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==Overview==
==Overview==
The exact pathogenesis of papillary thyroid cancer is not fully understood.
The exact pathogenesis of papillary thyroid cancer is not fully understood. Papillary thyroid cancer has been associated with somatic rearrangement of RET protooncogene. On gross pathology, an ill-defined [[tumor]], irregular borders, and firm consistency are characteristic findings of papillary thyroid cancer. There is no unique consensus on the definition of histological subtypes of papillary thyroid cancer. 
==Pathogenesis==
=Pathogenesis==
* The exact pathogenesis of papillary thyroid cancer is not fully understood.
* The exact pathogenesis of papillary thyroid cancer (PTC) is not fully understood.<ref>{{cite journal |vauthors=Nikiforov YE |title=RET/PTC rearrangement in thyroid tumors |journal=Endocr. Pathol. |volume=13 |issue=1 |pages=3–16 |date=2002 |pmid=12114746 |doi= |url=}}</ref><ref>{{cite journal |vauthors=Tallini G, Asa SL |title=RET oncogene activation in papillary thyroid carcinoma |journal=Adv Anat Pathol |volume=8 |issue=6 |pages=345–54 |date=November 2001 |pmid=11707626 |doi= |url=}}</ref><ref>{{cite journal |vauthors=Nikiforov YE, Koshoffer A, Nikiforova M, Stringer J, Fagin JA |title=Chromosomal breakpoint positions suggest a direct role for radiation in inducing illegitimate recombination between the ELE1 and RET genes in radiation-induced thyroid carcinomas |journal=Oncogene |volume=18 |issue=46 |pages=6330–4 |date=November 1999 |pmid=10597232 |doi=10.1038/sj.onc.1203019 |url=}}</ref>
*
* Papillary thyroid cancer has been associated with somatic rearrangement of RET protooncogene.
* Papillary thyroid tumors are most commonly unencapsulated, and they have a high tendency to metastasize locally to [[lymph nodes]], which may produce cystic structures near the thyroid that are difficult to diagnose because of the paucity of malignant tissue.<ref>{{cite journal|last1=Grani|first1=G|last2=Fumarola|first2=A|title=Thyroglobulin in Lymph Node Fine-Needle Aspiration Washout: A Systematic Review and Meta-analysis of Diagnostic Accuracy.|journal=The Journal of Clinical Endocrinology and Metabolism|date=Jun 2014|volume=99|issue=6|pages=1970–82|pmid=24617715|doi=10.1210/jc.2014-1098}}</ref><ref name="The Thyroid and its Diseases">{{cite web|url=http://www.thyroidmanager.org/Chapter18/18-cause.htm| title=The Thyroid and its Diseases|date=|accessdate= 2010-07-15}}</ref>
* The RET rearrangement encodes for a tyrosine kinase receptor.
* Although papillary carcinoma has a propensity to invade [[lymphatics]], it is less likely to invade [[blood vessels]].<ref>{{cite web|url=http://emedicine.medscape.com/article/282276-overview| title=Thyroid, Papillary Carcinoma|date=|accessdate= 2010-07-15}}</ref>
* This rearrangement has also been observed in mice with a history of ionizing radiation exposure.
* Furthermore, papillary tumors may metastasize to the [[lungs]] and produce a few nodules or the lung fields may exhibit a [[snowflake]] appearance throughout.
* Ionizing radiation has been well recognized for its role in papillary thyroid cancer etiology.
* Lateral aberrant thyroid is actually a [[lymph node]] metastasis from papillary thyroid carcinoma.<ref name="pmid17319317">{{cite journal |author=Escofet X, Khan AZ, Mazarani W, Woods WG |title=Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant? |journal=J R Soc Health |volume=127 |issue=1 |pages=45–6 |year=2007 |pmid=17319317 |doi=10.1177/1466424007073207}}</ref>
* The rearranged form of this gene is well-known as ret/PCT rearrangement and is believed to be related to PTC carcinogenesis.
* Other characteristics of the papillary carcinoma is that E.M. shows increased [[mitochondria]], increased RER, as well as increased apical microvilli. Moreover, papillary carcinomas have an indolent growth, and 40 percent of cases spread out of the [[capsule]].<ref>{{cite web|url=http://www.pathology.vcu.edu/education/endocrine/endocrine/newthyroid/| title=Papillary Carcinomas|date=|accessdate= 2010-07-15}} {{Dead link|date=October 2010|bot=H3llBot}}</ref>
* Papillary thyroid cancer metastatize through lymphatics.
==Genetics==
==Genetics==
*[[Genetic]] alteration [[Association (statistics)|associated]] with papillary thyroid cancer include:<ref name="LloydBuehler2011">{{cite journal|last1=Lloyd|first1=Ricardo V.|last2=Buehler|first2=Darya|last3=Khanafshar|first3=Elham|title=Papillary Thyroid Carcinoma Variants|journal=Head and Neck Pathology|volume=5|issue=1|year=2011|pages=51–56|issn=1936-055X|doi=10.1007/s12105-010-0236-9}}</ref>
*[[Genetic]] alteration [[Association (statistics)|associated]] with papillary thyroid cancer include:<ref name="LloydBuehler2011">{{cite journal|last1=Lloyd|first1=Ricardo V.|last2=Buehler|first2=Darya|last3=Khanafshar|first3=Elham|title=Papillary Thyroid Carcinoma Variants|journal=Head and Neck Pathology|volume=5|issue=1|year=2011|pages=51–56|issn=1936-055X|doi=10.1007/s12105-010-0236-9}}</ref>
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**[[TRK]] rearrangements
**[[TRK]] rearrangements
**[[HMGA2]] [[overexpression]]
**[[HMGA2]] [[overexpression]]
==Associated Conditions==
==Associated Conditions==
* Papillary thyroid cancer may be [[Association (statistics)|associated]] with:<ref name="LloydBuehler2011">{{cite journal|last1=Lloyd|first1=Ricardo V.|last2=Buehler|first2=Darya|last3=Khanafshar|first3=Elham|title=Papillary Thyroid Carcinoma Variants|journal=Head and Neck Pathology|volume=5|issue=1|year=2011|pages=51–56|issn=1936-055X|doi=10.1007/s12105-010-0236-9}}</ref><ref name="HallAbdollahian2013">{{cite journal|last1=Hall|first1=Joseph E.|last2=Abdollahian|first2=Davood J.|last3=Sinard|first3=Robert J.|last4=Eisele|first4=David W.|title=Thyroid disease associated with cowden syndrome: A meta-analysis|journal=Head & Neck|volume=35|issue=8|year=2013|pages=1189–1194|issn=10433074|doi=10.1002/hed.22971}}</ref>
* Papillary thyroid cancer may be [[Association (statistics)|associated]] with:<ref name="LloydBuehler2011">{{cite journal|last1=Lloyd|first1=Ricardo V.|last2=Buehler|first2=Darya|last3=Khanafshar|first3=Elham|title=Papillary Thyroid Carcinoma Variants|journal=Head and Neck Pathology|volume=5|issue=1|year=2011|pages=51–56|issn=1936-055X|doi=10.1007/s12105-010-0236-9}}</ref><ref name="HallAbdollahian2013">{{cite journal|last1=Hall|first1=Joseph E.|last2=Abdollahian|first2=Davood J.|last3=Sinard|first3=Robert J.|last4=Eisele|first4=David W.|title=Thyroid disease associated with cowden syndrome: A meta-analysis|journal=Head & Neck|volume=35|issue=8|year=2013|pages=1189–1194|issn=10433074|doi=10.1002/hed.22971}}</ref>

Revision as of 15:07, 13 August 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Overview

The exact pathogenesis of papillary thyroid cancer is not fully understood. Papillary thyroid cancer has been associated with somatic rearrangement of RET protooncogene. On gross pathology, an ill-defined tumor, irregular borders, and firm consistency are characteristic findings of papillary thyroid cancer. There is no unique consensus on the definition of histological subtypes of papillary thyroid cancer.

Pathogenesis=

  • The exact pathogenesis of papillary thyroid cancer (PTC) is not fully understood.[1][2][3]
  • Papillary thyroid cancer has been associated with somatic rearrangement of RET protooncogene.
  • The RET rearrangement encodes for a tyrosine kinase receptor.
  • This rearrangement has also been observed in mice with a history of ionizing radiation exposure.
  • Ionizing radiation has been well recognized for its role in papillary thyroid cancer etiology.
  • The rearranged form of this gene is well-known as ret/PCT rearrangement and is believed to be related to PTC carcinogenesis.
  • Papillary thyroid cancer metastatize through lymphatics.

Genetics

Associated Conditions

Gross Pathology

  • On gross pathology, an ill-defined tumor, irregular borders, and firm consistency are characteristic findings of papillary thyroid cancer.[6]
  • Calcification may also be present.
  • Other less common features include:
Papillary thyroid cancer gross pathology[7]

Microscopic Pathology

  • Papillary thyroid carcinoma has numerous histological subtypes. Each subtype has some specific characteristics.[6][4]
  • There is no unique consensus on the definition of each subtype, so different pathologists may not agree with these definitions.
  • Cytologic features of papillary thyroid cancer are diagnostic for this tumor. These features include:
    • Enlarged, irregular, oval shape nuclei that are overlapped because of the nuclear enlargement
    • Nuclear clearing
    • Ground glass appearance with prominent nuclear grooves
    • Pink cytoplasmic invaginations
Papillary thyroid cancer subtype Features on Histopathological Microscopic Analysis
Follicular
Conventional
Tall cell
Columnar cell
  • Pseudostratified cells
  • Overlapping enlarged nuclei
Oncocytic
Solid
Diffuse sclerosing
Papillary thyroid carcinoma with prominent hobnail features
Clear cell
Cribriform-Morular
Macrofollicular
  • Composed of macrofollicles
  • Cytological features of papillary thyroid cancer
Papillary thyroid cancer Image
  • Micrograph of papillary thyroid carcinoma, tall cell variant - high magnification
  • "Tall cells": the largest dimension is 3x the smaller dimension
  • Abundant eosinophilic cytoplasm
  • Lack of pseudostratification is a significant differentiator from columnar cell variant of papillary thyroid carcinoma
H&E stain. Contributed in wikimedia.commons
  • Micrograph showing oncocytic variant of papillary thyroid carcinoma
  • Large cells with abundant eosinophilic cytoplasm
H&E stain, Contributed in wikimedia.commons
  • Micrograph showing cribriform-Morular variant of papillary thyroid carcinoma
  • Cribriform pattern with solid and spindle cell areas
  • Squamous morules
H&E stain, Contributed in wikimedia.commons
  • Micrograph (high power view) showing nuclear changes in papillary thyroid carcinoma (PTC), which include:
    • Groove formation
    • Optical clearing
    • Eosinophilic inclusions and overlapping of nuclei
H&E stain. Contributed in wikimedia.commons
  • Micrograph (high power view) of PTC demonstrating nuclear clearing and overlapping nuclei
H&E stain. Contributed in wikimedia.commons
  • Micrograph of papillary thyroid carcinoma demonstrating prominent papillae with fibrovascular cores
H&E stain. Contributed in wikimedia.commons
H&E stain. Contributed in wikimedia.commons
H&E stain. Contributed in wikimedia.commons

Immunohistochemistry

Histopathological Video

Video

{{#ev:youtube|JwymE_Lfs44}}

References

  1. ↑ Nikiforov YE (2002). "RET/PTC rearrangement in thyroid tumors". Endocr. Pathol. 13 (1): 3–16. PMID 12114746.
  2. ↑ Tallini G, Asa SL (November 2001). "RET oncogene activation in papillary thyroid carcinoma". Adv Anat Pathol. 8 (6): 345–54. PMID 11707626.
  3. ↑ Nikiforov YE, Koshoffer A, Nikiforova M, Stringer J, Fagin JA (November 1999). "Chromosomal breakpoint positions suggest a direct role for radiation in inducing illegitimate recombination between the ELE1 and RET genes in radiation-induced thyroid carcinomas". Oncogene. 18 (46): 6330–4. doi:10.1038/sj.onc.1203019. PMID 10597232.
  4. ↑ 4.0 4.1 4.2 Lloyd, Ricardo V.; Buehler, Darya; Khanafshar, Elham (2011). "Papillary Thyroid Carcinoma Variants". Head and Neck Pathology. 5 (1): 51–56. doi:10.1007/s12105-010-0236-9. ISSN 1936-055X.
  5. ↑ Hall, Joseph E.; Abdollahian, Davood J.; Sinard, Robert J.; Eisele, David W. (2013). "Thyroid disease associated with cowden syndrome: A meta-analysis". Head & Neck. 35 (8): 1189–1194. doi:10.1002/hed.22971. ISSN 1043-3074.
  6. ↑ 6.0 6.1 6.2 Lloyd, Ricardo V. (2010). doi:10.1007/978-1-4419-1069-1. Missing or empty |title= (help)
  7. ↑ Image courtesy of Dr David Cuete. Radiopaedia (original file ‘’here’’.Creative Commons BY-SA-NC
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