PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
Histogenesis rather than anatomic extent determines the malignant gradient in thyroid cancer staging because it determines behavior clinically and pathologically.
PERSPECTIVE AND PATTERNS OF SPREAD
The thyroid nodule is a common occurrence in clinical medicine and most often nodular glands are benign and functioning. The concern as to the possibility of a malignancy is heightened with a history of irradiation as an infant for an “enlarged thymus” or for acne as a teenager. The thyroid scintiscan of concern is nonfunctioning (cold) compared with a hyperfunctioning (hot) nodule in thyrotoxic patients. Thyroid cancer is two to four times more common among women than men. Median age is 45 to 50 years with a wide range of young to older patients afflicted annually in the United States. There are 14,000 new cases and 1,100 deaths every year. The disparity between incidence and deaths represents their “benign” course as well as improvements in detection, diagnosis, and treatment. Patterns of Spread are presented as a cancer crab that can invade in six basic directions Superior-Inferior, Medial-Lateral, Anterior-Posterior (SIMLAP) of adjacent anatomic sites (Fig. 11.2; Table 11.2).
PATHOLOGY
The histopathology as well as the surrounding anatomy determines the spread patterns. There are five distinct different cancers, each with different management features (Table 11.1). The vectors of the more common differentiated variety tend to be local regional, although hematogenous and lymphatic dissemination occur (Fig. 11.1).
Figure 11.1| Papillary carcinoma of the thyroid. Branching papillae are lined by neoplastic columnar epithelium with clear nuclei. A calcospherite, or psammoma body, is evident.
Figure 11.2 | Patterns of spread. A. Coronal view: Note invasion or recurrent laryngeal nerve. B. Sagittal view: Note invasion of esophagus and trachea and substernal extension. The primary cancer (thyroid) invades in various directions, which are color-coded vectors (arrows) representing the stage of progression: T0, yellow; T1, green; T2, blue; T3, purple; T4a, red; and T4b, black. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six directional pattern i.e. SIMLAP Table 11.2.
TNM STAGING CRITERIA
TNM STAGING CRITERIA
Histogenesis is the major factor in thyroid cancer staging because it determines behavior clinically and pathologically (Fig. 11.3). Thyroid adenomas are by far the most common tumors of this endocrine gland. They are, for the most part, low-grade carcinomas, which invade into the gland substance and are considered multicentric in origin, although intraglandular spread may seem to be similar. Nodules of the thyroid are much more common than parathyroid adenomas, and malignant degeneration similarly is a much more likely event in the thyroid. Depending on the type of thyroid malignancy, different spread patterns occur. Common types can be divided into the follicular adenocarcinoma, papillary adenocarcinoma, medullary, and anaplastic tumors, which are either small or large cell carcinomas.
Follicular carcinoma tends to be nodular and encapsulated and is more likely to displace than invade into the gland substance and its surrounding structures. Its major spread pattern is via the venous system into the systemic circulation, leading to lung and bone metastases.
Papillary adenocarcinomas are the most common tumor of the thyroid and tend to be more invasive locally, breaking through and invading the thyroid capsule into surrounding tissues. They rarely tend to be locally recurrent after their resection, indicating only low-grade local aggressiveness. Distant hematogenous spread is uncommon; these cancers tend to invade into regional lymph nodes, which can be involved bilaterally. Occasionally, the oncologic presentations can be as metastatic cervical lymph nodes of unknown origin. Neck node dissections can be more effective treatments rather than radical neck node resections.
Medullary thyroid cancers account for 10% of all thyroid cancers, can be familial, and are transmitted as an autosomal-dominant trait with high penetrance. Multiple endocrine tumors can be present as pheochromocytomas, parathyroid adenomas, or ganglioneuromatosis. These medullary thyroid cancers tend to localize between the upper third and lower two thirds of the lobe and appear on cut section as a red hard lesion consisting of C-cells, physiologically producing calcitonin. They can be locally invasive, spreading into regional nodes, or form distant metastases in liver, lung, and bones. Fortunately, these lesions tend to be slow growing.
Anaplastic small and large cell carcinomas can be very rapidly growing tumors, very invasive, and aggressive locally, leading to tracheal and/or esophageal invasion and compression. If they extend into the superior mediastinum, they can lead to compression of the superior vena cava. The recurrent laryngeal nerves are very intimately involved posterior to the thyroid gland and can be invaded; these tumors aggressively infiltrate through the capsule of the thyroid gland.
All anaplastic cancers are considered as T4. Their staging has been modified into T4a and T4b as to resectability. The size of the tumor, as in other head and neck sites, does not apply; and T3. T4a is a cancer nodule with anterior extrathyroid extension involving the sternohyoid muscle surrounding soft tissues larynx, trachea, esophagus, and recurrent laryngeal nerve. T4b is for posterior extension and invasion into the prevertebral space.
In summary, the major spread patterns are intraglandular spread; T4a, extraglandular spread into the sternocleidomastoid muscle and skin; into surrounding structures such as the trachea and esophagus; and into the recurrent laryngeal nerves, particularly on the right side. T4b is spread posteriorly into the prevertebral muscle and/or inferiorly deep into the mediastinum, carotid artery.
SUMMARY OF CHANGES SEVENTH EDITION AMERICAN JOINT COMMITTEE ON CANCER (AJCC)
The TNM stages according to the 7th Edition of AJCC are illustrated in color code of advancement (Fig. 11.3).
• Tumor staging (T1) has been subdivided into T1a (≤1 cm) and T1b (>1–2 cm) limited to thyroid.
• The descriptors to subdivide T categories have been changed to solitary tumor(s) and multifocal tumor (m).
• The terms “resectable” and unresectable” are placed with “moderately advanced” and “very advanced.”
• The TNM Staging Matrix is color coded for identification of Stage Group once T and N stages are determined (Table 11.3).
THYROID
Figure 11.3 | TNM stage grouping. Thyroid cancers are highly varied histologically and their cellular phenotype determines their biologic behavior, which ranges from a benign course to highly malignant. Vertical presentations of stage groupings, which follow the same color code for cancer stage advancement, are organized in horizontal lanes: Stage 0, yellow; I, green; II, blue; III, purple; IVA, red; and IVB, and IVC, black. Definitions of TN on left and stage grouping on right.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The anatomic isocenter for thyroid gland is at C7 level and inferior to the cricoid cartilage, readily palpable on swallowing when the gland moves vertically. The anterior bullet enters below the cricoid cartilage (Fig. 11.4A) and the lateral bullet through the anterior surface of the trachea (Fig. 11.4B).
T-oncoanatomy
The thyroid gland is a bilobed structure, symmetrical in size, and connected by an isthmus. It is approximately 2 to 3 cm long and wide and is shaped like a horseshoe.
• Coronal plane (Fig. 11.5A): From the anterior view, the gland is in close proximity to the cervical portion of the trachea, below the thyroid cartilage. It is located deep to the strap muscles of the neck, which include the sternocleidomastoid, sternohyoid, and sternothyroid muscles.
• Sagittal plane (Fig. 11.5B): Deep to the thyroid gland are the internal jugular vein and the common carotid artery. The recurrent laryngeal nerve lies posterior to the thyroid gland, particularly on the left side where it courses along the gland's entire length into the thorax; the right recurrent laryngeal is more lateral in its location as it hooks around the subclavian artery.
• Transverse plane (Fig. 11.5C): Deep to the left lobe of the thyroid is the thoracic duct, which rises into the neck and extends anteriorly, inserting into the junction of the left internal jugular and subclavian veins.
Figure 11.4 | Orientation of three-planar T-oncoanatomy. The anatomic isocenter is at the axial level at C7. A. Coronal. B. Sagittal.
Figure 11.5 | T-oncoanatomy. The Color Code for the anatomic sites correlates with the color code for the stage group (Fig. 11.3) and patterns of spread (Fig. 11.2) and SIMLAP tables (Table 11.2). Connecting the dots in similar colors will provide an appreciation for the 3D Oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
The nodal drainage of the thyroid is into the anterior and deep cervical lymph nodes. There is a small Delphic node, which sits in the midline at the superior margin of the isthmus.
In a reported series of papillary thyroid cancers, the frequency and levels of lymph node metastases are noted in Figure 11.6 and Table 11.4. The incidence for clinically negative (N0) neck, prophylactic dissection found 61% with node involvement which increased to 95.8%. (Tables 11.5A and 11.5B; Fig. 11.7A,B).
M-ONCOANATOMY
The thyroid gland is supplied by branches from the external carotid artery, superior thyroid, and subclavian artery with the inferior thyroid artery, which arises directly from the carotid artery. The venous pattern follows the arterial blood supply and drains into the internal jugular vein via superior, middle, and inferior veins (see Figs. 1.6 and 11.7B).
Figure 11.6 | N-oncoanatomy. The red node highlights the sentinel node, which is after the jugulo-omohyoid node but all deep cervical jugular nodes are at risk on the ipsilateral side. A. Anterior view. B. Lateral view. M-oncoanatomy is determined by the jugular vein, which joins with the subclavian vein to form the superior vena cava on the right, and the Innominate vein, which drains into the right side of the heart and then into lung.
Figure 11.7 | A. Incidence and distribution of N0 neck node regional metastases. B. Incidence and distribution N+ according to AJCC neck regions.
STAGING WORKUP
RULES OF CLASSIFICATION AND STAGING
Clinical Staging and Imaging
Assessment of thyroid tumor depends on inspection and palpation of the thyroid gland and regional neck nodes. Indirect laryngoscopy is essential to determine if vocal cord paresis or paralysis is present because of the proximity of recurrent laryngeal nerves. A large variety of imaging procedures are available, particularly the I131 scintiscan and uptake, which requires no iodine contrast be used before this test is done. Technetium 99M pertechnetate is currently the most widely used thyroid imaging agent. Ultrasound is the most sensitive technique for detecting focal pathology and is used for screening persons at risk. Radionuclide single photon emission computed tomography utilizing a variety of agents is recommended in Table 11.6 and Figure 11.8.
Pathologic Staging
The gross specimen should be evaluated for margins. Unresected gross residual tumor must be included and marked with clips. All resected lymph node specimens should describe size, number, and level of involved nodes and whether there is extracapsular spread. Specimens taken after radiation and/or chemotherapy need to be so noted; specimen shrinkages may occur up to 30% after resection itself. Designations pT and pN should be used after histopathologic evaluation. Perineural invasion deserves special notation.
Oncoimaging Annotations
• Microcalcifications are almost exclusively found in malignancies, mainly papillary and medullary carcinomas.
• Ultrasound is the most sensitive technique for detecting focal pathology and plays an important role in screening those at risk of developing thyroid malignancy.
• Ultrasound-guided fine-needle aspiration remains the most accurate means of distinguishing between benign and malignant lesions.
• Cystic papillary carcinomas are anechoic, with solid nodules protruding into the cyst and calcification in intracystic nodules.
• Tc99m pertechnetate is the most widely used thyroid imaging agent; a solitary cold nodule is associated with malignancy in 10% to 20% of cases.
• Tc99m DMSA and In-111 pentreotide are the imaging agents of choice for medullary carcinoma.
• Computed tomography or magnetic resonance imaging of the thyroid demonstrating surrounding structures (strap muscles) and encasement of the great vessels and recurrent laryngeal nerve is pathognomonic for cancer.
PROGNOSIS AND SURVIVAL
• Enlarged cervical nodes, especially ipsilaterally, are common findings. Size per se is nonspecific, but the presence of microcalcifications or complete cystic degeneration is characteristic of cancer.
• Total body I131 scan is utilized in searching for functioning follicular and/or papillary metastatic pulmonary and osseous foci post total thyroidectomy.
PROGNOSTIC FACTORS
The seventh edition of the AJCC Cancer Staging Manual lists the following prognostic factors for nasal ethmoid sinus cancers:
• Size of lymph nodes
• Extracapsular extension from lymph nodes for head and neck
• Head and neck lymph nodes levels I-III
• Head and neck lymph nodes levels IV-V
• Head and neck lymph nodes levels VI-VII
• Other lymph node group
• Clinical location of cervical nodes
• Extracapsular spread (ECS) clinical
• Extracapsular spread (ECS) pathologic
• Human papillomavirus (HPV) status
• Tumor thickness
• Extra thyroid extension
• Histopathology*
CANCER STATISTICS AND SURVIVAL
Specifically, the success in treating thyroid cancer is reflected in the large population of patients who are long-term survivors. The dominant papillary and follicular carcinomas yield 80% to 95% 10-year survival. Anaplastic cancers, both small and large cell varieties, are highly lethal (Figure 11.9).
*The foregoing passage is from Edge SB, Byrd DR, and Compton CC, et al, AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010, p. 38.
Figure 11.8 | Neck and Larynx—Axial CT scan. The CT/MRI transverse section can be correlated with the anatomy in Figure 11.5C as an assist to staging.
There are an estimated 45,000 new cases on Thyroid cancer in 2011 in the United States with 75% in women. The incidence rate continues to increase annually since mid 1990s and is the fastest increasing cancer in both males and females. Fortunately, Thyroid cancers are highly curable with 1,690 deaths in 2010 with death rate increasing by 1% since 1983 in men and stable in women. Risk factors are family history and radiation exposure particularly with radioactive I131 fallout due to nuclear power plant accidents. The 5 year survival rate for all thyroid cancer patients is 97%, 100% for localized stages, 97% regional stage and even 59% for distant metastases. As noted in Figure 11.9for most histopathologic types, except for anaplastic cancers which are fatal.
Figure 11.9 | Five-year survival rates by stage at diagnosis. (Data from Edge SB, Byrd DR, and Compton CC, et al, AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010.)
SECTION 2
Thorax Primary Sites
