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Papillary Thyroid Carcinoma Workup

  • Author: Keith M Baldwin, DO; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
 
Updated: Oct 12, 2015
 

Approach Considerations

The following workup should be considered for the diagnosis of papillary carcinoma, a relatively common well-differentiated thyroid cancer:

  • Thyroid function studies
  • TSH suppression test
  • Thyroid ultrasound
  • Fine-needle aspiration biopsy (FNAB)

If possible, assessment of the RET proto-oncogene expression should be performed in any patient having a relative with a history of papillary thyroid cancer. Papillary thyroid cancer is strongly associated with some specific rearrangements of RET.[33]

The serum level of carcinoembryonic antigen (CEA) can be measured (reference range is < 3 ng/dL). However, the implications of an elevated CEA level are not specific; 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.

Procedures

FNAB is considered the best first-line diagnostic procedure for a thyroid nodule. 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.

Perform indirect or fiberoptic laryngoscopy to evaluate airway and vocal cord mobility and to have preoperative documentation of any unrelated abnormalities.

Imaging studies

Chest radiography, computed tomography (CT), and magnetic resonance imaging (MRI) are not usually used in the initial workup of a thyroid nodule. National Comprehensive Cancer Network (NCCN) guidelines recommend CT or MRI for the evaluation of fixed, bulky, or substernal lesions.[7] Chest x-ray may be considered in patients with apparent metastatic disease at presentation.

A study by Choi et al concluded that preoperative [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/CT did not provide any additional information compared with neck sonography in patients with papillary thyroid carcinoma.[34]

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Thyroid Function Studies

Perform a complete assessment of thyroid function in any patient with thyroid nodules. No available blood 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 or may not be associated with thyroid cancer.

Evaluate serum levels of thyroglobulin. Calcium and calcitonin may be elevated in medullary carcinoma of the thyroid.

TSH suppression test

Thyroid 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 TSH suppression 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.

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Thyroid Ultrasound

Thyroid ultrasound is the first imaging study to perform in any patient with possible thyroid malignancy. Ultrasound is noninvasive and inexpensive, and it represents the most sensitive procedure for identifying thyroid lesions and for determining the diameters of a nodule.

Ultrasound is also useful for localizing lesions when a nodule is difficult to palpate or is deeply seated. The images can help determine if a lesion is solid or cystic and can help detect the presence of calcifications.

Ultrasound may be used to help direct a fine-needle aspiration biopsy (FNAB).

Pulsed and power Doppler ultrasound 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.

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Scintigraphy

Before the advent of fine-needle aspiration biopsy (FNAB), thyroid scintigraphy (or thyroid scanning) performed with technetium Tc 99m pertechnetate (99mTc) or radioactive iodine (I131 or I123) 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. 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 because they are not functioning.

Findings from thyroid scanning are helpful and specific in 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).

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Fine-Needle Aspiration Biopsy

Fine-needle aspiration biopsy (FNAB) is considered the best first-line diagnostic procedure for a thyroid nodule. FNAB is a safe and minimally invasive procedure.

To perform FNAB, administer local anesthesia at the puncture site, then guide the aspiration biopsy needle (21- or 23-gauge) into the mass. Hold the nodule with the fingers of the left hand while introducing the needle through the skin into the thyroid nodule with the right hand. After aspiration, 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 detecting papillary thyroid carcinoma. 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, as the pathologist may experience difficulty distinguishing some benign cellular adenomas from their malignant counterparts.[35]

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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 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 psammoma bodies, probably the remnants of dead papillae.

On immunohistochemistry, papillary thyroid carcinoma usually exhibits the following pattern:

  • Carcinoembryonic antigen (CEA) negative
  • Calcitonin negative
  • Thyroglobulin positive
  • Keratin positive

A study by Liu et al found that when hematoxylin and eosin staining demonstrates loss of cellular polarity/cohesiveness (LOP/C) in the invasive front of papillary thyroid carcinoma, this finding may indicate lymph node metastasis and aggressive clinical behavior of the cancer. LOP/C of 20% or greater correlated significantly with extrathyroid invasion, advanced tumor stage, and recurrence after surgery.[36]

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Staging

The staging of well-differentiated thyroid cancers follows the tumor, node, metastasis (TNM) classification system. Staging differs, depending on whether the patient is younger than 45 years of age.

Staging for patients younger than 45 years is as follows:

  • Stage I - Any T, any N, M0 (cancer in thyroid only)
  • Stage II - Any T, any N, M1 (cancer spread cervical lymph nodes or to distant organs)

Staging for patients aged 45 years and older is as follows:

  • Stage I - T1, N0, M0 (cancer only in thyroid, and less than 2 cm)
  • Stage II - T2, N0, M0 and T3, N0, M0 (cancer only in thyroid and between 2-4 cm)
  • Stage III - T4, N0, M0 and any T, N1, M0 (tumor greater than 4 cm or cancer spread outside thyroid but not outside of the central neck compartment)
  • Stage IV - Any T, any N, M1 (cancer spread to either cervical lymph nodes outside of the central neck or distant organs)

See Thyroid Cancer Staging for more information.

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Contributor Information and Disclosures
Author

Keith M Baldwin, DO IMPH, Assistant Professor of Surgery, Boston University School of Medicine; Endocrine and Surgical Oncologist, Department of General Surgery, Roger Williams Cancer Center

Keith M Baldwin, DO is a member of the following medical societies: American College of Surgeons, Society of Surgical Oncology, American Association of Endocrine Surgeons, Americas Hepato-Pancreato-Biliary Association, Society of International Humanitarian Surgeons/Surgeons OverSeas (SOS)

Disclosure: Nothing to disclose.

Coauthor(s)

Andrew Scott Kennedy, MD Physician-in-Chief, Radiation Oncology

Andrew Scott Kennedy, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Society for Radiation Oncology, Radiological Society of North America, Americas Hepato-Pancreato-Biliary Association, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Lodovico Balducci, MD Professor, Oncology Fellowship Director, Department of Internal Medicine, Division of Adult Oncology, H Lee Moffitt Cancer Center and Research Institute, University of South Florida Morsani College of Medicine

Lodovico Balducci, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American College of Physicians, American Geriatrics Society, American Society of Hematology, New York Academy of Sciences, American Society of Clinical Oncology, Southern Society for Clinical Investigation, International Society for Experimental Hematology, American Federation for Clinical Research, American Society of Breast Disease

Disclosure: Nothing to disclose.

Acknowledgements

Silvia Gagliardi, MD Consulting Staff, Department of Surgery, Medical Center Vita, Italy

Disclosure: Nothing to disclose.

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