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papillary thyroid carcinoma

Etiology: 1) most likely tumor to occur as a result of previous radiation to the head & neck - may occur 30-40 years post-radiation exposure [3] 2) familial component of risk [4] Epidemiology: 1) most common thyroid cancer (75-85%) 2) most commonly occurs in the 3rd to 5th decade of life 3) female/male predominance of 3/1 4) papillary carcinomas are incidentally found in up to 1/3 of routine autopsies Pathology: 1) 50% present with lymph node involvement, 5% with distant metastases 2) tumors may range in size up to 10 cm in diameter 3) all papillary carcinomas have branching papillae witha fibrovascular stalk covered with multiple layers of cuboidal epithelial cells 4) tumors may have both papillary & follicular morphology 5) an encapsulated variant is described, but most papillary carcinomas are not encapsulated 6) 20-30% of papillary carcinomas are associated with translocations involving the tyrosine kinase domain of the RET proto-oncogene & the papillary thyroid carcinoma gene (PTC) 7) features of papillary carcinomas: a) hypochromatic 'empty' nuclei (orphan Annie eyes) nuclear grooves b) eosinophilic intranuclear inclusions representing invaginations of cytoplasm c) Psammoma bodies, usually within the cores of papillae, sometimes surrounded by calcific lamellations. 8) papillary thyroid carcinoma arises from thyroid follicular cells [2] Genetics: - familial component of risk [4] - chromosomal translocation t(10;12)(q11;p13) involving ERC1 & RET associated with thyroid papillary carcinoma - a chromosomal translocation t(1;3)(q21;q11) involving TFG with NTRK1 may be a cause of thyroid papillary carcinoma - chromosomal translocation t(7;10)(q32;q11) involving RET with TIF1/TRIM24 generates the TIF1/RET (PTC6) oncogene - chromosomal translocation t(8;10)(p21.3;q11.2) involving PCM1 with RET is found in thyroid papillary carcinoma the translocation links the protein kinase domain of RET to the major portion of PCM1 - chromosomal rearrangement involving TPM3 with NTRK1 may be a cause of thyroid papillary carcinoma - chromosomal rearrangement involving TPR may be a cause of thyroid papillary carcinoma - chromosomal inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene - other implicated genes GADD45GIP1, PDGFC, TSHR, BRAF Clinical manifestations: - uncommonly papillary carcinomas produce mild to moderate thyrotoxicosis Laboratory: 1) serum thyroglobulin may be used as a marker for residual or recurrent disease 2) PCR for BRAF mutation from fine-needle aspiration Special laboratory: - fine-needle aspiration (FNA) a) thyroid nodules > 1 cm b) analyze aspirate for BRAF mutation when diagnosis is indeterminate (specific for papillary thyroid carcinoma) [2] Radiology: - radiolabeled iodine uptake - more differentiated lesions may take-up radiolabeled iodine Management: 1) tumors < 1.5 cm in diameter in patients > 50 years of age (low risk) may be followed by active surveillance [5] 2) total thyroidectomy with lymph node dissection 3) radio-iodine ablation of remnant thyroid tissue 4-6 weeks following surgery a) a total body scan using 2 mCi of I-131 is used to search for residual thyroid tissue b) if residual thyroid tissue is found, a large therapeutic dose of 100-150 mCi is administered & another scan done in 7 days 4) prognosis a) good, 98% 5 year survival [2] - cumulative incidence of tumor growth 12% at 5 years for low-risk tumors followed by active surveillance [5] b) poorer prognosis occurs with larger, more poorly differentiated tumors with extension outside of thyroid & in older individuals, particularly men c) multifocality associated with an increased risk of recurrence - cancer-specific survival unchanged [6] d) relapse occurs in 12% of patients with no evidence of residual disease after thyroidectomy [2] 4) thyroid replacement with levothyroxine titrated to a) below the normal range* b) free thyroxine index &/or free T4 within normal range 5) follow-up evaluation for recurrence requires a) discontinuation of levothyroxine b) allowing the serum TSH to rise c) measuring serum thyroglobulin as a marker for residual thyroid tissue 6) family members, 1st & second degree relatives at higher risk for papllary thyoid carcinoma, 5 & 2-fold, respectively [4] * thyroid follicular cells, the origin of papillary thyroid carcinoma, are TSH-responsive [2]

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disease interactions

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ret proto-oncogene

General

papillary adenocarcinoma thyroid carcinoma

References

  1. Cotran et al Robbins Pathologic Basis of Disease, 5th ed. W.B. Saunders Co, Philadelphia, PA 1994 pg 1137
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2018, 2022.
  3. Solomon DH, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  4. Oakley GM et al Establishing a Familial Basis for Papillary Thyroid Carcinoma Using the Utah Population Database. JAMA Otolaryngol. Head Neck Surg. October 03, 2013 PMID: 24092278 http://archotol.jamanetwork.com/article.aspx?articleid=1745509
  5. Tuttle RM, Fagin JA, Minkowitz G et al Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance. JAMA Otolaryngol Head Neck Surg. Published online Aug 31, 2017 PMID: 28859191 Free PMC Article http://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2650803 - Scharpf J Achieving Active Surveillance for Thyroid Cancer - Not a Euphemism for Watching a Ticking Time Bomb. JAMA Otolaryngol Head Neck Surg. Published online Aug 31, 2017 PMID: 28859186 http://jamanetwork.com/journals/jamaotolaryngology/article-abstract/2650802
  6. Kim H, Kwon H, Moon BI et al Association of Multifocality With Prognosis of Papillary Thyroid Carcinoma. A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. 2021. August 19. PMID: 34410321 https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2783466

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