a) Papillary Carcinoma


The most common thyroid malignancy of childhood and adult life. Females are more common affected (4:1). Rates of the disease are increasing but cure rates are high (over 90% for those under 45 years of age).
Interestingly, the incidence of papillary thyroid cancer is between 5 and 35% in autopsy and thyroidectomy series. This suggests that many papillary carcinomas are relatively benign in their behaviour.


The aetiology of thyroid cancer is related to gender (through unknown mechanisms) and radiation exposure. Rates of papillary thyroid cancer in Eastern European countries was elevated following the Chernobyl accident. This was due to uptake of 131I in the developing thyroid gland, with a relative risk of 237 for those aged under 1 year.

Natural History

Papillary carcinoma frequently passes to regional lymph nodes but haematogenous spread is less common. There are often microscopic deposits of malignancy in macroscopically normal thyroid tissue, likely due to lymphatic spread within the gland itself.
Incidental papillary carcinomas found on imaging are thought to have a benign course in most patients. There is a 98% 20 year survival for patients with symptomatic disease with modern treatment and an argument can be made for observing asymptomatic thyroid nodules.

Clinical Features

The most common presenting features are:

  • Thyroid nodule
  • Cervical lymphadenopathy

Incidental findings of thyroid nodules are not uncommon.
Local disease can lead to dyspnoea or dysphagia with involvement of adjacent structures.


Nuclear medicine scans detect papillary carcinoma as a cold nodule in the thyroid gland. Ultrasound is the best modality currently for determination of the nature of a thyroid nodule (cystic or solid). CT and MRI do not add additional information except for mediastinal lymphadenopathy.

Tumour Features


Most tumours are grey-white, irregular lesions that may infiltrate the surrounding thyroid tissue. Small portions may be cystic.


Although papillary architecture is common it is not always present. Instead, diagnosis relies on nuclear features. There are several classical nuclear features of papillary thyroid cancer:

  • Elongation
  • Enlargement
  • Oval Shape
  • Overlapping
  • Grooving (due to folding of the nuclear membrane)
  • Ground glass chromatin

At least some of these features should be required for a diagnosis. Squamous metaplasia may also be seen. Psammoma bodies (calcium deposits) are also visible in some cases and aid in classification.


There are numerous subtypes of papillary carcinoma. Regardless of the growth pattern, the nuclei retain the features described above.

  • Follicular variant consists of small follicle-like structures with few papillae.
  • Oncocytic variant is a brown coloured tumour that may have follicular or papillary growth patterns.
  • Clear cell variant contains clear cells with either papillary or follicular growth patterns
  • Diffuse sclerosing variant often involves both lobes of the thyroid without a discrete mass. Calcification is frequent. This variant is associated with auto-immune thyroid disease and metastasises more frequently than other variants, usually to the lungs.

There are a number of rare variants that are not described here.


Positive for cytokeratins, thyroglobulin and TTF-1. The presence of thyroglobulin is helpful in distinguishing thyroid carcinoma from lung carcinoma. Further stains that try and highlight common genetic alterations in papillary carcinoma are in development.


The unique genetic change seen in papillary carcinoma is the RET/PTCH rearrangement, where the tyrosine kinase domain of RET is fused to another gene on the long arm of chromosome 10.
RET is a proto-oncogene that normally functions during foetal development, and is important in the development of the neural crest.
PTCH1 codes for patched-1, the receptor for the sonic hedgehog protein (SHH). When SHH binds to PTCH1, it dissociates from SMO (smoothened), leading to signal transduction that promotes cell proliferation.
Both RET and PTCH1 are essential in the normal embryological development of humans (and many other animals). The chimeric RET/PTCH1 gene leads to inappropriate activation of the RET tyrosine kinase which promotes cell survival and clonal expansion. There are a number of other PTCH proteins; RET/PTCH3 seems to be strongly associated with ionising radiation.
Other common genetic changes seen in papillary carcinoma are RAS and B-RAF mutations.


Staging of papillary carcinoma varies for those over and under 45. People under 45 years of age can only ever be Stage I or Stage II, depending on the presence of distant metastases. Those over 45 are staged normally (see the parent page).