Papillary thyroid cancer

Last revised by Mohammadtaghi Niknejad on 10 Jul 2023

Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland and frequently has nodal metastases at presentation.

When the tumor measures <1 cm, the term micropapillary carcinoma (mPTC) is used 14

Papillary thyroid cancer (as is the case with follicular thyroid cancer) typically occurs in the middle-aged, with a peak incidence in the 3rd and 4th decades. It is more common in women with an M:F ratio of 1:2.5 (range 1:1.6-3:1) 2.

It accounts for the majority (~70%) of all thyroid neoplasms and 85% of all thyroid cancers 2,4. There are 45,000 cases in the United States every year and this type of carcinoma has the fastest-increasing incidence of any malignancy in the thyroid.

  • family history

  • previous head/neck radiation

Presentation is usually with a solitary palpable thyroid mass.

Papillary carcinoma has a tendency to metastasize early to local lymph nodes, with 50% (39-90% 2) of patients having nodal involvement at presentation 1 (cf. 10% for follicular thyroid cancer). These metastases are usually to the ipsilateral jugular chain (~88%) and are commonly confined to the mid and lower lymph node levels; namely levels III and IV (73%) 1.

In ~20% of patients, lymph node metastases are the first presentation. In 50% of children and 20% of adults, a cervical lymph node is palpable at the time of diagnosis 4.

Distal hematogenous dissemination is less common than with follicular cancer, with a prevalence of only 5-10% of patients at presentation.

Lymphatic spread is more common than hematogenous spread (cf. follicular thyroid carcinoma) and multifocality is common.

Conventional/classical papillary thyroid cancer comprises about 50% of papillary thyroid cancers, with the other 50% made up of multiple variants that have been described according to biological behavior 13,16:

  • favorable

    • follicular/encapsulated variant: most common variant (~33%), resembles follicular thyroid carcinoma

    • cribriform/morula variant

    • Warthin-like variant

  • less favorable

    • solid variant

    • diffuse sclerosing variant

  • aggressive

    • tall cell variant

    • columnar cell variant

    • hobnail variant

Histologically papillary carcinoma demonstrates "delicate stalks of epithelial cells" 3, which account for its name. Neoplastic papilla with central fibrovascular core lined by cells with follicular epithelial cell differentiation  and unique nuclear features. Clear nuclear chromatin "Orphan Annie eye"   and longitudinal nuclear grooves, nuclear overlapping, intranuclear pseudo-inclusions, as well as irregular nuclear contours are the specific findings of papillary thyroid carcinoma. Psammoma bodies are common in PTC  and they are usually seen within the papillary structures or in the tumor stroma but not in the tumoral follicles. Psammoma bodies represent focal infarction and dead tip of papillae which is calcified.

Immunohistochemistry:

  • positive for CK 7, PAX 8, TTF1, Thyroglobulin

  • negative for: CK20 and calcitonin

Molecular pathology:

BRAF is the most frequent mutated gene, occurring in 60% of cases. RAS mutation and rearrangement of RET gen (RET/PTC)  have been recognized. 17

Imaging of the neck of a patient with papillary thyroid carcinoma involves both examination of the thyroid as well as careful assessment of the regional lymph nodes for the presence of metastases.

Papillary carcinoma within the thyroid usually appears as a solitary mass usually with an irregular outline, located in the subcapsular region and demonstrating vascularity 6. Small punctate regions of echogenicity representing microcalcifications (psammoma bodies) may be present 5.

Lymph node metastases have a tendency to completely cavitate (40%), and although usually multiple, in a minority of cases (6%) a single completely cystic node may be present 1. They tend to have septations, mural nodules and relatively thick walls 1.

Any thyroid nodule presents a diagnostic challenge as up to 50% of the general population will have thyroid nodules of some description on high-resolution thyroid ultrasound 9. There has previously been great variance in investigating thyroid nodules with some operators routinely aspirating thyroid lesions while others use traditional discriminators such as size in deciding whether or not to proceed to needle biopsy.

Recent research in North America, Korea, and Europe has demonstrated that traditional discriminators are poor correlates for thyroid cancer, which is most commonly papillary. Guidelines have now been produced to broadly categorize nodules as benign, indeterminate, or suspicious for malignancy with a shift in focus to looking at ultrasound appearances rather than simply size.

The U classification system is an example proposed by the British Thyroid Association 10.

CT is best at staging lymph node involvement (see thyroid cancer staging). Involved lymph nodes tend to have 1:

  • cystic components: ~35%

  • thick nodular walls: ~40%

  • septa: ~60%

  • purely cystic nodes are uncommon and more frequent in young patients

  • calcification may be seen occasionally

  • the so-called lateral aberrant thyroid is actually a lymph node metastasis from papillary thyroid carcinoma

MRI, although probably more sensitive than CT, is nonetheless still far from perfect with a sensitivity of only 67% 2. This is largely a result of the fact that as many as half of all involved nodes found histologically following surgery are <3 mm in diameter 2.

As discussed above, nodes have a tendency to become cystic. The cystic component will have near-fluid attenuation. The solid metastatic component will appear 2:

General signal characteristics include:

  • T1

    • hypointense to muscle

    • enhancement is best seen with fat suppression

  • T2: variable 2

    • hypointense: 34%

    • isointense: 45%

    • hyperintense: 21%

Papillary thyroid cancer usually concentrates radioiodine, but not pertechnetate.

  • FDG-avid

  • incidental FDG-avid thyroid nodules have ~40% risk of being a primary thyroid malignancy 9

Treatment involves both surgical resection and administration of radioactive iodine for lymph node metastases.

Overall papillary carcinoma carries a relatively good prognosis with a 20-year survival rate of approximately 90%. The 5-year survival is in the range of 95%. If the tumor is confined to the gland then mortality is less than 2.5%, with a sharp increase in mortality in patients with extension beyond the gland, to 38% 2.

There is a paucity of high-quality data on the extent of surgery required (thyroid lobectomy versus total thyroidectomy) for low-risk papillary thyroid cancer 12. A recent systematic review suggests that operative approach did not impact overall survival 12.

Patients with papillary thyroid cancer have an elevated risk for secondary primary cancer. Male gender and older age are recognized risks 15.  

Other thyroid neoplasms should be considered in the absence of cavitary cervical lymph nodes.

The differential of a cystic neck mass(es) includes:

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Cases and figures

  • Figure 1: gross specimen
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  • Figure 2: histology - orphan Annie eyes
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  • Case 1: with cystic nodal metastases
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  • Case 2
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  • Case 3
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  • Case 4: MRI
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  • Case 5: PET scan (FDG-avid)
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  • Case 6: with tracheal invasion
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  • Case 7
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  • Case 8: recurrent
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  • Case 9
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  • Case 10: invasive
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  • Case 11
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  • Case 12: with miliary lung metastases
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  • Case 13
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  • Case 14: with miliary lung metastases
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  • Case 15
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  • Case 16: incidental finding on FDG PET-CT
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  • Case 17: with cystic lymphadeopathy
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  • Case 18
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  • Case 19
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  • Case 20
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  • Case 29
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  • Case 30
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  • Case 31
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  • Case 32: with co-existing parathyroid adenoma
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