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eMedicine Specialties > Oncology > Carcinomas of Endocrine Organs

Thyroid, Papillary Carcinoma

Luigi Santacroce, MD, Assistant Professor, Medical School, State University at Bari, Italy
Silvia Gagliardi, MD, Consulting Staff, Department of Surgery, Medical Center Vita, Italy; Andrew Scott Kennedy, MD, Co-Medical Director, Wake Radiology Oncology

Updated: Aug 20, 2008

Introduction

Background

Papillary carcinoma is a relatively common well-differentiated thyroid cancer. Papillary/follicular carcinoma must be considered a variant of papillary thyroid carcinoma (mixed form). Despite its well-differentiated characteristics, papillary carcinoma may be overtly or minimally invasive. In fact, these tumors may spread easily to other organs. Papillary tumors have a propensity to invade lymphatics but are less likely to invade blood vessels. Papillary carcinoma appears as an irregular solid or cystic mass in a normal thyroid parenchyma.

Thyroid cancers are more often found in patients with a history of low- or high-dose external irradiation. Papillary tumors of the thyroid  are the most common form of thyroid cancer to result from exposure to radiation. The life expectancy of patients with this cancer is related to their age. The prognosis is better for younger patients than for patients who are older than 45 years. Of patients with papillary cancers, about 11% present with metastases outside the neck and mediastinum. Some years ago, lymph node metastases in the cervical area were thought to be aberrant (supernumerary) thyroids because they contained well-differentiated papillary thyroid cancer.

Pathophysiology

Papillary thyroid carcinoma seems closely related to the activation of trk and ret proto-oncogenes, both acting by amplifying and rearranging mechanisms. The trk proto-oncogene codes for tyrosine kinase receptors; the ret shows a paracentric inversion of chromosomes 10 and 11 in 30-35% of the cases. However, the met proto-oncogene is overexpressed and/or amplified in 3 of 4 patients.

In addition, evidence suggests that some molecules that physiologically regulate the growth of the thyrocytes, such as interleukin-1 and interleukin-8, or other cytokines (ie, insulinlike growth factor-1, transforming growth factor-beta, epidermal growth factor) could play a role in the pathogenesis of this cancer.

Frequency

United States

Approximately 74-80% of the thyroid cancers diagnosed each year in the United States are of the papillary type.

International

Thyroid cancers are quite rare, accounting for only 1.5% of all cancers in adults and 3% of all cancers in children, but the rate of new cases is increasing in the last decades. The highest incidence of thyroid carcinomas in the world is found among female Chinese residents of Hawaii. During the last few years, the frequency of papillary cancer has increased, but this increase in frequency is related to an improvement in diagnostic techniques and the information campaign about this carcinoma. Of all thyroid cancers, 74-80% of cases are papillary cancer. Follicular carcinoma incidences are higher in regions where incidence of endemic goiter is high.

Mortality/Morbidity

In contrast to other cancers, thyroid cancer is almost always curable. Most thyroid cancers grow slowly and are associated with a very favorable prognosis. The mean survival rate after 10 years is higher than 90% and is 100% in very young patients with minimal nonmetastatic disease.

  • Distant spread (ie, to lungs or bones) is very uncommon. Worldwide, autopsy reviews show a high incidence of microscopic foci of thyroid carcinoma.
  • Differing from medullary thyroid carcinoma, papillary thyroid cancer is not a part of multiple endocrine neoplasia syndromes. Uncommon familial syndromes such as familial adenomatous polyposis, Gardner syndrome (Gardner's syndrome), and Cowden disease (Cowden's disease) may be associated with thyroid papillary tumors in about 5% of cases.
  • The mean mortality rate is 1.5% for females and 1.4% for males.

Race

This cancer occurs more frequently in whites than in blacks.

Sex

The female-to-male ratio is near 3:1 and is related to the patient's age.

  • In patients younger than 19 years, the female-to-male ratio is 3.2:1.
  • In patients aged 20-45 years, the female-to-male ratio is 3.6:1.
  • In patients older than 45 years, the female-to-male ratio is 2.8:1.

A useful and updated source for informations about the epidemiology of papillary carcinoma of the thyroid is American Cancer Society's Cancer Facts and Figures. 

ACS Estimated New Thyroid Carcinoma Cases and Deaths by Sex, US, 2008

 Cases and Deaths

Total 

Males

Females

Estimated new cases

37,340

8,930

28,410

Estimated deaths  

1,590

680


 

910



Age

Thyroid carcinoma is common in persons of all ages, with a mean age of 49 years and an age range of 15-84 years. In the younger population, papillary thyroid carcinoma tends to occur more frequently than follicular carcinoma, with a peak in patients aged 30-50 years.

Clinical

History

Patients with papillary carcinoma, a relatively common well-differentiated thyroid cancer, may present with the following history:

  • Numerous cases of papillary thyroid cancer are subclinical.
  • The most common presentation of thyroid cancer is an asymptomatic thyroid mass or a nodule that can be felt in the neck.
  • Record a thorough medical history to identify any risk factors or symptoms.
  • For any patient with a thyroid lump that has developed recently, obtain a history regarding every prior exposure to ionizing radiation and the lifetime duration of the radiation exposure.
  • Consider a family history of thyroid cancer.
  • Some patients have persistent cough, difficulty breathing, or difficulty swallowing.
  • Pain is seldom an early warning sign of thyroid cancer.
  • Other symptoms (eg, pain, stridor, vocal cord paralysis, hemoptysis, rapid enlargement) are rare. These symptoms can be caused by less serious problems.
  • At the time of diagnosis, 10-15% of patients have distant metastases to the bones and lungs and, initially, are evaluated for pulmonary or osteoarticular symptoms (eg, pathologic fracture, spontaneous fracture).

Physical

  • Palpate the patient's neck to evaluate the size and firmness of the thyroid and to check for any thyroid nodules. The principal sign of thyroid carcinoma is a palpable, firm, and nontender nodule in the thyroid area. This mass is painless.
  • Some patients have a tight or full feeling in the neck, hoarseness, or signs of tracheal or esophageal compression.
  • With thyroid palpation, a usually solitary nodule that has a hard consistency, an average size of less than 5 cm, and ill-defined borders can be felt. This nodule is fixed in respect to surrounding tissues and moves with the trachea at swallowing.
  • Usually, signs of hyperthyroidism or hypothyroidism are not observed.

See related CME at Examining the Ears, Nose, and Oral Cavity in the Older Patient.

Causes

  • The thyroid is particularly sensitive to the effects of ionizing radiation. Exposure to ionizing radiation results in a 30% risk for thyroid cancer.
  • A history of exposure of the head and neck to x-ray beams, especially during childhood, has been recognized as an important contributing factor for the development of thyroid cancer. For example, 7% of individuals exposed to the atomic bomb in Japan developed thyroid cancers.1
  • From 1920-1960, therapeutic irradiation of body areas  was used to treat tumors and benign conditions (eg, acne; excessive facial hair; tuberculosis in the neck; fungus diseases of the scalp; sore throats; chronic coughs; enlargement of the thymus, tonsils, and adenoids). Approximately 10% of individuals who were treated with irradiation developed thyroid cancer after a latency period of 30 years.
  • Port et al report the "signature" of 7 genes (ie, SFRP1, MMP1, ESM1, KRTAP2-1, COL13A1, BAALC, PAGE1) in papillary thyroid cancers after the Chernobyl accident, demonstrating by PCR techniques their role in distinguishing such cases from sporadic forms.
  • Patients who need radiotherapy for certain types of cancer of the head and neck area also may have an increased risk of developing thyroid cancer.
  • Exposure to diagnostic x-ray beams does not increase the risk of developing thyroid cancers. Several reports have shown a relationship between iodine deficiency and the incidence of thyroid carcinomas.
  • Many other conditions  have been considered as predisposing to papillary thyroid cancer (oral contraceptive use, benign thyroid nodules, late menarche, late age at first birth).2,3
  • Tobacco smoking seems to be associated with a decreased risk of thyroid cancer, but, obviously, it poses more health hazards than benefits.4

Differential Diagnoses

De Quervain Thyroiditis
Thyroid Nodule
Goiter
Thyroid, Anaplastic Carcinoma
Goiter, Nontoxic
Thyroid, Follicular Carcinoma
Goiter, Toxic Nodular
Thyroid, Medullary Carcinoma
Graves Disease
Hurthle Cell Carcinoma
Thyroid Lymphoma

Other Problems to Be Considered

Metastatic cancer
Leukemias

Workup

Laboratory Studies

The following workup should be considered for patients with papillary carcinoma, a relatively common well-differentiated thyroid cancer:

  • Thyroid function
    • Perform a complete assessment of thyroid function in any patient with thyroid lumps.
    • Not all available tests are specific for papillary cancer of the thyroid. Higher-than-normal levels of thyroxine (reference range is 4.5-12.5 mcg/dL), triiodothyronine (reference range is 100-200 ng/dL), and thyroid-stimulating hormone (TSH) (reference range is 0.2-4.7 mIU/dL) may indicate thyroid cancer.
    • Evaluate serum levels of thyroglobulin, calcium, and calcitonin.
    • Determining the serum level of carcinoembryonic antigen (CEA) may be helpful (reference range is <3 ng/dL). However, the implications of the presence of CEA are not specific because CEA levels are high in several cancers, and numerous healthy people may have small amounts of CEA, especially pregnant women and persons who are heavy smokers.
  • TSH suppression test
    • Cancer is autonomous and does not require TSH for growth, whereas benign lesions do require TSH. When exogenous thyroid hormone feeds back to the pituitary to decrease the production of TSH, thyroid nodules that continue to enlarge are likely to be malignant. However, 15-20% of malignant nodules are suppressible.
    • Preoperatively, the test is useful for patients with nontoxic solitary benign nodules and for women with repeated nondiagnostic test results. Postoperatively, the test is useful for monitoring papillary thyroid cancer cases.

Imaging Studies

  • Chest radiography, CT scanning, and MRI: These tests are not usually used in the initial workup of a thyroid nodule, except in patients with clear metastatic disease at presentation. These tests are second-level diagnostic tools and are useful in preoperative patient assessment.
  • Echography
    • This imaging study must be performed first in any patient with possible thyroid malignancy. Echography is noninvasive and inexpensive, and it represents the most sensitive procedure for identifying thyroid lesions and for determining the diameters of a nodule (2-3 mm).
    • Echography is also useful for localizing lesions when a nodule is difficult to palpate or is deeply seated. Echography images can help determine if a lesion is solid or cystic and can help detect the presence of calcifications.
    • The accuracy rate of echography in categorizing nodules as solid, cystic, or mixed is near 90%. It may be used to help direct a fine-needle aspiration biopsy (FNAB).
    • Pulsed and power Doppler echography may provide important information about the vascular pattern and the velocimetric parameters. Such information can be useful preoperatively to reach a correct differential diagnosis of malignant or benign thyroid lesion.
  • Scintigraphy
    • Before FNAB, thyroid scintigraphy (or thyroid scanning) performed with technetium Tc 99m pertechnetate (99mTc) or radioactive iodine (iodine I 131 or iodine I 123) was the initial diagnostic procedure of choice for a thyroid evaluation.
    • The procedure is not as sensitive or specific as FNAB for distinguishing benign nodules from malignant nodules.
    • The scintigraphy procedure performed with 99mTc has a high error rate because 99mTc is trapped as iodide but is not organified in the thyroid.
    • The 99mTc has a short half-life and cannot help determine the functionality of a thyroid nodule. Radioactive iodine is trapped and organified in the thyroid and can help determine functionality of a thyroid nodule. Iodine-containing compounds and seafood interfere with any tests using radioactive iodine.
    • Scintigraphic images of the thyroid are acquired 20-40 minutes after intravenous administration of the radionuclide.
    • In more than 90% of cases, clearly benign nodules appear as hot nodules because they are hyperfunctioning and have a high captation rate of radionuclide and, physiologically, of iodine. Malignant nodules usually appear as cold nodules because they are not functioning.
    • Findings from thyroid scanning are helpful and specific in evaluating the preoperative and immediate postoperative periods for localization of cancer or residual thyroid tissue and in observing for tumor recurrence or metastasis. Thyroid scanning can also be useful for diagnosing benign lesions (by FNAB) or solid lesions (by echography).

Other Tests

  • Papillary thyroid cancer is strongly associated with some specific rearrangements of the RET proto-oncogene.5
  • If possible, the assessment of the RET proto-oncogene expression should be performed in any people having a relative with a history of papillary thyroid cancer.

Procedures

  • FNAB is considered the best first-line diagnostic procedure for a thyroid nodule; FNAB is a safe and minimally invasive procedure.
    • Local anesthesia is administered at the puncture site, and the aspiration biopsy needle is guided into the mass. Hold the nodule with the fingers of the left hand while introducing a needle through the skin into the thyroid nodule with the right hand.
    • After aspiration with a needle, 21- or 23-gauge, the material is deposited on a glass slide, fixed with alcohol-acetone, and then stained according to the Papanicolaou test protocol.
    • The accuracy of FNAB results is better than any other test for uninodular lesions. The sensitivity of the procedure is near 80%, the specificity is near 100%, and errors can be diminished using ultrasonographic guidance.
    • False-negative and false-positive results occur less than 6% of the time.
    • A thyroid biopsy can also be performed using the classic Tru-Cut or Vim-Silverman needles, but the FNAB technique is preferable. Patients comply best with FNAB.
    • A pathologist may experience difficulty distinguishing some benign cellular adenomas from their malignant counterparts.
  • Perform indirect or fiberoptic laryngoscopy to evaluate airway and vocal cord mobility and to have preoperative documentation of any unrelated abnormalities.

Histologic Findings

Papillary thyroid carcinoma usually appears as a grossly firm mass that is irregular and not encapsulated. Microscopically, it is multifocal, and a net invasion of the lymphatics may be demonstrated. Complete or partial papillary architecture with some follicles is present. Otherwise, in some patients, the tumor may lack any papillary pattern. The thyrocytes are large and show an abnormal nucleus and cytoplasm with several mitoses. In some cases, the thyrocytes may have the so-called "orphan Annie eyes," that is, large round cells with a dense nucleus and clear cytoplasm. Another typical feature of this cancer is the presence of the psammoma bodies, probably the remnants of dead papillae.

Immunohistochemistry findings usually have a CEA-negative, calcitonin-negative, thyroglobulin-positive, and keratin-positive pattern.

Definitive diagnosis is often not possible with samples obtained from the FNAB because findings cannot accurately distinguish between benign and malignant lesions.

Staging

The staging of well-differentiated thyroid cancers is related to age for the first and second stages, but it is not related to age for the third and fourth stages. In the staging protocol, T is tumor, N is node, and M is metastasis.

  • Younger than 45 years
    • Stage I - Any T, any N, M0 (cancer in thyroid only)
    • Stage II - Any T, any N, M1 (cancer spread to distant organs)
  • Older than 45 years
    • Stage I - T1, N0, M0 (cancer only in thyroid, may be found in one or both lobes)
    • Stage II - T2, N0, M0 and T3, N0, M0 (cancer only in thyroid and >1.5 cm)
    • Stage III - T4, N0, M0 and any T, N1, M0 (cancer spread outside thyroid but not outside of neck)
    • Stage IV - Any T, any N, M1 (cancer spread to other parts of body)

Treatment

Medical Care

The following medical care is appropriate for patients with papillary carcinoma, a relatively common well-differentiated thyroid cancer:

  • Approximately 4-6 weeks after surgical thyroid removal, patients must have radioiodine therapy to detect and destroy any metastasis and residual tissue in the thyroid. Administer therapy until radioiodine uptake is completely absent. Radioiodine treatment may be used again 6-12 months after initial treatment of metastatic disease where disease recurs or has not fully responded.  
  • When a large, unresectable tumor is present and the uptake of radioiodine is limited, when intractable bone pain exists, or if resection is not feasible, external beam radiation may be performed to control local tumor growth, including, but not limited to, the neck, lungs, mediastinum, bone, and CNS (stage T4).
  • Administer the thyroid hormone replacement levothyroxine to patients for life, especially after total thyroidectomy. Treatment consists of administering levothyroxine at 2.5-3.5 mcg/kg/d.
  • Chemotherapy with cisplatin or doxorubicin has limited efficacy, producing occasional objective responses (generally for short durations). Because of the high toxicity of chemotherapy with cisplatin or doxorubicin, chemotherapy may be considered in symptomatic patients with recurrent or advancing disease. However, chemotherapy could improve the quality of life in patients with bone metastases, but a standard protocol for chemotherapeutic management has not been developed for these patients.
  • A discussion of recently available targeted therapies for use in advanced differentiated thyroid cancer no longer responsive to radioablation may be found in the Chemotherapy section of Thyroid, Follicular Carcinoma.

See related CME at New Insights and New Challenges in Head and Neck Carcinoma.

Surgical Care

Surgery is the definitive management of thyroid cancer, and various types of operations may be performed.

  • Lobectomy with isthmectomy: This procedure is the minimal operation for a potentially malignant thyroid nodule.
  • Subtotal thyroidectomy
    • This is a near-total thyroidectomy. The argument for this form of surgical intervention is that total thyroidectomy does not improve long-term prognosis and the incidence of complications (eg, hypoparathyroidism, superior and/or recurrent laryngeal nerve injury) is lower with subtotal thyroidectomy.
    • Patients younger than 40 years who have papillary thyroid carcinoma nodules that are smaller than 1 cm, well-defined, minimally invasive, and isolated may be treated with hemithyroidectomy and isthmectomy. However, an important consideration in considering this approach is that approximately 10% of patients who have had only a lobectomy develop a recurrence in the contralateral lobe, and residual tissue has the potential to dedifferentiate to anaplastic cancer.
  • Total thyroidectomy
    • Perform a total thyroidectomy (removal of all thyroid tissue but preserving the contralateral parathyroid glands) in patients who are older than 40 years with papillary carcinoma and in any patient with bilateral disease. In addition, recommend total thyroidectomy to any patient with a thyroid nodule and a history of irradiation. In papillary tumors of the thyroid, total thyroidectomy is the surgical treatment of choice for a number of reasons. Papillary foci involving both lobes are found in some 60-85% of patients. About 5-10% of recurrences in patients who have only had a lobectomy develop in the remaining lobe. Also, at 20 years after initial surgery, patients who had undergone total thyroidectomy had a recurrence rate of 8%, whereas those who had received only a lobectomy had a recurrence rate of 22%. Survival rates were, however, comparable.
    • This surgical procedure also facilitates earlier detection and treatment of recurrent or metastatic carcinoma. This surgical option is mandatory in patients with papillary carcinoma discovered based on postoperative histology findings (ie, if a very well-differentiated tumor is discovered) after a one-sided lobectomy, with or without isthmectomy.
    • When the primary tumor spreads outside the thyroid and involves adjacent vital organs (eg, larynx, trachea, esophagus), preserve these organs at the first surgical approach. However, the surrounding soft tissues, including the muscles and involved areas of the trachea and/or esophagus, may be sacrificed if they are directly involved with the differentiated thyroid carcinoma and local resection is feasible.
  • Video-assisted thyroidectomy: This is rarely used to treat thyroid cancer.
  • External beam radiotherapy: This has been used as adjuvant therapy in patients with papillary thyroid cancer who were older than 45 years and had locally invasive disease. Some improvements in 10-year survival rates have been reported with this approach.
 
See related CME at NCCN Thyroid Carcinoma Guidelines Update (Slides With Transcript).

Consultations

  • Schedule elderly patients for an assessment by a cardiologist because of the high risk of subclinical hypothyroidism episodes.
  • Consult an otolaryngologist, especially in thyroid patients who have voice disturbances.

Medication

The most useful drugs for the treatment of papillary thyroid carcinomas (a relatively common well-differentiated thyroid cancer) after surgery are levothyroxine and radioiodine. For metastases, palliation with antineoplastic agents (eg, cisplatin, doxorubicin) may be useful.

Thyroid products

These drugs are useful to prevent hypothyroidism and to stop TSH stimulation.


Levothyroxine (Synthroid)

In active form, influences growth and maturation of tissues. Involved in normal growth, metabolism, and development.

Dosing

Adult

3-3.5 mcg/kg/d PO for life

Pediatric

Neonate to 6 months: 25-50 mcg/d PO
6-12 months: 50-75 mcg/d PO
1-5 years: 75-100 mcg/d PO
6-12 years: 100-150 mcg/d PO
>12 years: 150 mcg/d PO

Interactions

Cholestyramine may decrease absorption; estrogens may decrease response to thyroid hormone therapy in patients with nonfunctioning thyroid glands; effect of anticoagulants increased when coadministered; activity of some beta-blockers may decrease when hypothyroid patient is converted to a euthyroid state

Contraindications

Documented hypersensitivity; uncorrected adrenal insufficiency

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Maintain TSH at 0.1-0.2 mIU/mL; menopausal women may develop severe osteoporosis; caution in angina pectoris or cardiovascular disease

Antithyroid agents

These agents reduce serum thyroid hormone levels.


Sodium iodide I 131 (Iodotope)

Radioiodine is taken up by thyroid tissue and cannot be used in metabolic pathways. Emits beta and gamma radiation that causes destruction of thyroid tissue along a diameter of 400-2000 µm. Results in destruction of all residual thyroid tissues, either pathologic or normal.

Dosing

Adult

Nonmetastatic disease: 1110-3700 MBq (30-100 mCi) IV q3wk
Metastatic disease: 5550-7400 MBq (150-200 mCi) IV q3wk; discontinue treatment when scintigraphy findings negative

Pediatric

Not established

Interactions

Increases lithium toxicity by producing additive hypothyroid effects; uptake is affected by stable iodine, thyroid, and antithyroid agents

Contraindications

Documented hypersensitivity; <35 y

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in pregnancy and breastfeeding because drug may pass through placenta and is secreted into milk; may cause bone marrow depression, acute leukemia, anemia, blood dyscrasias, leukopenia, thrombocytopenia, radiation sickness, angina, sinus tachycardia, pruritus, skin rash, and hives

Antineoplastic agents

These medications inhibit cell growth and proliferation and may be helpful in palliating symptoms in progressive disease.


Cisplatin (Platinol)

Inhibits DNA synthesis and, thus, cell proliferation by causing DNA crosslinks and denaturation of double helix. Dose is related to body surface area.

Dosing

Adult

20-40 mg/m2/d IV for 3-5 d q3wk; alternatively, 20-120 mg/m2 IV once q3wk

Pediatric

Not established

Interactions

Increases toxicity of bleomycin and ethacrynic acid

Contraindications

Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Reduce dose in renal failure; administer adequate hydration before and 24 h after cisplatin dosing to reduce risk of nephrotoxicity; myelosuppression, ototoxicity, nausea, and vomiting may occur


Doxorubicin (Adriamycin)

Inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA. Combination of these 2 events, in turn, can inhibit growth of neoplastic cells.

Dosing

Adult

60-75 mg/m2 IV as a single dose q3-4wk; total dose not to exceed 550 mg/m2

Pediatric

Administer as in adults

Interactions

Verapamil may increase cell toxicity; mercaptopurine increases toxicities; streptozocin inhibits metabolism; cyclophosphamide increases cardiac toxicity; cyclosporine may result in coma and/or seizure; phenobarbital increases elimination; decreases level of digoxin and phenytoin

Contraindications

Documented hypersensitivity; severe CHF; cardiomyopathy; preexisting myelosuppression; impaired cardiac function; previous treatment with complete cumulative doses of doxorubicin, idarubicin, and/or daunorubicin

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Extravasation may occur, resulting in severe tissue necrosis; caution in patients with impaired hepatic function; in the short-term, nausea and reddish stain of urine (not blood in urine) may occur; may cause toxicity to heart, oral mucosa, hair (alopecia), and hematopoietic system

Follow-up

Further Inpatient Care

In patients with papillary thyroid carcinoma (a relatively common well-differentiated thyroid cancer), systematic psychotherapeutic intervention may be very helpful.

Further Outpatient Care

  • Periodic neck ultrasound is mandatory to monitor the patient status.
  • Perform a postoperative scintiscan of the neck 4-6 weeks after thyroid hormone replacement therapy is completed. At this time, a scan of the neck can help demonstrate if thyroid tissue is still present. If thyroid tissue is present, a dose of radioactive iodine is administered to destroy residual tissue. The patient is then placed back on thyroid hormone replacement (levothyroxine) therapy.
  • Repeat the scintiscan 6-12 months after ablation and, thereafter, every 2 years. Before the scan, levothyroxine must be withdrawn for approximately 4-6 weeks to maximize thyrotropin stimulation of the eventual remaining thyroid tissue.
  • Radioactive iodine may ablate the metastatic tissue in the lungs and bone. These metastases appear to be more amenable to radioiodine therapy than the metastases of papillary carcinoma.
  • Evaluate thyroglobulin serum levels every 6-12 months for at least 5 years. Consider a level greater than 20 ng/mL, after TSH suppression, to be abnormal. A recurrence of thyroid cancer can be detected if a rise in the thyroglobulin level occurs.
  • Perform thyroid hormone suppression tests in all patients who have undergone total thyroidectomy and in all patients who have had radioactive ablation of any remaining thyroid tissue. Individualize the degree of suppression to avoid complications, such as subclinical hyperthyroidism.
    • A recent meta-analysis of clinical data from several studies including a large number of subjects demonstrated that an undetectable serum thyroglobulin finding during thyroid hormone suppression of TSH is often misleading.
    • Accordingly, the authors propose a new surveillance guideline for patients who have undergone total or near-total thyroidectomy and radioactive iodine ablation and have no clinical evidence of residual tumor with a serum thyroglobulin level less than 1 mcg/L during thyroid hormone suppression of TSH.
  • A patient who has had a thyroidectomy without parathyroid preservation requires vitamin D and calcium supplementation for life.

Inpatient & Outpatient Medications

  • Any patient with a history of a papillary thyroid carcinoma must have, at 6 and 12 months after the cancer treatment (medical or surgical), a complete physical examination, TSH and thyroglobulin measurement, and antithyroglobulin antibodies titration.
  • If the patient is disease-free, these tests may be performed on annual basis. 

Deterrence/Prevention

No known preventative methods exist.

Complications

  • If neglected, any thyroid cancer may exhibit symptoms because of compression and/or infiltration of the cancer mass into the surrounding tissues, and the cancer may metastasize to lung and bone.
  • Surgical treatment of thyroid cancer may cause some complications, partially because of the variable anatomy of the neck. These possible complications include the following:
    • Hypothyroidism
    • Dysphagia due to damage of the upper laryngeal nerve
    • Vocal cord paralysis due to damage of recurrent laryngeal nerve
    • Hypoparathyroidism due to parathyroid gland ablation
  • Radioiodine administration may have several consequences, including the following:
    • Radiation thyroiditis and transient thyrotoxicosis in patients with simple lobectomy
    • Sialoadenitis because radioiodine is taken up by the salivary glands
    • Nausea, anorexia, and headache (uncommon)
    • Pulmonary fibrosis in patients with large lung metastases
    • Brain edema in patients with brain metastases (may be prevented by glucocorticoid therapy)
    • Permanent sterility and transient oligospermia or menstrual irregularities
    • Teratogenesis and spontaneous abortions
    • A small increase in the risk for leukemias or breast and bladder carcinomas
  • Metastases, in descending order of frequency, are most common in the neck lymph nodes and lung, followed by the bone, brain, liver, and other sites. Metastatic potential seems to be a function of the primary tumor size. Metastases in the absence of thyroid pathology in the physical examination findings are rare in patients with microscopic papillary carcinoma (occult carcinomas).

Prognosis

The prognosis of papillary thyroid cancer is related to age, sex, and stage. In general, if cancer is not extending beyond the capsule of the gland, life expectancy is minimally affected. Prognosis is better in female patients and in patients younger than 40 years. The survival rate is at least 95% with appropriate treatments.

Patient Education

  • Patients who discover a neck deformity or thyroid lumps or have a history of prior exposure to ionizing radiation must consult their physician.
  • For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

Miscellaneous

Medicolegal Pitfalls

The main medical and legal problems related to papillary thyroid cancer are vocal cord paralysis due to damage of the recurrent laryngeal nerve, damage of the parathyroid glands leading to temporary or permanent hypoparathyroidism, and toxic adverse effects of radioiodine administration. Always obtain informed consent for diagnostic procedures and treatments, explaining the procedures and their possible complications.

Special Concerns

Because radioiodine treatment may cause either teratogenesis or spontaneous abortions, patients should delay pregnancy for at least 1 year after radioiodine treatment.

References

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Keywords

papillary thyroid carcinoma, papillary carcinoma, thyroid cancer, thyroid carcinoma, papillary/follicular carcinoma, papillary-follicular carcinoma, papillary cancer of the thyroid, follicular cancer of the thyroid, irradiation, radiation therapy, radiation exposure, ionizing radiation, radiotherapy, thyroid mass, thyroid nodule, thyroid lump, iodine deficiency, familial adenomatous polyposis, Gardner syndrome, Gardner's syndrome, Cowden disease, Cowden's disease, thyroid disease, thyroid disorders

Contributor Information and Disclosures

Author

Luigi Santacroce, MD, Assistant Professor, Medical School, State University at Bari, Italy
Disclosure: Nothing to disclose.

Coauthor(s)

Silvia Gagliardi, MD, Consulting Staff, Department of Surgery, Medical Center Vita, Italy
Disclosure: Nothing to disclose.

Andrew Scott Kennedy, MD, Co-Medical Director, Wake Radiology Oncology
Andrew Scott Kennedy, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Hepato-Pancreato-Biliary Association, American Society for Therapeutic Radiology and Oncology, American Society of Clinical Oncology, and Radiological Society of North America
Disclosure: Nothing to disclose.

Medical Editor

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting

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