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eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery

Thyroid, Papillary Carcinoma, Early

Eric J Lentsch, MD, Assistant Professor of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina College of Medicine
M Boyd Gillespie, MD, MS, FACS, Associate Professor, Department of Otolaryngology, Associate Member of College of Graduate Studies, Medical University of South Carolina; Director, Medical University of South Carolina Snoring Clinics; Surgical Consultant, Medical University of South Carolina Sleep Disorders Center; John C Goddard, MD, Staff Physician, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina; Christina ST Wilhoit, EMT, CCRP, Program Coordinator for Head and Neck Surgery Clinical Trials, Department of Otolaryngology, Hollings Cancer Center, Medical University of South Carolina; Zoran Rumboldt, MD, Associate Professor, Department of Radiology, Medical University of South Carolina; Rana S Hoda, MD, FIAC, Professor of Pathology, Attending Pathologist and Director of Cytopathology, University of Rochester Medical Center; Allen O Mitchell, MD, Chairman, Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center, Portsmouth; Kenneth M Spicer, MD, PhD, Professor of Radiology with Tenure, Director of Nuclear Medicine Residency, Medical Director of Radiology Informatics, Medical University of South Carolina

Updated: Apr 24, 2009

Introduction

Much attention has been generated regarding the topic of thyroid neoplasia and papillary thyroid carcinoma. This attention can be attributed to the frequency of benign thyroid nodules and the clinical difficulty in distinguishing these nodules from malignant thyroid lesions.

Problem

Thyroid nodules are found in up to 7% of the population. Only 4-6.5% of these nodules are malignant. Malignant tumors of the thyroid account for only about 1% of all cancers and only 0.4% of cancer-related deaths. The prognosis for papillary thyroid carcinoma is favorable; however, controversy exists regarding management of this cancer. Surgery is the primary mode of therapy for treatment, but the most appropriate type of resection for this disease is controversial.

Frequency

Papillary thyroid carcinoma accounts for about 80% of all thyroid carcinomas in the United States. The incidence of thyroid cancer increased from 3.6 per 100,000 in 1973 to 8.7 per 100,000 in 2002—a 2.4-fold increase. Virtually the entire increase is attributable to an increase in the incidence of papillary thyroid cancer, which increased from 2.7 to 7.7 per 100,000—a 2.9-fold increase. Between 1988 (the first year SEER collected data on tumor size) and 2002, 49% of the increase consisted of cancers measuring 1 cm or smaller. These trends, combined with the known existence of a substantial reservoir of subclinical cancer and stable overall mortality, suggest that increasing incidence reflects increased detection of subclinical disease, not an increase in the true occurrence of thyroid cancer.

The tumor most often occurs in individuals aged 20-50 years. In adults, the female-to-male ratio of clinically diagnosed papillary carcinoma of the thyroid is 3:1; In children, the tumor is distributed by sex nearly equally. Although this condition is more common in females, they have a better overall prognosis. Papillary thyroid carcinoma occurs more often in whites than in blacks.

Etiology

The etiology of papillary carcinoma is yet to be elucidated, but a number of associations have been made.

  • Molecular
    • Activation of receptor tyrosine kinases (RET/PTC, TRK, MET), whether by rearrangement or gene amplification, appears to be specific for the transformation of thyroid follicular cells into papillary thyroid carcinomas. These rearrangements produce chimeric proteins with tyrosine kinase activities that contribute to the development of the malignant phenotype. Approximately 40% of adults with sporadic papillary carcinoma have RET gene rearrangement, and about 15% have NTRK1 rearrangement. This rearrangement is higher (60%) in children. Somatic point mutation in the BRAF gene may be the most common mutation among papillary thyroid cancers, varying from 29-69 % in different series. This gene encodes a serine/threonine kinase acting on the RAS-RAF-MEK-MAPK signaling pathway. BRAF mutations seem to be much less common in childhood thyroid carcinomas.
    • A 10-fold increased risk of thyroid cancer in relatives of patients with thyroid cancer suggests a genetic basis for susceptibility to these tumors. A correlation between papillary thyroid carcinoma and human leukocyte antigen (HLA)-DR7 has also been observed. Also, a parallel incidence has been described for this tumor in monozygotic twins.
  • Iodine excess
    • Papillary thyroid cancer has been induced in animals with the administration of excess iodine. In Vienna, Austria during a period when iodide intake was low in the population, papillary carcinoma accounted for only 25% of all thyroid cancers instead of the expected 80%.
    • In areas where goiters are endemic, the addition of iodine in the diet has increased the proportion of papillary carcinomas relative to follicular thyroid cancer. However, these cancers are less aggressive and have a better prognosis for long-term survival.
  • Radiation
    • External radiation to the neck increases the incidence of papillary carcinoma of the thyroid later in life. Irradiation during childhood has been associated with the greatest risk for acquiring papillary thyroid cancer. As many as 9% of children irradiated for conditions such as tonsillar hypertrophy, thymic enlargement, and acne have developed thyroid cancer over a period of 20 years. Of the survivors of the atomic bomb explosion in Japan, 6.7% developed papillary thyroid cancers.
    • This percentage is much higher than what is expected in the general population. More recently, data have become available from studies of over 4000 people who developed thyroid cancer after the Chernobyl nuclear accident in 1986.1 They revealed that radiation exposure during childhood carries an increased risk of thyroid cancer and that the risk is radiation dose dependent. The youngest children are most sensitive to radiation-induced carcinogenesis, and the minimal latent period for thyroid cancer development after exposure is as short as 4 years. The vast majority of these cancers are papillary carcinomas. On the molecular level, chromosomal rearrangements (such as RET/PTC) are more common than point mutations of BRAF and other genes. Radiation exposure only increases the risk of developing thyroid cancer; it does not affect the prognosis or the aggressiveness of the tumor. However, treatment with radioactive iodine has not been shown to increase the incidence of thyroidcancers.

Pathophysiology

Gross description

Papillary carcinomas can range in size from microscopic, clinically undetectable lesions to masses up to 10 cm in diameter. The average tumor size at diagnosis is 2.3 cm. As many as 75% of these tumors are multifocal in the thyroid gland. On gross examination, most are pale and firm; less than 10% of papillary carcinomas are truly encapsulated. The larger nodules are usually unencapsulated and locally invasive. Penetration of the capsule of the thyroid gland occurs in about 40% of cases.

Microscopic description

The most common types of thyroid carcinoma are the well-differentiated types, which include papillary and follicular thyroid carcinoma. Both papillary and follicular carcinomas arise from the endodermally derived follicular cell that synthesizes thyroxine and thyroglobulin. This is in contrast to medullary thyroid carcinoma, which is derived from the neuroendocrine calcitonin-producing parafollicular C cells of the thyroid.

Papillary tumors may have a pure papillary histopathology, but more than one half contain an admixture of follicular elements. Long-term follow-up care of patients with these mixed tumors shows that, regardless of the precise proportions, all neoplasms containing some papillary areas have identical biological behavior; therefore, these tumors are classified under papillary and not follicular carcinoma.

The histopathological diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Lloyd (2004) examined interobserver variation by 10 experienced thyroid pathologists in the diagnosis of FVPCA in 87 tumors.2 A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. Diagnostic criteria used to diagnose FVPCA, including pseudoinclusions, nuclear grooves, and powdery nuclei, are clearly not uniformly recognized even by experts; immunohistochemical markers may provide more objective diagnostic criteria.

However, as shown by Papotti (2005) and Sahoo (2001), the immunohistochemical expression of cytokeratin 19, galectin-3 and HBME-1, 3 malignancy-related markers in thyroid papillary carcinoma, including its follicular variant, is assuming increasing importance but should be used with caution.3,4

Thus, genetic alterations in papillary carcinoma of thyroid may hold the ultimate key to diagnosis. Three genetic alterations, including BRAF point mutations, RET/PTC rearrangements, or RAS point mutations, have been recognized in this regard. In a study by Adeniran (2006), these alterations have been shown to be associated with distinct microscopic, clinical, and biologic features of thyroid papillary carcinomas.5 BRAF mutations were associated with older age, taller cell appearance, and more advanced tumor stage at presentation. RET/PTC rearrangements presented at a younger age, showed typical papillary histology, and were associated with a high rate of lymph node metastases. Tumors with RAS mutations were exclusively of FVPCA type.

The identification of these alterations may lead to the increasing use of genetic studies in the diagnosis and in predicting the prognosis of papillary thyroid carcinoma. In addition, these involved genes may also serve as targets for cancer chemotherapy in patients in which standard thyroid cancer treatment is not effective.

The histological features of papillary carcinoma of the thyroid include branching papillae composed of a central fibrovascular core and a single or stratified lining of cuboidal to columnar cells. Tumor cells may form colloid-containing follicles, and foci of squamous metaplasia are frequently found. Nuclear atypia is also an important diagnostic feature.

In more than half of these tumors, the nuclei have a characteristic ground-glass appearance; laminated calcific spherules known as psammoma bodies are also often found within the histological framework. In fact, the presence of psammoma bodies is virtually diagnostic for papillary carcinoma because they are rarely found in other lesions.

Papillary thyroid carcinomas typically invade the lymphatics and spread to other sites within the thyroid gland, as well as to the regional lymph nodes. Lymph node metastases have been reported in the range of 46-90% of cases of papillary carcinoma. Vascular invasion is uncommon; however, if it does occur, the spread of tumor is usually to the lungs and bones. Direct extension into the soft tissues of the neck occurs in approximately 25% of cases.

Variants

The variants of papillary thyroid carcinoma include the following:

  • Encapsulated tumors: About 10% of papillary carcinomas are completely surrounded by a dense fibrous capsule. The prognosis for patients with such tumors is better than the prognosis for patients with unencapsulated papillary carcinoma.
  • Diffuse sclerosing variant: Occurring at a younger age, the diffuse sclerosing variant constitutes 2% of papillary carcinomas and may cause a diffuse goiter without palpable nodules that can be mistaken for goitrous autoimmune thyroiditis. Diffuse involvement of one or both lobes occurs with dense sclerosis, patchy lymphocytic infiltration, and abundant psammoma bodies. Prognosis for individuals with the diffuse sclerosing variant is less favorable than that for individuals with typical papillary thyroid carcinoma.
  • Oxyphilic (Hürthle) cell type: The oxyphilic (Hürthle) cell type variant has typical papillary architecture but may be more aggressive than usual papillary carcinoma.
  • Follicular variant: The follicular variant has a purely follicular architectural pattern but may be recognized by the typical cellular features of papillary carcinoma.
  • Tall-cell carcinoma: Tall-cell carcinoma is a more aggressive form of thyroid carcinoma that differs from the usual form by showing tall columnar cells. The frequency of more aggressive behavior is higher, but the carcinoma resembles papillary carcinoma in other morphologic and clinical aspects.
  • Columnar cell carcinoma: Columnar cell carcinoma is a distinctly more aggressive form of papillary thyroid carcinoma that occurs more often in older men and is associated with a poor prognosis.

Presentation

The mainstays of the preoperative diagnosis of papillary carcinoma are a thorough history and physical examination, including an assessment of risk factors, along with ancillary tests such as cervical ultrasonography and aspiration cytology.

The most common presentation of thyroid cancer is a nontender palpable nodule. However, a diagnostic dilemma is present as this is the presentation of most benign thyroid conditions. A palpable nodule occurs in up to 7% of the general female population. A single nodule has a 5-12% malignancy rate, while multiple nodules have a 3% malignancy rate in the general population.

Papillary carcinoma may also present as a nodule with enlarged cervical lymph nodes or cervical lymphadenopathy in the absence of a palpable thyroid nodule. Benign thyroid tissue can be found in the neck anywhere medial to the sternocleidomastoid muscle. Any thyroid tissue lateral to the sternocleidomastoid muscle should be considered malignant.

Unlike follicular thyroid carcinoma, distant metastases of papillary thyroid carcinoma are rarely observed at the time of presentation. When distant metastases are present at the time malignancy is discovered, the primary tumor is almost invariably large and easily palpable.

Indications

Symptoms of dysphagia, odynophagia, or shortness of breath may lead to the discovery of a thyroid mass during physical examination or ultrasound. Presence of a mass in the thyroid requires further investigation, especially in patients at high risk for carcinoma. A positive fine-needle aspiration finding is an indication for surgical removal of the mass. Some clinicians assert that a history of neck irradiation and a thyroid mass is in itself an indication for surgical excision.

Relevant Anatomy

Knowledge of the anatomy of the infrahyoid neck and thyroid region aids in the identification and preservation of structures (eg, recurrent laryngeal nerve, superior laryngeal nerve, superior thyroid artery, inferior thyroid artery). The isthmus of the thyroid usually overlies the third tracheal ring, although this middle portion of the gland may be absent altogether in some individuals. The thyroid gland consists of a superior pole that may extend as far as the oblique line of the thyroid cartilage, and an inferior pole that may extend as far as the sixth tracheal ring.

The external branch of the superior laryngeal nerve innervates the cricothyroid muscle near the superior pole. The left recurrent laryngeal nerve lies in the tracheoesophageal groove, while the right recurrent laryngeal nerve approaches the thyroid gland from a more lateral position. The superior thyroid artery is the first branch of the external carotid artery and often accompanies the external laryngeal branch of the superior laryngeal nerve near the superior pole of the thyroid as it runs superficially toward the isthmus. The inferior thyroid artery arises from the thyrocervical trunk, which comes off of the subclavian artery. This artery runs in the tracheoesophageal groove and sends branches to the posterior aspect of the lateral thyroid lobe. The inferior thyroid artery has a longitudinal branch that anastomoses with the superior thyroid artery near the superior pole.

Contraindications

Surgical excision of papillary thyroid carcinoma has no absolute contraindications. Even people with distant metastasis would benefit from surgical removal of the primary disease, neck dissection, and ablation with iodine-131.

A total thyroidectomy may be contraindicated in people with disease limited to only one lobe of the thyroid who are likely to be noncompliant with thyroid replacement therapy. These individuals may be better suited for a hemithyroidectomy.

Workup

Laboratory Studies

  • Fine-needle aspiration is one of the mainstays of preoperative diagnosis of papillary carcinoma of the thyroid. The use of fine-needle aspiration cytology can increase the diagnostic accuracy of thyroid malignancy cases to 92%.
  • Serum thyroglobulin level can be used as a postoperative tumor marker for well-differentiated thyroid cancer (ie, papillary, follicular).
  • Two-dimensional gel electrophoresis has also been used as a diagnostic tool to identify tumor-specific proteins from well-differentiated thyroid cancers, but this technique is still being investigated.

Imaging Studies

  • Ultrasonography: Cervical ultrasonography with fine needle aspiration cytology is the mainstay of the preoperative diagnosis of carcinoma of the thyroid.
  • Iodine-131 scans and CT scans occasionally reveal cold thyroid nodules, requiring a follow up ultrasound and fine-needle aspiration. Similarly,18 F-fluorodeoxyglucose (FDG) avid nodules incidentally found on PET scans are occurring with increasing frequency and may require similar clarification.
  • PET with FDG depicts many malignancies, including thyroid cancers.6 The role of FDG-PET scanning in differentiated thyroid cancer has been well described.7 Efforts to distinguish benign from malignant nodules remain controversial, and its expense precludes routine use when malignancy is first diagnosed.8,9
  • Undifferentiated thyroid carcinomas and recurrent or metastatic thyroid cancer my have decreased iodine-131 avidity and consequently present a diagnostic and therapeutic dilemma. In the setting of elevated thyroglobulins and a negative iodine-131 scan, FDG PET/CT offers improved sensitivity, frequently revealing abnormal, FDG avid lesions. Use of FDG-PET/CT during surgical planning for non-iodine avid recurrent disease has been shown significant benefit, especially when ultrasound is equivocal.
  • PET and PET/CT: In addition to data in the literature demonstrating accurate detection of thyroid cancer by PET, one study has hinted that PET may play a role in the management of patients with inconclusive cytologic diagnosis of a thyroid nodule. In this study, PET reduced the number of negative hemithyroidectomies by 66%. Whether the sensitivity of PET and its cost outweighs the costs and risks associated with thyroid surgery have yet to be determined.

Histologic Findings

See Pathophysiology.

Staging

Tumor, node, and metastasis (TNM) for papillary carcinoma of the thyroid are classified as follows:

  • Primary tumor (T)
    • TX: Primary tumor cannot be assessed.
    • T0: No evidence of primary tumor is found.
    • T1: Tumor size is 2 cm or less in greatest dimension and is limited to the thyroid.
    • T2: Tumor size is greater than 2 cm but less than 4 cm, and tumor is limited to the thyroid.
    • T3: Tumor size is greater than 4 cm, and tumor is limited to the thyroid or any tumor with minimal extrathyroidal extension (extension to sternothyroid muscle of perithyroid soft tissues).
    • T4a: Tumor extends beyond the thyroid capsule and invades any of the following: subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve.
    • T4b: Tumor invades prevertebral fascia, mediastinal vessels, or encases the carotid artery.
  • Regional lymph nodes (N)
    • NX: Regional nodes cannot be assessed.
    • N0: No regional node metastasis is found.
    • N1a: Metastasis is found in level VI (pretracheal and paratracheal, including prelaryngeal and Delphian) lymph nodes.
    • N1b: Metastasis is found in unilateral, bilateral, or contralateral cervical or upper/superior mediastinal lymph nodes.
  • Distant metastasis (M)
    • MX: Distant metastasis cannot be assessed.
    • M0: No distant metastasis is found.
    • M1: Distant metastasis is present.

Stages of Papillary Carcinoma of the Thyroid

 Younger Than 45 YearsAge 45 Years and Older
Stage IAny T, Any N, M0T1, N0, M0
Stage IIAny T, Any N, M1T2, N0, M0
Stage III T3, N0, M0, T1, T2, T3, N1a, M0
Stage IVa T1, T2, T3, N1b, M0, T4a, N0, N1, M0
Stage IVb T4b, any N, M0
Stage IVc Any T, any N, M1


Treatment

Medical Therapy

Adjuvant therapy

Thyroid-stimulating hormone (TSH) suppression therapy using administration of thyroid hormone has been used for many years; however, the recurrence rate and survival rate among TSH-suppressed and TSH-nonsuppressed postoperative patients with low-risk papillary thyroid carcinoma are similar. Most centers do not administer thyroid hormone to suppress TSH in euthyroid patients with low-risk papillary thyroid carcinoma.10

Iodine-131 can be used to ablate the remaining thyroid gland in patients with a near-total thyroidectomy and in high-risk patients with persistent disease. If uptake of iodine-131 is inadequate, external beam radiation can be used.

Surgical resection of any involved structures from local extrathyroidal spread is also used in adjuvant therapy.

Surgical Therapy

Thyroidectomy, Surgical Technique

  • Conventional thyroidectomy
    • Thyroidectomy dates to around 1170; however, in the early centuries it remained a rarely performed procedure because of its high morbidity and mortality. The danger of the operation usually came from uncontrolled bleeding and sepsis. However, in the last century, advances in general anesthesia, antisepsis, and hemostasis have paved the way for safe thyroid surgery.
    • At the forefront of these developments was Theodor Kocher, who performed thousands of thyroidectomies and, through development of specific surgical technique, was able to decrease the mortality of the procedure to less than 1%. Today, we continue to use his time-honored technique for thyroidectomy. This technique involves a midline cervical incision, usually 4-8 cm in length; careful ligation of the thyroid vasculature; identification and preservation of the parathyroid glands; identification and preservation of the recurrent laryngeal nerve; mobilization and removal of the gland; and meticulous hemostasis and closure. In the hands of an experienced surgeon, conventional thyroidectomy is an extremely safe and effective procedure.
  • Minimally invasive endoscopic thyroidectomy
    • Over the last several years, novel endoscopic approaches to thyroidectomy have been developed because of a growing desire for the establishment of less-invasive approaches throughout the surgical community. Minimally invasive procedures involve smaller neck incisions compared with conventional thyroidectomy and, as such, tend to demonstrate improved cosmesis, reduced postoperative pain, and shortened hospital stays.
    • Minimally invasive thyroid surgery can be performed in various ways. True “endoscopic” techniques create a working space within the neck using CO2 insufflation, with both axillary and neck approaches as starting points for dissection. This technique, however, has resulted in severe hypercarbia and massive cervical subcutaneous emphysema. A more popular technique is the video-assisted technique, which has been developed, refined and popularized in Italy and Japan, and has more recently been established in the United States.
    • Perhaps the biggest proponent of this technique is Paolo Miccoli, who published his experience with over 550 minimally invasive video-assisted thyroidectomies between 1998 and 2003.11 The procedure requires a small central neck incision and uses external retraction without neck insufflation. This approach combines a mini incision (1-2 cm) and an approach that is familiar to head and neck surgeons. More importantly, this technique allows treatment of both small benign nodules and small thyroid malignancies. Miccoli showed that patients treated with minimally invasive thyroidectomy demonstrated significantly lower postoperative pain, reduced postoperative distress, and improved cosmesis compared with patients undergoing conventional thyroidectomy procedures.
    • Other issues regarding the development of minimally invasive techniques for thyroid surgery include their safety, morbidity, and ease of performance when compared with conventional open techniques. Complications rates for recurrent laryngeal nerve palsy and hypoparathyroidism have been similar to those found in open procedures. Operative times appear to be equivalent, after a moderate learning curve is taken into consideration.
    • Although the indications for minimally invasive thyroidectomy procedures have become standardized for thyroid nodules, some controversy still exists regarding its appropriateness for known thyroid cancer. Recently, several studies have attempted to clarify the growing role for these procedures in thyroid cancer.
    • In a 2006 report, Takami and Ikeda noted that patients with benign follicular adenomas, low-risk papillary carcinomas less than 10 mm, and oxyphilic cell tumors less than 4 cm could be managed with endoscopic thyroidectomy.12 In 2005, Caliceti et al examined 15 patients with papillary thyroid carcinoma (none > 2 cm) who underwent minimally invasive total thyroidectomy.13 Although follow-up was limited, they found that results of this technique were similar to those obtained with open thyroidectomy, except that shorter hospital stays and smaller neck wounds were more common in the minimally invasive group.
    • These studies indicate that minimally invasive techniques are safe for some thyroid cancer patients, but what about the oncologic effectiveness of the technique? In short, no long-term studies on its oncologic effectiveness in comparison to conventional techniques exist. However, some preliminary data exists that shows minimally invasive techniques to be oncologically effective.
    • In 2002, Miccoli et al studied the completeness of thyroid resection when performed via a minimally invasive video-assisted technique. A prospective study of patients with papillary thyroid carcinoma was performed by measuring iodine-131 thyroid bed uptake and serum thyroglobulin levels one month after either minimally invasive thyroidectomy or conventional thyroidectomy. The differences between the 2 techniques were not statistically significant. Several follow-up studies have reinforced these findings, hinting that it is a good surgical option in patients with small papillary thyroid carcinoma. However, long-term results must be evaluated before declaring it equivalent to conventional thyroidectomy.
Thyroidectomy, Extent of Surgery
  • Hemithyroidectomy: Patients with papillary carcinoma can be separated into low- and high-risk categories for mortality based on prognostic factors. These factors include age, distant metastatic disease, extrathyroidal invasion, and size of primary lesion. Some surgeons believe that hemithyroidectomy is the most appropriate treatment for low-risk papillary carcinoma that is macroscopically localized in one lobe or for patients with occult papillary thyroid cancers. This balances the risk of complications from a more involved surgery with the chance of recurrence. This surgery may be a good choice for patients who may not be compliant with thyroid hormone replacement postoperatively.
  • Near-total thyroidectomy: A near-total thyroidectomy can be performed to decrease the risk of damage to the recurrent laryngeal nerve or parathyroid glands. Some thyroid tissue is left during the resection and subsequently can be ablated with iodine-131.
  • Total thyroidectomy: Total thyroidectomy remains the criterion standard treatment for papillary thyroid carcinoma. Total thyroidectomy is recommended if the primary tumor is 1.0 cm or greater, or if extrathyroidal extension or metastases is present. This surgical procedure removes all thyroid tissue so that postoperative iodine-131 is more effective in treating occult disease, eliminates the risk of leaving occult disease in the thyroid, and allows serum thyroglobulin levels to be more sensitive in detecting recurrent or persistent disease. Although the risk of surgical complication is higher than that of hemithyroidectomy or near-total thyroidectomy, most experts agree that the risk of recurrent disease is lower and the survival rate is higher after total thyroidectomy.

Neck Disease
The thyroid gland has a rich lymphatic network. Papillary thyroid carcinoma readily enters the intrathyroidal lymphatics and spreads to lymph nodes in the anterior compartment of the neck.

Cervical lymph node involvement is common in papillary thyroid carcinoma, with positive adenopathy in 35% of cases and micrometastatic lymphatic deposits in up to 80% of cases. Up to 10% of patients with papillary thyroid carcinoma have a recurrence in the neck; however, prolonged survival is the norm even in the setting of extensive neck disease. In large longitudinal and case-control studies, positive neck disease had little impact on survival from papillary thyroid carcinoma after controlling for patient age, male sex, extent of disease, and tumor grade.

Elective neck dissection does not offer a benefit in the setting of small (<1 cm) primary papillary cancers since the 5-year recurrence rates are extremely low in both undissected and dissected necks (<0.5%). In the setting of multifocal disease within the thyroid, however, the odds of nodal recurrence are 6 times greater than those seen with a single foci of tumor. Performing elective central node dissection in the setting of larger (> 1 cm) and multifocal papillary thyroid carcinomas has several advantages. The are as follows:

  • Provides more tissue for accurate tumor staging
  • Decreases rate of local recurrence
  • Reduces likelihood of a more challenging reoperation that carries a higher risk of complications
  • Reduces local tumor load, which may increase radioactive iodine uptake in distant metastatic foci, if present
  • Renders more patients athyroglobulinemic, again by reducing local tumor load and thus allowing better surveillance
  • Addresses tumors with poor radioactive iodine uptake (papillary tall cell variant, Hürthle cell carcinoma)

Elective neck dissection results in higher rates of temporary recurrent nerve paresis and hypocalcemia; however, these risks may be reduced by injecting the thyroid with isosulfan blue or other tracer to clearly visualize the draining lymph nodes. Lateral neck dissections are reserved for palpable neck disease since subclinical disease usually responds to postoperative radioactive iodine.

Preoperative Details

See Staging.

Follow-up

For long-term follow-up care, perform a physical examination and obtain serum thyroglobulin level every 2 months for the first year, every 3 months for the next 2 years, every 6 months for the following 2 years, and then annually for the rest of the patient's life. Supplement this regimen with cervical ultrasonography and chest radiograph annually and total body iodine scintigraphy every 2 years. If relapse is suspected, PET scanning or PET/CT may be helpful. At this point in time the role of PET and PET/CT is evolving. Its greatest utility seems to be in the group of patients who during follow-up are found to have elevated thyroglobulin levels, but a negative iodine-131 scan. In this group of patients, the reported sensitivity, specificity, and accuracy of PET/CT was 68%, 82%, and 74%, respectively, for detection and localization of recurrence. Other studies have demonstrated similar results.

Complications

Complications of resection of papillary thyroid carcinoma are those associated with thyroidectomy. Damage to the recurrent laryngeal nerve can lead to vocal cord paralysis and hoarseness. Damage to the external laryngeal branch of the superior laryngeal nerve may produce dysphonia because it denervates the cricothyroid muscle, which regulates pitch. Transection of the internal branch of the superior laryngeal nerve causes the mucosa of the piriform sinus and false vocal cords to become insensate, thereby placing the patient at an increased risk for chronic aspiration. Resection of the thyroid without reimplantation of parathyroidal tissue may result in hypocalcemia.

Outcome and Prognosis

In general, the prognosis for papillary carcinoma of the thyroid is excellent. A long-term survival rate of approximately 90% exists. One study showed a 1-year survival rate of 97.5%, a 5-year survival rate of 92.8%, a 10-year survival rate of 89.5%, and a 20-year survival rate of 83.9%.

Prognostic factors include tumor size, patient age, extrathyroidal spread, and histological variant. The presence of vascular invasion, even within the thyroid gland, is associated with more aggressive disease at diagnosis and has a higher incidence of tumor recurrence. About 30% of patients develop tumor recurrence. Two thirds of recurrences are within the first decade after therapy. Tumors recur outside of the neck in about 21% of those patients with recurrence. The most common site for distant metastasis is the lung. Mortality rates are lower when recurrences are detected early based on radioiodine scans rather than clinical signs. A long delay in initiating the previously described treatment results in more than 2 times the 30-year cancer mortality rate.

Quality of life and psychosocial issues

Despite the relatively favorable prognosis of papillary thyroid carcinoma, multiple studies have demonstrated that the quality of life among these patients is lower than would be expected, both in the initial year after diagnosis and long term.

Follow-up monitoring for thyroid cancer can have profound effects on patients' lives, as they are required to undergo levothyroxine withdrawal for 4-6 weeks prior to whole-body scanning. This places the patient in the position of trying to maintain normal activity and function while experiencing the well-documented effects of hypothyroidism, including increased fatigue, memory loss, mood disturbances, decreased motor skills, and the many other effects of thyroid dysregulation. The impact of this experience on work performance, family relationships, and social life can be detrimental to the well-being of these patients.

Although the significant effects of levothyroxine withdrawal have been documented for some time, significant deficits in the health-related quality of life and psychometric functionality of patients while on maintenance levothyroxine have recently been reported. Although these deficits are less severe than those experienced during periods of levothyroxine withdrawal, they can be significant, as levothyroxine supplementation therapy typically continues for the remainder of a patient's life.

Future and Controversies

Controversy exists regarding the treatment of papillary thyroid carcinoma. Treatment with total or near-total thyroidectomy results in a higher surgical complication rate, but more conservative measures result in a higher rate of postoperative cancer recurrence. Determination of prognostic factors to classify patients with papillary carcinoma into high- or low-risk categories for mortality after surgery is ongoing. To date, these prognostic factors include age, histologic grade, extrathyroidal invasion, distant metastases, and sex. Classification into high- and low-risk categories can aid in the determination of the most appropriate type of resection.

Much of current clinical research on papillary thyroid carcinoma is focused on finding better methods of detection and better prognostic indicators. Headway is being made in the identification of genetic markers in tumor cells that indicate prognosis in general, as well as in the tendency of the cancer to metastasize. Gene expression patterns have been found that can differentiate between benign thyroid tissue and papillary thyroid carcinomas, as well as between papillary and follicular carcinomas. One example involves the measurement of thyroglobulin concentration in the biopsy tissue obtained from fine-needle aspiration biopsy, which may be useful to determine the involvement of lymph nodes either at initial presentation or in recurrent disease.

Perhaps the most exciting potential for postoperative papillary thyroid patients is the discovery that the administration of rhTSH can stimulate thyroid remnants without causing symptoms of hypothyroidism. At this point in time, rhTSH has been used effectively for the follow-up of thyroid cancer patients and in thyroid remnant ablation, and studies are ongoing to show it’s efficacy in these areas and others.  In the future, patients may be given rhTSH to prepare them for whole-body scanning and to entirely avoid the 4-6 week ordeal of levothyroxine withdrawal.14

Multimedia

Standard open thyroidectomy.

Media file 1: Standard open thyroidectomy.

Minimally invasive video-assisted thyroidectomy. ...

Media file 2: Minimally invasive video-assisted thyroidectomy. Courtesy of Ruggieri et al. BMC Surgery 2005 5:9 doi:10.1186/1471-2482-5-9

Media file 3: Minimally invasive thyroidectomy; identification of the recurrent laryngeal nerve.

Video available at http://img.medscape.com/pi/emed/ckb/otolaryngology/834279-846565-849000-1662288.flv.

Media file 4: Minimally invasive thyroidectomy closure.

Video available at http://img.medscape.com/pi/emed/ckb/otolaryngology/834279-846565-849000-1662289.flv.

Media file 5: Minimally invasive thyroidectomy; division of isthmus and delivery.

Video available at http://img.medscape.com/pi/emed/ckb/otolaryngology/834279-846565-849000-1662291.flv.

Media file 6: Minimally invasive thyroidectomy; incision and exposure.

Video available at http://img.medscape.com/pi/emed/ckb/otolaryngology/834279-846565-849000-1662292.flv.

Media file 7: Minimally invasive thyroidectomy; initial dissection.

Video available at http://img.medscape.com/pi/emed/ckb/otolaryngology/834279-846565-849000-1662293.flv.

Media file 8: Minimally invasive thyroidectomy; superior pole release.

Video available at http://img.medscape.com/pi/emed/ckb/otolaryngology/834279-846565-849000-1662294.flv.

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Keywords

papillary carcinoma, thyroid carcinoma, thyroid carcinomas, papillary carcinomas, thyroid cancer, thyroid neoplasia, thyroid neoplasias, papillary and follicular carcinoma, thyroid tumor, thyroid tumors, diffuse sclerosing variant, Hürthle cell, oxyphilic cell, tall-cell carcinoma, columnar cell carcinoma, thyroid mass, thyroid masses, hemithyroidectomy, near-total thyroidectomy, thyroidectomy, modified radical neck dissection, ipsilateral radical neck dissection, psammoma bodies

Contributor Information and Disclosures

Author

Eric J Lentsch, MD, Assistant Professor of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

M Boyd Gillespie, MD, MS, FACS, Associate Professor, Department of Otolaryngology, Associate Member of College of Graduate Studies, Medical University of South Carolina; Director, Medical University of South Carolina Snoring Clinics; Surgical Consultant, Medical University of South Carolina Sleep Disorders Center
M Boyd Gillespie, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American Academy of Sleep Medicine, American College of Surgeons, American Head and Neck Society, American Medical Association, Johns Hopkins Medical and Surgical Association, Phi Beta Kappa, and South Carolina Medical Association
Disclosure: Nothing to disclose.

John C Goddard, MD, Staff Physician, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina
John C Goddard, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American Medical Association, and South Carolina Medical Association
Disclosure: Nothing to disclose.

Christina ST Wilhoit, EMT, CCRP, Program Coordinator for Head and Neck Surgery Clinical Trials, Department of Otolaryngology, Hollings Cancer Center, Medical University of South Carolina
Disclosure: Nothing to disclose.

Zoran Rumboldt, MD, Associate Professor, Department of Radiology, Medical University of South Carolina
Zoran Rumboldt, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, American Society of Neuroradiology, and Radiological Society of North America
Disclosure: Bracco Grant/research funds Other

Rana S Hoda, MD, FIAC, Professor of Pathology, Attending Pathologist and Director of Cytopathology, University of Rochester Medical Center
Rana S Hoda, MD, FIAC is a member of the following medical societies: American Society for Clinical Pathology, American Society of Cytopathology, College of American Pathologists, College of American Pathologists, International Academy of Cytology, South Carolina Medical Association, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Allen O Mitchell, MD, Chairman, Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center, Portsmouth
Allen O Mitchell, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, and American Medical Association
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Kenneth M Spicer, MD, PhD, Professor of Radiology with Tenure, Director of Nuclear Medicine Residency, Medical Director of Radiology Informatics, Medical University of South Carolina
Kenneth M Spicer, MD, PhD is a member of the following medical societies: American College of Nuclear Medicine, American College of Nuclear Physicians, American College of Radiology, Association of University Radiologists, Radiological Society of North America, Society of Nuclear Medicine, and South Carolina Medical Association
Disclosure: Nothing to disclose.

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Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
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Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Terry A Day, MD; Michael C Noone, MD; Joshua D Hornig, MD, FRCSC; Jyotika K Fernandes, MBBS, MD; and Anand K Sharma, MBBS, to the development and writing of this article.

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