Papillary thyroid carcinoma (PTC) is an epithelial malignancy showing evidence of follicular cell differentiation and a set of distinctive nuclear features. It is the most frequent thyroid neoplasm and carries the best overall prognosis.
Known risk factors for PTC include:
Radiation exposure:The incidence of papillary thyroid cancer is greater in people who have a history of exposure to significant ionizing radiation.
Childhood exposure:External low-dose radiation therapy to the head and neck during childhood, used in the 1940s to 1960s to treat various benign diseases, predispose to PTC. The average time from irradiation to the recognition of the tumor is approximately 10 years but may be longer than 30 years. Medical Therapy:High radiation doses (> 2000 cGy) used in the treatment of malignant diseases have also been associated with an increased risk of PTC. Environmental exposure:The Chernobyl nuclear accident, which occurred on April 26, 1986, led to a 3- to 75-fold increase in the incidence of PTC in fallout regions, especially in younger children.
There are few familial syndromes associated with PTC, including familial adenomatous polyposis—Gardner syndrome, Werner syndrome, and Carney complex type 1. Familial PTC cases have been reported in 5% of all patients with PTC and may portend a more aggressive disease course.
There is also a higher incidence of PTC in regions with high dietary iodine intake and in patients who have preexisting benign thyroid disease.
Papillary thyroid carcinoma is the predominant form of thyroid cancer accounting for 80-85% of all thyroid cancer cases In a report based upon the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2012, the incidence of PTC increased from 4.8 to 14.9 per 100,000. Papillary thyroid carcinoma occurs predominantly in middle-aged adults with a 3:1 female-to-male ratio and the median age at presentation is 50 years. Even though rare in children, PTC is still the most common pediatric thyroid malignancy. It affects whites more commonly than blacks.
Grossly, PTC typically presents as an invasive neoplasm with poorly defined margins, a firm consistency, and a granular white cut surface. Calcifications may be present. The size is widely variable, with a mean diameter of 2-3 cm. Papillary thyroid carcinoma has three classification categories based on the size and extent of the primary lesion. Minimal carcinoma or occult carcinoma/micro-carcinoma tumors are 1.5 cm or smaller and show no evidence of invasiveness through the thyroid capsule or to cervical lymph nodes. These lesions are typically nonpalpable and are usually incidental findings during operative or autopsy examination. Intra-thyroid tumors are greater than 1.5 cm in diameter but remain confined to the thyroid gland with no evidence of extra-thyroid invasion. Extra-thyroid tumors extend through the thyroid capsule to involve the surrounding viscera.
The two cardinal morphological features of conventional PTC are the papillae and the nuclear changes. The papillae are composed of a central fibrovascular stalk covered by a neoplastic epithelial lining. The papillae may be long, straight, or arborizing; arranged in a parallel, regimented fashion; short and stubby, or tightly packed. The thickness and composition of the papillary stalk are variable. The stalk is usually made up of loose connective tissue and variously sized thin-walled vessels.
The diagnosis of papillary carcinoma has as its basis the nuclear morphology of a thyroid neoplasm. The existence of multiple architectural variants proves the irrelevance of architecture. The following constellation of features characterize the diagnostic nuclear morphology :
Immunohistochemistry is seldom of value in diagnosing PTC although it may play a role in metastatic disease. The neoplastic cells are strongly and diffusely immunoreactive with keratin, CK7, thyroglobulin, TTF1, and PAX8, while other markers (HBME-1, Galectin-3, S100 protein, CITED1, CK19) yield variable results.
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.
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.
Thyroid function testing has limited utility in the diagnosis of PTC because most patients have normal thyroid function.
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.
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.
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. 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. 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 :
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 a 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.
The primary differential diagnoses of PTC are:
Any of these risk-stratification systems can be used to assign patients to the high-risk or low-risk group (MACIS is utilized only for PTC), based on well-established prognostic factors, but TNM and MACIS probably yield the most useful prognostic information.
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.
Poor prognostic factors of PTC include:
Extra-thyroidal extension occurs in 8% to 32% of cases.
Local or regional recurrences:
Local or regional recurrences occur in 5 to 15% of patients with PTC.
Distant metastasis occurs in only 1% to 25% mostly in the lungs and bones. Other less common sites are the brain, liver, and skin.
Papillary thyroid cancer is ideally managed by a multidisciplinary team that consists of an endocrinologist, general surgeon, oncologist, radiation oncologist, and an internist. With early diagnosis and prompt treatment, the prognosis for most patients is excellent.
|||Mao XC,Yu WQ,Shang JB,Wang KJ, Clinical characteristics and treatment of thyroid cancer in children and adolescents: a retrospective analysis of 83 patients. Journal of Zhejiang University. Science. B. 2017 May [PubMed PMID: 28471115]|
|||Mileva M,Stoilovska B,Jovanovska A,Ugrinska A,Petrushevska G,Kostadinova-Kunovska S,Miladinova D,Majstorov V, Thyroid cancer detection rate and associated risk factors in patients with thyroid nodules classified as Bethesda category III. Radiology and oncology. 2018 Sep 27 [PubMed PMID: 30265655]|
|||Davies L,Welch HG, Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006 May 10 [PubMed PMID: 16684987]|
|||Casella C,Fusco M, Thyroid cancer. Epidemiologia e prevenzione. 2004 Mar-Apr [PubMed PMID: 15281612]|
|||Lim H,Devesa SS,Sosa JA,Check D,Kitahara CM, Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974-2013. JAMA. 2017 Apr 4 [PubMed PMID: 28362912]|
|||Choi JB,Lee SG,Kim MJ,Kim TH,Ban EJ,Lee CR,Lee J,Kang SW,Jeong JJ,Nam KH,Chung WY,Park CS, Oncologic outcomes in patients with 1-cm to 4-cm differentiated thyroid carcinoma according to extent of thyroidectomy. Head [PubMed PMID: 30536465]|
|||Al-Brahim N,Asa SL, Papillary thyroid carcinoma: an overview. Archives of pathology [PubMed PMID: 16831036]|
|||Cho H,Kim JY,Oh YL, Diagnostic value of HBME-1, CK19, Galectin 3, and CD56 in the subtypes of follicular variant of papillary thyroid carcinoma. Pathology international. 2018 Nov [PubMed PMID: 30350394]|
|||Rahmat F,Kumar Marutha Muthu A,S Raja Gopal N,Jo Han S,Yahaya AS, Papillary Thyroid Carcinoma as a Lateral Neck Cyst: A Cystic Metastatic Node versus an Ectopic Thyroid Tissue. Case reports in endocrinology. 2018 [PubMed PMID: 30420925]|
|||Nasser SM,Pitman MB,Pilch BZ,Faquin WC, Fine-needle aspiration biopsy of papillary thyroid carcinoma: diagnostic utility of cytokeratin 19 immunostaining. Cancer. 2000 Oct 25 [PubMed PMID: 11038428]|
|||Nishino M,Krane JF, Updates in Thyroid Cytology. Surgical pathology clinics. 2018 Sep [PubMed PMID: 30190135]|
|||[PubMed PMID: 30548366]|
|||[PubMed PMID: 30547520]|
|||Haugen BR, 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: What is new and what has changed? Cancer. 2017 Feb 1 [PubMed PMID: 27741354]|
|||[PubMed PMID: 29950860]|
|||LiVolsi VA,Merino MJ, Worrisome histologic alterations following fine-needle aspiration of the thyroid (WHAFFT). Pathology annual. 1994 [PubMed PMID: 7936753]|
|||Baloch ZW,LiVolsi VA, Fine-needle aspiration of thyroid nodules: past, present, and future. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2004 May-Jun [PubMed PMID: 15310542]|
|||Wong RM,Bresee C,Braunstein GD, Comparison with published systems of a new staging system for papillary and follicular thyroid carcinoma. Thyroid : official journal of the American Thyroid Association. 2013 May [PubMed PMID: 23106409]|
|||Loh KC,Greenspan FS,Gee L,Miller TR,Yeo PP, Pathological tumor-node-metastasis (pTNM) staging for papillary and follicular thyroid carcinomas: a retrospective analysis of 700 patients. The Journal of clinical endocrinology and metabolism. 1997 Nov [PubMed PMID: 9360506]|
|||D'Avanzo A,Ituarte P,Treseler P,Kebebew E,Wu J,Wong M,Duh QY,Siperstein AE,Clark OH, Prognostic scoring systems in patients with follicular thyroid cancer: a comparison of different staging systems in predicting the patient outcome. Thyroid : official journal of the American Thyroid Association. 2004 Jun [PubMed PMID: 15242573]|
|||Ito Y,Miyauchi A,Kihara M,Fukushima M,Higashiyama T,Miya A, Overall Survival of Papillary Thyroid Carcinoma Patients: A Single-Institution Long-Term Follow-Up of 5897 Patients. World journal of surgery. 2018 Mar [PubMed PMID: 29349484]|
|||Mazzaferri EL,Jhiang SM, Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. The American journal of medicine. 1994 Nov [PubMed PMID: 7977430]|
|||DeGroot LJ,Kaplan EL,McCormick M,Straus FH, Natural history, treatment, and course of papillary thyroid carcinoma. The Journal of clinical endocrinology and metabolism. 1990 Aug [PubMed PMID: 2380337]|
|||Sebastian SO,Gonzalez JM,Paricio PP,Perez JS,Flores DP,Madrona AP,Romero PR,Tebar FJ, Papillary thyroid carcinoma: prognostic index for survival including the histological variety. Archives of surgery (Chicago, Ill. : 1960). 2000 Mar [PubMed PMID: 10722027]|