection is shown in Fig. 12.7 . Similarly, large cystic lesions with an intracystic growth with papillary fronds is highly suspicious for carcinoma, as can be seen on a CT scan in Fig. 12.8 . The sonographic features with increasing index of suspicion for cancer to warrant the need for fine-needle aspiration biopsy are described in Table 12.1 . In addition, ultrasound is a cost-effective and convenient way for imaging follow up after surgery, particularly in the office setting. On the other hand, CT scan is the most accurate structural study for the thyroid gland, the central compartment, lateral neck, and the mediastinum. In the past, it was felt that a contrast-enhanced CT scan should not be performed as initial imaging since iodinated intravenous contrast would interfere with radioactive iodine uptake and can compromise timing of postoperative adjuvant radioiodine treatment. However, it is now understood that delay in the administration of radioactive iodine by a few weeks does not have a negative impact in the overall outcome of patients with thyroid cancer. On the other hand, if extrathyroid extension of a thyroid tumor is suspected, or if lymph node metastases are identified clinically, good-quality cross-sectional imaging can provide crucial information regarding the relationship of the tumor to the central compartment viscera and the carotid artery and provide more comprehensive mapping of regional lymph nodes in the neck and mediastinum. Thus a contrast-enhanced CT scan is an important study in these patients for optimal assessment.
The patient shown in Fig. 12.9 has a 4- by 6-cm mass involving the upper pole of the right lobe of the thyroid gland that is adherent to the thyroid cartilage. The CT scan of the same patient ( Fig. 12.10 ) shows invasion of the strap muscles with fixation of the tumor to the ala of the thyroid cartilage on the right-hand side. This patient requires resection of the thyroid ala for adequate excision of the thyroid cancer.
The patient shown in Fig. 12.11 has extensive recurrent carcinoma of the thyroid gland extending from the root of the neck into the superior mediastinum with encasement of the common carotid artery. A contrast-enhanced CT scan of the same patient ( Fig. 12.12 ) clearly shows the common carotid artery completely surrounded by the recurrent tumor mass. This information greatly facilitates planning of surgical treatment, which in this patient required resection of the common carotid artery and replacement with a bypass graft.
MRI also provides anatomic information about the relationship of the tumor to the central compartment viscera and has the advantage of not interfering with radioactive iodine administration. It is also a study of choice for patients who have allergy to iodine contrast dye. However, the study takes considerably longer time to acquire compared with a CT scan and may be difficult to obtain in patients who are unable to lie flat or have difficulty swallowing with pooling of saliva. An axial image of the MRI scan of a patient with thyroid cancer demonstrates a locally advanced carcinoma with extension through the anterior tracheal wall into the lumen of the trachea and the subglottic larynx ( Fig. 12.13 ). A sagittal view of the MRI scan of the same patient clearly demonstrates extension of tumor through the cricoid cartilage into the distal part of the subglottic larynx and proximal trachea ( Fig. 12.14 ). An axial view of the MRI scan of another patient demonstrates a large recurrent mass of thyroid cancer extending up to the prevertebral space and displacing the trachea and esophagus with invasion of the muscular wall of the esophagus ( Fig. 12.15 ). A sagittal view of the MRI scan of the same patient clearly shows the presence of the tumor between the trachea and the esophagus, causing anterior displacement of the membranous trachea with partial compromise of the air column ( Fig. 12.16 ).
The greatest value of an MRI scan is in the assessment of a retrosternal goiter, particularly with respect to its relation to the great vessels in the mediastinum. An axial plane MRI scan of a patient with a large retrosternal goiter shows the location of the goiter in the mediastinum in relation to the great vessels ( Fig. 12.17 ). A coronal MRI scan of the same patient shows a 10- by 17-cm mass lateral to the trachea and just above the mainstem bronchus on the right-hand side in the mediastinum ( Fig. 12.18 ). The sagittal section of the MRI scan clearly shows this massive retrosternal goiter in the anterosuperior mediastinum ( Fig. 12.19 ).
MRI is also quite informative in demonstrating parathyroid abnormalities.
FDG-PET scanning relies on the demonstration of tumor-bearing tissue with increased glucose metabolism. This technique has been of immense value in identifying tumor deposits not seen on radioactive iodine scans or on routine imaging with CT or MRI. It is of value in patients with thyroid cancer that does not concentrate radioactive iodine (poorly differentiated carcinoma) and in patients with medullary carcinoma. It is well known that a direct relationship exists between the degree of differentiation of the tumor and its ability to concentrate radioactive iodine. In general, FDG-avid tumors are poorly differentiated, do not concentrate radioactive iodine, and have a worse prognosis compared with radioactive iodine–avid well-differentiated tumors that generally show low FDG avidity. Thus, with progressive anaplasia from well differentiated papillary carcinoma to poorly differentiated carcinoma and anaplastic carcinoma, one can anticipate increasing FDG avidity (see Fig. 12.3 ). An example is a patient with extensive metastatic disease whose posttherapy radioactive iodine-131 scan showed very little presence of metastatic disease, but a whole-body PET scan shows extensive metastatic disease ( Fig. 12.20 ). In addition, PET scan often detects clinically occult thyroid cancer. For example, PET scans done for other cancers often identify an incidental FDG-avid lesion in the thyroid gland. While diffuse uptake in the thyroid gland is often present in patients with Hashimoto's thyroiditis, focal uptake in a single lesion with the remaining thyroid gland not showing any FDG avidity demands further work up ( Fig. 12.21 ). The risk of such a focal FDG-avid lesion being a primary thyroid carcinoma is nearly 60%. PET scanning also may be of value for localizing metastases in patients with medullary carcinoma with persistently high calcitonin levels after thyroidectomy.
Radioactive iodine (RAI) scanning was popular in the past for initial diagnostic workup imaging for thyroid nodules, but ultrasound has replaced it as the initial imaging study. However, occasionally, RAI scans may be done for initial workup. Four patterns can be seen on RAI scanning: (1) hot nodule, (2) cold nodule, (3) diffuse increased uptake, and (4) multinodular goiter ( Fig. 12.22 ). Hot nodules are rarely malignant (3%–5%). Most cold nodules are benign. Diffuse increased uptake represents hyperthyroidism, and multinodular goiter is manifested by a mixed picture of cold and warm nodules. Currently, RAI scanning is used under three circumstances: (1) postsurgical assessment of residual functioning thyroid tissue, (2) post–RAI therapy whole body scan for demonstration of iodine avid disease, and (3) follow-up of iodine-avid residual, recurrent, or metastatic disease. However, it should be remembered that iodine avidity is essential for disease to be seen on an RAI scan. Generally, iodine avidity diminishes as the histologic differentiation of thyroid cancer progresses toward poorly differentiated and anaplastic carcinoma. Conversely, FDG avidity on PET scan increases as the tumor becomes less well-differentiated and metabolically more active ( Fig. 12.23 ).
Pathology
Papillary carcinoma is the most common histologic type of thyroid cancer. The histologic spectrum comprises the classic papillary carcinoma and other variants such as tall cell variant, which are thought to have a more aggressive clinical behavior. The most recent World Health Organization classification of thyroid tumors is shown in Table 12.2 . An important and common variant is the follicular variant of papillary thyroid carcinoma, which is defined by the presence of follicles lined by cells having the nuclear features of papillary carcinoma. The follicular variant can be separated into completely encapsulated/well defined and infiltrative (either partially or not encapsulated). The encapsulated follicular variant without invasion has been shown to be very indolent, behaving like a follicular adenoma. It was therefore renamed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This diagnosis avoids overtreatment with aggressive surgery and/or radioactive iodine therapy.
Table 12.2
World Health Organization Classification of Thyroid Tumors
| Follicular adenoma | 8330/0 |
| Hyalinizing trabecular tumor | 8336/1 |
| Other encapsulated follicular-patterned thyroid tumors | |
| Follicular tumor of uncertain malignant potential | 8335/1 |
| Well-differentiated tumor of uncertain malignant potential | 8348/1 |
| Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) | 8349/1 |
| Papillary thyroid carcinoma (PTC) | |
| Papillary carcinoma | 8260/3 |
| Follicular variant of PTC | 8340/3 |
| Encapsulated variant of PTC | 8343/3 |
| Papillary microcarcinoma | 8341/3 |
| Columnar cell variant of PTC | 8344/3 |
| Oncocytic variant of PTC | 8342/3 |
| Follicular thyroid carcinoma (FTC), NOS | 8330/3 |
| FTC, minimally invasive | 8335/3 |
| FTC, encapsulated angioinvasive | 8339/3 |
| FTC, widely invasive | 8330/3 |
| Hürthle (oncocytic) cell tumors | |
| Hürthle cell adenoma | 8290/0 |
| Hürthle cell carcinoma | 8290/3 |
| Poorly differentiated thyroid carcinoma | 8337/3 |
| Anaplastic thyroid carcinoma | 8020/3 |
| Squamous cell carcinoma | 8070/3 |
| Medullary thyroid carcinoma | 8345/3 |
| Mixed medullary and follicular thyroid carcinoma | 8346/3 |
| Mucoepidermoid carcinoma | 8430/3 |
| Sclerosing mucoepidermoid carcinoma with eosinophilia | 8430/3 |
| Mucinous carcinoma | 8480/3 |
NOS, Not otherwise specified.
Papillary carcinomas can be solid, cystic, or mixed cystic and solid on gross examination. They may be encapsulated and exhibit calcification on cut sections. The thyroid gland sometimes presents as a completely black gland, the so-called “black thyroid.” This presentation occurs in patients who have undergone long-term therapy with tetracycline and particularly minocycline. The surgical specimen of a patient with multifocal papillary carcinoma in a black thyroid is shown in Fig. 12.24 .
The differential diagnosis of follicular and Hürthle cell carcinomas from their adenoma counterparts is based on the demonstration of vascular and/or capsular invasion. This diagnosis is not feasible with cytologic evaluation and requires histologic evaluation of the thyroid nodule. Hürthle cell carcinomas tend to be more aggressive than follicular carcinomas and are now considered as a separate entity from follicular carcinomas. Poorly differentiated carcinomas are at the histologic and behavior level intermediate between well-differentiated thyroid carcinoma and anaplastic thyroid carcinomas. Anaplastic thyroid carcinomas are characterized by pleomorphic cells (often spindle in shape), marked mitotic activity, tumor necrosis, and a lack of organoid formation (follicles, papillae, nests). These carcinomas have considerable genomic instability and a highly complex genome. Well-differentiated thyroid carcinomas exhibit immunoreactivity for thyroglobulin, PAX8 and thyroid transcription factor 1 (TTF-1), and the expression of these markers progressively diminishes with poorer differentiation. As the progression from a well-differentiated papillary carcinoma to anaplastic carcinoma takes place, there is progressive anaplasia with decreased RAI avidity and increased FDG avidity on a PET scan (see Figs. 12.3 and 12.23 ).
Medullary thyroid carcinomas are encountered more frequently in the middle third or upper half of the gland, and this distribution is thought to be due to the greater concentration of C cells in this region. The presence of amyloid is a characteristic histologic feature. Immunohistochemical diagnosis is very reliable and depends on demonstrating reactivity to calcitonin and carcinoembryonic antigen (CEA). Other neuroendocrine markers such as neuron-specific enolase (NSE) and chromogranins also may be positive.
Treatment
Surgery is the mainstay of treatment for nearly all thyroid neoplasms and symptomatic goiters as well as other conditions, such as thyroglossal duct cysts. The ultimate goal in the treatment of cancer of the thyroid gland is cure of cancer with minimal or no impact on the quality of life. Surgery plays a central role in the management of all types of thyroid cancers, with RAI-131 therapy used as adjuvant treatment. Administration of RAI is indicated for treatment of residual local or regional disease and for distant metastases and also for ablation of any remnant thyroid tissue left behind after surgery. However, RAI is beneficial only in patients who have iodine-avid differentiated cancer of the thyroid gland. Unfortunately, poorly differentiated and undifferentiated carcinomas that are clinically more aggressive do not concentrate iodine, and therefore radioactive iodine is of little value in these patients. Nonetheless, RAI often is administered even in these patients, because many poorly differentiated tumors manifest heterogeneity and may have well-differentiated areas within the tumor that are RAI avid. Hürthle cell carcinomas also tend to take up RAI less often (in ~25% of cases). Treatment with RAI is not recommended in persons with anaplastic carcinomas, because these tumors do not concentrate iodine. Postoperative RAI therapy should follow a period of a low-iodine diet and a hypothyroid state induced by either thyroxine withdrawal or by administration of recombinant human (rh) TSH.
The role of external beam radiation therapy in the management of thyroid carcinoma remains controversial. However, it may be used in selected patients who have a high risk for failure in the central compartment. External beam radiation therapy is the mainstay of treatment for anaplastic carcinoma in combination with cytotoxic chemotherapy. The recent availability of targeted agents such kinase inhibitors that target the RET gene, vascular endothelial growth factor (VEGF) inhibitors, epidermal growth factor receptor (EGFR) inhibitors, and BRAF V600E inhibitors have opened a whole new landscape of systemic therapies in patients with metastatic disease and RAI refractory tumors. Clinical trials and early but limited data show effectiveness of drugs such as Vandetanib, Sorafenib, Lenvatinib, Selumetinib, Pazopanib, Cabozantinib in selected patients.
Treatment for MTC consists of surgery for the primary tumor and regional lymph nodes and occasionally for distant metastasis. External beam radiation therapy has a limited role and generally is used in an adjunctive or in a palliative setting. Similarly, systemic treatments have a role in the setting of a clinical trial or for palliation of symptoms.
Surgical Treatment
Neoplasms of Follicular Cell Origin
Benign adenomas confined to one lobe of the gland without any abnormality in the contralateral lobe are cured by an ipsilateral lobectomy. A total thyroidectomy is indicated for bilateral involvement. Patients with retrosternal extension require appropriate surgical intervention with a curative intent.
Management of patients with carcinomas of follicular cell origin is dictated by risk group stratification based on prognostic factors related to patient and tumor characteristics. The prognostic importance of age (≤55 versus >55 years), the size of the tumor (≤4 versus >4 cm), the extent of the tumor (i.e., the presence or absence of gross extrathyroid extension), the histologic differentiation (well versus poorly differentiated), and distant metastasis (present or absent) have been reported in several classification systems ( Table 12.3 ). Based on these prognostic factors, risk groups can be identified to facilitate selection of therapy ( Fig. 12.25 ). The intermediate-risk group consists of young patients with high-risk tumors or older patients with low-risk tumors.
Table 12.3
The Prognostic Importance of Age and Gender of the Patient and the Size, Local Extent, Histologic Grade, and Deoxyribonucleic Acid Ploidy of the Primary Tumor, as Well as the Presence or Absence of Distant Metastasis, Have Been Reported in Several Major Studies.
(Courtesy Memorial Sloan Kettering Cancer Center.)
| MSKCC | MAYO CLINIC, 1987 | MAYO CLINIC, 1993 | LAHEY CLINIC | KAROLINSKA INSTITUTE |
|---|---|---|---|---|
| GAMES | AGES | MACIS | AMES | DAMES |
| G rade | A ge | Distant M etastases | A ge | D NA |
| A ge | G rade Age | A ge | M etastases | A ge |
| M etastases | E xtension | C ompleteness of Resection | E xtension | M etastases |
| E xtension | S ize | I nvasion | S ize | E xtension |
| S ize | S ize | S ize |
All surgical procedures for the treatment of thyroid carcinoma or for tumors suspected to be cancers should be extracapsular operations leaving no residual thyroid tissue in the surgical bed. Procedures commonly described as a “subtotal” and “near-total” thyroidectomy are incomplete operations for malignant disease and are discouraged. In performing a true extracapsular thyroidectomy, particular attention should be paid to the pyramidal lobe, the upper pole, and the region of the Berry's ligament, where no thyroid tissue should be left behind. Following a “true extracapsular” total thyroidectomy, patients should not have any measurable serum Thyroglobulin (usually <1), thus avoiding the need for RAI ablation for “potential residual thyroid tissue (thyroid remnant).”
Low-risk patients with a unifocal, intrathyroidal tumor and a sonographically normal opposite lobe need an ipsilateral extracapsular lobectomy (including patients with tumors staged T1 and T2). Inasmuch as the primary tumor is intrathyroidal, the size difference between 1 cm and 4 cm has little impact on local control, regional lymph node metastasis, distant metastasis, or survival. An ipsilateral lobectomy is an adequate operation for definitive treatment in this setting. A total thyroidectomy should be considered for patients with bilateral nodularity (either clinically or sonographically identified thyroid abnormalities), regardless of the size of the primary cancer. Other indications for considering a total thyroidectomy in low-risk patients include a high-risk ipsilateral tumor with gross extrathyroidal extension, a history of radiation exposure, a strong family history of thyroid cancer, and extensive regional nodal metastases.
For high-risk patients, an extracapsular total thyroidectomy is the recommended surgical procedure. Minor extrathyroid extension (ETE) is no longer considered to upstage a tumor to T3. For a tumor to be staged T3, it has to be larger than 4 cm (T3a) or may have gross extrathyroid extension involving strap muscles (T3b). This degree of ETE is easily encompassed in a properly done total thyroidectomy with resection of the strap muscles, easily achieving an R0 resection. On the other hand, major or gross ETE to the posterior aspect of the thyroid gland is staged T4a with involvement of either the trachea, larynx, esophagus, or recurrent laryngeal nerve. These extensive tumors require adequate preoperative imaging for detailed assessment of the extent of the tumor to facilitate surgical treatment planning for complete resection. Preoperative CT scan with contrast is quite helpful in evaluating the extent of disease. An MRI may be complementary to give added information in a three-dimensional manner. The aim of surgical resection should be to achieve gross total clearance of all demonstrable disease (R0 resection). However, a primary total laryngectomy is required only rarely and is performed in highly selected patients based on histology and the probability of lack of iodine avidity of the cancer.
Patients in the intermediate-risk group require individualized treatment selection. Older patients with a low-risk, unifocal intrathyroidal tumor are equally well treated with a lobectomy. On the other hand, younger patients with high-risk tumors may require not only a total thyroidectomy but also more extensive operations based on the extent of their disease. Decisions about the extent of thyroidectomy are best made based on initial extent of disease, prognostic factors, risk group stratification, and anticipated need of RAI.
Completion total thyroidectomy is required in some patients who have undergone inadequate initial surgery, such as those who had an open biopsy or less than a lobectomy when a total thyroidectomy would have been indicated as the initial surgical procedure. Other indications for completion of a total thyroidectomy are patients who have undergone a lobectomy and (1) have indications for postoperative RAI, (2) have gross residual tumor that is resectable, or (3) have contralateral gross nodular disease that is suspicious for multifocal thyroid carcinoma.
Recurrent thyroid carcinoma poses specific challenges regarding preservation of the larynx and its function, the parathyroid glands, and the integrity of the esophagus and adjacent neurovascular structures. Historically, in the past the most common cause of mortality from carcinoma of the thyroid was uncontrolled local/regional disease leading to asphyxia, hemorrhage, and inanition. However, in the past three decades that scenario has changed due to appropriate selection of cases and aggressive initial surgical procedures achieving an R0 resection. Thus control of disease in the central compartment is of paramount importance because it improves longevity in many patients and quality of life in nearly all. The issues to be considered in resection include (1) the goal of surgical intervention (i.e., curative treatment versus symptomatic palliation), (2) the feasibility of (R0) gross total resection, (3) the availability and efficacy of alternate means of treatment, and (4) the sequelae of surgery.
Anaplastic thyroid carcinoma poses unique challenges for the surgeon. The role of the surgeon is generally to establish tissue diagnosis and management of the airway. In rare circumstances, anaplastic carcinoma may be surgically resectable, as in the case of anaplastic carcinoma developing in a preexisting nodular goiter and confined to the goiter or as a small component of a poorly differentiated resectable carcinoma. An elective tracheostomy for prevention of airway distress in most patients with an anaplastic carcinoma requires careful consideration of the overall treatment plan and prognosis and is rarely indicated unless the patient is in impending airway distress. Multidisciplinary discussion is required to inform the patient and the family of the dismal prognosis and the anticipated course of events. If a decision is made to perform a tracheostomy, it should be done after endotracheal intubation under general anesthesia in the operating room with all available support. Technically, tracheostomy may be very difficult due to the presence of gross disease in front of the trachea, and also, the potential of the tumor which may grow through the tracheostomy. Therefore, if possible, placing the tracheostomy in the usual suprasternal location should be avoided. It is desirable to perform a cricothyrotomy and use a long tracheostomy tube to provide a safe airway into the distal trachea.
Regional lymph node dissection is recommended for clinically palpable or radiologically identified metastatic lymph nodes on imaging studies (ultrasound or CT scan) before thyroidectomy. Routine elective dissection for removal of possible micrometastases in regional lymph nodes is not recommended, because it offers no benefit to the patient and may increase morbidity. Elective dissection of central compartment lymph nodes may be considered in patients undergoing thyroidectomy for advanced primary tumors. The surgical procedure for excision of gross metastases should be a systematic compartmental dissection of regional lymph node groups. Excision of isolated lymph nodes (“berry-picking”) is not recommended. The presence of lymph node metastases in the central compartment (N1a) requires a systematic dissection of lymph nodes from the hyoid bone cephalad to the innominate artery caudad, and between the two carotid sheaths (levels VI and VII). Lateral neck metastases (N1b) require a systematic dissection of lymph nodes from levels IIA to V. Metastatic disease at level I and level IIB is rare, and dissection of these regions is recommended only if contiguous gross nodal metastases are present. Involvement of mediastinal lymph nodes below the innominate artery is infrequent, and surgical resection should be considered carefully in the context of the overall status of the disease and the patient. On the other hand, dissection of anterosuperior mediastinal lymph nodes (level VII) is feasible through the cervical approach and should be included in central compartment node dissection. However, massive metastases or metastatic disease inferior to the innominate artery may require a sternotomy.
Medullary Thyroid Carcinoma
Surgery is the only effective treatment for MTC, and thus comprehensive surgical resection of the primary tumor and involved lymph nodes is crucial to achieve local/regional control and improve survival. Lobectomy for a small unifocal intrathyroidal primary tumor in a patient with sporadic MTC is acceptable. On the other hand, a total thyroidectomy with central compartment lymph node dissection is the recommended surgical procedure for most patients whose diagnosis is confirmed preoperatively. Elective dissection of lymph node groups at risk in the lateral neck is controversial. However, if metastatic disease is identified clinically or radiologically, a comprehensive systematic compartmental neck dissection is required. The decision about elective lateral neck dissection is also made based on the size of the primary tumor, presence of central compartment nodal metastases, and preoperative calcitonin level. Surgery on the thyroid gland and regional lymph nodes is recommended even in the presence of distant metastases, because control of disease in the neck directly affects the quality of life of these patients. When the diagnosis of MTC is made as an incidental finding in a thyroidectomy specimen, the patient should undergo studies for calcitonin levels, ultrasound of the neck, and RET mutation. If findings of these studies are normal, further surgery is not necessary.
Genetic testing is indicated in family members of a patient who tests positive for RET mutation. The timing of genetic testing and the treatment of family members is based on the type of mutation present in the patient. The ATA has classified mutations into four risk groups. Level A mutations include 768, 790, 791, and 891. Persons with these mutations generally have indolent, late-onset MTC. Testing for RET mutation in children of these patients is recommended at 3 to 5 years of age, and prophylactic surgical treatment may be deferred until an older age (>5 years) as long as thyroid ultrasound and serum calcitonin levels are normal. The rationale to delay treatment is to minimize the risk of permanent hypoparathyroidism in infants. ATA level B mutations include 609, 611, 618, 620, and 630. Patients with these mutations have slightly earlier onset of MTC, and a prophylactic thyroidectomy is recommended for their children before age 5 years who have the RET mutation. ATA level C includes patients with mutation 634. Elective thyroidectomy is recommended in children harboring this mutation before the age of 5 years, because MTC develops earlier and clinically is more aggressive. Finally, the ATA level D risk group, which includes mutations 883 and 918, is associated with very early onset of medullary thyroid cancer that often is aggressive. Elective treatment of children who test positive for these mutations is recommended as soon as possible, even before age 1 year.
Surgical Anatomy
The thyroid gland descends from the foramen cecum of the base of the tongue to the lower part of the neck during embryonic development. During this descent, the normal thyroid remnant or the entire thyroid may remain at the foramen cecum (lingual thyroid) or along the thyroglossal tract. The presence and extent of thyroid tissue along the thyroglossal tract determines the presence or absence of the pyramidal lobe. In some instances, thyroid tissue gets sequestered along the thyroglossal tract and may present as a thyroglossal duct cyst. Occasionally, sequestered thyroid tissue may be found in the mediastinum below the normal position of the gland in the neck.
The blood supply to the thyroid gland is derived from the branches of the superior and inferior thyroid arteries. Occasionally, a midline thyroidea ima provides blood supply to the isthmus directly from the innominate artery. Numerous venous tributaries drain into the internal jugular and innominate veins. The primary lymphatic drainage of the thyroid gland is to the perithyroid and paratracheal lymph nodes. Anteriorly, it may drain into the Delphian lymph node. Secondary drainage occurs into lymph nodes in the anterosuperior mediastinum and deep jugular nodes.
The laryngeal nerves lie in close juxtaposition to the thyroid gland and hence are important in thyroid surgery. The superior laryngeal nerve arises from the vagus and traverses posteromedial to the superior thyroid artery. It divides into an internal branch, which enters the larynx through the thyrohyoid membrane, and an external laryngeal branch which descends with the superior thyroid artery and turns medially over the cricothyroid muscle, for which it is the motor nerve. Usually it is located just cephalad to the superior pole of the thyroid lobe. The terminal branches of the superior laryngeal nerve have a variable relationship with the distal branches of the superior thyroid artery, the cricothyroid muscle, and the superior pole of the thyroid gland ( Fig. 12.26 ). The recurrent (inferior) laryngeal nerves arise from the vagus in the mediastinum and return to the neck around the arch of the aorta on the left-hand side and around the innominate artery on the right-hand side. Thus the left recurrent laryngeal nerve ascends parallel to the trachea while the right nerve travels from lateral to medial as it ascends in the neck. Normally the inferior thyroid artery is located anterior to the recurrent laryngeal nerve, but numerous variations are seen in this relationship ( Fig. 12.27 ). The recurrent laryngeal nerve may divide into several branches before entering the larynx ( Fig. 12.28 ). In such instances it is vital that each of these branches be carefully preserved during thyroid surgery, because it is impossible to predict which particular branch will have the major role in function of the vocal cord. Occasionally the right recurrent laryngeal nerve does not ascend from the mediastinum but arises from the vagus nerve in the neck to directly enter the larynx (nonrecurrent right inferior laryngeal nerve) ( Fig. 12.29 ). An example is shown in Fig. 12.30 .
Blood supply to the parathyroid glands is derived from the inferior and superior thyroid arteries. Careful dissection of the parathyroid glands with their blood supply intact is crucial during thyroidectomy. While the major blood supply to both parathyroid glands comes from the inferior thyroid artery, several small collateral arterial branches from the superior thyroid artery also provide blood supply to the superior thyroid glands.
Procedures
Minimally Invasive, Endoscopic/Video-Assisted, and Remote Access/Robotic Techniques of Thyroidectomy
Over the course of the past two decades, there has been increasing interest in employing minimally invasive or remote access techniques for thyroidectomy to avoid a scar in the neck resulting from a “conventional thyroidectomy.” The explicit purpose for using these approaches is to minimize the length of the scar in the neck or to avoid an incision in the neck altogether for thyroid lobectomy or total thyroidectomy. These techniques have gained popularity among some surgeons largely because of the availability of endoscopic and robotic instrumentation and are fueled by technologic developments and industry. In general, the concept of minimally invasive surgery is gaining popularity in all specialties, largely because of the reduction of surgical morbidity associated with conventional open operations and improved aesthetic appeal of smaller scars or no visible scars as a result of incisions in remote locations. This is particularly true for surgical procedures in the abdomen and in the thorax. When resections of neoplasms, particularly malignant neoplasms, are dealt with, however, strict criteria for using minimally invasive procedures must be adhered to so as not to compromise an oncologically complete and safe surgical procedure. Clearly, thyroid surgery is no exception to these general guidelines. With increasing concern on the part of patients undergoing thyroid surgery, with reference to the aesthetic result of the surgical scar in the neck, thyroid surgeons have become sensitive to these concerns of the patients and have used smaller and smaller incisions, placed in natural skin creases, where appropriate, for thyroidectomy.
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