Difference between revisions of "Thyroid gland"

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==Pitfalls/weird stuff==
==Pitfalls/weird stuff==
*Thyroid tissue lateral to the jugular vein (often referred to as ''lateral aberrant thyroid tissue'') is generally considered metastatic thyroid carcinoma ([[papillary thyroid carcinoma]]) even if it looks benign.<ref name=pmid14452106>{{Cite journal  | last1 = JOHNSON | first1 = RW. | last2 = SAHA | first2 = NC. | title = The so-called lateral aberrant thyroid. | journal = Br Med J | volume = 1 | issue = 5293 | pages = 1668-9 | month = Jun | year = 1962 | doi =  | PMID = 14452106 | PMC = 1958877 }}</ref>
*Thyroid tissue lateral to the jugular vein (often referred to as ''[[lateral aberrant thyroid tissue]]'') is generally considered metastatic thyroid carcinoma ([[papillary thyroid carcinoma]]) even if it looks benign.<ref name=pmid14452106>{{Cite journal  | last1 = JOHNSON | first1 = RW. | last2 = SAHA | first2 = NC. | title = The so-called lateral aberrant thyroid. | journal = Br Med J | volume = 1 | issue = 5293 | pages = 1668-9 | month = Jun | year = 1962 | doi =  | PMID = 14452106 | PMC = 1958877 }}</ref>
**This dictum is disputed.<ref name=pmid17319317>{{Cite journal  | last1 = Escofet | first1 = X. | last2 = Khan | first2 = AZ. | last3 = Mazarani | first3 = W. | last4 = Woods | first4 = WG. | title = Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant? | journal = J R Soc Promot Health | volume = 127 | issue = 1 | pages = 45-6 | month = Jan | year = 2007 | doi =  | PMID = 17319317 }}</ref>
**This dictum is disputed.<ref name=pmid17319317>{{Cite journal  | last1 = Escofet | first1 = X. | last2 = Khan | first2 = AZ. | last3 = Mazarani | first3 = W. | last4 = Woods | first4 = WG. | title = Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant? | journal = J R Soc Promot Health | volume = 127 | issue = 1 | pages = 45-6 | month = Jan | year = 2007 | doi =  | PMID = 17319317 }}</ref>
**The level VI and VII [[lymph nodes]] are medial to the jugular.
**The level VI and VII [[lymph nodes]] are medial to the jugular.
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*[[Follicular thyroid carcinoma|Follicular carinoma]].
*[[Follicular thyroid carcinoma|Follicular carinoma]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*Undifferentiated (anaplastic) carcinoma.
*[[Anaplastic thyroid carcinoma|Undifferentiated (anaplastic) carcinoma]].


*Poorly differentiated carcinoma.
*[[Poorly differentiated thyroid carcinoma|Poorly differentiated carcinoma]].
*[[Squamous cell carcinoma]].
*[[Squamous cell carcinoma]].
*[[Mucoepidermoid carcinoma]].
*[[Mucoepidermoid carcinoma]].
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*p63 +ve.
*p63 +ve.
**-ve in clear cells.
**-ve in clear cells.
*CEA +ve (polyconal).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>
*[[CEA]] +ve (polyconal).<ref name=pmid7509563>{{cite journal |author=Mizukami Y, Nonomura A, Michigishi T, ''et al.'' |title=Solid cell nests of the thyroid. A histologic and immunohistochemical study |journal=Am. J. Clin. Pathol. |volume=101 |issue=2 |pages=186–91 |year=1994 |month=February |pmid=7509563 |doi= |url=}}</ref>
**+ve also in clear cells.
**+ve also in clear cells.
*Chromogranin A +ve ~45% of cases.<ref name=pmid7509563/>
*Chromogranin A +ve ~45% of cases.<ref name=pmid7509563/>
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*[[AKA]] ''[[nodular hyperplasia]]''.
*[[AKA]] ''[[nodular hyperplasia]]''.
*[[AKA]] ''adenomatoid nodule''.
*[[AKA]] ''adenomatoid nodule''.
 
{{Main|Thyroid gland nodular hyperplasia}}
===General===
*Clinical diagnosis: ''goitre'', [[AKA]] ''sporadic goitre'', AKA ''multinodular goitre'' (MNG).
*Most common diagnosis in the thyroid.
**If you've seen a handful of thyroids you've seen this.
 
Notes:
*Large lesions may be clonal; however, this is clinically irrelevant.
 
===Gross===
Features:
*Enlarge thyroid gland.
*+/-Distinct (well-circumscribed) nodules.
 
===Microscopic===
Features:
*Follicles of variable size - '''key feature'''.
**Should be obvious at low power, i.e. with the 2.5x objective.
*+/-Nodules.
**Do not have a thick fibrous capsule.
**May have a high cellularity.
**Architecture: solid or microfollicular.<ref name=Ref_EP36>{{Ref EP|36}}</ref>
 
Negatives:
*No nuclear features suggestive of malignancy (at lower power).
**One should not look at high power.
*Not cellular.
 
DDx:
*[[Papillary thyroid carcinoma]] - esp. [[papillary thyroid carcinoma follicular variant]].
*[[Follicular thyroid adenoma]] - contained in a fibrous capsule.
*[[Follicular thyroid carcinoma]] - has fibrous capsule and invasion through it.
 
===Sign out===
<pre>
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>
 
<pre>
HEMITHYROID, RIGHT, HEMITHYROIDECTOMY:
- CELLULAR ADENOMATOID NODULE ON A BACKGROUND OF NODULAR HYPERPLASIA.
- NEGATIVE FOR MALIGNANCY.
</pre>


==Follicular thyroid adenoma==
==Follicular thyroid adenoma==
*[[AKA]] follicular adenoma, [[AKA]] thyroid follicular adenoma.
*[[AKA]] follicular adenoma, [[AKA]] thyroid follicular adenoma.
===General===
{{Main|Follicular thyroid adenoma}}
*Most common neoplasm of thyroid.<ref name=Ref_EP51>{{Ref EP|51}}</ref>
*Encapusled lesion (surrounded by fibrous capsule).
 
===Gross===
*Thick capsule.
 
Notes:
*The entire capsule should be submitted.<ref>SR. 17 January 2011.</ref>
**A good start for most thyroid specimens with a thick capsule is 10 blocks.
 
===Microsopic===
Features:
*Cellular.
*Thick capsule - '''key feature'''.
 
Negatives.
*No invasion of the capsule (see ''[[follicular thyroid carcinoma]]'' section).
*No nuclear features suggestive of [[papillary thyroid carcinoma]].
 
DDx:
*[[Thyroid gland nodular hyperplasia]] with an encapsulated nodule - not as cellular.


==Graves disease==
==Graves disease==
===General===
{{Main|Graves' disease}}
*Often misspelled "Grave's disease".
*Autoimmune disease leading to hyperthyroidism.
*Eye problems not resolved with thyroid removal.{{fact}}
*Higher risk of [[papillary thyroid carcinoma]].
 
Clinical:
*TSH-receptor antibody +ve.<ref name=pmid19576193>{{Cite journal  | last1 = Massart | first1 = C. | last2 = Gibassier | first2 = J. | last3 = d'Herbomez | first3 = M. | title = Clinical value of M22-based assays for TSH-receptor antibody (TRAb) in the follow-up of antithyroid drug treated Graves' disease: comparison with the second generation human TRAb assay. | journal = Clin Chim Acta | volume = 407 | issue = 1-2 | pages = 62-6 | month = Sep | year = 2009 | doi = 10.1016/j.cca.2009.06.033 | PMID = 19576193 }}</ref>
 
===Gross===
Features:<ref>{{Ref EP|30}}</ref>
*Enlarged 50-150 g.
*"Beefy-red" appearance, looks like raw beef.
 
===Microscopic===
Features:
*Classic:
**Hypercellular
**Patchy lymphocytes.
**Little colloid.
*Scalloping of colloid; colloid has undulating border.
**Non-specific finding.
*+/-Nuclear clearing.
*+/-Papillae (may mimic papillary thyroid carcinoma in this respect).
 
Notes:
*Usually has an unimpressive appearance... as it is treated, i.e. history is important.
*Nuclear clearing and papillae are usu. diffuse in Graves disease - unlike in papillary thyroid carcinoma.
 
Image:
*[http://library.med.utah.edu/WebPath/jpeg4/ENDO022.jpg Graves disease (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/enfrm.html]. Accessed on: 4 December 2011.</ref>


==Idiopathic granulomatous thyroiditis==
==Idiopathic granulomatous thyroiditis==
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Clinical:
Clinical:
*Tenderness.<ref name=pmid22538753>{{Cite journal  | last1 = Szczepanek-Parulska | first1 = E. | last2 = Zybek | first2 = A. | last3 = Biczysko | first3 = M. | last4 = Majewski | first4 = P. | last5 = Ruchała | first5 = M. | title = What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation. | journal = Endokrynol Pol | volume = 63 | issue = 2 | pages = 138-42 | month =  | year = 2012 | doi =  | PMID = 22538753 }}</ref>
*Tenderness.<ref name=pmid22538753>{{Cite journal  | last1 = Szczepanek-Parulska | first1 = E. | last2 = Zybek | first2 = A. | last3 = Biczysko | first3 = M. | last4 = Majewski | first4 = P. | last5 = Ruchała | first5 = M. | title = What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation. | journal = Endokrynol Pol | volume = 63 | issue = 2 | pages = 138-42 | month =  | year = 2012 | doi =  | PMID = 22538753 }}</ref>
Management:
*Medical.
*Rarely surgery.<ref>{{Cite journal  | last1 = Volpé | first1 = R. | title = The management of subacute (DeQuervain's) thyroiditis. | journal = Thyroid | volume = 3 | issue = 3 | pages = 253-5 | month =  | year = 1993 | doi =  | PMID = 8257868 }}</ref>


===Microscopic===
===Microscopic===
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==Riedel thyroiditis==
==Riedel thyroiditis==
*[[AKA]] ''invasive fibrous thyroiditis''.<ref name=pmid21568724>{{Cite journal  | last1 = Fatourechi | first1 = MM. | last2 = Hay | first2 = ID. | last3 = McIver | first3 = B. | last4 = Sebo | first4 = TJ. | last5 = Fatourechi | first5 = V. | title = Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008. | journal = Thyroid | volume = 21 | issue = 7 | pages = 765-72 | month = Jul | year = 2011 | doi = 10.1089/thy.2010.0453 | PMID = 21568724 }}</ref>
*[[AKA]] ''invasive fibrous thyroiditis''.<ref name=pmid21568724>{{Cite journal  | last1 = Fatourechi | first1 = MM. | last2 = Hay | first2 = ID. | last3 = McIver | first3 = B. | last4 = Sebo | first4 = TJ. | last5 = Fatourechi | first5 = V. | title = Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008. | journal = Thyroid | volume = 21 | issue = 7 | pages = 765-72 | month = Jul | year = 2011 | doi = 10.1089/thy.2010.0453 | PMID = 21568724 }}</ref>
===General===
{{Main|Riedel thyroiditis}}
Clinical features:<ref name=pmid21568724/>
*Extremely rare.
*Women > men.
*Usually smokers.
*May be associated with ''[[retroperitoneal fibrosis]]''.
*May be hypothyroid.
*+/-Obstructive symptoms.
 
===Microscopic===
Features:
*Fibrosis.
*Specimen often fragmented as it was difficult to remove.
 
DDx:
*[[Anaplastic thyroid carcinoma|Anaplastic carcinoma]], spindle cell variant.


==Hashimoto thyroiditis==
==Hashimoto thyroiditis==
===General===
{{Main|Hashimoto's thyroiditis}}
*'''This is a clinical diagnosis'''.
**The histomorphologic findings, generally, are '''not''' diagnostic.
 
Etiology:
*Autoimmune disease leading to hypothyroidism.
**Often genetic/part of a syndrome.
 
====Clinical====
Serology:<ref name=pmid7813361>{{cite journal |author=Poropatich C, Marcus D, Oertel YC |title=Hashimoto's thyroiditis: fine-needle aspirations of 50 asymptomatic cases |journal=Diagn. Cytopathol. |volume=11 |issue=2 |pages=141–5 |year=1994 |pmid=7813361 |doi= |url=http://www3.interscience.wiley.com/journal/112701408/abstract?CRETRY=1&SRETRY=0}}</ref>
*Antimicrosomal (antithyroid peroxidase) +ve.
*Antithyroglobulin +ve.
 
Associated pathology:<ref name=pmid7813361/>
*Increased risk of B-cell lymphoma; these are classically:<ref name=pmid18018576 >{{Cite journal  | last1 = Ohye | first1 = H. | last2 = Fukata | first2 = S. | last3 = Hirokawa | first3 = M. | title = [Malignant lymphoma of the thyroid]. | journal = Nihon Rinsho | volume = 65 | issue = 11 | pages = 2092-8 | month = Nov | year = 2007 | doi =  | PMID = 18018576 }}</ref>
**[[MALT lymphoma]].
**[[Diffuse large B cell lymphoma]] (DLBCL).
 
===Microscopic===
Features:
*Lymphocytic infiltrate - '''key feature'''.
*Nuclear clearing common.
**May confuse with [[papillary thyroid carcinoma]].
*Polymorphous lymphoplasmacytic infiltrate with germinal centres.<ref name=Ref_APBR672>{{Ref APBR|672}}</ref>
*+/-Oncocytic metaplasia.
 
Notes:
*Histologically often '''not''' possible to separate from "non-specific" thyroiditis.<ref name=Ref_Sternberg4_560>{{Ref Sternberg4|560}}</ref>
 
DDx:
*[[Lymphocytic thyroiditis]].
*[[Papillary thyroid carcinoma]].
*[[MALT lymphoma]].
*[[Diffuse large B cell lymphoma]].
 
===IHC===
*Panel to exclude lymphoma may be required, e.g. CD3, CD20, CD10, BCL6, BCL2, kappa, lambda.
 
===Molecular===
*Occasionally done to exclude lymphoma - see ''[[MALT lymphoma]]'' and ''[[DLBCL]]''.


==C-cell hyperplasia==
==C-cell hyperplasia==
*Abbreviated ''CCH''.
*Abbreviated ''CCH''.
===General===
{{Main|C-cell hyperplasia}}
*Screening for C-cell hyperplasia/[[medullary thyroid carcinoma]] done with ''serum calcitonin level''.<ref name=pmid19726541>{{cite journal |author=Machens A, Hoffmann F, Sekulla C, Dralle H |title=Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer |journal=Endocr. Relat. Cancer |volume=16 |issue=4 |pages=1291–8 |year=2009 |month=December |pmid=19726541 |doi=10.1677/ERC-09-0136 |url=http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291}}</ref>
 
===Gross===
*Not visible.
 
===Microscopic===
Features:
*Location:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Thyroid_11protocol.pdf]. Accessed on: 7 April 2012.</ref>
**Mid portion of lobe to upper third of lobe.
***Not at the poles.
***Not in the isthmus.
 
*Definitions vary.<ref>SR. 17 January 2011.</ref>
 
One definition - either of the following:<ref name=pmid19726541>{{cite journal |author=Machens A, Hoffmann F, Sekulla C, Dralle H |title=Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer |journal=Endocr. Relat. Cancer |volume=16 |issue=4 |pages=1291–8 |year=2009 |month=December |pmid=19726541 |doi=10.1677/ERC-09-0136 |url=http://erc.endocrinology-journals.org/cgi/content/full/16/4/1291}}</ref>
#>50 C-cells per low-power field (x100).
#*This part of the definition suffers from [[LPFitis]]. The paper should have been rejected.
#Confined to the thyroid gland and no larger than 10 mm in greatest dimension.
 
Another definition:
*Invasion of the basement membrane with stromal reaction.
 
A third definition:
*"Several clusters" of more than six C cells.


====Images====
==Adenolipoma of the thyroid==
*[http://www.nature.com/modpathol/journal/v16/n8/fig_tab/3880836f2.html CCH - crappy B&W image (nature.com)].<ref>{{Cite journal  | last1 = Guyétant | first1 = S. | last2 = Josselin | first2 = N. | last3 = Savagner | first3 = F. | last4 = Rohmer | first4 = V. | last5 = Michalak | first5 = S. | last6 = Saint-André | first6 = JP. | title = C-cell hyperplasia and medullary thyroid carcinoma: clinicopathological and genetic correlations in 66 consecutive patients. | journal = Mod Pathol | volume = 16 | issue = 8 | pages = 756-63 | month = Aug | year = 2003 | doi = 10.1097/01.MP.0000081727.75778.0C | PMID = 12920219 }}</ref>
{{Main|Adenolipoma of the thyroid}}
*[http://www.nature.com/modpathol/journal/v16/n8/fig_tab/3880836f3.htm CCH - crappy B&W image (nature.com)].
*[http://www.forpath.org/workshops/0201/photos/fullsize/cas7c.jpg CCH (forpath.org)].<ref>URL: [http://www.forpath.org/workshops/0201/html/case_7.asp http://www.forpath.org/workshops/0201/html/case_7.asp]. Accessed on: 21 May 2013.</ref>
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=4849 CCH (unibas.ch)].
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=10739 Nodular CCH (unibas.ch)].


=Malignant neoplasm=
=Malignant neoplasm=
Line 397: Line 224:
==Papillary thyroid carcinoma==
==Papillary thyroid carcinoma==
*Abbreviated ''PTC''.
*Abbreviated ''PTC''.
===General===
{{Main|Papillary thyroid carcinoma}}
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>


==Insular carcinoma==
==Insular carcinoma==
===General===
{{Main|Insular thyroid carcinoma}}
Features:<ref name=pmid17665497>{{cite journal |author=Rufini V, Salvatori M, Fadda G, ''et al.'' |title=Thyroid carcinomas with a variable insular component: prognostic significance of histopathologic patterns |journal=Cancer |volume=110 |issue=6 |pages=1209–17 |year=2007 |month=September |pmid=17665497 |doi=10.1002/cncr.22913 |url=}}</ref>
*Rare - approximately 5% of all thyroid carcinomas.
*Thought to be a separate tumour from papillary thyroid carcinoma and follicular thyroid carcinoma with a focal insular pattern.
*Some lump this entity with papillary carcinoma, i.e. consider it a variant of papillary thyroid carcinoma.
 
===Microscopic===
Features:<ref name=pmid17665497/>
*Islands of cells - '''key feature'''.
*Scant cytoplasm.
*Nuclei monomorphic and round.
 
DDx:<ref>Endo. fellow. 17 September 2009.</ref>
*[[Medullary thyroid carcinoma]].
*Poorly differentiated thyroid carcinoma.


==Follicular thyroid carcinoma==
==Follicular thyroid carcinoma==
*[[AKA]] ''follicular carcinoma''.
*[[AKA]] ''follicular carcinoma''.
===Clinical===
{{Main|Follicular thyroid carcinoma}}
Medical school memory device ''4 Fs'':
*FNA NOT diagnosable.
*Far away mets (sometimes).
*Female predominant.
*Favourable prognosis.
 
Notes:
*Usu. has a hematologic spread.
**PTC usu. spread via lymphatics.
 
===Microscopic===
Features:
*Defined by either:
*#Invasion through the capsule:
*#*Should be all the way through.<ref>SR. 17 January 2011.</ref>
*#**1/2 does not count.
*#**Fibrous reaction does not count.
*#**"Above the contour" does not count.
*#Vascular invasion (all of the following):
*##In a small vein (not a capillary), that is outside of the tumour mass.
*##Tumour adherent to the side of the vessel.
*##Tumour must be re-endothelialized.
 
Notes:
*'''Impossible''' to differentiate from ''[[follicular thyroid adenoma|follicular adenoma]]'' on FNA (no cytologic differences).
*Described as "over-diagnosed" ... misdiagnoses: PTC follicular variant, follicular adenoma, multinodular goitre with a thick capsule.
 
Images:
*[http://path.upmc.edu/cases/case653.html Follicular thyroid carcinoma - several images (upmc.edu)].


==Medullary thyroid carcinoma==
==Medullary thyroid carcinoma==
*Abbreviated ''MTC''.
*Abbreviated ''MTC''.
===General===
{{Main|Medullary thyroid carcinoma}}
Medical school memory device - 3 M's:
*[[amyloid|aMyloid]].
*Median node dissection done.
*[[MEN IIa syndrome]]/[[MEN IIb syndrome]].
**Medullary thyroid carcinoma.
**[[Pheochromocytoma]].
**[[Parathyroid adenoma]].
 
Epidemiology:
*Very rare.
*Poor prognosis.
*May be genetic (MEN IIa/b syndrome).
*Arises from C cells (which produce calcitonin).
 
Syndromic tumours - typically:<ref name=pmid21455198>{{Cite journal  | last1 = Nosé | first1 = V. | title = Familial thyroid cancer: a review. | journal = Mod Pathol | volume = 24 Suppl 2 | issue =  | pages = S19-33 | month = Apr | year = 2011 | doi = 10.1038/modpathol.2010.147 | PMID = 21455198 |URL = http://www.nature.com/modpathol/journal/v24/n2s/full/modpathol2010147a.html }}</ref>
*Present in 30s or 40s.
*+/-Multifocal.
*+/-Bilateral.
*[[C-cell hyperplasia]].
 
===Gross===
Features:<ref name=pmid21455198/>
*Usu. well-circumscribed.
*White, gray or yellow.
*Gritty.
*Firm.


Image:
==Poorly differentiated thyroid carcinoma==
*[http://www.nature.com/modpathol/journal/v24/n2s/fig_tab/modpathol2010147f2.html MTC (nature.com)].
{{Main|Poorly differentiated thyroid carcinoma}}
 
===Microscopic===
Features:
*Nuclei with "neuroendocrine features".
**Small, round nuclei.
**Coarse chromatin (''salt and pepper nuclei'').
*+/-[[Amyloid]] deposits - fluffy appearing acellular eosinophilic material in the cytoplasm.
*+/-[[C-cell hyperplasia]] - seen with familial forms of MTC.
**C cells (AKA ''parafollicular cell''): abundant cytoplasm - clear/pale.
 
Note:
*The amyloid is formed from ''calcitonin''.<ref name=pmid15459123>{{Cite journal  | last1 = Khurana | first1 = R. | last2 = Agarwal | first2 = A. | last3 = Bajpai | first3 = VK. | last4 = Verma | first4 = N. | last5 = Sharma | first5 = AK. | last6 = Gupta | first6 = RP. | last7 = Madhusudan | first7 = KP. | title = Unraveling the amyloid associated with human medullary thyroid carcinoma. | journal = Endocrinology | volume = 145 | issue = 12 | pages = 5465-70 | month = Dec | year = 2004 | doi = 10.1210/en.2004-0780 | PMID = 15459123 }}</ref>
 
Images:
*www:
**[http://jcp.bmj.com/content/vol57/issue3/images/large/cp8474.f16.jpeg Medullary thyroid carcinoma (bmj.com)].
**[http://www.nature.com/ki/journal/v70/n11/fig_tab/5001888f2.html C cell hyperplasia (nature.com)].
**[http://lifesci.rutgers.edu/~babiarz/Review3/Lp6/scope8.htm C cell (rutgers.edu)].
**[http://www.anatomyatlases.org/MicroscopicAnatomy/Images/Plate287.jpg Parafollicular cells (anatomyatlases.org)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_low_mag.jpg MTC - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_high_mag.jpg MTC - high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Medullary_thyroid_carcinoma_-_2_-_high_mag.jpg MTC and amyloid - high mag. (WC)].
 
===IHC===
Features:<ref>URL: [http://pathologyoutlines.com/thyroid.html#medullary http://pathologyoutlines.com/thyroid.html#medullary]. Accessed on: 17 January 2011.</ref>
*[[Calcitonin]] +ve - it arises from C cells (which produce calcitonin).
*Congo-red +ve (amyloid present) - mnemonic: ''CRAP'' -- congo red amyloid protein.
*Neuroendocrine markers.
**[[Chromogranin A]].
**[[Synaptophysin]].
*CEA +ve (often better staining than calcitonin).<ref>SB. 7 January 2010.</ref>
*Thyroglobulin usu. -ve.<ref name=pmid8454270>{{Cite journal  | last1 = de Micco | first1 = C. | last2 = Chapel | first2 = F. | last3 = Dor | first3 = AM. | last4 = Garcia | first4 = S. | last5 = Ruf | first5 = J. | last6 = Carayon | first6 = P. | last7 = Henry | first7 = JF. | last8 = Lebreuil | first8 = G. | title = Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies. | journal = Hum Pathol | volume = 24 | issue = 3 | pages = 256-62 | month = Mar | year = 1993 | doi =  | PMID = 8454270 }}</ref>
 
===EM===
*Neurosecretory granules.
**Feature seen in neuroendocrine tumours.
 
Images: [http://pathhsw5m54.ucsf.edu/case7/image77.html Neurosecretory granules (ucsf.edu)].


==Anaplastic thyroid carcinoma==
==Anaplastic thyroid carcinoma==
===Epidemiology===
{{Main|Anaplastic thyroid carcinoma}}
*Very rare.
*Horrible prognosis.
*Often presents with obstruction.
*Typically there is a history of a thyroid mass.
 
===Microscopic===
Features:
*Cytologically malignant:
**Huge [[NC ratio]].
**Mitoses.
*+/-[[Necrosis]].
 
Notes:
*May have features of other thyroid carcinomas, e.g. psammoma bodies, papillae, nuclear changes of PTC.
 
Image: [http://commons.wikimedia.org/wiki/File:Anaplastic_thyroid_carcinoma_low_mag.jpg Anaplastic thyroid carcinoma with a component of papillary thyroid carcinoma (WC)].
 
DDx:
*[[Poorly differentiated carcinoma of the thyroid|Poorly differentiated carcinoma]].
*[[Squamous cell carcinoma]].
*[[Medullary thyroid carcinoma]].
*Sarcoma.
 
===IHC===
*Keratin (AE1/AE3) +ve.
*Vimentin +ve, >90%.<ref name=pmid1712540>{{cite journal |author=Ordóñez NG, El-Naggar AK, Hickey RC, Samaan NA |title=Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases |journal=Am. J. Clin. Pathol. |volume=96 |issue=1 |pages=15–24 |year=1991 |month=July |pmid=1712540 |doi= |url=}}</ref>
*Thyroglobulin - rarely +ve (~15%).<ref name=pmid1712540/>
*CEA -ve, calcitonin -ve; to r/o medullary.
*p53 +ve.
*TTF-1 +ve.


==Lymphomas of the thyroid==
==Lymphomas of the thyroid==
Line 820: Line 260:
*[[AKA]] ''hyalinizing trabecular adenoma''.
*[[AKA]] ''hyalinizing trabecular adenoma''.
*Abbreviated ''HTT''.
*Abbreviated ''HTT''.
===General===
{{Main|Hyalinizing trabecular tumour}}
*Considered by some (e.g. Silvia Asa) to be a variant of [[papillary thyroid carcinoma]].<ref name=pmid11117782>{{cite journal |author=Cheung CC, Boerner SL, MacMillan CM, Ramyar L, Asa SL |title=Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics |journal=Am. J. Surg. Pathol. |volume=24 |issue=12 |pages=1622–6 |year=2000 |month=December |pmid=11117782 |doi= |url=}}</ref>
*Behaviour similar to papillary thyroid carcinoma - indolent.
 
===Microscopic===
Features:
*Trabecular arrangement of cells.
**May have "curved" trabeculae.
*Extracellular space has hyaline material - '''key feature'''.
*Cytoplasm mimics hyaline material in the extracellular space.
 
DDx:
*[[Papillary thyroid carcinoma]] (if one believes this is a separate entity).
*[[Medullary thyroid carcinoma]] - not trabecular, nuclei not [[PTC]]-like.
*[[Paraganglioma]].<ref>URL: [http://path.upmc.edu/cases/case465/dx.html http://path.upmc.edu/cases/case465/dx.html]. Accessed on: 17 January 2011.</ref>
 
====Images====
<gallery>
Image: Hyalinized trabecular tumour - low mag.jpg | HHT - low mag. (WC)
Image: Hyalinized trabecular tumour - intermed mag.jpg | HHT - intermed. mag. (WC)
Image: Hyalinized trabecular tumour - high mag.jpg | HHT - high mag. (WC)
Image: Thyroid gland - high mag.jpg | Thyroid gland - high mag. (WC)
 
Image: Hyalinized trabecular tumour - 2 - intermed mag.jpg | HHT - intermed. mag. (WC)
Image: Hyalinized trabecular tumour - 2 - high mag.jpg | HHT - high mag. (WC)
 
Image: Hyalinized trabecular tumour - 3 - intermed mag.jpg | HHT - intermed. mag. (WC)
Image: Hyalinized trabecular tumour - 3 - high mag.jpg | HHT - high mag. (WC)
Image: Hyalinized trabecular tumour - 3 - very high mag.jpg | HHT - very high mag. (WC)
</gallery>
www:
*[http://archive.biomedcentral.com/1742-6413/3/17/figure/F2?highres=y HTT (biomedcentral.com)].<ref name=pmid16867191>{{Cite journal  | last1 = Baloch | first1 = ZW. | last2 = Puttaswamy | first2 = K. | last3 = Brose | first3 = M. | last4 = LiVolsi | first4 = VA. | title = Lack of BRAF mutations in hyalinizing trabecular neoplasm. | journal = Cytojournal | volume = 3 | issue =  | pages = 17 | month =  | year = 2006 | doi = 10.1186/1742-6413-3-17 | PMID = 16867191 }}</ref>
*[http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.article-g01.fs.jpg HTT (ispub.com)].<ref>URL: [http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html http://www.ispub.com/journal/the-internet-journal-of-endocrinology/volume-2-number-1/hyalinizing-trabecular-neoplasm-of-the-thyroid-controversies-in-management.html]. Accessed on: 1 January 2012.</ref>
 
===IHC===
*Thyroglobulin +ve.
*NSE +ve.


==Hürthle cell neoplasm==
==Hürthle cell neoplasm==
*[[AKA]] ''oncocytic neoplasm''.
*[[AKA]] ''oncocytic neoplasm''.
*Also spelled ''Hurthle cell neoplasm''.
*Also spelled ''Hurthle cell neoplasm''.
 
{{Main|Hürthle cell neoplasm}}
===General===
*Incidence: uncommon.
*This is a general category - includes:
**Hürthle cell adenoma.
**Hürthle cell carcinoma.
 
*Some advocate ''total thyroidectomy'' for all Hürthle cell neoplasms, as it is difficult to reliably differentiate adenomas and carcinomas.<ref name=pmid9697901>{{Cite journal  | last1 = Wasvary | first1 = H. | last2 = Czako | first2 = P. | last3 = Poulik | first3 = J. | last4 = Lucas | first4 = R. | title = Unilateral lobectomy for Hurthle cell adenoma. | journal = Am Surg | volume = 64 | issue = 8 | pages = 729-32; discussion 732-3 | month = Aug | year = 1998 | doi =  | PMID = 9697901 }}</ref>
*It can be understood as a special type of ''follicular neoplasm'' (including ''[[follicular thyroid adenoma]]'' and ''[[follicular thyroid carcinoma]]'').<ref name=Ref_EP104>{{Ref EP|104}}</ref>
 
====Adenoma vs. carcinoma====
Suggestive for carcinoma:<ref name=pmid9697901/>
*Male.
*>4 cm
**Adenomas usu. <3 cm.
Definite for carcinoma:<ref name=pmid9697901/>
*Lymphovascular invasion.
*Capsular invasion.
 
===Gross===
*Yellow.
*Encapsulated.
 
===Microscopic===
Features:<ref name=Ref_EP104>{{Ref EP|104}}</ref>
*Oncocytes >= 75% of cells:
**Abundant granular, eosinophilic cytoplasm.
**Round regular nucleus +/- prominent nucleolus.
*+/-Degenerative changes.
 
Negatives:
*Lack nuclear features of [[papillary thyroid carcinoma]].
*Lack features of [[medullary thyroid carcinoma]].
 
DDx:<ref name=pmid18684023>{{cite journal |author=Montone KT, Baloch ZW, LiVolsi VA |title=The thyroid Hürthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=8 |pages=1241–50 |year=2008 |month=August |pmid=18684023 |doi= |url=}}</ref>
*Papillary thyroid carcinoma oncocytic variant.
*Medullary thyroid carcinoma oncocytic variant.
*Others.


==Minocycline associated thyroid pigmentation==
==Minocycline associated thyroid pigmentation==
Line 905: Line 272:
===General===
===General===
*Benign pigmentation of the thyroid due to ''minocycline'', an antibiotic.
*Benign pigmentation of the thyroid due to ''minocycline'', an antibiotic.
**Reported at other sites, e.g. [[heart valves]],<ref name=pmid10615019/> coronary arteries.
**Reported at other sites, e.g. [[heart valves]],<ref name=pmid10615019/> [[skin]],<ref name=pmid19595269>{{cite journal |author=Geria AN, Tajirian AL, Kihiczak G, Schwartz RA |title=Minocycline-induced skin pigmentation: an update |journal=Acta Dermatovenerol Croat |volume=17 |issue=2 |pages=123–6 |year=2009 |pmid=19595269 |doi= |url=}}</ref> coronary arteries.


===Gross===
===Gross===
Line 925: Line 292:
*Pigment described as ''lipofuscin-like''.<ref name=pmid6435454>{{Cite journal  | last1 = Gordon | first1 = G. | last2 = Sparano | first2 = BM. | last3 = Kramer | first3 = AW. | last4 = Kelly | first4 = RG. | last5 = Iatropoulos | first5 = MJ. | title = Thyroid gland pigmentation and minocycline therapy. | journal = Am J Pathol | volume = 117 | issue = 1 | pages = 98-109 | month = Oct | year = 1984 | doi =  | PMID = 6435454 | PMC = 1900569 }}</ref>
*Pigment described as ''lipofuscin-like''.<ref name=pmid6435454>{{Cite journal  | last1 = Gordon | first1 = G. | last2 = Sparano | first2 = BM. | last3 = Kramer | first3 = AW. | last4 = Kelly | first4 = RG. | last5 = Iatropoulos | first5 = MJ. | title = Thyroid gland pigmentation and minocycline therapy. | journal = Am J Pathol | volume = 117 | issue = 1 | pages = 98-109 | month = Oct | year = 1984 | doi =  | PMID = 6435454 | PMC = 1900569 }}</ref>


Images:
====Images====
*[http://flylib.com/books/2/953/1/html/2/44%20-%20Thyroid_files/DA11C44FF7.png Pigmentation due to minocycline (flylib.com)].<ref>URL: [http://flylib.com/books/en/2.953.1.50/1/ http://flylib.com/books/en/2.953.1.50/1/]. Accessed on: 11 March 2012.</ref>
*[http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2004)128%3C355:PQCTIP%3E2.0.CO;2 Minocycline thyroid - gross and microscopic (archivesofpathology.org)].<ref name=pmid14987144>{{Cite journal  | last1 = Raghavan | first1 = R. | last2 = Snyder | first2 = WH. | last3 = Sharma | first3 = S. | title = Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland. | journal = Arch Pathol Lab Med | volume = 128 | issue = 3 | pages = 355-6 | month = Mar | year = 2004 | doi = 10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2 | PMID = 14987144 }}</ref>
*[http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2004)128%3C355:PQCTIP%3E2.0.CO;2 Minocycline thyroid - gross and microscopic (archivesofpathology.org)].<ref name=pmid14987144>{{Cite journal  | last1 = Raghavan | first1 = R. | last2 = Snyder | first2 = WH. | last3 = Sharma | first3 = S. | title = Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland. | journal = Arch Pathol Lab Med | volume = 128 | issue = 3 | pages = 355-6 | month = Mar | year = 2004 | doi = 10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2 | PMID = 14987144 }}</ref>


===Stains===
===Stains===
*Fontana-Masson stain +ve.<ref name=pmid10615019>{{Cite journal  | last1 = Sant'Ambrogio | first1 = S. | last2 = Connelly | first2 = J. | last3 = DiMaio | first3 = D. | title = Minocycline pigmentation of heart valves. | journal = Cardiovasc Pathol | volume = 8 | issue = 6 | pages = 329-32 | month =  | year =  | doi =  | PMID = 10615019 }}</ref>
*[[Fontana-Masson stain]] +ve.<ref name=pmid10615019>{{Cite journal  | last1 = Sant'Ambrogio | first1 = S. | last2 = Connelly | first2 = J. | last3 = DiMaio | first3 = D. | title = Minocycline pigmentation of heart valves. | journal = Cardiovasc Pathol | volume = 8 | issue = 6 | pages = 329-32 | month =  | year =  | doi =  | PMID = 10615019 }}</ref>
 
==Sclerosing mucoepidermoid carcinoma with eosinophilia==
{{Main|Sclerosing mucoepidermoid carcinoma with eosinophilia}}


=See also=
=See also=

Latest revision as of 03:43, 20 March 2018

The thyroid gland is an important little endocrine organ in the anterior neck. It is frequently afflicted by cancer... but the common cancer has such a good prognosis there is debate about how aggressively it should be treated. The cytopathology of the thyroid gland is dealt with in the thyroid cytology article.

The gland frustrates a significant number of pathologists, as the criteria for cancer are considered a bit wishy-washy.

Thyroid specimens

They come in three common varieties

  • FNA (fine needle aspiration).
  • Hemithyroid.
    • Done to get a definitive diagnosis.
    • May be a "completion" - removal of the other half following definitive diagnosis.
  • Total thyroid.
    • Done for malignancy or follicular lesion.

Gross pathology

  • White nodules - think:
    • Lymphoid tissue.
    • Papillary thyroid carcinoma - may be calcified.[1]

Diagnoses

Common

Pitfalls/weird stuff

  • Thyroid tissue lateral to the jugular vein (often referred to as lateral aberrant thyroid tissue) is generally considered metastatic thyroid carcinoma (papillary thyroid carcinoma) even if it looks benign.[2]
    • This dictum is disputed.[3]
    • The level VI and VII lymph nodes are medial to the jugular.
  • Hashimoto's disease may have so many lymphocytes that it mimics a lymph node -- may lead to misdiagnosis of PTC.
  • Parasitic nodule: clump of thyroid that is attached by a thin thread... but looks like a separate nodule; may lead to misdiagnosis of PTC.

Image:

Diagnostic keys

The following should prompt careful examination:[5]

  • Architecture: microfollicular, trabecular, solid, insular.
  • Thick capsule.
  • Necrosis - rare in the thyroid.

Thyroid IHC - general comments

  • Not really useful.
  • Papers with very small sample sizes abound.

Follicular thyroid carcinoma vs. papillary thyroid carcinoma

  • CD31 more frequently positive in follicular lesions.[6]
    • CD31 is a marker for microvessel density.
  • Galectin-3 thought to be positive in papillary carcinoma.[6]
  • HBME-1 thought to be positive in papillary lesions.[7]

Thyroid lesions per WHO

  • Adapted from the Washington Manual of Surgical Pathology.[8]

Adenoma

  • Follicular adenoma.
  • Hyalinizing trabecular tumour.

Carcinoma

  • Mixed medullary and follicular carinoma.
  • Spindle cell tumour with thymus-like differentiation.
  • Carcinoma showing thymus-like differentiation.

Others

Parathyroid glands

Main article: Parathyroid glands
  • May make an appearance in the context of thyroid surgery.

Benign

Solid cell nest of the thyroid gland

  • AKA solid cell nest of thyroid.

General

  • Embryonic remnants endodermal origin.[9]
  • Incidental finding.

Note:

Microscopic

Features:[9]

  • Cellular solid or cystic cluster of variable size with:
    • Cuboidal cellular morphology.
      • May have columnar morphology.
    • Moderate-to-scant eosinophilic cytoplasm.
    • Round/ovoid nuclei with finely granular chromatin.
  • +/-Goblet cells (~30% of cases).[12]

DDx:[9]

Images

  • Solid cell nest of the thyroid gland - intermed. mag. (WC)

  • Solid cell nest of the thyroid gland - high mag. (WC)

  • Solid cell nest of the thyroid gland - very high mag. (WC)

www:

IHC

Features:[9]

  • p63 +ve.
    • -ve in clear cells.
  • CEA +ve (polyconal).[12]
    • +ve also in clear cells.
  • Chromogranin A +ve ~45% of cases.[12]

Sign out

Solid cell nests of the thyroid gland are usually not reported.

Thyroid gland nodular hyperplasia

Main article: Thyroid gland nodular hyperplasia

Follicular thyroid adenoma

  • AKA follicular adenoma, AKA thyroid follicular adenoma.
Main article: Follicular thyroid adenoma

Graves disease

Main article: Graves' disease

Idiopathic granulomatous thyroiditis

  • AKA granulomatous thyroiditis - non-specific term; granulomas may be due a number of causes.
  • AKA subacute thyroiditis.
  • AKA de Quervain thyroiditis.
    • Should not be confused with de Quervain's disease (AKA gamer's thumb) something completely unrelated to the thyroid.

General

  • Women > men.
  • Etiology: possibly viral.[13]

Clinical:

Management:

  • Medical.
  • Rarely surgery.[15]

Microscopic

Features:[16][13]

  • Granulomas with multinucleated giant cells - usu. with engulfed colloid.
  • Lymphocytes.
  • Plasma cells.
  • +/-Fibrosis.

DDx:

Images

  • Subacute thyroiditis - intermed. mag. (WC)

  • Subacute thyroiditis - high mag. (WC)

  • Subacute thyroiditis - very high mag. (WC)

Stains

  • ZN -ve.
  • GMS -ve.

Palpation thyroiditis

General

  • Granulomatous inflammation due to palpation.
    • Incidence of granulomas higher in surgical thyroid specimens than autopsies.[13]

Microscopic

Features:[13]

  • Granulomas involving the follicle.
    • Histiocytes within the colloid.

DDx:

Stains

  • ZN -ve.
  • GMS -ve.

Riedel thyroiditis

  • AKA invasive fibrous thyroiditis.[17]
Main article: Riedel thyroiditis

Hashimoto thyroiditis

Main article: Hashimoto's thyroiditis

C-cell hyperplasia

  • Abbreviated CCH.
Main article: C-cell hyperplasia

Adenolipoma of the thyroid

Main article: Adenolipoma of the thyroid

Malignant neoplasm

There are a bunch of 'em. The most common, by far, is papillary.

Papillary thyroid carcinoma

  • Abbreviated PTC.
Main article: Papillary thyroid carcinoma

Insular carcinoma

Main article: Insular thyroid carcinoma

Follicular thyroid carcinoma

  • AKA follicular carcinoma.
Main article: Follicular thyroid carcinoma

Medullary thyroid carcinoma

  • Abbreviated MTC.
Main article: Medullary thyroid carcinoma

Poorly differentiated thyroid carcinoma

Main article: Poorly differentiated thyroid carcinoma

Anaplastic thyroid carcinoma

Main article: Anaplastic thyroid carcinoma

Lymphomas of the thyroid

Main article: Lymphoma

General

  • Rare.
  • Increased risk with chronic inflammatory conditions.
  • Fit in the the greater category of MALT lymphoma.

Microscopic

Features:

  • Lymphoepithelial lesion - key feature.
  • Plasma cells.
  • "Overgrowth" - thyroid parenchyma displaced by lymphocytes.

Weird stuff

Hyalinizing trabecular tumour

  • AKA hyalinizing trabecular adenoma.
  • Abbreviated HTT.
Main article: Hyalinizing trabecular tumour

Hürthle cell neoplasm

  • AKA oncocytic neoplasm.
  • Also spelled Hurthle cell neoplasm.
Main article: Hürthle cell neoplasm

Minocycline associated thyroid pigmentation

  • AKA minocycline thyroid.

General

  • Benign pigmentation of the thyroid due to minocycline, an antibiotic.

Gross

Images:

Microscopic

Features:

  • Granular yellow blobs:
    • Location:
      • Intracytoplasmic in the follicule-lining cells, i.e. follicular cells.
      • Intrafollicular.
    • Variable size ~0.5-4 micrometers.

Notes:

  • Pigment described as lipofuscin-like.[22]

Images

Stains

Sclerosing mucoepidermoid carcinoma with eosinophilia

Main article: Sclerosing mucoepidermoid carcinoma with eosinophilia

See also

References

  1. ↑ BEC. 20 October 2009.
  2. ↑ JOHNSON, RW.; SAHA, NC. (Jun 1962). "The so-called lateral aberrant thyroid.". Br Med J 1 (5293): 1668-9. PMC 1958877. PMID 14452106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1958877/.
  3. ↑ Escofet, X.; Khan, AZ.; Mazarani, W.; Woods, WG. (Jan 2007). "Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant?". J R Soc Promot Health 127 (1): 45-6. PMID 17319317.
  4. ↑ URL: http://radiopaedia.org/articles/lymph-node-levels-of-the-neck. Accessed on: 5 November 2012.
  5. ↑ SR. 17 January 2011.
  6. ↑ 6.0 6.1 Rydlova, M.; Ludvikova, M.; Stankova, I. (Jun 2008). "Potential diagnostic markers in nodular lesions of the thyroid gland: an immunohistochemical study.". Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 152 (1): 53-9. PMID 18795075.
  7. ↑ Papotti, M.; Rodriguez, J.; De Pompa, R.; Bartolazzi, A.; Rosai, J. (Apr 2005). "Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential.". Mod Pathol 18 (4): 541-6. doi:10.1038/modpathol.3800321. PMID 15529186.
  8. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 331. ISBN 978-0781765275.
  9. ↑ 9.0 9.1 9.2 9.3 Reis-Filho JS, Preto A, Soares P, Ricardo S, Cameselle-Teijeiro J, Sobrinho-Simões M (January 2003). "p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin". Mod. Pathol. 16 (1): 43–8. doi:10.1097/01.MP.0000047306.72278.39. PMID 12527712. http://www.nature.com/modpathol/journal/v16/n1/full/3880708a.html.
  10. ↑ Ozaki, O.; Ito, K.; Sugino, K.; Yasuda, K.; Yamashita, T.; Toshima, K.. "Solid cell nests of the thyroid gland: precursor of mucoepidermoid carcinoma?". World J Surg 16 (4): 685-8; discussion 688-9. PMID 1413837.
  11. ↑ Prichard, RS.; Lee, JC.; Gill, AJ.; Sywak, MS.; Fingleton, L.; Robinson, BG.; Sidhu, SB.; Delbridge, LW. (Feb 2012). "Mucoepidermoid carcinoma of the thyroid: a report of three cases and postulated histogenesis.". Thyroid 22 (2): 205-9. doi:10.1089/thy.2011.0276. PMID 22224821.
  12. ↑ 12.0 12.1 12.2 Mizukami Y, Nonomura A, Michigishi T, et al. (February 1994). "Solid cell nests of the thyroid. A histologic and immunohistochemical study". Am. J. Clin. Pathol. 101 (2): 186–91. PMID 7509563.
  13. ↑ 13.0 13.1 13.2 13.3 Lloyd, Ricardo V. (2002). Endocrine Diseases (AFIP Atlas of Nontumor Pathology). Toronto: American Registry of Pathology. ISBN 978-1881041733. http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735.
  14. ↑ Szczepanek-Parulska, E.; Zybek, A.; Biczysko, M.; Majewski, P.; Ruchała, M. (2012). "What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation.". Endokrynol Pol 63 (2): 138-42. PMID 22538753.
  15. ↑ Volpé, R. (1993). "The management of subacute (DeQuervain's) thyroiditis.". Thyroid 3 (3): 253-5. PMID 8257868.
  16. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 559. ISBN 978-0781740517.
  17. ↑ Fatourechi, MM.; Hay, ID.; McIver, B.; Sebo, TJ.; Fatourechi, V. (Jul 2011). "Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008.". Thyroid 21 (7): 765-72. doi:10.1089/thy.2010.0453. PMID 21568724.
  18. ↑ 18.0 18.1 Sant'Ambrogio, S.; Connelly, J.; DiMaio, D.. "Minocycline pigmentation of heart valves.". Cardiovasc Pathol 8 (6): 329-32. PMID 10615019.
  19. ↑ Geria AN, Tajirian AL, Kihiczak G, Schwartz RA (2009). "Minocycline-induced skin pigmentation: an update". Acta Dermatovenerol Croat 17 (2): 123–6. PMID 19595269.
  20. ↑ Noble, JG.; Christmas, TJ.; Chapple, C.; Katz, D.; Milroy, EJ. (Jan 1989). "The black thyroid: an unusual finding during neck exploration.". Postgrad Med J 65 (759): 34-5. PMC 2429157. PMID 2780449. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429157/.
  21. ↑ 21.0 21.1 Raghavan, R.; Snyder, WH.; Sharma, S. (Mar 2004). "Pathologic quiz case: tumor in pigmented thyroid gland in a young man. Papillary thyroid carcinoma in a minocycline-induced, diffusely pigmented thyroid gland.". Arch Pathol Lab Med 128 (3): 355-6. doi:10.1043/1543-2165(2004)128355:PQCTIP2.0.CO;2. PMID 14987144.
  22. ↑ Gordon, G.; Sparano, BM.; Kramer, AW.; Kelly, RG.; Iatropoulos, MJ. (Oct 1984). "Thyroid gland pigmentation and minocycline therapy.". Am J Pathol 117 (1): 98-109. PMC 1900569. PMID 6435454. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1900569/.
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