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The '''thyroid gland''' is an important little endocrine organ in the anterior [[neck]].  It is not infrequently 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.  It frustrates a significant number of pathologists, as the criteria for cancer are considered a bit wishy-washy.  
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=
=Thyroid specimens=
They come in 3 common varieties:
==They come in three common varieties==
*FNA (fine needle aspiration).
**Done to triage patients/rule-out malignancy - discussed in the article ''[[thyroid cytopathology]]''.
*Hemithyroid.
*Hemithyroid.
**Done to get a definitive diagnosis.
**Done to get a definitive diagnosis.
Line 8: Line 12:
*Total thyroid.
*Total thyroid.
**Done for malignancy or follicular lesion.
**Done for malignancy or follicular lesion.
*FNA (fine needle aspiration).
**done to r/o malignancy.


Gross pathology:
==Gross pathology==
*White nodules - think:
*White nodules - think:
**Lymphoid tissue.
**Lymphoid tissue.
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=Diagnoses=
=Diagnoses=
==Common==
==Common==
*Nodular hyperplasia -- most common.
*[[Thyroid gland nodular hyperplasia|Nodular hyperplasia]] -- most common.
*Lymphocytic thyroiditis.
*[[Lymphocytic thyroiditis]].
*Papillary thyroid carcinoma (PTC) -- most common cancer.
*Papillary thyroid carcinoma (PTC) -- most common cancer.
*Follicular adenoma.
**[[Papillary thyroid carcinoma follicular variant]].
*Follicular thryoid carcinoma.
*[[Parathyroid]] tissue.
*Parathyroid tissue.


==Pitfalls/weird stuff==
==Pitfalls/weird stuff==
*Thyroid tissue lateral to the jugular vein = metastatic PTC... even if it looks benign.
*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>
*Hashimoto's disease may have so many lymphocytes that it mimics a lymph node -- may lead to misdiagnosis of PTC.
**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.
*[[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.
*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:
*[http://images.radiopaedia.org/images/26383/ad505c78a87e71180792049299f5cd_big_gallery.jpg Neck levels (radiopaedia.org)].<ref>URL: [http://radiopaedia.org/articles/lymph-node-levels-of-the-neck http://radiopaedia.org/articles/lymph-node-levels-of-the-neck]. Accessed on: 5 November 2012.</ref>


==Diagnostic keys==
==Diagnostic keys==
Line 36: Line 42:
*Necrosis - rare in the thyroid.
*Necrosis - rare in the thyroid.


=Parathyroid tissue=
==Thyroid IHC - general comments==
General:
*Not really useful.
*Identification of normal can be tricky.
*Papers with very small sample sizes abound.
===Follicular thyroid carcinoma vs. papillary thyroid carcinoma===
*CD31 more frequently positive in follicular lesions.<ref name=pmid18795075>{{Cite journal  | last1 = Rydlova | first1 = M. | last2 = Ludvikova | first2 = M. | last3 = Stankova | first3 = I. | title = Potential diagnostic markers in nodular lesions of the thyroid gland: an immunohistochemical study. | journal = Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub | volume = 152 | issue = 1 | pages = 53-9 | month = Jun | year = 2008 | doi =  | PMID = 18795075 }}</ref>
**CD31 is a marker for microvessel density.
*Galectin-3 thought to be positive in papillary carcinoma.<ref name=pmid18795075/>
*HBME-1 thought to be positive in papillary lesions.<ref name=pmid15529186>{{Cite journal  | last1 = Papotti | first1 = M. | last2 = Rodriguez | first2 = J. | last3 = De Pompa | first3 = R. | last4 = Bartolazzi | first4 = A. | last5 = Rosai | first5 = J. | title = Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. | journal = Mod Pathol | volume = 18 | issue = 4 | pages = 541-6 | month = Apr | year = 2005 | doi = 10.1038/modpathol.3800321 | PMID = 15529186 }}</ref>


Features:<ref>[http://www.medicalhistology.us/twiki/pub/Main/ChapterFourteenSlides/b56b_parathyroid_40x_he_labeled.jpg http://www.medicalhistology.us/twiki/pub/Main/ChapterFourteenSlides/b56b_parathyroid_40x_he_labeled.jpg]</ref>
==Thyroid lesions per WHO==
*Low power:
*Adapted from the ''Washington Manual of Surgical Pathology''.<ref name=Ref_WMSP331>{{Ref WMSP|331}}</ref>
**May vaguely resemble lymphoid tissue - may have hyperchromatic cytoplasm.
===Adenoma===
***Does ''not'' have follicular centres like a lymph node.
*Follicular adenoma.
**May form gland-like structure and vaguely resemble the thyroid at low power.
*Hyalinizing trabecular tumour.
**Cytoplasm may be clear<ref>[http://pathology.mc.duke.edu/research/Histo_course/parathyroid2.jpg http://pathology.mc.duke.edu/research/Histo_course/parathyroid2.jpg]</ref> - '''key feature'''.
**Surrounded by a thin fibrous capsule.
*High power:
**Mixed cell population:<ref>[http://www.bu.edu/histology/p/15002loa.htm http://www.bu.edu/histology/p/15002loa.htm]</ref>  
***Chief cells - predominant cell type, small, cytoplasm has variable staining (hyperchromatic-clear-eosinophilic).
***Oxyphil cells (''acid staining'' cells<ref>[http://dictionary.reference.com/search?q=oxyphil%20cell http://dictionary.reference.com/search?q=oxyphil%20cell]</ref>) - abundant cytoplasm.
***Adipocytes - increased with age, may be used to help differentiate from thyroid - '''key feature'''.


===Carcinoma===
*[[Papillary thyroid carcinoma|Papillary carcinoma]].
*[[Follicular thyroid carcinoma|Follicular carinoma]].
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*[[Anaplastic thyroid carcinoma|Undifferentiated (anaplastic) carcinoma]].


{| class="wikitable"
*[[Poorly differentiated thyroid carcinoma|Poorly differentiated carcinoma]].
| '''Name''' || '''Staining (cytoplasm)''' || '''Quantity of cells''' ||  '''Cytoplasm (quantity)''' || '''Function'''
*[[Squamous cell carcinoma]].
|-
*[[Mucoepidermoid carcinoma]].
| (parathyroid) chief cells  || intense hyperchromatic to eosinophilic (see note) || abundant || moderate || manufacture PTH
*Sclerosing mucoepidermoid carcinoma with eosinophilia.
|-
*Mucinous carcinoma.
| oxyphil cells  || moderate/light hyperchromatic to eosinophilic || rare || abundant || ?
|}
Notes:
*Cytoplasmic staining varies considerably on H&E preparations - it may vary from hyperchromatic<ref>[http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg]</ref> to clear to eosinophilic<ref>[http://instruction.cvhs.okstate.edu/Histology/HistologyReference/hrendo.htm http://instruction.cvhs.okstate.edu/Histology/HistologyReference/hrendo.htm]</ref>.
*Chief cells tend to stain more intensely than oxyphil cells.


Thyroid vs. parathyroid (see: [http://instruction.cvhs.okstate.edu/Histology/HistologyReference/imagesco/parathyroid2F.jpg parathyroid image]):
*Mixed medullary and follicular carinoma.
*Parathyroid cytoplasm:
*Spindle cell tumour with thymus-like differentiation.
**Hyperchromatic.
*Carcinoma showing thymus-like differentiation.


Parathyroid vs. lymphoid tissue (see [http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/parathyroid_and_thyroid_glands_20x.jpg parathyroid image]):
===Others===
*Parathyroid:
*[[Teratoma]].
**No germinal centres.
*[[Lymphoma]].
**Gland-like/follicular-like arrangement -- much smaller than normal follicles of
*Ectopic thymoma.
**Occasional cell with rim of clear cytoplasm (oxyphil?).
*[[Angiosarcoma]] + other [[soft tissue lesions]].
*[[Paraganglioma]].
*[[Solitary fibrous tumour]].
*[[Follicular dendritic cell tumour]].
*[[Langerhans cell histiocytosis]].
*[[Metastasis]].


Images:
=Parathyroid glands=
*[http://library.med.utah.edu/WebPath/ENDOHTML/ENDO031.html Parathyroid - med.utah.edu].
{{Main|Parathyroid glands}}
*[http://pathology.mc.duke.edu/research/PTH225.html Histology - several images. - pathology.mc.duke.edu].
*May make an appearance in the context of thyroid surgery.
 
==Parathyroid hyperplasia==
*Parathyroid hyperplasia - classically assoc. with renal failure.
*Chief cell hyperplasia - associated with MEN I, MEN IIa.<ref>URL: [http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970475-2 http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970475-2]. Accessed on: 29 July 2010.</ref>
 
==Parathryoid adenoma==
*One parathyroid is big... the others are small.
*Associated with [[MEN I]] and [[MEN]] IIa/b (II/III).
 
MEN I:
*Parathyroid adenoma.
*Pancreatic neuroendocrine tumours.
*[[Pituitary adenoma]].
 
MEN IIa/IIb (II/III):
*Parathyroid adenoma.
*Medullary thyroid carcinoma.
*[[Pheochromocytoma]].
 
Image: [http://library.med.utah.edu/WebPath/jpeg4/ENDO091.jpg Parathyroid adenoma (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: 6 December 2010.</ref>


=Benign=
=Benign=
==Solid cell nest of thyroid==
==Solid cell nest of the thyroid gland==
*[[AKA]] ''solid cell nest of thyroid''.
===General===
===General===
*Embryonic remnants endodermal origin.<ref name=pmid12527712>{{cite journal |author=Reis-Filho JS, Preto A, Soares P, Ricardo S, Cameselle-Teijeiro J, Sobrinho-Simões M |title=p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin |journal=Mod. Pathol. |volume=16 |issue=1 |pages=43–8 |year=2003 |month=January |pmid=12527712 |doi=10.1097/01.MP.0000047306.72278.39 |url=http://www.nature.com/modpathol/journal/v16/n1/full/3880708a.html}}</ref>
*Embryonic remnants endodermal origin.<ref name=pmid12527712>{{cite journal |author=Reis-Filho JS, Preto A, Soares P, Ricardo S, Cameselle-Teijeiro J, Sobrinho-Simões M |title=p63 expression in solid cell nests of the thyroid: further evidence for a stem cell origin |journal=Mod. Pathol. |volume=16 |issue=1 |pages=43–8 |year=2003 |month=January |pmid=12527712 |doi=10.1097/01.MP.0000047306.72278.39 |url=http://www.nature.com/modpathol/journal/v16/n1/full/3880708a.html}}</ref>
*Incidental finding.
*Incidental finding.
Note:
*Hypothesized to have some relation to [[mucoepidermoid carcinoma]] of the thyroid gland;<ref name=pmid1413837>{{Cite journal  | last1 = Ozaki | first1 = O. | last2 = Ito | first2 = K. | last3 = Sugino | first3 = K. | last4 = Yasuda | first4 = K. | last5 = Yamashita | first5 = T. | last6 = Toshima | first6 = K. | title = Solid cell nests of the thyroid gland: precursor of mucoepidermoid carcinoma? | journal = World J Surg | volume = 16 | issue = 4 | pages = 685-8; discussion 688-9 | month =  | year =  | doi =  | PMID = 1413837 }}</ref> however, another study suspects a relationship with [[papillary thyroid carcinoma]].<ref name=pmid22224821>{{Cite journal  | last1 = Prichard | first1 = RS. | last2 = Lee | first2 = JC. | last3 = Gill | first3 = AJ. | last4 = Sywak | first4 = MS. | last5 = Fingleton | first5 = L. | last6 = Robinson | first6 = BG. | last7 = Sidhu | first7 = SB. | last8 = Delbridge | first8 = LW. | title = Mucoepidermoid carcinoma of the thyroid: a report of three cases and postulated histogenesis. | journal = Thyroid | volume = 22 | issue = 2 | pages = 205-9 | month = Feb | year = 2012 | doi = 10.1089/thy.2011.0276 | PMID = 22224821 }}</ref>


===Microscopic===
===Microscopic===
Features:<ref name=pmid12527712/>
Features:<ref name=pmid12527712/>
*Solid or cystic cluster or variable size.
*Cellular solid ''or'' cystic cluster of variable size with:
*Cuboidal-to-columnar morphology.
**Cuboidal cellular morphology.
*Eosinophilic cytoplasm.
***May have columnar morphology.
*Round/ovoid nuclei with finely granular chromatin.
**Moderate-to-scant eosinophilic cytoplasm.
**Round/ovoid nuclei with finely granular chromatin.
*+/-Goblet cells (~30% of cases).<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>
*+/-Goblet cells (~30% of cases).<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>
Image:
*[http://www.nature.com/modpathol/journal/v16/n1/fig_tab/3880708f1.html#figure-title Crappy B&W of solid cell nest (nature.com)].


DDx:<ref name=pmid12527712/>
DDx:<ref name=pmid12527712/>
*C-cell hyperplasia.
*[[C-cell hyperplasia]].
*Medullary carcinoma.
*[[Medullary thyroid carcinoma|Medullary carcinoma]].
*Squamous lesions.
*Squamous lesions.
====Images====
<gallery>
Image:Solid_cell_nest_of_the_thyroid_gland_-_intermed_mag.jpg | Solid cell nest of the thyroid gland - intermed. mag. (WC)
Image:Solid_cell_nest_of_the_thyroid_gland_-_high_mag.jpg | Solid cell nest of the thyroid gland - high mag. (WC)
Image:Solid_cell_nest_of_the_thyroid_gland_-_very_high_mag.jpg | Solid cell nest of the thyroid gland - very high mag. (WC)
</gallery>
www:
*[http://farm6.static.flickr.com/5143/5685400518_c4f506d370.jpg Solid cell next (flickr.com)].
*[http://www.nature.com/modpathol/journal/v16/n1/fig_tab/3880708f1.html#figure-title Crappy B&W of solid cell nest (nature.com)].


===IHC===
===IHC===
Line 125: Line 127:
*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/>
===Sign out===
Solid cell nests of the thyroid gland are usually not reported.


==Nodular hyperplasia==
==Thyroid gland nodular hyperplasia==
===General===
*[[AKA]] ''[[nodular hyperplasia]]''.
*[[AKA]] ''goitre'', AKA sporadic goitre, AKA multinodular goitre (MNG).
*[[AKA]] ''adenomatoid nodule''.
*Most common diagnosis in the thyroid.
{{Main|Thyroid gland nodular hyperplasia}}
**If you've seen a handful of thyroids you've seen this.


Notes:
==Follicular thyroid adenoma==
*Large lesions may be clonal; however, this is clinically irrelevant.  
*[[AKA]] follicular adenoma, [[AKA]] thyroid follicular adenoma.
{{Main|Follicular thyroid adenoma}}


===Microscopic===
==Graves disease==
Features:
{{Main|Graves' disease}}
*Follicles of variable size - '''key feature'''.
**Should be obvious at low power, i.e. ~2.5x objective.
*Nodules maybe well circumscribed (on gross), but do not have a thick fibrous capsule.


Negatives:
==Idiopathic granulomatous thyroiditis==
*No nuclear features suggestive of malignancy (at lower power).
*[[AKA]] ''granulomatous thyroiditis'' - non-specific term; granulomas may be due a number of causes.
**One should not look at high power.
*AKA ''subacute thyroiditis''.
*Not cellular.
*[[AKA]] ''de Quervain thyroiditis''.
**Should '''not''' be confused with ''[[de Quervain's disease]]'' (AKA ''gamer's thumb'') something completely unrelated to the thyroid.


==Follicular adenoma==
===General===
===General===
*Most common neoplasm of thyroid.<ref>{{Ref EP|51}}</ref>
*Women > men.
*Encapusled lesion (surrounded by fibrous capsule).
*Etiology: possibly viral.<ref name=llyod/>


===Gross===
Clinical:
*Thick capsule.
*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>


Notes:
Management:
*The entire capsule should be submitted.<ref>SR. 17 January 2011.</ref>
*Medical.
**A good start for most thyroid specimens with a thick capsule is 10 blocks.
*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>
 
===Microsopic===
Features:
*Cellular.
 
Negatives.
*No invasion of the capsule (see ''[[follicular thyroid carcinoma]]'' section).
*No nuclear features suggestive of papillary carcinoma.
 
==Graves disease==
===General===
*Often misspelled "Grave's disease".
*Autoimmune disease leading to hyperthyroidism.
*Eye problems not resolved with thyroid removal. (???)
*Higher risk of papillary thyroid carcinoma.
 
===Gross===
Features:<ref>{{Ref EP|30}}</ref>
*Enlarged 50-150 g.
*"Beefy-red" appearance, looks like raw beef.


===Microscopic===
===Microscopic===
Features:
Features:<ref name=Ref_Sternberg4_559>{{Ref Sternberg4|559}}</ref><ref name=llyod>{{cite book |title=Endocrine Diseases (AFIP Atlas of Nontumor Pathology) |last= Lloyd |first = Ricardo V. |authorlink= |coauthors= |year= 2002 |publisher= American Registry of Pathology |location= Toronto |isbn=978-1881041733 |page= |pages= |url=http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735 |accessdate=}}</ref>
*Classic:  
*[[Granulomas]] with multinucleated giant cells - usu. with engulfed colloid.
**Hypercellular
*Lymphocytes.
**Patchy lymphocytes.
*Plasma cells.
**Little colloid.
*+/-Fibrosis.
*Scalloping of colloid; colloid has undulating border.
**Non-specific finding.
*+/-Nuclear clearing.
*+/-Papillae (may mimic papillary thyroid carcinoma in this respect).


Notes:
DDx:
*Usually has an unimpressive appearance... as it is treated, i.e. history is important.
*Infectious granulomatous disease (fungal, microbacterial).
*Nuclear clearing and papillae are usu. diffuse in Graves disease - unlike in papillary thyroid carcinoma.
*[[Palpation thyroiditis]].
*[[Sarcoidosis]] (classically intrafollicular distribution).


==Granulomatous thyoiditis==
====Images====
===General===
<gallery>
*[[AKA]] ''de Quervain disease'', AKA subacute thyroiditis.<ref>SR. 17 January 2011.</ref>
Image:Subacute_thyroiditis_-_intermed_mag.jpg | Subacute thyroiditis - intermed. mag. (WC)
*Women > men.
Image:Subacute_thyroiditis_-_high_mag.jpg | Subacute thyroiditis - high mag. (WC)
Image:Subacute_thyroiditis_-_very_high_mag.jpg | Subacute thyroiditis - very high mag. (WC)
</gallery>


===Microscopic===
===Stains===
Features:<ref name=Ref_Sternberg4_559>{{Ref Sternberg4|559}}</ref>
*ZN -ve.
*[[Granulomas]].
*GMS -ve.


==Ridel thyroiditis==
==Palpation thyroiditis==
===General===
===General===
*Disease of the neck.
*Granulomatous inflammation due to palpation.
*Thought to be related to ''[[retroperitoneal fibrosis]]''.
**Incidence of granulomas higher in surgical thyroid specimens than autopsies.<ref name=llyod/>
*Usually hypothyroid.
*+/-Obstructive symptoms.


===Microscopic===
===Microscopic===
Features:
Features:<ref name=llyod>{{cite book |title=Endocrine Diseases (AFIP Atlas of Nontumor Pathology) |last= Lloyd |first = Ricardo V. |authorlink= |coauthors= |year= 2002 |publisher= American Registry of Pathology |location= Toronto |isbn=978-1881041733 |page= |pages= |url=http://www.amazon.com/Endocrine-Diseases-Atlas-Nontumer-Pathology/dp/1881041735 |accessdate=}}</ref>
*Fibrosis.
*[[Granuloma]]s involving the follicle.
*Specimen often fragmented as it was difficult to remove.
**Histiocytes within the colloid.


DDx:
DDx:
*Anaplastic carcinoma - spindle cell variant.
*[[Idiopathic granulomatous thyroiditis]].
*[[Sarcoidosis]].
*Infectious granulomatous thyroiditis.
 
===Stains===
*ZN -ve.
*GMS -ve.


==Hashimoto's thyroiditis==
==Riedel thyroiditis==
===General===
*[[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>
*Autoimmune disease leading to hypothyroidism.
{{Main|Riedel thyroiditis}}
**Often genetic/part of a syndrome.


Associations:<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>
==Hashimoto thyroiditis==
*Antimicrosomal (antithyroid peroxidase) +ve.
{{Main|Hashimoto's thyroiditis}}
*Antithyroglobulin +ve.
*Increased risk of B-cell lymphoma.


===Microscopic===
==C-cell hyperplasia==
Features:
*Abbreviated ''CCH''.
*Lymphocytic infiltrate.
{{Main|C-cell hyperplasia}}
*Nuclear clearing common.  
**May confuse with papillary carcinoma.
*Polymorphous lymphoplasmacytic infiltrate with germinal centres.<ref name=Ref_APBR672>{{Ref APBR|672}}</ref>
*+/-Oncocytic metaplasia.


Notes:
==Adenolipoma of the thyroid==
*Histologically often not possible to separate from "nonspecific" thyroiditis.<ref name=Ref_Sternberg4_560>{{Ref Sternberg4|560}}</ref>
{{Main|Adenolipoma of the thyroid}}


=Malignant neoplasm=
=Malignant neoplasm=
Line 245: 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:
==Insular carcinoma==
*Associated with radiation exposure.<ref name=Ref_Sternberg4_564>{{Ref Sternberg4|564}}</ref>
{{Main|Insular thyroid carcinoma}}


===Microscopic===
==Follicular thyroid carcinoma==
Features:
*[[AKA]] ''follicular carcinoma''.
*Nuclear changes - '''key feature'''.
{{Main|Follicular thyroid carcinoma}}
*#"Shrivelled nuclei"/"raisin" like nuclei, nuclei with a wavy nuclear membrane -- usu. easy to find.
*#[[Nuclear inclusions]] - usu. harder to find; have high specificity.
*#Nuclear grooves.
*#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:
==Medullary thyroid carcinoma==
*Psammoma bodies are awesome if you see 'em, i.e. useful for arriving at the diagnosis.
*Abbreviated ''MTC''.
**If there are no papillae structures -- you're unlikely to see psammoma bodies.
{{Main|Medullary thyroid carcinoma}}
*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.


===Subtypes of papillary thyroid carcinoma===
==Poorly differentiated thyroid carcinoma==
There are many.
{{Main|Poorly differentiated thyroid carcinoma}}


===Tall cell variant===
==Anaplastic thyroid carcinoma==
====General====
{{Main|Anaplastic thyroid carcinoma}}
*~10% of PTC.


====Microscopic====
==Lymphomas of the thyroid==
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>
{{Main|Lymphoma}}
*50% of cells with height 2x the width.<ref>[http://pathologyoutlines.com/thyroid.html#tallcellvariant http://pathologyoutlines.com/thyroid.html#tallcellvariant]</ref><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>
===General===
**There is some disagreement on these criteria;<ref name=pmid18925842/> SR believes height ought to be ~3x width, for 50% of the cells.<ref>SR. 17 January 2011.</ref>
*Rare.
*Eosinophilic cytoplasm.
*Increased risk with chronic inflammatory conditions.
*Well-defined cell borders.
*Fit in the the greater category of ''[[MALT lymphoma]]''.
*Nucleus stratified; basal location, i.e. closer to the basement membrane.


Negative:
===Microscopic===
*Nuclei ''not'' pseudostratified, if pseudostratified consider ''columnar cell variant''.
 
===Columnar cell variant===
====General====
Epidemiology:
*Poor prognosis.
*Very rare.
 
====Microscopic====
Features:
Features:
*Elongated nuclei (similar to colorectal adenocarcinoma) - '''key feature'''.
*Lymphoepithelial lesion - '''key feature'''.
*Pseudostratification of the nuclei (like in colorectal adenocarcinoma), differentiates from ''tall cell variant'' - '''key feature'''.
*Plasma cells.
*"Minimal" papillary features.
*"Overgrowth" - thyroid parenchyma displaced by lymphocytes.
*"Tall cells".
*Clear-eosinophilic cytoplasm.
*Mitoses common.
Image: [http://www3.interscience.wiley.com/cgi-bin/fulltext/75000320/nfig003a?CRETRY=1&SRETRY=0 Tall cell variant Pa ca (wiley.com)].
===Follicular variant===
====General====
May be confused with follicular carcinoma or follicular adenoma.


====Microscopic====
=Weird stuff=
Features:
==Hyalinizing trabecular tumour==
*Prominent follicles.
*[[AKA]] ''hyalinizing trabecular adenoma''.
*Abbreviated ''HTT''.
{{Main|Hyalinizing trabecular tumour}}


===Cribriform-morular variant===
==Hürthle cell neoplasm==
====General====
*[[AKA]] ''oncocytic neoplasm''.
*Associated [[familial adenomatous polyposis]] (FAP).
*Also spelled ''Hurthle cell neoplasm''.
{{Main|Hürthle cell neoplasm}}


====Microscopic====
==Minocycline associated thyroid pigmentation==
Features:
*[[AKA]] ''minocycline thyroid''.
*Cribriform pattern.
*Morules - balls of tissue.


==Insular carcinoma==
===General===
===General===
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>
*Benign pigmentation of the thyroid due to ''minocycline'', an antibiotic.
*Rare - approximately 5% of all thyroid carcinomas.
**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.
*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===
===Gross===
Features:<ref name=pmid17665497/>
*Black thyroid.<ref name=pmid2780449>{{Cite journal  | last1 = Noble | first1 = JG. | last2 = Christmas | first2 = TJ. | last3 = Chapple | first3 = C. | last4 = Katz | first4 = D. | last5 = Milroy | first5 = EJ. | title = The black thyroid: an unusual finding during neck exploration. | journal = Postgrad Med J | volume = 65 | issue = 759 | pages = 34-5 | month = Jan | year = 1989 | doi =  | PMID = 2780449 | PMC = 2429157 }}</ref>
*Islands of cells - '''key feature'''.
*Scant cytoplasm.
*Nuclei monomorphic and round.


DDx:<ref>Endo. fellow. 17 September 2009.</ref>
Images:
*Medullary thyroid carcinoma.
*[http://images.rheumatology.org/viewphoto.php?albumId=89099&imageId=5231272 Pigmented thyroid gland (rheumatology.org)].
*Poorly differentiated thyroid carcinoma.
*[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>
 
==Follicular thyroid carcinoma==
===Clinical===
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===
===Microscopic===
Features:
Features:
*Defined by either:
*Granular yellow blobs:
*#Invasion through the capsule:
**Location:
*#*Should be all the way through.<ref>SR. 17 January 2011.</ref>
***Intracytoplasmic in the follicule-lining cells, i.e. follicular cells.
*#**1/2 does not count.
***Intrafollicular.
*#**Fibrous reaction does not count.
**Variable size ~0.5-4 micrometers.
*#**"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:
Notes:
*'''Impossible''' to differentiate from ''follicular adenoma'' on FNA (no cytologic differences).
*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>
*Described as "over-diagnosed" ... misdiagnoses: PTC follicular variant, follicular adenoma, multinodular goitre with a thick capsule.
 
==Medullary thyroid carcinoma==
===General===
*Abbreviated ''MTC''.
 
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).
 
===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 (associated with familial forms of MTC).
**C cells (AKA ''parafollicular cell''): abundant cytoplasm - clear/pale.


IHC:<ref>[http://pathologyoutlines.com/thyroid.html#medullary http://pathologyoutlines.com/thyroid.html#medullary]</ref>
====Images====
*[[Calcitonin]] +ve - it arises from C cells (which produce calcitonin).
*[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>
*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>


Image:
===Stains===
*[http://jcp.bmj.com/content/vol57/issue3/images/large/cp8474.f16.jpeg Medullary thyroid carcinoma (bmj.com)].
*[[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>
*[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)].


==Anaplastic thyroid carcinoma==
==Sclerosing mucoepidermoid carcinoma with eosinophilia==
===Epidemiology===
{{Main|Sclerosing mucoepidermoid carcinoma with eosinophilia}}
*Very rare.
*Horrible prognosis.
 
===Microscopic===
Features:
*Cytologically malignant:
**Huge NC ratio.
**Mitoses.
**+/-[[Necrosis]].
 
Image: [http://commons.wikimedia.org/wiki/File:Anaplastic_thyroid_carcinoma_low_mag.jpg Anaplastic thyroid carcinoma with a component of papillary thyroid carcinoma (WC)].
 
===IHC===
*Keratin (AE1/AE3).
*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.
 
==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.<ref name=pmid18795075>{{Cite journal  | last1 = Rydlova | first1 = M. | last2 = Ludvikova | first2 = M. | last3 = Stankova | first3 = I. | title = Potential diagnostic markers in nodular lesions of the thyroid gland: an immunohistochemical study. | journal = Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub | volume = 152 | issue = 1 | pages = 53-9 | month = Jun | year = 2008 | doi =  | PMID = 18795075 }}</ref>
**CD31 is a marker for microvessel density.
*Galectin-3 thought to be positive in papillary carcinoma.<ref name=pmid18795075/>
*HBME-1 thought to be positive in papillary lesions.<ref name=pmid15529186>{{Cite journal  | last1 = Papotti | first1 = M. | last2 = Rodriguez | first2 = J. | last3 = De Pompa | first3 = R. | last4 = Bartolazzi | first4 = A. | last5 = Rosai | first5 = J. | title = Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. | journal = Mod Pathol | volume = 18 | issue = 4 | pages = 541-6 | month = Apr | year = 2005 | doi = 10.1038/modpathol.3800321 | PMID = 15529186 }}</ref>


=See also=
=See also=
Michael
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