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Papillary Thyroid Carcinoma


Papillary thyroid carcinoma is the most common malignant neoplasm of the thyroid gland.


Most patients merely present with a palpable mass in the anterior region of the neck. Usually, no other symptoms are reported. Occasionally, patients may claim difficulties to breath or swallow. Cough may be observed.

Although PTC are malignant tumors, they are most frequently rather slow growing. Thus, if symptoms are present, they are rarely of sudden onset. Rapid increases in tumor volume and additional symptoms such as pain point at differential diagnoses.

Of note, symptoms caused by regional and distant metastases may predominate in some cases. They largely depend on the precise localization of the secondary tumor.

Cervical Lymphadenopathy
  • There was no cervical lymphadenopathy. Flexible endoscopy revealed mobile true vocal folds bilaterally. Laboratory studies revealed a normal CBC, Chem-7, and LFTs. Her TSH, T3, fT4 were normal as well.[web.archive.org]
  • The most frequent presentation of papillary thyroid cancer is a palpable thyroid nodule, cervical lymphadenopathy, or incidental detection on imaging. Locally advanced disease can present with hoarseness or voice alteration.[mdedge.com]
  • lymphadenopathy, and fixation of the nodule to surrounding tissue. 2 Evidence does not support routine thyroid cancer screening. 2 People with a family history of familial follicular cell-derived DTC may have an increased risk for this disease, but no[endocrinologyadvisor.com]
  • There was left cervical lymphadenopathy and bilateral supraclavicular lymphadenopathy. Biopsy revealed Hodgkin's disease of the nodular sclerosing variety. The result of staging laparotomy was negative.[web.archive.org]
  • RECOMMENDATION 28 * Therapeutic lateral neck compartmental lymph node dissection should be performed for patients with biopsy-proven metastatic lateral cervical lymphadenopathy.[doi.org]
Thyroid Nodule
  • Similarly, in HL patients with suspicious thyroid nodule, ultrasound-guided fine needle aspiration of thyroid nodule should be performed to exclude thyroid malignancy.[ncbi.nlm.nih.gov]
  • We report on a case of papillary carcinoma in an autonomously functioning thyroid nodule in a 39 year-old female patient.[scielo.br]
  • We report a case of pituitary macroadenoma, with clinical syndromes of acromegaly and hyperthyroidism, and a thyroid nodule, with cytologically confirmed to be a papillary thyroid carcinoma.[ncbi.nlm.nih.gov]
  • During investigation for an underlying cause of his HLH computed tomographic scan of the neck discovered thyroid nodules that were confirmed with biopsy to be papillary thyroid carcinoma.[ncbi.nlm.nih.gov]
  • Abstract Thyroid carcinoma presenting as a hyperfunctioning thyroid nodule is rare. A further complexity is added when interpretation of the histopathology itself is not straightforward.[ncbi.nlm.nih.gov]
  • The purpose of this study was to evaluate the rate of papillary thyroid cancer (PTC) in patients thyroidectomized for benign multinodular goiter.[ncbi.nlm.nih.gov]
  • When she was 12 years old, multi-nodular goiter was detected by physical examination and ultrasonography. She underwent thyroidectomy and histopathologic investigation revealed a papillary carcinoma with follicular variant.[ncbi.nlm.nih.gov]
  • […] most common type of thyroid neoplasias; however, primary thyroid gland lymphoma (PTL) is uncommon and their simultaneous occurrence is very rare.Herein, we reported a 25-year-old female patient with Hashimoto's thyroiditis (HT), who developed a small goiter[ncbi.nlm.nih.gov]
  • BACKGROUND: Benign thyroid goiter (BTG) and papillary thyroid carcinoma (PTC) are often interchangeably misdiagnosed.[ncbi.nlm.nih.gov]
  • Thyroid ultrasound examination displayed diffuse goiter. The patient was presumptively diagnosed as primary hyperthyroidism and treated with anti-thyroid drugs. Her condition was then improved, but the serum TSH was persistently unrepressed.[ncbi.nlm.nih.gov]
  • A plethora of other mutations has been related to PTC.[symptoma.com]
Malignant Pleural Effusion
  • In rare instances, this disease may metastasize to the pleura and manifest as a malignant pleural effusion. We report 3 female patients of Japanese/Okinawan ancestry with a history of PTC who presented with hydrothorax.[ncbi.nlm.nih.gov]
  • In rare instances, this disease may metastasize to the pleura and manifest as a malignant pleural effusion (MPE) and portend poor prognosis.[ncbi.nlm.nih.gov]
  • A 40-year-old man presented with polyuria and polydipsia for 5 years. The symptoms had been relieved well by drug therapy for 4 years, until the drugs could not control the symptoms anymore and an extensively enlarged thyroid gland was noticed.[ncbi.nlm.nih.gov]
  • She had a generalized lack of subcutaneous fat, including the palmar and plantar regions, muscle hypertrophy, intense acanthosis nigricans, hepatomegaly, hypertriglyceridemia, severe insulin resistance, and hypoleptinemia.[ncbi.nlm.nih.gov]
  • A 57-year-old man presented with left temporal hemianopsia of his left eye without any sign of hyperthyroidism. A mass lesion in the sellar and suprasellar region compressing the optic nerves was identified via magnetic resonance imaging.[ncbi.nlm.nih.gov]
Neck Mass
  • The authors present a case of CMV-PTC in a 10-year-old girl patient without FAP history, who presented with a left neck mass. The patient underwent total thyroidectomy with central compartment neck dissection.[ncbi.nlm.nih.gov]
  • A 54-year-old woman presented with an anterior neck mass measuring 4cm on clinical examination. Imaging showed a suspicious thyroid nodule invading the trachea. Total thyroidectomy with bilateral central lymph node resection was performed.[ncbi.nlm.nih.gov]
  • The patient, a 36 year old woman, presented with a neck mass of 1 year's duration. Imaging studies showed a tumor involving most of the thyroid with enlarged regional lymph nodes. FNA biopsy yielded a diagnosis of "papillary thyroid carcinoma".[ncbi.nlm.nih.gov]
  • Other clinical signs that could indicate papillary thyroid are fixation to the trachea, a firm neck mass, damage to recurrent laryngeal or cervical sympathetic nerves.[en.wikipedia.org]
  • The differential of a cystic neck mass(es) includes: thyroglossal duct cyst (only if single) branchial cleft cyst (only if single) cystic metastasis to thyroid abscess including tuberculous lymphadenitis multiple neurofibromas[radiopaedia.org]


A thorough anamnesis may reveal childhood exposure to radiation, dietary deficits resulting in iodine deficiency or familial history of endocrine neoplasms. These may indicate an increased individual risk of papillary, follicular or medullary thyroid carcinoma.

Thyroid masses are generally evaluated by histopathological analysis of samples obtained by fine needle aspiration. The latter is best conducted after carrying out a sonographic examination of the thyroid gland. Sonography allows for localization of the pathological mass, for visualization of characteristic cysts and calcifications and this information may help to guide the fine needle aspiration. PTC are well-differentiated neoplasms whose cells are often crowded with large, oval nuclei of pale, ground glass-like appearance. Nucleic indentations convey the impression of cytoplasmatic inclusions.

A similar approach is recommended in case of lymph node alterations. It is not uncommon to detect metastases before the primary tumor. On the other hand, diagnosis of PTC should prompt an extensive revision of regional lymph nodes for possible metastases. Scintigraphy is generally applied to this end. Radiography, magnetic resonance imaging or computed tomography scans are not routinely performed to confirm or stage thyroid cancer. They may, however, be employed as supplemental diagnostic measures.

Staging is important for choosing an adequate therapeutic approach. Staging considers the size of the tumor (T), the presence of metastases in regional lymph nodes (N) and distant tissues (M). In case of PTC, it also depends on the patient's age:

  • Patients aged less than 45 years are always considered stage I unless distant metastases are detected, which would lead to their tumor being classified as stage II.
  • In patients older than 45 years, stage I corresponds to a tumor that measures < 2 cm in diameter and no metastases. Larger tumors, i.e., those that measure up to 4 cm in diameter, are classified stage II if no metastases are present. Very large tumors (> 4 cm in diameter) or those that metastasized to regional lymph nodes correspond to stage III. The presence of distant metastases indicates stage IV.


Surgical resection of degenerated tissue, subsequent radiation therapy and replacement of thyroid hormones by administrating the respective drugs are the mainstays of PTC therapy.

The following schemes are recommended according to tumor staging:

  • Stage I and stage II. If possible, a hemithyroidectomy should be preferred over a near-total or total thyroidectomy. The former is associated with less severe complications for lack of thyroid hormones, but also bears a greater risk of recurrence and should therefore be performed only if the neoplasm is well-delimited to one thyroid lobe. The parathyroid glands should be spared. Removal of lymph nodes may be necessary. Post-operative radioactive iodine therapy decreases the probability of relapses. Life-long substitution of thyroid hormones is usually required. Doses should be adjusted to the individual case and results of blood sample analyses.
  • Stage III. These tumors require total thyroidectomy and neck dissection in order to resect affected lymph nodes. Post-operative radioactive iodine therapy should be applied if the tumor has not lost radioiodine avidity. Otherwise, external radiation therapy is indicated. Hormonal therapy should be carried out as described for stages I and II. If parathyroid glands had to be removed in order to completely resect the neoplasm, calcium and vitamin D should be supplemented.
  • Stage IV. Treatment largely corresponds to the approach described for stage III. Additional surgical interventions are necessary to resect distant metastases.


The overall prognosis is good. However, it largely depends on tumor stage and age of the patient upon diagnosis. Involvement of lymph nodes, peripheric metastases and old age are unfavorable prognostic factors. Females tend to have a better outcome than males.


PTC are strongly related to irradiation and history provides scary yet impressive examples that underscore this fact. Very high incidence rates have been detected among survivors of the atomic bombing of Hiroshima and Nagasaki in 1945. Studies have shown that the individual risk of thyroid cancer increases with lower ages at the time of exposure [3]. Because tumor development after irradiation is a long-term consequence of this event - latency periods of 30 years have been estimated -, such studies could not yet be conducted with children who lived close to where the Chernobyl nuclear accident happened in 1986. Unfortunately, similarly high incidence rates of PTC have to be expected.

While today, patients who undergo radiographic examinations are usually provided a thyroid collar, head and neck irradiation was a applied as a common therapeutic measure before associated risks were known. In this context, infectious diseases, acne and even aesthetic flaws have been treated with radiation therapy during large parts of the 20th century. These patients may have an increased risk for PTC, but their individual condition will largely depend on the radiation dose they received and on their age during treatment.

If irradiation is used today, either because images of the head and neck region are required for diagnostic purposes or because pathological conditions indicate radiation therapy, the thyroid gland is protected as far as possible. However, some types of cancer require head and neck irradiation and particularly pediatric patients who receive such treatment may have an increased risk of developing PTC. An average exposure to irradiation due to occasional radiographies has not been proven to increase the individual risk for PTC. Nevertheless, any form diagnostic and therapeutic irradiation should always be justified.

In rare cases, gene mutations may account for familial accumulation of PTC cases [4].

Iodine deficiencies are typically associated with follicular thyroid carcinoma while genetic disorders usually account for medullary thyroid carcinoma [5].


Incidence rates for PTC among the above mentioned risk groups, i.e., atomic bomb and Chernobyl survivors as well as those people who received considerable head and neck irradiation, may be as high as 10%. And even though the overall incidence of thyroid cancer is much lower, it is still considered a frequent type of cancer. Annually, about 15 per 100,000 women are diagnosed with thyroid cancer, while three times less men are affected. For as of yet unknown reasons, incidence rates have been increasing over the last decades [6]. Improved diagnostic techniques may at least partially explain this apparent trend.

Sex distribution
Age distribution


Chromosomal rearrangements affecting the RET (rearranged during transfection) proto-oncogene have been related to PTC [7]. The gene encodes for a receptor tyrosine kinase and gain-of-function mutations presumably contribute to tumor development. Here, constitutive activation of the kinase is triggered by juxtaposition to distinct DNA sequences that are designated papillary thyroid carcinoma (PTC) proteins.

A mutation of the gene encoding for MET receptor tyrosine kinase, a growth factor receptor, has been detected in many cases of thyroid cancer, but an association between gene mutation and tumor characteristics could not yet be established [8]. Different growth factors, e.g., EGF, IGF-1 and TGFβ, have been suggested to play a role in PTC pathogenesis. And although neither of these growth factors binds to the aforementioned MET receptor tyrosine kinase, their pro-oncogenic characteristics make this hypothesis plausible.

Another proto-oncogene frequently mutated in PTC is BRAF, encoding for serine/threonine protein kinase B-Raf. B-RAf is involved in intracellular MAPK signaling and may affect cell growth, proliferation, differentiation and apoptosis. Indeed, the incidence of BRAF mutations seems to have increased simultaneously with PTC incidence rates and has been proposed as a potential explanation for the latter [9].

A plethora of other mutations has been related to PTC. There seem to be clear differences in mutation patterns encountered in patients who developed PTC after receiving high doses of radiation and those who present with sporadic tumors and without a history of irradiation [10].


Other than avoiding irradiation whenever possible, no preventive measures can be recommended.


Thyroid cancer refers to any malignant neoplasm of the thyroid gland. In this context papillary, follicular and medullary carcinoma are distinguished. The papillary thyroid carcinoma (PTC) type accounts for two out of three cases of thyroid cancer and is thus the most common form of this disease. There's a strong correlation between exposure to radiation and the individual risk of PTC.

The name of this tumor derives from its papilla-like outgrowths that are, however, not necessarily present at the time of diagnosis. PC may develop as solitary or multiple tumors. They are solid or may include cysts and/or calcifications. Usually, they are hardened, off-white and well-delimited against unaltered thyroid tissue. However, some PC grow infiltratively and their macroscopic appearance does not allow an unmistaken differentiation from other forms of thyroid cancer. Histopathological analyses are required to this end and tissue samples are either obtained by fine-needle aspiration or standard biopsy. PC are well-differentiated and its cells are further characterized by overlapping, oval, ground glass nuclei. Nuclear grooves are commonly found. Of note, mixed forms of papillary and follicular thyroid carcinoma have been described and should be taken into account when analyzing resected tissue [1]. PTC are likely to metastasize via lymphatic vessels and secondary tumors are frequently detected in regional lymph nodes. Hematogenous metastases are less likely. Surgical resection is the therapy of choice and should include all affected lymph nodes to avoid relapses [2]. Post-operative radioactive iodine therapy may be employed to destroy any residual neoplastic tissue.

Patient Information

Papillary thyroid carcinoma (PTC) is the most common type of malignant tumor that develops within the thyroid gland.


There is a strong correlation between irradiation, especially exposure to high radiation doses during childhood, and the individual risk for PTC. In this context, those that survived the atomic bombing of Japan in 1945 or the nuclear accident in Chernobyl in 1986 have very high risks of thyroid cancer. Another risk factor is head and neck irradiation, which has been applied without reservation to treat infectious diseases, acne and even aesthetic flaws until about 1960.

An average exposure to irradiation due to occasional radiographies does not increase the individual risk for PTC.


Most patients present with a painless, slowly-growing mass in their anterior neck region. Possibly, no other symptoms are experienced. Some patients report problems to swallow or breath or claim persistent cough.


An ultrasonographic examination allows the physician to localize the tumor and to assess its extension. It is also useful to guide tissue sampling, which will be done afterwards by aspirating tumor cells with a fine needle. These cells are histopathologically analyzed. Typical features allow for the diagnosis of PTC.

Because PTC tend to spread to regional lymph nodes, these have to be revised for possible metastases. This is usually done with scintigraphy.


PTC require surgical removal. In mild cases, parts of the thyroid gland may be preserved. This is worth striving for since the lack of thyroid hormones after surgery is less severe if these are still produced endogenously. However, partial resection of the thyroid gland is associated with a higher risk of recurrence. Thus, the decision for a partial or total thyroidectomy is based on the characteristics of the individual case.

After surgery, patients are treated with radioactive iodine. It is absorbed by possible remaining cancerous tissue. Thus, at this specific site, a high dose of irradiation is achieved. This treatment destroys residual cancer cells and therefore decreases the risk of recurrence.

In some cases, PTC have lost their avidity for iodine. Such tumors require external radiation therapy after surgery.

Thyroid hormones have to be substituted after thyroidectomy. Patients usually take one dose daily for the rest of their lives.



  1. Wreesmann VB, Ghossein RA, Hezel M, et al. Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity. Genes Chromosomes Cancer. 2004; 40(4):355-364.
  2. Clayman GL, Shellenberger TD, Ginsberg LE, et al. Approach and safety of comprehensive central compartment dissection in patients with recurrent papillary thyroid carcinoma. Head Neck. 2009; 31(9):1152-1163.
  3. Imaizumi M, Ohishi W, Nakashima E, et al. Association of radiation dose with prevalence of thyroid nodules among atomic bomb survivors exposed in childhood (2007-2011). JAMA Intern Med. 2015; 175(2):228-236.
  4. Musholt TJ, Musholt PB, Petrich T, Oetting G, Knapp WH, Klempnauer J. Familial papillary thyroid carcinoma: genetics, criteria for diagnosis, clinical features, and surgical treatment. World J Surg. 2000; 24(11):1409-1417.
  5. Monson JP. The epidemiology of endocrine tumours. Endocr Relat Cancer. 2000; 7(1):29-36.
  6. Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014; 140(4):317-322.
  7. Romei C, Ciampi R, Elisei R. A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma. Nat Rev Endocrinol. 2016; 12(4):192-202.
  8. Wasenius VM, Hemmer S, Karjalainen-Lindsberg ML, Nupponen NN, Franssila K, Joensuu H. MET receptor tyrosine kinase sequence alterations in differentiated thyroid carcinoma. Am J Surg Pathol. 2005; 29(4):544-549.
  9. Mathur A, Moses W, Rahbari R, et al. Higher rate of BRAF mutation in papillary thyroid cancer over time: a single-institution study. Cancer. 2011; 117(19):4390-4395.
  10. Port M, Boltze C, Wang Y, Roper B, Meineke V, Abend M. A radiation-induced gene signature distinguishes post-Chernobyl from sporadic papillary thyroid cancers. Radiat Res. 2007; 168(6):639-649.

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Last updated: 2019-07-11 20:22