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#redirect [[Thyroid_gland#Papillary_thyroid_carcinoma]]
'''Papillary thyroid carcinoma''', abbreviated '''PTC''', is the most common [[thyroid gland]] malignancy. It usually has an indolent course.
 
==General==
Medical school memory device P's:
*Palpable nodes.
*Popular (most common malignant neoplasm of the thyroid).
*Prognosis is good.
*Pre-Tx iodine scan.
*Post-Sx iodine scan.
*[[Psammoma bodies]].
 
Notes:
*PTC is associated with radiation exposure.<ref name=Ref_Sternberg4_564>{{Ref Sternberg4|564}}</ref>
*''Papillary thyroid microcarcinoma'' is defined as a tumour with a maximal dimension of 1.0 cm or less.<ref name=pmid21267823>{{Cite journal  | last1 = Sethom | first1 = A. | last2 = Riahi | first2 = I. | last3 = Riahi | first3 = K. | last4 = Akkari | first4 = K. | last5 = Benzarti | first5 = S. | last6 = Miled | first6 = I. | last7 = Chebbi | first7 = MK. | title = [Management of thyroid microcarcinoma. Report of 13 cases]. | journal = Tunis Med | volume = 89 | issue = 1 | pages = 23-5 | month = Jan | year = 2011 | doi =  | PMID = 21267823 }}</ref>
 
===Prognosis===
Prognosis can be predicted by ''MAICS'' score. It which includes:<ref name=pmid12016468>{{Cite journal  | last1 = Hay | first1 = ID. | last2 = Thompson | first2 = GB. | last3 = Grant | first3 = CS. | last4 = Bergstralh | first4 = EJ. | last5 = Dvorak | first5 = CE. | last6 = Gorman | first6 = CA. | last7 = Maurer | first7 = MS. | last8 = McIver | first8 = B. | last9 = Mullan | first9 = BP. | title = Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients. | journal = World J Surg | volume = 26 | issue = 8 | pages = 879-85 | month = Aug | year = 2002 | doi = 10.1007/s00268-002-6612-1 | PMID = 12016468 }}</ref>
*'''M'''etastases.
*'''A'''ge.
*'''I'''nvasion of surround tissues.
*'''C'''completeness of excision.
*'''S'''ize of tumour.
 
==Microscopic==
Features:
*Nuclear changes - '''key feature'''.
*#"Shrivelled nuclei"/"raisin" like nuclei, nuclei with a wavy ("textured", convoluted) nuclear membrane -- usu. easy to find.
*#[[Nuclear pseudoinclusions]] -- usu. harder to find; have high [[specificity]] (nuclear pseudoinclusions appear as a result of the very convoluted nuclear membrane wrapping around parts of the cytoplasm; true nuclear inclusions in contrast are seen only in viral infections).
*#Nuclear grooves, seen as a result of the highly "textured" nuclear membrane.
*#Nuclear clearing (only on permanent section) - also known as "Orphan Annie eyes".
*Overlap of nuclei - "cells do not respect each other's borders" (easy to see at '''key feature at low power''').
*Classically has papillae (nipple-like shape); papilla (definition): epithelium on fibrovascular core.
**Absence of papillae does not exclude diagnosis.
*[[Psammoma bodies]].
**Circular, acellular, eosinophilic whorled bodies.
**Not necessary to make diagnosis - but very specific in the context of a specimen labeled "thyroid".
**Arise from infarction & calcification of papilla tips.<ref name=Ref_Sternberg4_565>{{Ref Sternberg4|565}}</ref>
 
Notes:
*Psammoma bodies are awesome if you see 'em, i.e. useful for arriving at the diagnosis.
**If there are no papillae structures -- you're unlikely to see psammoma bodies.
*At low power look for cellular areas/loss of follicles.
*Nuclear clearing seen in:
**Hashimoto's and papillary thyroid carcinoma.<ref name=Ref_Sternberg4_566>{{Ref Sternberg4|566}}</ref>
**May be an artifact of [[fixation]]/processing.
*Nuclear overlapping is easy to see at lower power-- should be the tip-off to look at high power for nuclear features.
*Nuclear inclusions are quite rare and not required to make the diagnosis -- but a very convincing feature if seen.
*Papillae may be seen in Graves disease.
 
DDx:
*[[Lymphocytic thyroiditis]]:
**[[Graves disease]].
**[[Hashimoto thyroiditis]].
*[[Solid cell nest of thyroid]].<ref name=pmid16830963>{{Cite journal  | last1 = Baloch | first1 = ZW. | last2 = LiVolsi | first2 = VA. | title = Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. | journal = Am J Clin Pathol | volume = 125 Suppl | issue =  | pages = S135-44 | month = Jun | year = 2006 | doi =  | PMID = 16830963 | URL = http://ajcp.ascpjournals.org/content/supplements/125/Suppl_1/S135.full.pdf }}</ref>
 
===Subtypes of papillary thyroid carcinoma===
There are many.
 
Poor prognosis variants:
*[[Papillary thyroid carcinoma tall cell variant|Tall cell variant]].<ref name=pmid22432054>{{Cite journal  | last1 = Gonzalez-Gonzalez | first1 = R. | last2 = Bologna-Molina | first2 = R. | last3 = Carreon-Burciaga | first3 = RG. | last4 = Gómezpalacio-Gastelum | first4 = M. | last5 = Molina-Frechero | first5 = N. | last6 = Salazar-Rodríguez | first6 = S. | title = Papillary thyroid carcinoma: differential diagnosis and prognostic values of its different variants: review of the literature. | journal = ISRN Oncol | volume = 2011 | issue =  | pages = 915925 | month =  | year = 2011 | doi = 10.5402/2011/915925 | PMID = 22432054 | PMC = 3302055 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22432054/?tool=pubmed }}</ref>
*[[Papillary thyroid carcinoma columnar cell variant|Columnar cell variant]].<ref name=pmid22432054/>
*[[Papillary thyroid carcinoma solid variant|Solid variant]].<ref name=pmid22432054/>
*[[Papillary thyroid carcinoma diffuse sclerosing variant|Diffuse sclerosing variant]].<ref>URL: [http://emedicine.medscape.com/article/849000-overview#a0104 http://emedicine.medscape.com/article/849000-overview#a0104]. Accessed on: 1 May 2012.</ref>
 
====Papillary thyroid carcinoma tall cell variant====
=====General=====
*~10% of PTC.<ref>{{Ref Sternberg5|505}}</ref>
*Often large > 6 cm.
 
=====Microscopic=====
Features:<ref name=pmid19373912>{{cite journal |author=Urano M, Kiriyama Y, Takakuwa Y, Kuroda M |title=Tall cell variant of papillary thyroid carcinoma: Its characteristic features demonstrated by fine-needle aspiration cytology and immunohistochemical study |journal=Diagn. Cytopathol. |volume= |issue= |pages= |year=2009 |month=April |pmid=19373912 |doi=10.1002/dc.21086 |url=}}</ref>
*50% of cells with height 2x the width.<ref name=pmid18925842>{{cite journal |author=Ghossein R, Livolsi VA |title=Papillary thyroid carcinoma tall cell variant |journal=Thyroid |volume=18 |issue=11 |pages=1179–81 |year=2008 |month=November |pmid=18925842 |doi=10.1089/thy.2008.0164 |url=}}</ref>
**There is some disagreement on these criteria;<ref name=pmid18925842/> Raphael believes the height ought to be ~3x width, for 50% of the cells.<ref>S. Raphael. 17 January 2011.</ref>
*Eosinophilic cytoplasm.
*Well-defined cell borders.
*Nucleus stratified; basal location, i.e. closer to the basement membrane.
 
Negative:
*Nuclei ''not'' pseudostratified, if pseudostratified consider ''columnar cell variant''.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Papillary_thyroid_carcinoma_tall_cell_var_intermed_mag.jpg PTC tall cell variant - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Papillary_thyroid_carcinoma_tall_cell_var_high_mag.jpg PTC tall cell variant - high mag. (WC)].
 
====Papillary thyroid carcinoma columnar cell variant====
=====General=====
Epidemiology:
*Poor prognosis.
*Very rare.
 
=====Microscopic=====
Features:<ref name=Ref_Sternberg5_506>{{Ref Sternberg5|506}}</ref>
*Elongated nuclei (similar to colorectal adenocarcinoma) - '''key feature'''.
*+/-Pseudostratification of the nuclei (like in colorectal adenocarcinoma), differentiates from ''tall cell variant''.
*Nuclear stratification - '''key feature'''.
*"Minimal" papillary features.
*"Tall cells".
*Clear-eosinophilic cytoplasm.
*Mitoses common.
Image: [http://www3.interscience.wiley.com/cgi-bin/fulltext/75000320/nfig003a?CRETRY=1&SRETRY=0 Columnar variant PTC (wiley.com)].
====Papillary thyroid carcinoma follicular variant====
=====General=====
*May be confused with [[follicular thyroid carcinoma|follicular carcinoma]] or [[follicular thyroid adenoma|follicular adenoma]].
*Pathologists often disagree about this diagnosis.<ref name=pmid21940284>{{Cite journal  | last1 = Daniels | first1 = GH. | title = What if many follicular variant papillary thyroid carcinomas are not malignant? A review of follicular variant papillary thyroid carcinoma and a proposal for a new classification. | journal = Endocr Pract | volume = 17 | issue = 5 | pages = 768-87 | month =  | year =  | doi = 10.4158/EP10407.RA | PMID = 21940284 }}</ref>
 
=====Microscopic=====
Features:<ref name=Ref_EP88>{{Ref EP|88}}</ref>
*Small tightly packed follicles - '''key feature'''.
*Hypereosinophilic colloid.
*Nuclear features of PTC.
**Large nuclei.
**Typically have less [[nuclear pseudoinclusion]]s than the conventional type.
*+/-Fibrous capsule (common).
 
DDx:
*[[Follicular thyroid carcinoma]] - has a fibrous capsule and invasion though it.
*[[Follicular thyroid adenoma]] - surrounded by a fibrous capsule.
*[[Adenomatoid nodule]] - round nuclei, no nuclear features of PTC.
 
Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=2008080217023776 PTC follicular variant (surgicalpathologyatlas.com)].
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=2008080216593186 PTC follicular variant (surgicalpathologyatlas.com)].
*[http://www.thyroidcancercanada.org/userfiles/images/Follicular_slide.jpg PTC follicular variant (thyroidcancercanada.org)].<ref>URL: [http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en]. Accessed on: 9 January 2013.</ref>
 
====Papillary thyroid carcinoma cribriform-morular variant====
=====General=====
*Associated with [[familial adenomatous polyposis]] (FAP).<ref name=pmid18612695>{{cite journal |author=Groen EJ, Roos A, Muntinghe FL, ''et al.'' |title=Extra-intestinal manifestations of familial adenomatous polyposis |journal=Ann. Surg. Oncol. |volume=15 |issue=9 |pages=2439–50 |year=2008 |month=September |pmid=18612695 |pmc=2518080 |doi=10.1245/s10434-008-9981-3 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518080/?tool=pubmed}}</ref>
 
=====Microscopic=====
Features:
*Cribriform architectural pattern.
*Morules - balls of tissue.
 
====Papillary thyroid carcinoma diffuse sclerosing variant====
=====General=====
*Usually young adults, children.
 
=====Microscopic=====
Features:<ref>{{Ref PBoD8|1122}}</ref>
*Papillae - usu. prominent.
*Squamous morules - '''key features'''.<ref name=pmid15233643>{{Cite journal  | last1 = Hirokawa | first1 = M. | last2 = Kuma | first2 = S. | last3 = Miyauchi | first3 = A. | last4 = Qian | first4 = ZR. | last5 = Nakasono | first5 = M. | last6 = Sano | first6 = T. | last7 = Kakudo | first7 = K. | title = Morules in cribriform-morular variant of papillary thyroid carcinoma: Immunohistochemical characteristics and distinction from squamous metaplasia. | journal = APMIS | volume = 112 | issue = 4-5 | pages = 275-82 | month =  | year =  | doi = 10.1111/j.1600-0463.2004.apm11204-0508.x | PMID = 15233643 }}
</ref>
*Lymphocytes - abundant.
*Fibrosis.
 
DDx:
*Lymphocytic thyroiditis (esp. Hashimoto's thyroiditis).
 
====Papillary thyroid carcinoma warthin-like variant====
*Resemble [[Warthin tumour]].
=====Microscopic=====
Features:<ref name=Ref_Sternberg5_506>{{Ref Sternberg5|506}}</ref>
*Eosinophilic cytoplasm.
*Lymphocytic thyroiditis.
*Papillae.
 
====Papillary thyroid carcinoma solid variant====
Features:<ref name=pmid22432054/>
*Some studies suggest this has a poor prognosis.
*More common in children.
*Associated with Chernobyl nuclear accident.
 
=====Microscopic=====
Features:
*Solid sheets >50% of tumour mass.<ref name=pmid22432054/>
 
====Papillary thyroid carcinoma oncocytic variant====
Features:
*Possible association with [[autoimmune thyroiditis]].<ref name=pmid9013831>{{Cite journal  | last1 = Berho | first1 = M. | last2 = Suster | first2 = S. | title = The oncocytic variant of papillary carcinoma of the thyroid: a clinicopathologic study of 15 cases. | journal = Hum Pathol | volume = 28 | issue = 1 | pages = 47-53 | month = Jan | year = 1997 | doi =  | PMID = 9013831 }}</ref>
 
=====Microscopic=====
Features:<ref name=pmid9013831/>
*Abundant oncocytic tumour cells with apical nuclei.
*Classic features of PTC:
**Grooves and and abundant pseudoinclusions.<ref name=Ref_EP86>{{Ref EP|86}}</ref>
*>70% papillary architecture.<ref name=Ref_EP86>{{Ref EP|86}}</ref>
*+/-Degenerative changes.
 
Note:
*CK19 +ve -- though ''not'' specific or sensitive.
 
===IHC===
Thyroid versus something else:
*Thyroglobulin +ve.
*TTF-1 (thyroid transcription factor-1) +ve.
*CD15 +ve.{{fact}}
 
PTC versus benign:<ref>{{Cite journal  | last1 = Mataraci | first1 = EA. | last2 = Ozgüven | first2 = BY. | last3 = Kabukçuoglu | first3 = F. | title = Expression of cytokeratin 19, HBME-1 and galectin-3 in neoplastic and nonneoplastic thyroid lesions. | journal = Pol J Pathol | volume = 63 | issue = 1 | pages = 58-64 | month = Mar | year = 2012 | doi =  | PMID = 22535608 }}</ref>
*HBME-1 +ve (strong, diffuse).
*CK19 +ve (strong, diffuse).
*Galectin-3 +ve (strong, diffuse).
 
===Molecular===
*Currently not widely used in a diagnostic context.
 
====Tabular summary====
Molecular changes in papillary thyroid carcinoma as per ''Adeniran et al'':<ref name=pmid16434896>{{Cite journal  | last1 = Adeniran | first1 = AJ. | last2 = Zhu | first2 = Z. | last3 = Gandhi | first3 = M. | last4 = Steward | first4 = DL. | last5 = Fidler | first5 = JP. | last6 = Giordano | first6 = TJ. | last7 = Biddinger | first7 = PW. | last8 = Nikiforov | first8 = YE. | title = Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. | journal = Am J Surg Pathol | volume = 30 | issue = 2 | pages = 216-22 | month = Feb | year = 2006 | doi =  | PMID = 16434896 }}</ref>
{| class="wikitable sortable"
! Molecular change
! Frequency
! Histology
! Notes
|-
|BRAF point mutations
| ~ 40%
| [[papillary thyroid carcinoma tall cell variant|tall cell variant]]
| poorer prognosis, older individuals
|-
|RET/PTC rearrangments 
| ~ 20%
| papillary architecture, [[psammoma bodies]]
| younger individuals
|-
|RAS point mutations
| ~ 15%
| exclusively [[papillary thyroid carcinoma follicular variant|follicular variant]]
| -
|}
 
==Sign out==
<pre>
HEMITHYROID, RIGHT, COMPLETION OF TOTAL THYROIDECTOMY:
- PAPILLARY THYROID CARCINOMA, FOLLICULAR VARIANT.
-- TUMOUR SIZE: 4 MM (MAXIMAL).
-- ARCHITECTURE: FOLLICULAR.
-- CYTOMORPHOLOGY: CLASSICAL.
-- HISTOLOGIC GRADE: G1 (WELL DIFFERENTIATED).
-- NO TUMOUR CAPSULE IDENTIFIED.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
-- NEGATIVE FOR EXTRATHYROIDAL EXTENSION.
-- SURGICAL MARGINS NEGATIVE FOR MALIGNANCY.
</pre>
 
Note:
*If it is a completion thyroidectomy and the staging changes one should do a full synoptic report.
 
===Microcarcinoma===
<pre>
A. LEFT HEMITHYROID, THYROIDECTOMY COMPLETION:
- PAPILLARY THYROID MICROCARCINOMA.
-- MARGINS NEGATIVE FOR MALIGNANCY.
-- TUMOUR SIZE ~ 1 MM.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
- PALPATION THYROIDITIS, FOCAL.
- NODULAR HYPERPLASIA.
 
B. LYMPH NODES, LEVEL 6 AND 7, LYMPH NODE DISSECTION:
- TWO LYMPH NODES, NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 2 ).
</pre>
 
==See also==
*[[Thyroid gland]].
 
==References==
{{Reflist|2}}
 
[[Category:Diagnosis]]
[[Category:Thyroid gland]]
Michael
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