Papillary thyroid cancers (PTC) are the most common thyroid malignancy, and typically, they have an indolent course with a low long-term mortality rate.
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Terminology
When the tumor measures ≤10 mm, the terms papillary thyroid microcarcinoma (PTMC) 18 or micropapillary carcinoma (mPTC) 14 can be used 14.
Epidemiology
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 most (~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 ref.
Associations
familial adenomatous polyposis (FAP): usually associated with the cribriform-morular variant
Risk factors
family history
previous head/neck radiation
Clinical presentation
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.
Pathology
Lymphatic spread is more common than hematogenous spread (cf. follicular thyroid carcinoma) and multifocality is common.
Subtypes
Conventional/classical papillary thyroid cancer comprises ~50% of papillary thyroid cancers, with the other ~50% made up of multiple variants that have been described according to biological behavior:
-
favorable 13,16
follicular/encapsulated variant: most common variant (~33%), resembles follicular thyroid carcinoma
cribriform/morula variant
Warthin-like variant
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aggressive 19
solid variant
diffuse sclerosing variant
tall cell variant
columnar cell variant
hobnail variant
Microscopic appearance
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
Staging
Radiographic features
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.
Ultrasound
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.
Fine needle aspiration
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.
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
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
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%
Nuclear medicine
Papillary thyroid cancer usually concentrates radioiodine, but not pertechnetate.
FDG-PET
FDG-avid
incidental FDG-avid thyroid nodules have ~40% risk of being a primary thyroid malignancy 9
Treatment and prognosis
Treatment involves both surgical resection and administration of radioactive iodine for lymph node metastases. For papillary microcarcinomas (≤10 mm), active surveillance is a viable option instead of immediate surgery 18.
Overall, papillary carcinoma carries a relatively good prognosis with a 20-year survival rate of ~90%. The 5-year survival is in the range of 95%. If the tumor is confined to the gland then mortality is <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 (c. 2019) on the extent of surgery required (thyroid lobectomy versus total thyroidectomy) for low-risk papillary thyroid cancer 12. A systematic review suggests that operative approach did not impact overall survival 12.
Complications
Patients with papillary thyroid cancer have an elevated risk for secondary primary cancer. Male gender and older age are recognized risks 15.
Differential diagnosis
Other thyroid neoplasms should be considered in the absence of cavitary cervical lymph nodes.
The differential of a cystic neck mass(es) includes:
thyroglossal duct cyst (only if single)
branchial cleft cyst (only if single)
cystic metastasis to the thyroid
abscess including tuberculous lymphadenitis
multiple neurofibromas
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