Difference between revisions of "Thyroid cytopathology"

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[[Image:Benign thyroid - FNA -- very high mag.jpg|thumb|right|Benign thyroid cells. FNA specimens. (WC)]]
'''[[Thyroid]] cytopathology''' is a large part of cytopathology.
'''[[Thyroid]] cytopathology''' is a large part of cytopathology.


This article deals only with thyroid cytopathology.  An introduction to cytopathology is in the ''[[cytopathology]]'' article.  Head and neck cytopathology is dealt with in the ''[[Head and neck cytopathology]]'' article.
This article deals only with thyroid cytopathology.  An introduction to cytopathology is in the ''[[cytopathology]]'' article.  Head and neck cytopathology is dealt with in the ''[[Head and neck cytopathology]]'' article.


==Normal==
=Normal thyroid=
Follicular cells:
===Radiology===
Benign features - terms:<ref name=pmid19542415>{{Cite journal  | last1 = Bonavita | first1 = JA. | last2 = Mayo | first2 = J. | last3 = Babb | first3 = J. | last4 = Bennett | first4 = G. | last5 = Oweity | first5 = T. | last6 = Macari | first6 = M. | last7 = Yee | first7 = J. | title = Pattern recognition of benign nodules at ultrasound of the thyroid: which nodules can be left alone? | journal = AJR Am J Roentgenol | volume = 193 | issue = 1 | pages = 207-13 | month = Jul | year = 2009 | doi = 10.2214/AJR.08.1820 | PMID = 19542415 }}</ref>
*Spongiform configuration.
*Colloid clot - cyst.
*Giraffe pattern.
*Diffuse hyperechogenicity.
===Follicular cells===
*Uniform spacing of cells.
*Uniform spacing of cells.
*"Cracks" (spaces) between cell - "crazy paving".<ref name=Ref_APBR672>{{Ref APBR|672}}</ref>
*"Cracks" (spaces) between cell - "crazy paving".<ref name=Ref_APBR672>{{Ref APBR|672}}</ref>


Colloid - acellular crap with:
Note:
*It is interesting that uniform spacing in the context of thyroid is benign... in breast suggests [[DCIS]].
 
====Microfollicles====
Definition:<ref name=pmid16454552>{{Cite journal  | last1 = Renshaw | first1 = AA. | last2 = Wang | first2 = E. | last3 = Wilbur | first3 = D. | last4 = Hughes | first4 = JH. | last5 = Haja | first5 = J. | last6 = Henry | first6 = MR. | title = Interobserver agreement on microfollicles in thyroid fine-needle aspirates. | journal = Arch Pathol Lab Med | volume = 130 | issue = 2 | pages = 148-52 | month = Feb | year = 2006 | doi = 10.1043/1543-2165(2006)130[148:IAOMIT]2.0.CO;2 | PMID = 16454552 }}</ref>
*<15 follicular cells forming at least two thirds of a circle.
*Usually flat, i.e. not three dimensional.
 
Note:
*A small number of microfollicles is considered normal.
 
====Images====
<gallery>
Image: Benign thyroid - FNA -- high mag.jpg | Thyroid - high mag. (WC)
Image: Benign thyroid - FNA -- very high mag.jpg | Thyroid - very high mag. (WC)
</gallery>
<gallery>
Image: Endocrine atypia in thyroid - 1 -- high mag.jpg | Colloid and [[endocrine atypia]] - high mag. (WC)
Image: Endocrine atypia in thyroid - 2 -- very high mag.jpg | Colloid and endocrine atypia - very high mag. (WC)
</gallery>
 
===Colloid===
Paucicellular/acellular material with:<ref name=pmid15987502>{{cite journal |authors=Nguyen GK, Lee MW, Ginsberg J, Wragg T, Bilodeau D |title=Fine-needle aspiration of the thyroid: an overview |journal=Cytojournal |volume=2 |issue=1 |pages=12 |date=June 2005 |pmid=15987502 |pmc=1184092 |doi=10.1186/1742-6413-2-12 |url=}}</ref>
*Irregular/sharp borders.
*Irregular/sharp borders.
*Cracks - '''key feature'''.
*Cracks - '''key feature'''.
*Dark (uniform) staining with Romanowsky type stains.
*Bubble pattern.
**Green edge + red/orange centre with Pap stain.
*Dark (uniform) staining with [[Romanowsky stain|Romanowsky type stains]].
**Green edge + red/orange centre with [[Pap stain]].
*+/-Entraped red blood cells (RBCs).
*+/-Entraped red blood cells (RBCs).


Note:
====Images====
*It is interesting that uniform spacing in the context of thyroid is benign... in breast suggests DCIS.
<gallery>
Image: Thyroid colloid - FNA -- high mag.jpg | Colloid - high mag. (WC)
Image: Thyroid colloid - FNA -- very high mag.jpg | Colloid - very high mag. (WC)
</gallery>
 
===Hurthle cells===
:May be spelled ''Hürthle cells''.
Features:
*Large epithelioid cells with red granular material on Pap stain.
*Should ''not'' form 3-D balls.
 
====Images====
<gallery>
Image: Hurthle cells - thyroid FNA -- high mag.jpg | HC - high mag. (WC)
Image: Hurthle cells - thyroid FNA -- very high mag.jpg | HC - very high mag. (WC)
</gallery>
 
=Normal parathyroid cytology=
{{Main|Parathyroid gland}}
===General===
*May be confused with thyroid.
**No single feature can be use to reliably separate them, though several features may allow this.<ref name=pmid11891946/>
*FNAs are not useful for parathyroid lesions;<ref name=pmid19283690/> however, a parathyroid may be sampled inadvertently.
 
===Cytology===
Chief cells:<ref name=pmid11891946>{{Cite journal  | last1 = Absher | first1 = KJ. | last2 = Truong | first2 = LD. | last3 = Khurana | first3 = KK. | last4 = Ramzy | first4 = I. | title = Parathyroid cytology: avoiding diagnostic pitfalls. | journal = Head Neck | volume = 24 | issue = 2 | pages = 157-64 | month = Feb | year = 2002 | doi =  | PMID = 11891946 }}</ref>
*Small round-to-oval nucleus.
*Granular chromatin.
*Cytoplasm - often not distinct.
*Scattered naked nuclei.<ref name=pmid24255635>{{Cite journal  | last1 = Heo | first1 = I. | last2 = Park | first2 = S. | last3 = Jung | first3 = CW. | last4 = Koh | first4 = JS. | last5 = Lee | first5 = SS. | last6 = Seol | first6 = H. | last7 = Choi | first7 = HS. | last8 = Cho | first8 = SY. | title = Fine needle aspiration cytology of parathyroid lesions. | journal = Korean J Pathol | volume = 47 | issue = 5 | pages = 466-71 | month = Oct | year = 2013 | doi = 10.4132/KoreanJPathol.2013.47.5.466 | PMID = 24255635 }}</ref>
*+/-Nuclear moulding.
*+/-Nuclear overlap.
*+/-Papillary fragments - uncommon.<ref name=pmid19283690>{{Cite journal  | last1 = Agarwal | first1 = AM. | last2 = Bentz | first2 = JS. | last3 = Hungerford | first3 = R. | last4 = Abraham | first4 = D. | title = Parathyroid fine-needle aspiration cytology in the evaluation of parathyroid adenoma: cytologic findings from 53 patients. | journal = Diagn Cytopathol | volume = 37 | issue = 6 | pages = 407-10 | month = Jun | year = 2009 | doi = 10.1002/dc.21020 | PMID = 19283690 }}</ref>
 
Images:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770637/figure/f1/ Parathyroid gland (nih.gov)].<ref name=pmid15790694>{{Cite journal  | last1 = Johnson | first1 = SJ. | last2 = Sheffield | first2 = EA. | last3 = McNicol | first3 = AM. | title = Best practice no 183. Examination of parathyroid gland specimens. | journal = J Clin Pathol | volume = 58 | issue = 4 | pages = 338-42 | month = Apr | year = 2005 | doi = 10.1136/jcp.2002.002550 | PMID = 15790694 | PMC = 1770637 }}</ref>
 
DDx of naked nuclei:
*[[Granular cell tumour]].
*Parathyroid.<ref name=pmid19283690/>
 
=Adequacy criteria=
*>=60 follicular cells. †
**If abundant colloid is present less follicular cells are accepted.
*No atypical cells.
 
Note 1:
*† Typically described as: at least 6 groups (with 10 or more follicular cells) on at least two smears.<ref name=pmid9809173>{{Cite journal  | last1 = Carpi | first1 = A. | last2 = Sagripanti | first2 = A. | last3 = Nicolini | first3 = A. | last4 = Santini | first4 = S. | last5 = Ferrari | first5 = E. | last6 = Romani | first6 = R. | last7 = Di Coscio | first7 = G. | title = Large needle aspiration biopsy for reducing the rate of inadequate cytology on fine needle aspiration specimens from palpable thyroid nodules. | journal = Biomed Pharmacother | volume = 52 | issue = 7-8 | pages = 303-7 | month =  | year = 1998 | doi =  | PMID = 9809173 }}</ref>
 
Note 2:
*The inadequate & suspicious rate with these criteria is 10-30%. In excision specimens, 75-80% are benign.<ref name=pmid11940037>{{Cite journal  | last1 = Haugen | first1 = BR. | last2 = Woodmansee | first2 = WW. | last3 = McDermott | first3 = MT. | title = Towards improving the utility of fine-needle aspiration biopsy for the diagnosis of thyroid tumours. | journal = Clin Endocrinol (Oxf) | volume = 56 | issue = 3 | pages = 281-90 | month = Mar | year = 2002 | doi =  | PMID = 11940037 }}</ref>
**The above begs the question - should the criteria be changed?
 
===Sign out===
<pre>
Thyroid Gland, Right Lobe, Fine Needle Aspiration:
- Unsatisfactory; specimen processed and examined, but unsatisfactory due to insufficient
  material. Scant follicular cells, Hurthle cells and colloid present in a background of
  mixed inflammatory cells and abundant macrophages. 
 
Note: A repeat aspiration should be considered if clinically warranted.  
</pre>
 
====Alternate====
<pre>
Thyroid Gland, Right Lobe, Fine Needle Aspiration:
- Non-diagnostic. (Category I)
Specimen processed and examined, but unsatisfactory due to scant cellularity. 
Some cellular degeneration noted, rare colloid and inflammatory cells present.
 
Note: A repeat aspiration should be considered if clinically warranted.
</pre>
 
====Abundant colloid====
<pre>
Left Thyroid, FNA: BENIGN, see comment.
 
Note:
The specimen has abundant colloid. The background consists of histiocytes in keeping with a cyst.  The number of follicular cells falls below the typically desired threshold; however, the case is sufficient on the basis of the abundant colloid, as per the 2023 Bethesda System for Reporting Thyroid Cytopathology. The clinical impression is noted.
</pre>


==Standard sign-out language==
=Standard sign-out language=
There is a standard way of describing thyroid cytopathology results.
There is a standard way of describing thyroid cytopathology results.
===Bethesda (2023)===
*A new iteration of Bethesda 2009.


===Bethesda (2009)===
===Bethesda (2009)===
The NCI classification of 2008 was revised in 2009 and dubbed "The Bethesda System for Reporting Thyroid Cytopathology":<ref name=pmid19888858>{{cite journal |author=Cibas ES, Ali SZ |title=The Bethesda System for Reporting Thyroid Cytopathology |journal=Thyroid |volume=19 |issue=11 |pages=1159–65 |year=2009 |month=November |pmid=19888858 |doi=10.1089/thy.2009.0274 |url=}}</ref>
This is formally known as the "The Bethesda System for Reporting Thyroid Cytopathology"; it is based on the NCI classification of 2008:<ref name=pmid19888858>{{cite journal |author=Cibas ES, Ali SZ |title=The Bethesda System for Reporting Thyroid Cytopathology |journal=Thyroid |volume=19 |issue=11 |pages=1159–65 |year=2009 |month=November |pmid=19888858 |doi=10.1089/thy.2009.0274 |url=}}</ref>
{| class="wikitable"
{| class="wikitable"
|-
|-
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| Follow-up, clinical
| Follow-up, clinical
|-
|-
| Follicular lesion of undetermined significance (FLUS) ''or'' atypia of undetermined significance
| Follicular lesion of undetermined significance (FLUS)<br> ''or'' atypia of undetermined significance
| Uncertain, favour benign
| Uncertain, favour benign
| 5-15%
| 5-15%
| Repeat FNA
| Repeat FNA
|-
|-
| Follicular neoplasm ''or'' suspicious for follicular neoplasm
| Follicular neoplasm<br> ''or'' suspicious for follicular neoplasm; if oncocytic type it should be noted
| Uncertain, favour malignant
| Uncertain, favour malignant
| 15-30%
| 15-30%
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| Repeat FNA in 3 months
| Repeat FNA in 3 months
|}
|}
=Benign disease=
==Adenomatoid nodule==
{{Main|Adenomatoid nodule of the thyroid gland}}
===General===
*Diagnosis ''benign thyroid tissue''.
===Cytology===
Features:
*Benign follicular cells (abundant) with relatively little colloid.
DDx:
*[[Colloid nodule]] - has more colloid.
===Sign out===
<pre>
Thyroid Gland, Left, Fine Needle Aspiration:
- Benign.
- Cellular aspirate.
- Benign-appearing follicular cells with colloid, consistent with an adenomatous nodule.
</pre>
==Colloid nodule==
===General===
*Diagnosis ''benign thyroid tissue''.
===Cytology===
Features:
*Colloid - paucicellular material:
**"Thick" colloid = dense appearing blob, well-circumscribed +/- "cracking".
**"Watery" colloid = light, whispy/fluffy material.
*Macrofollicles:
**Ball of cells ~ 20 cells across.
====Images====
<gallery>
Image: Thyroid colloid - FNA -- high mag.jpg | Colloid - high mag. (WC)
Image: Thyroid colloid - FNA -- very high mag.jpg | Colloid - very high mag. (WC)
</gallery>
==Graves disease==
{{Main|Graves disease}}
===General===
*'''Clinical diagnosis''' - based on serology.
===Cytology===
Features:
*+/-Flame cells on [[Romanowsky stain]], e.g. Diff-Quik.<ref name=ouhsc_37>URL: [http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-037-M.htm http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-037-M.htm]. Accessed on: 10 April 2012.</ref>
**Red granular discolourization of the cytoplasm - thought to be endoplasmic reticulum.
Notes:
*Flame cells are indicative of cellular hyperactivity.
**Not pathognomonic for Graves disease, e.g. may be seen in early [[Hashimoto disease]],
Images:
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CI-Image-0803/FQ-057a.gif Flame cells (ouhsc.edu)].<ref name=ouhsc_37/>
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CI-Image-0803/FQ-057b.gif Flame cells (ouhsc.edu)].


==Lymphocytic thyroiditis==
==Lymphocytic thyroiditis==
===Microscopic===
===General===
*Non-specific finding.
**May represent [[Hashimoto thyroiditis]].
**Can be seen in [[Graves' disease]].<ref name=pmid6129766>{{Cite journal  | last1 = Leövey | first1 = A. | last2 = Bakó | first2 = G. | last3 = Sztojka | first3 = I. | last4 = Bordán | first4 = L. | last5 = Szabó | first5 = T. | last6 = Kálmán | first6 = K. | last7 = Balázs | first7 = C. | title = The pathogenetic connection between Graves' disease and chronic lymphocytic thyroiditis. (The role and incidence of thyroid stimulating antibodies). | journal = Acta Med Acad Sci Hung | volume = 39 | issue = 1-2 | pages = 1-6 | month =  | year = 1982 | doi =  | PMID = 6129766 }}</ref>
===Cytology===
Features:
Features:
#Lymphocytes not typical of circulating blood:
#Lymphocytes not typical of circulating blood:
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#**Small lymphocytes with a cleft.
#**Small lymphocytes with a cleft.
#*Centroblasts.
#*Centroblasts.
#**Large lymphocytes with nucleolus and eccentric nucleus.
#**Large lymphocytes with [[nucleolus]] and eccentric nucleus.
#*Plasma cells.
#*Plasma cells.
#**Cells with a "clockface nucleus".
#**Cells with a "clockface nucleus".
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*Usually #1 and #2 are seen.
*Usually #1 and #2 are seen.


===Hashimoto's thyroiditis===
===Hashimoto thyroiditis===
{{Main|Hashimoto thyroiditis}}
====General====
*'''This is a clinical diagnosis'''.
**It should be reported by the pathologist as "lymphocytic thyroiditis".
 
Associations:<ref name=Ref_APBR672>{{Ref APBR|672}}</ref><ref name=pmid7813361/>
Associations:<ref name=Ref_APBR672>{{Ref APBR|672}}</ref><ref name=pmid7813361/>
*AMA +ve.
*AMA +ve.
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*Increased risk of B-cell lymphoma.
*Increased risk of B-cell lymphoma.


====Cytology====
Features:<ref name=Ref_APBR672>{{Ref APBR|672}}</ref>
Features:<ref name=Ref_APBR672>{{Ref APBR|672}}</ref>
*Polymorphous lymphoplasmacytic infiltrate with germinal centres.
*Polymorphous lymphoplasmacytic infiltrate with germinal centres.
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**Found in almost 100% of cases.<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>
**Found in almost 100% of cases.<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>
*Lymphoglandular bodies.
*Lymphoglandular bodies.
**Cytoplasmic fragment of a lymphoid cell.<ref>[http://www.definition-of.com/lymphoglandular+body http://www.definition-of.com/lymphoglandular+body]</ref>
**Cytoplasmic fragment of a lymphoid cell.<ref>URL: [http://www.definition-of.com/lymphoglandular+body http://www.definition-of.com/lymphoglandular+body]. Accessed on: 27 January 2012.</ref>


====Diagnosis====
Note:
*This is a clinical diagnosis.
*Lymphocyte infiltration into fragments of oncocytic cells - strongly suggestive of Hashimoto disease. (???)
**It should be reported by the pathologist as "lymphocytic thyroiditis".


=Waffle category=
==Follicular lesion of undetermined significance==
==Follicular lesion of undetermined significance==
Abbreviated ''FLUS''.
*Abbreviated ''FLUS''.
*Also known as ''atypia of undetermined significance'' (abbreviated ''AUS'').


===General===
===General===
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**Mild accentuation of nuclear staining.
**Mild accentuation of nuclear staining.


===Sign out===
<pre>
Atypia of undetermined significance (AUS).
</pre>
=Neoplastic and malignant=
==Papillary carcinoma==
==Papillary carcinoma==
{{Main|Papillary thyroid carcinoma}}
{{Main|Papillary thyroid carcinoma}}
===General===
*[[Papillary thyroid carcinoma]] is basically the only entity (in cytopathology) that has near universally accepted criteria.
*[[Papillary thyroid carcinoma]] is basically the only entity (in cytopathology) that has near universally accepted criteria.
**This is why radiation oncologists say... "Basing stuff on pathology is like basing something on shifting sand."
**This is why radiation oncologists say... "Basing stuff on pathology is like basing something on shifting sand."
Line 191: Line 379:
**Clump of epithelial cells with attached fibrous tissue "tail" - that has a smooth edge.
**Clump of epithelial cells with attached fibrous tissue "tail" - that has a smooth edge.
*Cellular/nuclear membrane overlapping; cells do not respect one another (very common).
*Cellular/nuclear membrane overlapping; cells do not respect one another (very common).
*+/-Psammoma bodies (uncommon - but helpful if seen).  
*+/-[[Psammoma bodies]] (uncommon - but helpful if seen).  


Notes:
Notes:
*Nuclear enlargement may be seen in Hashimoto's disease.<ref>WG. 8 January 2010.</ref>
*Nuclear enlargement may be seen in Hashimoto's disease.<ref>WG. 8 January 2010.</ref>
*Nuclear grooves may be seen in Hashimoto's disease.<ref>WG. 8 January 2010.</ref>
*Nuclear grooves may be seen in Hashimoto's disease.<ref>WG. 8 January 2010.</ref>
*Papillary architecture may be seen in Graves's disease.<ref>Biopsy Interpretation of the Thyroid. PP.97-98.</ref>
*Papillary architecture may be seen in [[Graves disease]].<ref>Biopsy Interpretation of the Thyroid. PP.97-98.</ref>
*Thick (dense) colloid common - described as "bubble gum". (???)
 
====Images====
<gallery>
Image: Papillary thyroid carcinoma -- intermed mag.jpg | PTC - intermed. mag. (WC)
Image: Papillary thyroid carcinoma -- high mag.jpg | PTC - high mag. (WC)
Image: Papillary thyroid carcinoma -- very high mag.jpg | PTC - very high mag. (WC)
 
Image: Papillary thyroid carcinoma - pi -- high mag.jpg | PTC - high mag. (WC)
Image: Papillary thyroid carcinoma - pi -- very high mag.jpg | PTC - very high mag. (WC)
</gallery>
<gallery>
Image:Papillary_Carcinoma_of_the_Thyroid.jpg | PTC. (WC)
</gallery>


===Variants of PTC===
===Variants of PTC===
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==Follicular neoplasm==
==Follicular neoplasm==
*Sort of a garbage category for the thyroid.
===General===
*Can be thought of as a (neoplasm) garbage category for the thyroid gland - may represent:
**[[Follicular adenoma]].
**[[Follicular carcinoma]].
 
Management:
*Hemithyroidectomy.


===Cytology===
===Cytology===
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#Nuclear overlap/crowding.
#Nuclear overlap/crowding.
#+/-Microfollicles, numerous.
#+/-Microfollicles, numerous.
#*Microfollicles are defined as: <15 cells forming at least two thirds of a circle.
#*[[Microfollicles]] are defined as: <15 cells forming at least two thirds of a circle.
#+/-Atypia marked.
#+/-Atypia marked.


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*A few microfollicles are normal.
*A few microfollicles are normal.
*''Atypia'' alone - "suspicious for malignancy" or "malignant".
*''Atypia'' alone - "suspicious for malignancy" or "malignant".
*Nuclei are described as having the shape of an ''orange'' in follicular neoplasms... and ''potatoes'' in papillary thyroid carcinomas.


Management:
==Oncocytic neoplasm==
*Hemithyroidectomy.
{{Main|Hürthle cell neoplasm}}
 
*[[AKA]] ''Hurthle cell neoplasm''.
==Oncocytic neoplasm (Hurthle cell neoplasm)==
===General===
General:
*''Oncocytic'' perferred by WHO over ''Hurthle cell''.
*''Oncocytic'' perferred by WHO over ''Hurthle cell''.


===Cytology===
Features:<ref name=pmid18478609/>
Features:<ref name=pmid18478609/>
#Single cells or sheets of oncocytic cells.
#Single cells or sheets of oncocytic cells.
Line 249: Line 458:
**Multinucleation.
**Multinucleation.


Diagnosis by MB:
DDx:
*If single cells -- need abundant.
*[[Granular cell tumour]].


Image:
====Images====
*[http://commons.wikimedia.org/wiki/File:Hurthle_cell_neoplasm.jpg Hurthle cell neoplasm (WC)].
<gallery>
Image:Hurthle_cell_neoplasm.jpg | Hurthle cell neoplasm. (WC)
</gallery>
www:
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CI-Image-0803/FQ-059b.gif ON - Diff-Quik - intermed. mag. (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-039-M.htm http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-039-M.htm]. Accessed on: 10 April 2012.</ref>
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CI-Image-0803/FQ-059c.gif ON - Pap stain - high mag. (ouhsc.edu)].


==Medullary thryoid carcinoma==
==Medullary thryoid carcinoma==
{{Main|Medullary thyroid carcinoma}}
{{Main|Medullary thyroid carcinoma}}
===General===
*May be familial - associated with MEN II syndrome.
*May be familial - associated with MEN II syndrome.
*Sometimes described as the ''melanoma of the thyroid'' - as it can look like almost anything.


===Cytology===
===Cytology===
Line 279: Line 495:


DDx:
DDx:
*Anaplastic carcinoma.
*[[anaplastic thyroid carcinoma|Anaplastic carcinoma]].


Images:
Images:
Line 290: Line 506:
*Congo-red +ve (if amyloid present) - mnemonic: ''CRAP'' -- congo red amyloid protein.
*Congo-red +ve (if amyloid present) - mnemonic: ''CRAP'' -- congo red amyloid protein.


==Anaplastic carcinoma==
==Anaplastic thyroid carcinoma==
{{Main|Anaplastic thyroid carcinoma}}
===General===
*Prognosis: very crappy.
*Prognosis: very crappy.
*Classically rapid growth.
Note:
*Other fast growing lesion:
**Lymphoma (faster than anaplastic carcinoma).
**Blood accumulation.


===Cytology===
===Cytology===
Line 302: Line 526:


DDx:
DDx:
*Medullary carcinoma.
*Medullary thyroid carcinoma.


==See also==
=See also=
*[[Cytopathology]].
*[[Cytopathology]].
*[[Thyroid]].
*[[Thyroid gland]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


[[Category:Cytopathology]]
[[Category:Cytopathology]]

Latest revision as of 13:12, 19 September 2024

Benign thyroid cells. FNA specimens. (WC)

Thyroid cytopathology is a large part of cytopathology.

This article deals only with thyroid cytopathology. An introduction to cytopathology is in the cytopathology article. Head and neck cytopathology is dealt with in the Head and neck cytopathology article.

Normal thyroid

Radiology

Benign features - terms:[1]

  • Spongiform configuration.
  • Colloid clot - cyst.
  • Giraffe pattern.
  • Diffuse hyperechogenicity.

Follicular cells

  • Uniform spacing of cells.
  • "Cracks" (spaces) between cell - "crazy paving".[2]

Note:

  • It is interesting that uniform spacing in the context of thyroid is benign... in breast suggests DCIS.

Microfollicles

Definition:[3]

  • <15 follicular cells forming at least two thirds of a circle.
  • Usually flat, i.e. not three dimensional.

Note:

  • A small number of microfollicles is considered normal.

Images

Colloid

Paucicellular/acellular material with:[4]

  • Irregular/sharp borders.
  • Cracks - key feature.
  • Bubble pattern.
  • Dark (uniform) staining with Romanowsky type stains.
    • Green edge + red/orange centre with Pap stain.
  • +/-Entraped red blood cells (RBCs).

Images

Hurthle cells

May be spelled Hürthle cells.

Features:

  • Large epithelioid cells with red granular material on Pap stain.
  • Should not form 3-D balls.

Images

Normal parathyroid cytology

General

  • May be confused with thyroid.
    • No single feature can be use to reliably separate them, though several features may allow this.[5]
  • FNAs are not useful for parathyroid lesions;[6] however, a parathyroid may be sampled inadvertently.

Cytology

Chief cells:[5]

  • Small round-to-oval nucleus.
  • Granular chromatin.
  • Cytoplasm - often not distinct.
  • Scattered naked nuclei.[7]
  • +/-Nuclear moulding.
  • +/-Nuclear overlap.
  • +/-Papillary fragments - uncommon.[6]

Images:

DDx of naked nuclei:

Adequacy criteria

  • >=60 follicular cells. †
    • If abundant colloid is present less follicular cells are accepted.
  • No atypical cells.

Note 1:

  • † Typically described as: at least 6 groups (with 10 or more follicular cells) on at least two smears.[9]

Note 2:

  • The inadequate & suspicious rate with these criteria is 10-30%. In excision specimens, 75-80% are benign.[10]
    • The above begs the question - should the criteria be changed?

Sign out

Thyroid Gland, Right Lobe, Fine Needle Aspiration:
- Unsatisfactory; specimen processed and examined, but unsatisfactory due to insufficient 
  material. Scant follicular cells, Hurthle cells and colloid present in a background of 
  mixed inflammatory cells and abundant macrophages.  

Note: A repeat aspiration should be considered if clinically warranted. 

Alternate

Thyroid Gland, Right Lobe, Fine Needle Aspiration:
- Non-diagnostic. (Category I)
 
Specimen processed and examined, but unsatisfactory due to scant cellularity.  
Some cellular degeneration noted, rare colloid and inflammatory cells present.

Note: A repeat aspiration should be considered if clinically warranted. 

Abundant colloid

Left Thyroid, FNA: BENIGN, see comment.

Note: 
The specimen has abundant colloid. The background consists of histiocytes in keeping with a cyst.  The number of follicular cells falls below the typically desired threshold; however, the case is sufficient on the basis of the abundant colloid, as per the 2023 Bethesda System for Reporting Thyroid Cytopathology. The clinical impression is noted.

Standard sign-out language

There is a standard way of describing thyroid cytopathology results.

Bethesda (2023)

  • A new iteration of Bethesda 2009.

Bethesda (2009)

This is formally known as the "The Bethesda System for Reporting Thyroid Cytopathology"; it is based on the NCI classification of 2008:[11]

Preferred Plain language Risk of malignancy Usual management
Benign Benign ~ 0-3% Follow-up, clinical
Follicular lesion of undetermined significance (FLUS)
or atypia of undetermined significance
Uncertain, favour benign 5-15% Repeat FNA
Follicular neoplasm
or suspicious for follicular neoplasm; if oncocytic type it should be noted
Uncertain, favour malignant 15-30% Hemithyroidectomy
Suspicious for malignancy Probably malignant 60-75% Repeat vs. hemithyroidectomy
Malignant Cancer ~ 97-99% Excise (total thyroidectomy)
Nondiagnostic or unsatisfactory Lesion missed or inadequate 1-4% Repeat FNA

NCI (2008)

A National Cancer Institute (NCI) consensus conference in 2008:[12]

Preferred (NIC) Alternate (NIC) Plain language Risk of malignancy Usual management
Benign - Benign ~ 1% Follow/nothing
Follicular lesion of undetermined significance (FLUS) 1. Atypia of undetermined significance
2. Rule-out neoplasm
3. Atypical follicular lesion
4. Cellular follicular lesion
Uncertain, favour benign 5-10% Repeat FNA in 3 months
Follicular neoplasm Suspicious for follicular neoplasm Uncertain, favour malignant 20-30% Hemithyroidectomy
Hurthle cell neoplasm Suspicious for Hurthle cell neoplasm Uncertain, favour malignant 20-30% Hemithyroidectomy
Suspicious for malignancy - Probably malignant 50-75% Repeat vs. hemithyroidectomy
Malignant - Cancer ~ 99% Excise
Nondiagnostic - Lesion missed or inadequate Unknown Repeat FNA in 3 months

Benign disease

Adenomatoid nodule

General

  • Diagnosis benign thyroid tissue.

Cytology

Features:

  • Benign follicular cells (abundant) with relatively little colloid.

DDx:

Sign out

Thyroid Gland, Left, Fine Needle Aspiration: 
- Benign. 
- Cellular aspirate. 
- Benign-appearing follicular cells with colloid, consistent with an adenomatous nodule. 

Colloid nodule

General

  • Diagnosis benign thyroid tissue.

Cytology

Features:

  • Colloid - paucicellular material:
    • "Thick" colloid = dense appearing blob, well-circumscribed +/- "cracking".
    • "Watery" colloid = light, whispy/fluffy material.
  • Macrofollicles:
    • Ball of cells ~ 20 cells across.

Images

Graves disease

General

  • Clinical diagnosis - based on serology.

Cytology

Features:

  • +/-Flame cells on Romanowsky stain, e.g. Diff-Quik.[13]
    • Red granular discolourization of the cytoplasm - thought to be endoplasmic reticulum.

Notes:

  • Flame cells are indicative of cellular hyperactivity.

Images:

Lymphocytic thyroiditis

General

Cytology

Features:

  1. Lymphocytes not typical of circulating blood:
    • Centrocytes.
      • Small lymphocytes with a cleft.
    • Centroblasts.
      • Large lymphocytes with nucleolus and eccentric nucleus.
    • Plasma cells.
      • Cells with a "clockface nucleus".
  2. Small mature lymphocytes in fragments of follicular cells - raise the suspicion of lymphocytic thyroiditis.[15]
    • Small mature lymphocytes are not a reliable indicator of inflammation, as cells may layer during tissue preparation.[16]

Notes:

  • Usually #1 and #2 are seen.

Hashimoto thyroiditis

General

  • This is a clinical diagnosis.
    • It should be reported by the pathologist as "lymphocytic thyroiditis".

Associations:[2][17]

  • AMA +ve.
  • Antithyroid antibody +ve.
    • Antimicrosomal (antithyroid peroxidase).
    • Antithyroglobulin.
  • Increased risk of B-cell lymphoma.

Cytology

Features:[2]

  • Polymorphous lymphoplasmacytic infiltrate with germinal centres.
  • Tingible body macrophages.
    • Found in germinal centres; have condensed chromatin fragments.[18]
  • Lymphoid tangles.
    • Found in almost 100% of cases.[17]
  • Lymphoglandular bodies.
    • Cytoplasmic fragment of a lymphoid cell.[19]

Note:

  • Lymphocyte infiltration into fragments of oncocytic cells - strongly suggestive of Hashimoto disease. (???)

Waffle category

Follicular lesion of undetermined significance

  • Abbreviated FLUS.
  • Also known as atypia of undetermined significance (abbreviated AUS).

General

  • This is waffle diagnosis, i.e. something the pathologist diagnoses when they cannot decide whether it is benign or suspicious for malignant (follicular neoplasm or suspicious for malignancy).[20]
    • Like all waffle diagnoses...
      • Use should be minimized; < 7% is suggested, though it varies considerably between pathologists and institutions.[20]

Cytology

Features:

  • Mild nuclear atypia - that by definition is insufficient for follicular neoplasm or suspicious for malignancy.
    • Mild irregularities in the nuclear contour.
    • Mild size variation or nuclear enlargement.
    • Mild accentuation of nuclear staining.

Sign out

Atypia of undetermined significance (AUS).

Neoplastic and malignant

Papillary carcinoma

General

  • Papillary thyroid carcinoma is basically the only entity (in cytopathology) that has near universally accepted criteria.
    • This is why radiation oncologists say... "Basing stuff on pathology is like basing something on shifting sand."

Cytology

Criteria for papillary thyroid carcinoma:[21][22]

  1. Nuclear inclusion (really pseudoinclusions):[23]
    1. Edge of inclusion must be sharp (nuclear membrane-like).
    2. Size: at least 1/4 of the nucleus.
    3. Round, regular.
    4. Within epithelial cell.
    • Additional criteria:[24] Inclusion center should match cytoplasm.
  2. Nucleoli (micro or macro).
  3. Nuclear grooves.
    • No universal criteria; some believe grooves should go from edge-to-edge, i.e. across the nucleus.
  4. Nuclear enlargement.
  5. Changes in chromatin - patterns:
    • Granular.
    • Washed-out.

Additional features:

  • Papillary architecture (not commonly seen).
    • Clump of epithelial cells with attached fibrous tissue "tail" - that has a smooth edge.
  • Cellular/nuclear membrane overlapping; cells do not respect one another (very common).
  • +/-Psammoma bodies (uncommon - but helpful if seen).

Notes:

  • Nuclear enlargement may be seen in Hashimoto's disease.[25]
  • Nuclear grooves may be seen in Hashimoto's disease.[26]
  • Papillary architecture may be seen in Graves disease.[27]
  • Thick (dense) colloid common - described as "bubble gum". (???)

Images

Variants of PTC

  • Tall cell variant.
    • May mimic Hurthle cell neoplasm.
  • Warthin-like variant.
    • Superficially resembles Warthin tumour (presence of lymphocytes).
  • Follicular variant of PTC; memory device ECT: Elongation, Clearing, Thick membranes.
    • Nuclear elongation.
    • Chromatin clearing.
    • Thick nuclear membranes.
      • Classic features of PTC (esp. pseudo-inclusions) are usually scarce in this variant.

Follicular neoplasm

General

Management:

  • Hemithyroidectomy.

Cytology

Features:[12]

  1. Hypercellular lesion.
  2. 3-dimensional clusters of cells.
  3. Nuclear overlap/crowding.
  4. +/-Microfollicles, numerous.
    • Microfollicles are defined as: <15 cells forming at least two thirds of a circle.
  5. +/-Atypia marked.

Diagnosis (follicular neoplasm) per MB:

  • Either: 1-3 or 3-5.

Notes:

  • A few microfollicles are normal.
  • Atypia alone - "suspicious for malignancy" or "malignant".
  • Nuclei are described as having the shape of an orange in follicular neoplasms... and potatoes in papillary thyroid carcinomas.

Oncocytic neoplasm

  • AKA Hurthle cell neoplasm.

General

  • Oncocytic perferred by WHO over Hurthle cell.

Cytology

Features:[12]

  1. Single cells or sheets of oncocytic cells.
    • 3-D clusters.
    • +/-Transgressing vessels - cluster of oncocytes surrounding vessels.
  2. Oncocytic cells:
    • Well-defined cellular borders.
    • Finely granular abundant cytoplasm.
    • Nucleoli, may be prominent.

Notes:

  • Benign (oncocytic) thyroid tissue may have:
    • Significant nuclear pleomorphism.
    • Multinucleation.

DDx:

Images

www:

Medullary thryoid carcinoma

General

  • May be familial - associated with MEN II syndrome.
  • Sometimes described as the melanoma of the thyroid - as it can look like almost anything.

Cytology

Features:[12]

  1. Single or loosely cohesive cells.
    • Spindle cell morphology common.
  2. Abundant eosinophilc granular cytoplasm - key feature
  3. Salt and pepper chromatin - key feature; no nucleoli.
  4. Nucleus eccentric and round/oval - plasmacytoid appearance.
  5. Amyloid - acellular, amorphous material may be present; cotton candy-like.
    • May be confused with fibrin...
      • Fibrin = fluffy edge vs. amyloid = sharp border. (???)
      • Fibrin - associated with PMNs/has PMNs within it.
    • Amyloid cannot be definitively differentiated on morphologic grounds from colloid.
    • Described by Halliday et al. as:[29]
      • Romanowsky type staining: "amorphous, irregular, waxy basophilic to metachromatic clump".
      • Pap staining: "cyanophilic-organophilic clumps of material + occasional prominent fissures".

Notes:

DDx:

Images:

IHC

  • Calcitonin +ve - it arises from C cells (which produce calcitonin)
  • CEA +ve (often better staining than calcitonin).[31]
  • Congo-red +ve (if amyloid present) - mnemonic: CRAP -- congo red amyloid protein.

Anaplastic thyroid carcinoma

General

  • Prognosis: very crappy.
  • Classically rapid growth.

Note:

  • Other fast growing lesion:
    • Lymphoma (faster than anaplastic carcinoma).
    • Blood accumulation.

Cytology

Features:

  • Nuclear atypia - marked.
  • Spindle cell morphology common.
  • Nucleolus.
  • Usually scant cellularity.[32]
  • Necrosis very common.

DDx:

  • Medullary thyroid carcinoma.

See also

References

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  2. 2.0 2.1 2.2 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 672. ISBN 978-1416025887.
  3. Renshaw, AA.; Wang, E.; Wilbur, D.; Hughes, JH.; Haja, J.; Henry, MR. (Feb 2006). "Interobserver agreement on microfollicles in thyroid fine-needle aspirates.". Arch Pathol Lab Med 130 (2): 148-52. doi:10.1043/1543-2165(2006)130[148:IAOMIT]2.0.CO;2. PMID 16454552.
  4. Nguyen GK, Lee MW, Ginsberg J, Wragg T, Bilodeau D (June 2005). "Fine-needle aspiration of the thyroid: an overview". Cytojournal 2 (1): 12. doi:10.1186/1742-6413-2-12. PMC 1184092. PMID 15987502. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1184092/.
  5. 5.0 5.1 Absher, KJ.; Truong, LD.; Khurana, KK.; Ramzy, I. (Feb 2002). "Parathyroid cytology: avoiding diagnostic pitfalls.". Head Neck 24 (2): 157-64. PMID 11891946.
  6. 6.0 6.1 6.2 Agarwal, AM.; Bentz, JS.; Hungerford, R.; Abraham, D. (Jun 2009). "Parathyroid fine-needle aspiration cytology in the evaluation of parathyroid adenoma: cytologic findings from 53 patients.". Diagn Cytopathol 37 (6): 407-10. doi:10.1002/dc.21020. PMID 19283690.
  7. Heo, I.; Park, S.; Jung, CW.; Koh, JS.; Lee, SS.; Seol, H.; Choi, HS.; Cho, SY. (Oct 2013). "Fine needle aspiration cytology of parathyroid lesions.". Korean J Pathol 47 (5): 466-71. doi:10.4132/KoreanJPathol.2013.47.5.466. PMID 24255635.
  8. Johnson, SJ.; Sheffield, EA.; McNicol, AM. (Apr 2005). "Best practice no 183. Examination of parathyroid gland specimens.". J Clin Pathol 58 (4): 338-42. doi:10.1136/jcp.2002.002550. PMC 1770637. PMID 15790694. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770637/.
  9. Carpi, A.; Sagripanti, A.; Nicolini, A.; Santini, S.; Ferrari, E.; Romani, R.; Di Coscio, G. (1998). "Large needle aspiration biopsy for reducing the rate of inadequate cytology on fine needle aspiration specimens from palpable thyroid nodules.". Biomed Pharmacother 52 (7-8): 303-7. PMID 9809173.
  10. Haugen, BR.; Woodmansee, WW.; McDermott, MT. (Mar 2002). "Towards improving the utility of fine-needle aspiration biopsy for the diagnosis of thyroid tumours.". Clin Endocrinol (Oxf) 56 (3): 281-90. PMID 11940037.
  11. Cibas ES, Ali SZ (November 2009). "The Bethesda System for Reporting Thyroid Cytopathology". Thyroid 19 (11): 1159–65. doi:10.1089/thy.2009.0274. PMID 19888858.
  12. 12.0 12.1 12.2 12.3 Baloch ZW, LiVolsi VA, Asa SL, et al. (June 2008). "Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference". Diagn. Cytopathol. 36 (6): 425-37. doi:10.1002/dc.20830. PMID 18478609.
  13. 13.0 13.1 URL: http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-037-M.htm. Accessed on: 10 April 2012.
  14. Leövey, A.; Bakó, G.; Sztojka, I.; Bordán, L.; Szabó, T.; Kálmán, K.; Balázs, C. (1982). "The pathogenetic connection between Graves' disease and chronic lymphocytic thyroiditis. (The role and incidence of thyroid stimulating antibodies).". Acta Med Acad Sci Hung 39 (1-2): 1-6. PMID 6129766.
  15. GD. 2 February 2010.
  16. SB. ~29 January 2010.
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  21. SM. 12 January 2010.
  22. Kini SR. Guides to clinical aspiration biopsy: thryoid. 2nd Ed. 1996. P.134.
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  24. SB. 8 January 2010.
  25. WG. 8 January 2010.
  26. WG. 8 January 2010.
  27. Biopsy Interpretation of the Thyroid. PP.97-98.
  28. URL: http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-021-040/CQ-039-M.htm. Accessed on: 10 April 2012.
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