Thyroid, Papillary Carcinoma, Early Treatment & Management

  • Author: Eric J Lentsch, MD; Chief Editor: Arlen D Meyers, MD, MBA   more...
 
Updated: Apr 3, 2012
 

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.

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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.
    • Recent evidence suggests that the use of robotic technology may enhance the effectiveness of endoscopic techniques; however, these data are very preliminary.[14]
    • The videos below demonstrate several aspects of minimally invasive thyroidectomy.
      Minimally invasive thyroidectomy; incision and exposure.
      Minimally invasive thyroidectomy; initial dissection.
      Minimally invasive thyroidectomy; identification of the recurrent laryngeal nerve.
      Minimally invasive thyroidectomy; superior pole release.
      Minimally invasive thyroidectomy; division of isthmus and delivery.
      Minimally invasive thyroidectomy closure.

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. A study of 889 patients, 528 who underwent total thyroidectomy and 361 who underwent hemithyroidectomy, showed similar survival rates among both groups. Comparison of both groups showed no difference in local or regional recurrence.[15] 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.

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Preoperative Details

See Staging.

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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.

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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.

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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.

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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.[16]

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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: Medtronic Consulting fee Consulting; Gyrus Grant/research funds Other; Karl Storz Honoraria None

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, MD, EMT, CCRP  Clinical Research Specialist, Head and Neck Tumor Program, Department of Otolaryngology-Head and Neck Surgery, 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: Siemens 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

Disclosure: Nothing to disclose.

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.

Specialty Editor Board

David J Terris, MD, FACS  Porubsky Professor and Chairman, Department of Otolaryngology, Medical College of Georgia

David J Terris, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American Association for the Advancement of Science, American Bronchoesophagological Association, American College of Surgeons, American Head and Neck Society, Federation of American Societies for Experimental Biology, International Association of Endocrine Surgeons, Phi Beta Kappa, Radiation Research Society, Society of University Otolaryngologists-Head and Neck Surgeons, and Triological Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Nader Sadeghi, MD, FRCSC  Professor, Otolaryngology-Head and Neck Surgery, Director of Head and Neck Surgery, George Washington University School of Medicine and Health Sciences

Nader Sadeghi, MD, FRCSC is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society, American Thyroid Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Christopher L Slack, MD  Private Practice in Otolaryngology and Facial Plastic Surgery, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders

Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA  Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society

Disclosure: Covidien Corp Consulting fee Consulting; US Tobacco Corporation Unrestricted gift Unknown; Axis Three Corporation Ownership interest Consulting; Omni Biosciences Ownership interest Consulting; Sentegra Ownership interest Board membership; Medvoy Ownership interest Management position; Cerescan Imaging Consulting; Headwatersmb Consulting fee Consulting; Venturequest Royalty Consulting

Additional Contributors

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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Standard open thyroidectomy.
Minimally invasive video-assisted thyroidectomy. Courtesy of Ruggieri et al. BMC Surgery 2005 5:9 doi:10.1186/1471-2482-5-9
Minimally invasive thyroidectomy; identification of the recurrent laryngeal nerve.
Minimally invasive thyroidectomy closure.
Minimally invasive thyroidectomy; division of isthmus and delivery.
Minimally invasive thyroidectomy; incision and exposure.
Minimally invasive thyroidectomy; initial dissection.
Minimally invasive thyroidectomy; superior pole release.
Table 1. 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 IIIT3, N0, M0, T1, T2, T3, N1a, M0
Stage IVaT1, T2, T3, N1b, M0, T4a, N0, N1, M0
Stage IVbT4b, any N, M0
Stage IVcAny T, any N, M1
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