Papillary thyroid carcinoma usually presents as an asymptomatic (painless) thyroid mass with or without enlargement of regional (cervical) lymph nodes. Hoarseness and dysphagia occur in approximately 20% of cases, signaling recurrent laryngeal nerve involvement with vocal cord paralysis or tracheal compression. Nodal metastases in the lateral neck are reported in 27% of patients at presentation most often originating from tumors in the ipsilateral thyroid lobe.[9]

The examination usually reveals a painless hard lesion that is usually less than 5 cm. The mass is usually fixed and has irregular borders.

Fine needle aspiration:

It is often is the initial diagnostic method used in the detection of PTC. Fine-needle aspiration specimens from conventional PTC are usually cellular and may show papillary structures, monolayer sheets, and 3D groups in a background of watery or thick so-called ropy colloid, nuclear or calcific debris, macrophages, and stromal fragments. The individual tumor cells are enlarged, elongated, or oval, with eosinophilic cytoplasm. The nuclei show elongation, membrane thickening, chromatin clearing, grooves, and pseudo-inclusions. These tumors usually show enlarged follicular cells arranged in monolayer sheets and follicular groups in a background of thin and thick colloid.[10][11]

Laboratory tests: 

Thyroid function testing has limited utility in the diagnosis of PTC because most patients have normal thyroid function.[12]

Radiographic features:

On thyroid scan, PTCs typically appear as cold (hypo-functioning) nodules, but rarely can appear as hot (hyperfunctioning) nodules.

Ultrasound examination is the imaging modality of choice for PTC. Sonographic features include a hypoechoic or isoechoic solid nodule with irregular or poorly defined margins, micro-calcifications, taller-than-wide shape, and disorganized internal vascularity. Ultrasound findings are also invaluable for guiding fine-needle aspiration biopsy of abnormal nodes. Microcalcifications are highly specific for this cancer.

Other imaging modalities, including CT, MRI, and FDG-PET/CT, may be needed to assess the extent of extra-thyroidal extension, to evaluate the presence of substernal masses, to detect recurrent tumors, and to improve diagnostic accuracy.[13]

Surgery:

Primary treatment decisions have as their basis a preoperative risk assessment that includes clinical, imaging, and cytological data. Choices depend on the location and extent of identifiable disease and the risk that unidentifiable disease foci are also present. With increasing emphasis on risk-stratified management, the treatment approaches recommended by the 2015 ATA guidelines are more conservative than in the past.[14] A lobectomy is an option for unifocal tumors smaller than 4 cm with no evidence of extra-thyroidal extension or lymph node metastasis. For patients with PTC >4 cm, or with gross extra-thyroidal extension (clinical T4), or clinically apparent metastatic disease to nodes (clinical N1) or distant sites (clinical M1), the initial surgical procedure should include a near-total or total thyroidectomy and gross removal of all primary tumor unless there are contraindications to this procedure. If surgery is chosen for patients with thyroid cancer <1 cm without extra-thyroidal extension and cN0, the initial surgical procedure should be a thyroid lobectomy unless there are clear indications to remove the contralateral lobe. Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas in the absence of prior head and neck radiation, familial thyroid carcinoma, or clinically detectable cervical nodal metastases.[14] Prophylactic central-compartment neck dissection (ipsilateral or bilateral) should be a consideration in patients with PTC with clinically uninvolved central neck lymph nodes (cN0) who have advanced primary tumors (T3 or T4) or clinically involved lateral neck nodes (cN1b), or if the information will be used to plan further steps in therapy.

Adjuvant Radioiodine Therapy:

After thyroidectomy, radioiodine is the therapy of choice in patients with PTC to ablate residual normal thyroid tissue. 

Radioiodine therapy is indicated  in the following cases [15]:

• Patients with tumor >2 cm and one of the following risk factors: gross extra-thyroidal extension, age >45 years, lymph node and distant metastases
• Patients with tumor <2 cm and distant metastasis

Radioactive iodine therapy is given 4-6 weeks after surgery. Prior to treatment, a hypothyroid state is induced by stopping thyroid hormone replacement treatment. The therapy is continued until no more radioactive iodine uptake is seen. Potential adverse effects of radioactive iodine include:

• Sialoadenitis
• Transient thyrotoxicosis
• Pulmonary fibrosis
• Emesis
• Brain edema (can be prevented with the use of corticosteroids)
• Infertility
• Small risk of leukemia, breast or bladder cancer

Thyroid Hormone Treatment:

After thyroidectomy, patients require lifelong thyroid hormone therapy, usually as monotherapy with levothyroxine (LT4). Since TSH can promote the growth of remaining PTC cells, the dosage of LT4 should initially be high enough to achieve suppression of thyrotropin. The thyroid function should be checked after 6 to 8 weeks. Depending on the result, the dosage should be adjusted; the use of TSH suppressive therapy should merit careful consideration since it carries an increased risk of complications.[14]

NCCN Guidelines for Total thyroidectomy:

• Known distant metastases
• History of radiation
• Extrathyroidal extension
• Bilateral nodules
• The tumor measures more than 4 cm
• Poorly differentiate lesion
• Positive cervical lymph nodes

Routine cervical node dissection continues to be debated. Some literature notes fewer recurrences but other studies note a higher incidence of recurrent nerve injury.

The primary differential diagnoses of PTC are:

• Reactive changes following fine-needle aspiration.[16] This condition characteristically shows nuclear enlargement, chromatin clearing, and micro-nucleoli similar to nuclei of PTC.

• Severe chronic lymphocytic thyroiditis, where the reactive atypia attributed to inflammation results in nuclear morphology similar to that of PTC.[17]

• Other differential diagnoses include adenomatoid nodules, diffuse hyperplasia, dyshormonogenetic goiter, follicular adenoma, follicular thyroid carcinoma, medullary thyroid carcinoma, and metastatic tumors.

Several staging systems have been proposed for PTC and continue to evolve. The most commonly used are [18][19][18]:

For patients less than 45 years:

• Stage l: any Tm any N, MO (cancer localized to the thyroid)
• Stage ll: Any T, any N, MI (cancer spread to cervical nodes or to distant organs)

For patients older than 45 years:

• Stage l: T1, N0, M0 (cancer less than 2 cm)
• Stage ll: T2, N0, M0, and T3 (cancer localized to the thyroid and is between 2-4 cm)
• Stage lll: T4, N0, MO, and any T, N1, M0 (lesion more than 4 cm and spread limited to the neck)
• Stage lV: Any T, any N, M1 (cancer spread outside the neck and to distant organs)

Although PTC frequently metastasizes to regional lymph nodes, it still generally carries an excellent prognosis. There are, however, several clinicopathological and background features that can lead to a poor prognosis.[20]

Poor prognostic factors of PTC include:

• Older age at diagnosis
• Large tumor size
• Extra-thyroidal growth
• Male sex
• Less differentiated or solid areas, vascular invasion, and aneuploid cell population
• Subtypes of PTC that associate with a more aggressive clinical behavior: tall cell variant, diffuse sclerosis variant, solid variant, and follicular variant

Extra-thyroidal extension:

Extra-thyroidal extension occurs in 8% to 32% of cases.[21]

Local or regional recurrences:

Local or regional recurrences occur in 5 to 15% of patients with PTC.[22]

Distant metastases:

Distant metastasis occurs in only 1% to 25% mostly in the lungs and bones. Other less common sites are the brain, liver, and skin.[23]

Long term monitoring is necessary every 6-12 months to look for recurrence for at least 5 years

Levels of TSH and thyroglobulin must be measured

Papillary thyroid cancer is ideally managed by an interprofessional team that consists of an endocrinologist, general surgeon, oncologist, radiation oncologist, nuclear medicine physician, internist, pharmacists, and specialty care nurses. The majority of patients present to the primary provider or nurse practitioner with a painless mass in the neck. Once the FNA is performed, the patient should be referred to an oncologist and a surgeon. Patients need to know that the sole treatment for PTC is surgery. Patients treated with radioactive iodine need to be educated about this therapy and warned about the potential adverse effects. Following surgery, the patient requires long term monitoring for recurrence. Most patients require long term thyroid hormone replacement. Specialty care nurses in oncology assist with treatment, monitor and educate patients, and provide updates to the team. [Level 5] 

With early diagnosis and prompt treatment, the prognosis for most patients is excellent.