Thyroid, Papillary Carcinoma, Early Workup

Updated: May 07, 2021
  • Author: Eric J Lentsch, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Laboratory Studies

Lab studies in the evaluation of papillary thyroid carcinoma include the following:

  • Fine-needle aspiration cytology: Fine-needle aspiration is a mainstay 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%

  • Molecular markers: Molecular markers can be used to guide therapy in patients with indeterminate cytology [25]

  • Thyroid-stimulating hormone (TSH): Serum thyroid-stimulating hormone (TSH) levels, along with imaging studies, should be obtained if a thyroid nodule of over 1 cm (any diameter) is found or if diffuse or focal thyroidal uptake occurs on an 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan [25]

  • Thyroglobulin: Serum thyroglobulin level can be used as a postoperative tumor marker for well-differentiated thyroid cancer (ie, papillary, follicular); however, it is not recommended that routine serum thyroglobulin measurement be used in the initial evaluation of thyroid nodules [25]

  • Electrophoresis: 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

New diagnostic tests are emerging that offer more precise diagnosis of papillary thyroid carcinoma in its earliest stages. For example, the companies Illumina, Inc. and Life Technologies Corp. developed MiSeq and Ion Torrent, respectively, as research-use-only tests to screen for cancer-specific gene mutations. The ThyroSeq panel, a customized Ion Torrent platform developed at an academic center, identifies 12 genes specific to thyroid cancer, including RAS, BRAF, RET, and TP53. Several tests have become commercially available, with the companies Veracyte, Inc. and Asuragen, Inc. having developed Afirma and miRInform Thyroid, respectively. As it stands, Afirma has greater clinical utility for its sensitivity, while miRInform functions best for its specificity. These tests have made their way into clinical practice, but controversy exists over their best use, and their full potential has yet to be determined. [21, 22]

Fine-needle aspiration

For years no central method for the evaluation of fine-needle aspiration existed. This led to much confusion among cytopathologists and referring physicians until the Bethesda System for Reporting Thyroid Cytopathology was developed by the National Cancer Institute to address terminology and other issues related to fine-needle aspiration. The following are the recommended diagnostic categories:

  • Nondiagnostic or unsatisfactory: Cyst fluid only, virtually acellular specimen, other (obscuring blood, clotting artifact, etc.)

  • Benign: (a) Consistent with a benign follicular nodule (includes adenomatoid nodule, colloid nodule, etc.), (b) consistent with lymphocytic (Hashimoto) thyroiditis in the proper clinical context, (c) consistent with granulomatous (subacute) thyroiditis

  • Atypia of undetermined significance or follicular lesion of undetermined significance

  • Follicular neoplasm or suspicious for a follicular neoplasm

  • Suspicious for malignancy: (a) Suspicious for papillary carcinoma, (b) suspicious for medullary carcinoma, (c) suspicious for metastatic carcinoma, (d) suspicious for lymphoma, (e) other

  • Malignant: (a) Papillary thyroid carcinoma, (b) poorly differentiated carcinoma, (c) medullary thyroid carcinoma, (d) undifferentiated (anaplastic) carcinoma, (e) squamous cell carcinoma, (f) carcinoma with mixed features (specify), (g) metastatic carcinoma, (h) non-Hodgkin lymphoma, (i) other [26]


Imaging Studies

Routine preoperative use of computed tomography (CT) scanning, magnetic resonance imaging (MRI), or PET scanning is not recommended.


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 ultrasonogram and fine-needle aspiration. Similarly, FDG-avid nodules incidentally found on PET scans are occurring with increasing frequency and may require similar clarification.

FDG-PET scanning

PET scanning with FDG depicts many malignancies, including thyroid cancers. The role of FDG-PET scanning in differentiated thyroid cancer has been well described. [27] Efforts to distinguish benign from malignant nodules remain controversial, however, and the modality's expense precludes routine use when malignancy is first diagnosed. [28, 29]

Undifferentiated thyroid carcinomas and recurrent or metastatic thyroid cancer may 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 to have significant benefit, especially when ultrasonography is equivocal.

Relative to ultrasonography, the use of FDG-PET scanning as a staging tool remains an expensive imaging modality. It fails to provide any additional staging information that would change surgical treatment, therefore it still has not been recommended as a preoperative diagnostic tool. However, it does continue to have utility in less-differentiated cancers such as H ü rthle cell or anaplastic thyroid carcinoma. [30]

PET and PET/CT scans

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.


Diagnostic Procedures

Ultrasonographically guided fine-needle aspiration remains the mainstay diagnostic procedure for papillary thyroid cancer. However, a noninvasive technique, real-time ultrasonographic elastography (USE), can be used to evaluate the stiffness of tissue caused by malignancies. Using external pressure, it measures tissue elasticity by distorting tissue structures. Differences in the hardness of the tissues are displayed in color. Malignant histology in thyroid nodules has been predicted to satisfactory levels of certainty using this technique. [31, 32]


Histologic Findings

See Pathophysiology.



Tumors, nodes, and metastases for papillary carcinoma of the thyroid are classified as follows using the American Joint Committee on Cancer (AJCC) staging system:

  • 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.

Table 1. Stages of Papillary Carcinoma of the Thyroid (Open Table in a new window)


Younger Than 45 Years

Age 45 Years and Older

Stage I

Any T, Any N, M0

T1, N0, M0

Stage II

Any T, Any N, M1

T2, 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