Difference between revisions of "Salivary glands"

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The '''salivary glands''' help digest food.  ENT surgeons take 'em out and want you to diagnose 'em. [[Cytopathology]] of the salivary glands is covered in the ''[[Head and neck cytopathology]]'' article.
[[Image:Blausen_0780_SalivaryGlands.png|thumb|300px|Schematic showing the major salivary glands. (WC)]]
The '''salivary glands''' help digest food.  ENT surgeons excise them if a malignancy is suspected.  
 
The [[cytopathology]] of the salivary glands is covered in the ''[[Head and neck cytopathology]]'' article.


=Normal salivary glands=
=Normal salivary glands=
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|[[Pleomorphic adenoma]]
|[[Pleomorphic adenoma]]
| var.
| var.
| '''mixed pop.'''; must include: (1) myoepithelium, (2) epithelium (ductal cells), (3) [[chondromyxoid stroma]] 
| '''mixed pop.'''; must include: (1) myoepithelium, (2) mesenchymal stroma, and (3) epithelium (ductal cells) ''or'' [[chondromyxoid stroma]] 
| var.
| var.
| var.
| var.
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| [[basal cell adenoma]]
| [[basal cell adenoma]]
| exclusively oral cavity, 80% in upper lip; IHC: p63-
| exclusively oral cavity, 80% in upper lip; IHC: p63-
| [http://www.webpathology.com/image.asp?n=1&Case=116 (webpathology.com)], [http://www.webpathology.com/image.asp?n=2&Case=116 (webpathology.com)]
| [[Image:Canalicular_adenoma_--_high_mag.jpg | thumb | center |150px| CA. (WC)]]
|-
|-
|[[Sialoblastoma]]
|[[Sialoblastoma]]
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|-
|-
|[[Adenoid cystic carcinoma]] (AdCC)  
|[[Adenoid cystic carcinoma]] (AdCC)  
| pseudocysts,<br>'''cribriform''', solid,<br>hyaline stroma  
| pseudocysts,<br>'''[[cribriform]]''', solid,<br>hyaline stroma  
| epithelioid
| epithelioid
| subtle  
| subtle  
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|-
|-
|[[Salivary duct carcinoma]]  
|[[Salivary duct carcinoma]]  
| glandular, cribriform  
| glandular, [[cribriform]]
| columnar  
| columnar  
| subtle/clear  
| subtle/clear  
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| ovoid & small with<br>small nucleoli  
| ovoid & small with<br>small nucleoli  
| AdCC  
| AdCC  
| minor salivary gland tumour,<br>often in palate,<br> cytologically monotonous; IHC: S100+, CK+, vim.+, GFAP+/-, BCL2+/-
| minor salivary gland tumour,<br>often in palate,<br> cytologically monotonous; IHC: [[S-100]]+, CK+, vim.+, GFAP+/-, BCL2+/-
| [[Image:Polymorphous_low-grade_adenocarcinoma_-_very_low_mag.jpg|thumb|center|150px|PLGA. (WC/Nephron)]]
| [[Image:Polymorphous_low-grade_adenocarcinoma_-_very_low_mag.jpg|thumb|center|150px|PLGA. (WC/Nephron)]]
|-
|-
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*Metastatic [[clear cell carcinoma]].
*Metastatic [[clear cell carcinoma]].
**Metastatic [[clear cell renal cell carcinoma]].
**Metastatic [[clear cell renal cell carcinoma]].
===Basaloid neoplasms===
*[[Basal cell adenoma]].
*[[Basal cell adenocarcinoma]]
*[[Pleomorphic adenoma]].<ref name=pmi12478487/>
*[[Adenoid cystic carcinoma]].<ref name=pmi12478487/>
*[[Small cell carcinoma]].<ref name=pmi12478487>{{Cite journal  | last1 = Chhieng | first1 = DC. | last2 = Paulino | first2 = AF. | title = Basaloid tumors of the salivary glands. | journal = Ann Diagn Pathol | volume = 6 | issue = 6 | pages = 364-72 | month = Dec | year = 2002 | doi = 10.1053/adpa.2002.37013 | PMID = 12478487 }}</ref>


==IHC overview==
==IHC overview==
General:
General:
*Usually has limited value.
*Usually has limited value. <!--as per Ilan Weinreb-->


Specifics:
Overview:
*Luminal markers: CK7, CK19, CAM5.2 (LMWK).
*Luminal markers: [[CK7]], [[CK19]], CAM5.2 (LMWK).
*Basal markers: p63, HMWK, CK14.
*Basal markers: p63, HMWK, CK14.
*Myoepithelial markers: calponin, actin.
*Myoepithelial markers: calponin, actin.
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Notes:
Notes:
*p63 and S-100 are sometimes call myoepithelial.
*p63 and S-100 are sometimes call myoepithelial.
Specifics:
*Calponin, S-100, Ki-67 may be useful as per Nagao ''et al.''<ref>{{Cite journal  | last1 = Nagao | first1 = T. | last2 = Sato | first2 = E. | last3 = Inoue | first3 = R. | last4 = Oshiro | first4 = H. | last5 = H Takahashi | first5 = R. | last6 = Nagai | first6 = T. | last7 = Yoshida | first7 = M. | last8 = Suzuki | first8 = F. | last9 = Obikane | first9 = H. | title = Immunohistochemical analysis of salivary gland tumors: application for surgical pathology practice. | journal = Acta Histochem Cytochem | volume = 45 | issue = 5 | pages = 269-82 | month = Oct | year = 2012 | doi = 10.1267/ahc.12019 | PMID = 23209336 }}</ref>


=Benign=
=Benign=
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==Chronic sialadenitis==
==Chronic sialadenitis==
===General===
{{Main|Chronic sialadenitis}}
Etiology:<ref>URL: [http://emedicine.medscape.com/article/882358-overview http://emedicine.medscape.com/article/882358-overviewhttp://emedicine.medscape.com/article/882358-overview]. Accessed on: 10 January 2011.</ref>
*Infection.
*Autoimmune (e.g. [[Sjögren syndrome]], [[systemic lupus erythematosus]]).
*Other.
 
===Microscopic===
Features:
*+/-Fibrosis.
*Non-neoplastic mononuclear inflammatory infiltrate (lymphocytes, [[plasma cell]]s).
 
Note:
*If the infiltrate is predominantly lymphocytes Sjögren's is a possibility, and reporting a ''[[Focus score]]'' should be considered.


DDx:
*[[Lymphoma]] - especially [[MALT lymphoma]].<ref name=pmid22475637>{{Cite journal  | last1 = Beasley | first1 = MJ. | title = Lymphoma of the Thyroid and Head and Neck. | journal = Clin Oncol (R Coll Radiol) | volume =  | issue =  | pages =  | month = Apr | year = 2012 | doi = 10.1016/j.clon.2012.02.010 | PMID = 22475637 }}</ref>
====Image====
<gallery>
Image:Chronic_sialadenitis.jpg | Chronic sialadenitis. (WC/Nephron)
</gallery>
==Salivary gland mucocele==
==Salivary gland mucocele==
*[[AKA]] ''salivary mucocele''.
*[[AKA]] ''salivary mucocele''.
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*[http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=292590975 Mucocele (dermatlas.med.jhmi.edu)].
*[http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=292590975 Mucocele (dermatlas.med.jhmi.edu)].


==Pleomorphic adenoma==
===Sign out===
*Abbreviated ''PA''.
<pre>
LESION, LEFT LOWER LIP, EXCISION:
- BENIGN MUCOCELE.
</pre>


===General===
====Micro====
Features:
The sections show a stratified squamous epithelium with a thin layer of parakeratosis,
*Very common - approx. 60% of parotid gland tumours.<ref name=Ref_HaNP295>{{Ref HaNP|295}}</ref>
minor salivary glands, and a well-circumscribed cystic lesion.
*May transform into a malignant tumour.
**Other benign salivary gland tumours do not do this.
*Only benign childhood salivary gland tumour of significance.


====Weinreb's dictums====
The cystic lesion has a mildly fibrotic appearing wall, is lined by histiocytes intermixed with rare lymphocytes, and contains mucous and macrophages. No significant nuclear atypia is identified. Mitotic activity is not readily apparent.
#Most common salivary tumour in all age groups.
#Seen in all sites (unlike other benign tumours).
#Recurrence and malignancy risk (unlike other benign salivary gland tumours).
#Any part of a tumour that looks like PA makes it a PA.


===Gross===
==Pleomorphic adenoma==
*May be cartilaginous appearing.
{{Main|Pleomorphic adenoma}}
 
Image:
*[http://screening.iarc.fr/atlasoral_detail.php?flag=1&lang=1&Id=C0100002&cat=C1 PA in situ (iarc.fr)].
 
===Microscopic===
Features:<ref name=Ref_HaNP295>{{Ref HaNP|295}}</ref>
*Proliferation of myoepithelium and epithelium (ductal cells) in mesenchymal stroma.
**Cells in ducts = epithelial.
**Cells not in ducts = myoepithelial.<ref name=IW_10jan2011>IW. 10 January 2011.</ref>
*Mesenchymal stroma - '''important feature'''.
**May be any of following: [[myxoid stroma|myxoid]], mucochondroid, hyalinized, osseous, fatty.
***[[chondromyxoid stroma|Chondroid]] = specific for PA; can diagnose PA without an epithelial (ductal) component if chondroid is present.
***Myxoid = not specific for PA.
 
Notes:
*Mesenchymal stroma not required for diagnosis -- if >5% ducts.<ref name=IW_10jan2011>IW. 10 January 2011.</ref>
**No chondroid stroma ''and'' <5% ductal cells = '''[[myoepithelioma]]'''.
*Complete excision is often elusive; stating "completely excised" on a surgical pathology report is unwise.
*Look for, i.e. rule-out, poorly differentiated carcinoma: ''carcinoma ex pleomorphic adenoma''.
 
Memory device: '''MEC''' = '''m'''yoepithelium, '''e'''pithelium, '''c'''hondromyxoid stroma.
 
DDx:
*[[Myoepithelioma]].
*[[Carcinoma ex pleomorphic adenoma]].
*[[Epithelial-myoepithelial carcinoma]].
 
====Images====
<gallery>
Image:Pleomorphic_adenoma_%281%29_parotid_gland.jpg | PA. (WC)
Image:Pleomorphic_adenoma_%282%29_parotid_gland.jpg | PA. (WC)
Image:Pleomorphic_adenoma_%283%29_parotid_gland.jpg | PA. (WC)
Image:Pleomorphic_adenoma_%284%29_parotid_gland.jpg | PA. (WC)
</gallery>
www:
*[http://www.webpathology.com/image.asp?n=7&Case=111 PA - myxoid stroma (webpathology.com)].
 
===IHC===
*S-100 +ve, SMA +ve, GFAP +ve.


==Myoepithelioma==
==Myoepithelioma==
===General===
{{Main|Myoepithelioma}}
*Usually benign.
**May be malignant.
 
Location:<ref name=pmid2982059>{{Cite journal  | last1 = Barnes | first1 = L. | last2 = Appel | first2 = BN. | last3 = Perez | first3 = H. | last4 = El-Attar | first4 = AM. | title = Myoepithelioma of the head and neck: case report and review. | journal = J Surg Oncol | volume = 28 | issue = 1 | pages = 21-8 | month = Jan | year = 1985 | doi =  | PMID = 2982059 }}</ref>
*Parotid gland ~50%.
*Palate ~25%
*Submandibular gland ~12%.
 
Notes:
*First described in 1972.<ref name=pmid5075358>{{Cite journal  | last1 = Saksela | first1 = E. | last2 = Tarkkanen | first2 = J. | last3 = Wartiovaara | first3 = J. | title = Parotid clear-cell adenoma of possible myoepithelial origin. | journal = Cancer | volume = 30 | issue = 3 | pages = 742-8 | month = Sep | year = 1972 | doi =  | PMID = 5075358 }}</ref>
===Microsopic===
Features:<ref name=Ref_DCHH130>{{Ref DCHH|130}}</ref>
*Myoepithelial cells - may be:
**Spindled.
**Plasmacytoid.
**Epithelioid.
**Clear (rare).
*Lack tubules, i.e. epithelial component.
**May be up to 10% (or 5%<ref>I. Weinreb. 24 October 2011.</ref>).
 
DDx:
*[[Pleomorphic adenoma]].
 
====Images====
<gallery>
Image: Myoepithelioma - low mag.jpg | Myoepithelioma - low mag. (WC/Nephron)
Image: Myoepithelioma_-_intermed_mag.jpg | Myoepithelioma - intermed. mag. (WC/Nephron)
Image: Myoepithelioma - high mag.jpg | Myoepithelioma - high mag. (WC/Nephron)
Image: Myoepithelioma_-_very_high_mag.jpg | Myoepithelioma - very high mag. (WC/Nephron)
</gallery>
 
===IHC===
Features:<ref name=Ref_DCHH130>{{Ref DCHH|130}}</ref>
*S100 +ve.
*GFAP +ve.
*CK14 +ve.
 
Others:<ref name=Ref_DCHH18>{{Ref DCHH|18}}</ref>
*SMA +ve.
*Calponin +ve.


==Basal cell adenoma==
==Basal cell adenoma==
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*Luminal stains +ve: CK7 +ve, CAM5.2 +ve.
*Luminal stains +ve: CK7 +ve, CAM5.2 +ve.
*p63 +ve -- basal component.
*p63 +ve -- basal component.
*S100 +ve -- spindle cells in the stroma.
*[[S-100]] +ve -- spindle cells in the stroma.


==Canalicular adenoma==
==Canalicular adenoma==
===General===
{{Main|Canalicular adenoma}}
*Exclusively oral cavity.
**80% of lesions on upper lip.
 
===Microscopic===
Features:
*Channels - "beading of cell".
*Mucoid/hemorrhagic stroma.
 
DDx:
*Basal cell adenoma.
 
Images:
*[http://www.webpathology.com/image.asp?n=1&Case=116 Canalicular adenoma - low mag. (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=116&n=2 Canalicular adenoma - high mag. (webpathology.com)].
 
===IHC===
*p63 -ve.
**Basal cell adenoma p63 +ve.


==Warthin tumour==
==Warthin tumour==
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==Sebaceous lymphadenoma==
==Sebaceous lymphadenoma==
===General===
{{Main|Sebaceous lymphadenoma}}
*Rare salivary gland tumour.<ref name=pmid21393895/>
*Benign.
 
===Microscopic===
Features:<ref name=pmid21393895>{{Cite journal  | last1 = Mishra | first1 = A. | last2 = Tripathi | first2 = K. | last3 = Mohanty | first3 = L. | last4 = Nayak | first4 = M. | title = Sebaceous lymphadenoma of the parotid gland. | journal = Indian J Pathol Microbiol | volume = 54 | issue = 1 | pages = 131-2 | month =  | year =  | doi = 10.4103/0377-4929.77364 | PMID = 21393895 | url = http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2011;volume=54;issue=1;spage=131;epage=132;aulast=Mishra }}</ref>
*Sebaceous glands within lymphoid tissue - '''key feature'''.
 
DDx:<ref name=pmid20737364>{{Cite journal  | last1 = While | first1 = B. | last2 = Whiteside | first2 = OJ. | last3 = Desai | first3 = V. | last4 = Gurr | first4 = P. | title = Sebaceous lymphadenoma: a case report and review of the literature. | journal = Ear Nose Throat J | volume = 89 | issue = 8 | pages = E22-3 | month = Aug | year = 2010 | doi =  | PMID = 20737364 }}</ref>
*[[Warthin tumour]].
*Sebaceous lymphadenocarcinoma.
*[[Mucoepidermoid carcinoma]].
*Lymphoma.
 
====Images====
<gallery>
Image:Sebaceous_lymphadenoma_-_low_mag.jpg| Sebaceous lymphadenoma - low mag. (WC/Nephron)
Image:Sebaceous_lymphadenoma_-_intermed_mag.jpg| Sebaceous lymphadenoma - intermed. mag. (WC/Nephron)
Image:Sebaceous_lymphadenoma_-_high_mag.jpg| Sebaceous lymphadenoma - high mag. (WC/Nephron)
Image:Sebaceous_lymphadenoma_-_very_high_mag.jpg| Sebaceous lymphadenoma - very high mag. (WC/Nephron)
</gallery>
www:
*[http://path.upmc.edu/cases/case281.html Sebaceous lymphadenoma (upmc.edu)].


==Oncocytoma of the salivary gland==
==Oncocytoma of the salivary gland==
*[[AKA]] ''salivary gland oncocytoma''.
*[[AKA]] ''salivary gland oncocytoma''.
===General===
{{Main|Oncocytoma of the salivary gland}}
*No risk of malignant transformation.
*~1% of all salivary gland tumours.
*Typical age: 60s-80s.
*Associated with radiation exposure.
*Major salivary glands - usually parotid gland.<ref name=pmid19796983>{{Cite journal  | last1 = Zhou | first1 = CX. | last2 = Gao | first2 = Y. | title = Oncocytoma of the salivary glands: a clinicopathologic and immunohistochemical study. | journal = Oral Oncol | volume = 45 | issue = 12 | pages = e232-8 | month = Dec | year = 2009 | doi = 10.1016/j.oraloncology.2009.08.004 | PMID = 19796983 }}</ref>
 
===Gross===
*Golden brown appearance.
 
====Image====
<gallery>
Image:Oncocytoma_of_the_Salivary_Gland.jpg | Salivary gland oncocytoma (WC/euthman)
</gallery>
===Microscopic===
Features:
*Like [[oncocytoma]]s elsewhere.
**Eosinophilic cytoplasm (on [[H&E stain]]).
***Due to increased number of mitochrondria.
**Fine capillaries.
*Architecture: solid sheets, trabeculae or duct-like structure.<ref name=pmid19796983/>
 
Notes:
*May have clear cell change.
*Multiple small incidental lesions = oncocytosis - ''not'' oncocytoma.
 
DDx:
*[[Acinic cell carcinoma]].
 
====Images====
www:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807526/figure/Fig1/ Salivary gland oncocytoma (nih.gov)].<ref name=pmid20614263/>
<gallery>
Image:Parotid_gland_oncocytoma_-_intermed_mag.jpg | Parotid gland oncocytoma - intermed. mag. (WC/Nephron)
Image: Parotid gland oncocytoma - high mag.jpg | Parotid gland oncocytoma - high mag. (WC/Nephron)
Image:Parotid_gland_oncocytoma_-_very_high_mag.jpg | Parotid gland oncocytoma - very high mag. (WC/Nephron)
</gallery>
 
===IHC===
*p63 +ve<ref name=pmid20614263>{{Cite journal  | last1 = McHugh | first1 = JB. | last2 = Hoschar | first2 = AP. | last3 = Dvorakova | first3 = M. | last4 = Parwani | first4 = AV. | last5 = Barnes | first5 = EL. | last6 = Seethala | first6 = RR. | title = p63 immunohistochemistry differentiates salivary gland oncocytoma and oncocytic carcinoma from metastatic renal cell carcinoma. | journal = Head Neck Pathol | volume = 1 | issue = 2 | pages = 123-31 | month = Dec | year = 2007 | doi = 10.1007/s12105-007-0031-4 | PMID = 20614263 | PMC = 2807526}}</ref> focally in nucleus.


=Malignant=
=Malignant=
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==Mucoepidermoid carcinoma==
==Mucoepidermoid carcinoma==
*Abbreviated ''MEC''.
{{Main|Mucoepidermoid carcinoma}}
 
===General===
*Most common malignant neoplasm of salivary gland in all age groups.<ref>URL: [http://path.upmc.edu/cases/case715/dx.html http://path.upmc.edu/cases/case715/dx.html]. Accessed on: 2 February 2012.</ref>
*Female:male ~= 3:2.
*Site: parotid > submandibular.
 
===Gross===
*Cystic or solid, usu. a mix of both.
 
===Microscopic===
Features:
*Architecture:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/D2A001-PQ01-M.htm http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/D2A001-PQ01-M.htm]. Accessed on: 19 October 2010.</ref>
**Cystic (low grade).
**Solid (high grade).
*Mucous cells with abundant fluffy cytoplasm and large mucin vacuoles - '''key feature'''.
**Nucleus distorted by mucin vacuole.
**Mucous cell may be scarce - more difficult to diagnose.
*Epidermoid cells:
**Non-keratinized, polygonal squamoid cell with clear or oncocytic cytoplasm.
***Clear cells contain glycogen ([[PAS]] +ve, [[PAS-D]] -ve).
 
Notes:
*The classic description - composed of 3 cell types: epidermoid, intermediate, and mucin producing.<ref>{{Cite journal  | last1 = Lennerz | first1 = JK. | last2 = Perry | first2 = A. | last3 = Mills | first3 = JC. | last4 = Huettner | first4 = PC. | last5 = Pfeifer | first5 = JD. | title = Mucoepidermoid carcinoma of the cervix: another tumor with the t(11;19)-associated CRTC1-MAML2 gene fusion. | journal = Am J Surg Pathol | volume = 33 | issue = 6 | pages = 835-43 | month = Jun | year = 2009 | doi = 10.1097/PAS.0b013e318190cf5b | PMID = 19092631 }}</ref>
**"Intermediate cells" are described in textbooks. Weinreb thinks they are a pretty much a myth.<ref name=IW_10jan2011>IW. 10 January 2011.</ref>
*Mucin vacuoles may be rare; in a superficial glance -- it may mimic [[squamous cell carcinoma]].
*The thought of high-grade MEC should prompt consideration of squamous cell carcinoma.
 
====Images====
<gallery>
Image:Mucoepidermoid_carcinoma_%282%29_HE_stain.jpg | Mucoepidermoid carcinoma 2. (WC)
Image:Mucoepidermoid_carcinoma_%283%29_HE_stain.jpg | Mucoepidermoid carcinoma 3. (WC)
Image:Mucoepidermoid_carcinoma_-_2_-_intermed_mag.jpg | Mucoepidermoid carcinoma - 2 - intermed. mag. (WC/Nephron)
Image:Mucoepidermoid_carcinoma_-_2_-_high_mag.jpg | Mucoepidermoid carcinoma - 2 - high mag. (WC/Nephron)
Image:Mucoepidermoid_carcinoma_-_2a_-_very_high_mag.jpg | Mucoepidermoid carcinoma - 2 - very high mag. (WC/Nephron)
</gallery>
www:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/D2A001-PQ01-M.htm Mucoepidermoid carcinoma (ouhsc.edu)].
 
====Subtypes====
*Conventional.
*Oncocytic.
**Definition: composed of 50% oncocytes.
**Good outcome.<ref name=pmid18971778>{{cite journal |author=Weinreb I, Seethala RR, Perez-Ordoñez B, Chetty R, Hoschar AP, Hunt JL |title=Oncocytic mucoepidermoid carcinoma: clinicopathologic description in a series of 12 cases |journal=Am. J. Surg. Pathol. |volume=33 |issue=3 |pages=409–16 |year=2009 |month=March |pmid=18971778 |doi=10.1097/PAS.0b013e318184b36d |url=}}</ref>
*Clear cell.
*Unicystic (cystadenocarcinoma).
**Based on the gross. (???)
*Sclerosing MEC +/- eosinophilia.
**Rare.
 
====Grading====
General:
*Two competing system exist:
**AFIP.<ref name=pmid9529011>{{cite journal |author=Goode RK, Auclair PL, Ellis GL |title=Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria |journal=Cancer |volume=82 |issue=7 |pages=1217–24 |year=1998 |month=April |pmid=9529011 |doi= |url=}}</ref>
**Brandwein.<ref name=pmid11420454>{{cite journal |author=Brandwein MS, Ivanov K, Wallace DI, ''et al.'' |title=Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading |journal=Am. J. Surg. Pathol. |volume=25 |issue=7 |pages=835–45 |year=2001 |month=July |pmid=11420454 |doi= |url=}}</ref>
 
Notes:
*Both systems have their pros and cons.
*Weinreb uses the AFIP system with a slight modification.
 
=====AFIP=====
#Low cystic content (<20%) - 2 points.
#[[Perineural invasion]] - 2 points.
#[[Necrosis]] - 3 points.
#Mitoses > 4 per 10 HPFs (HPF not defined in paper - see [[HPFitis]]) - 3 points.
#Anaplasia - 4 points.
 
Scoring:
*Low grade = 0-4 points.
*Intermediate grade = 5-6 points.
*High grade = 7+ points.
 
======Weinreb modification======
Weinreb looks for the following:
*Tumour invades in small nests/islands - 2 points.
**If applicable, the two points are added to the AFIP score.
**The tumour is graded using the AFIP (scoring) cut points -- see above.
 
Notes:
*It seems pointless to memorize this but it is occasionally asked on exams.
**How to remember: think of the Nottingham grading system (architecture, mitoses, nuclear grade) + necrosis + LVI.
 
===Stains===
Mucous cells:
*Alcian blue +ve.
*Mucicarcmine +ve.
 
===Molecular===
*t(11;19)(q21;p13) -- MECT1-MAML2 fusion.<ref name=pmid12539049>{{cite journal |author=Tonon G, Modi S, Wu L, ''et al.'' |title=t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway |journal=Nat. Genet. |volume=33 |issue=2 |pages=208–13 |year=2003 |month=February |pmid=12539049 |doi=10.1038/ng1083 |url=}}</ref><ref name=pmid20588178>{{cite journal |author=Seethala RR, Dacic S, Cieply K, Kelly LM, Nikiforova MN |title=A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas |journal=Am. J. Surg. Pathol. |volume=34 |issue=8 |pages=1106–21 |year=2010 |month=August |pmid=20588178 |doi=10.1097/PAS.0b013e3181de3021 |url=}}</ref>
**Present in ~65% of MECs.
**Presence assoc. with low-grade MEC (vs. high-grade MEC) & favourable prognosis.
**Not seen in tumours that are in the DDx of MEC.


==Acinic cell carcinoma==
==Acinic cell carcinoma==
:'''Not''' to be confused with ''[[pancreatic acinar cell carcinoma]]''.
{{Main|Acinic cell carcinoma}}
*Abbreviated ''AcCC''.
*[[AKA]] ''acinic cell adenocarcinoma''.
 
===General===
*Malignant neoplasm of salivary gland arising from acinic cells.
*The relative prevalence of the neoplasm in the various salivary gland reflects the abundance of acinic cells: parotid gland (~80%) > minor salivary glands (~17%) > submandibular glands (~3%).
*Affects wide age range -- including children.
*Site affect prognosis (most aggressive to least aggressive): submandibular > parotid > minor salivary.
===Gross===
*Tan or reddish.
 
===Microscopic===
Features:
*Sheets of acinic cells with:
**Abundant finely vacuolated cytoplasm with basophilic granules - '''key feature'''.
***Granules may be focal.
**Small nuclei stippled chromatin.
*Scattered intercalcated duct type cells with:
**Eosinophilic cytoplasm with moderate amount of cytoplasm.
**Bland nuclei with slightly larger than seen in acinic cells.
*+/-Peri-tumoural lymphocytes.
*+/-Glassy extracellular bluish/purple blobs.
 
Notes:
*Adipose tissue -- present in the salivary glands -- is absent in AcCC.
*May focally resemble thyroid tissue.
*Smaller (characteristic) microvacuoles (unreported in the literature) may be present that have a bubbly appearance and glassy basophilic inclusions.<ref name=IW_10jan2011>IW. 11 January 2011.</ref>
 
Memory device:
*AcCC - lots of "C"s - '''c'''hromatin stipled, '''c'''ytoplasm generous.
 
DDx:
*[[Oncocytoma of the salivary gland]].
*Adenocarcinoma not otherwise specified.<ref name=pmid12608654>{{Cite journal  | last1 = Ihrler | first1 = S. | last2 = Blasenbreu-Vogt | first2 = S. | last3 = Sendelhofert | first3 = A. | last4 = Lang | first4 = S. | last5 = Zietz | first5 = C. | last6 = Löhrs | first6 = U. | title = Differential diagnosis of salivary acinic cell carcinoma and adenocarcinoma (NOS). A comparison of (immuno-)histochemical markers. | journal = Pathol Res Pract | volume = 198 | issue = 12 | pages = 777-83 | month =  | year = 2002 | doi =  | PMID = 12608654 }}</ref>
 
====Images====
<gallery>
Image:Acinic_cell_carcinoma_-_intermed_mag.jpg | AcCC - intermed. mag. (WC/Nephron)
Image:Acinic_cell_carcinoma_-_high_mag.jpg | AcCC - high mag. (WC/Nephron)
Image:Acinic_cell_carcinoma_-_very_high_mag.jpg | AcCC - very high mag. (WC/Nephron)
</gallery>
www:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=20080802170246445 AcCC (surgicalpathologyatlas.com)].
*[http://www.brown.edu/Courses/Digital_Path/systemic_path/hn/acinic.html AcCC (brown.edu)].
*[http://www.aciniccell.org/acc_images14.html AcCC (aciniccell.org)] - image collection.
 
====Grading====
General:
*Not prognostic.
*Done to avoid phone calls from clinician.
 
Factors Weinreb uses:<ref name=IW_10jan2011>IW. 11 January 2011.</ref>
*[[Necrosis]].
*Nuclear atypia.
*[[Perineural invasion]].
*[[Mitoses]].
*Infiltrative margin.
*Tumour sclerosis.
 
====Subtypes====
*Oncocytic variant - rare.
*Clear cell variant - rare.
*Papillary cystic variant.
 
===Stains===
*PAS +ve.
*PAS-D +ve.
 
===IHC===
*S-100 -ve.
*p63 -ve.
**p63 +ve in mucoepidermoid carcinoma.
 
There are a bunch of other [[stains]] that are touted to be useful (amylase, anti-chymotrypsin, lactoferrin). Weinreb thinks these are '''not''' helpful.<ref name=IW_10jan2011>IW. 11 January 2011.</ref>
 
===EM===
*[[Zymogen granules]].<ref name=pmid14991547>{{Cite journal  | last1 = Sun | first1 = Y. | last2 = Wasserman | first2 = PG. | title = Acinar cell carcinoma arising in the stomach: a case report with literature review. | journal = Hum Pathol | volume = 35 | issue = 2 | pages = 263-5 | month = Feb | year = 2004 | doi =  | PMID = 14991547 }}</ref>


==Adenoid cystic carcinoma==
==Adenoid cystic carcinoma==
:See: ''[[Adenoid cystic carcinoma of the breast]]'' for the [[breast]] tumour.
{{Main|Adenoid cystic carcinoma}}
{{Main|Adenoid cystic carcinoma}}
Note: The [[breast]] tumour is dealt with in ''[[adenoid cystic carcinoma of the breast]]''.


==Salivary duct carcinoma==
==Salivary duct carcinoma==
{{Main|Salivary duct carcinoma}}
{{Main|Salivary duct carcinoma}}
==Intraductal carcinoma of the salivary gland==
{{Main|Intraductal carcinoma of the salivary gland}}


==Polymorphous low-grade adenocarcinoma==
==Polymorphous low-grade adenocarcinoma==
*Abbreviated ''PLGA''.
*Abbreviated ''PLGA''.
 
{{Main|Polymorphous low-grade adenocarcinoma}}
===General===
*Almost exclusively in the oral cavity.
**Classically found in the palate -- 60% of PLGAs in palate.
*Tumour of the minor salivary glands.
*Always a low-grade tumour - by definition.
*Female:male ~= 2:1.
*Older people ~50-70 years old.
 
===Microscopic===
Features:<ref name=Ref_WMSP74>{{Ref WMSP|74}} <!-- Mike S. --></ref>
*Architecture: often small nests, may be targetoid.
**Classically has whorling with '''eye-of-storm''' & '''single file'''.
*Cytologically monotonous (uniform) with variable architecture - '''key feature'''.
**Nucleus: ovoid & small, small nucleoli, powdery chromatin.
***'''[[Papillary thyroid carcinoma]]-like appearance'''.
**Cytoplasm: eosinophilic.
*Indistinct cell borders.
 
DDx:
*[[Adenoid cystic carcinoma]].
*[[Pleomorphic adenoma]].
*Cribriform adenocarcinoma of the minor salivary gland.<ref name=pmid21716087>{{Cite journal  | last1 = Skalova | first1 = A. | last2 = Sima | first2 = R. | last3 = Kaspirkova-Nemcova | first3 = J. | last4 = Simpson | first4 = RH. | last5 = Elmberger | first5 = G. | last6 = Leivo | first6 = I. | last7 = Di Palma | first7 = S. | last8 = Jirasek | first8 = T. | last9 = Gnepp | first9 = DR. | title = Cribriform adenocarcinoma of minor salivary gland origin principally affecting the tongue: characterization of new entity. | journal = Am J Surg Pathol | volume = 35 | issue = 8 | pages = 1168-76 | month = Aug | year = 2011 | doi = 10.1097/PAS.0b013e31821e1f54 | PMID = 21716087 }}
</ref>
 
====Images====
<gallery>
Image:Polymorphous_low-grade_adenocarcinoma_-_very_low_mag.jpg | PLGA - very low mag. (WC/Nephron)
Image:Polymorphous_low-grade_adenocarcinoma_high_mag.jpg | PLGA - high mag. (WC/Nephron)
</gallery>
===IHC===
*S100 +ve, CK +ve, vimentin +ve.
*GFAP +ve/-ve.
*BCL2 +ve/-ve.
*Generally negative for myoepithelial markers (calponin, actin) - '''useful if negative'''.


==Carcinoma ex pleomorphic adenoma==
==Carcinoma ex pleomorphic adenoma==
*Abbreviated ''Ca ex PA''.
*Abbreviated ''Ca ex PA''.
 
{{Main|Carcinoma ex pleomorphic adenoma}}
===General===
Definition:
*Malignant transformation of a ''[[pleomorphic adenoma]]''.
 
Diagnosis (either 1 or 2):
#History of a pleomorphic adenoma at the same site.
#Features of a pleomorphic adenoma and a carcinoma.
 
Epidemiology:
*Rare.
 
===Microscopic===
Features:
*Cells with cytologic features of malignancy.
*Architecture (any of the following):
**Glands.
**Nests.
**Single cells (may be subtle).
 
Architectural patterns:
*Ductal carcinoma NOS (arising from ductal cells) - most common pattern for Ca ex PA.
*Myoepithelial cacinoma NOS (arising from myoepithelial cells).
*"Named carcinoma":
**Salivary duct carcinoma - second most common pattern for Ca ex PA.
**Mucoepidermoid carcinoma.
**Adenoid cystic carcinoma.
 
Note:
*Often adenocarcinoma-like.
*Myoepithelial cells may be clear cells. (???)
 
====Subclassification====
Extent of invasion:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/MajorSalGlands_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/MajorSalGlands_11protocol.pdf]. Accessed on: 2 April 2012.</ref>
#Non-invasive [[AKA]] ''intracapsular'' [[AKA]] ''in situ''.
#Minimally invasive <=1.5 mm beyond the capsule.
#Widely invasive >1.5 mm beyond the capsule.


==Epithelial-myoepithelial carcinoma==
==Epithelial-myoepithelial carcinoma==
*Abbreviated ''EMCa''.
{{Main|Epithelial-myoepithelial carcinoma}}
 
===General===
*Rare ~1% of salivary gland tumours.<ref  name=pmid9568184>{{Cite journal  | last1 = Tralongo | first1 = V. | last2 = Daniele | first2 = E. | title = Epithelial-myoepithelial carcinoma of the salivary glands: a review of literature. | journal = Anticancer Res | volume = 18 | issue = 1B | pages = 603-8 | month =  | year =  | doi =  | PMID = 9568184 }}</ref>
*Female:male = 1.5:1.<ref name=pmid17197918>{{Cite journal  | last1 = Seethala | first1 = RR. | last2 = Barnes | first2 = EL. | last3 = Hunt | first3 = JL. | title = Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract. | journal = Am J Surg Pathol | volume = 31 | issue = 1 | pages = 44-57 | month = Jan | year = 2007 | doi = 10.1097/01.pas.0000213314.74423.d8 | PMID = 17197918 }}</ref>
*Usu. older people - 50s or 60s.
*Usu. parotid gland ~ 60% of cases.<ref name=pmid17197918/>
*Prognosis: usually good; 5-year and 10-year survival over 90% and 80% respectively.<ref name=pmid17197918/>
 
Notes:
*Most common malignant component in ''[[carcinoma ex pleomorphic adenoma]]''.
*May be the same tumour as ''[[adenomyoepithelioma]] of the breast''.<ref name=pmid9769134>{{Cite journal  | last1 = Seifert | first1 = G. | title = Are adenomyoepithelioma of the breast and epithelial-myoepithelial carcinoma of the salivary glands identical tumours? | journal = Virchows Arch | volume = 433 | issue = 3 | pages = 285-8 | month = Sep | year = 1998 | doi =  | PMID = 9769134 }}</ref>
 
===Microscopic===
Features:
*Biphasic tumour:<ref name=pmid17197918/>
*#Epithelial layer.
*#Myoepithelial layer - '''key feature'''.
*Architecture: variable (solid, cystic, tubular, papillary).
*+/-Spindle cells.
*Basement membrane-like material; may mimic adenoid cystic carcinoma.
 
Notes:
*Usually few mitoses.
 
DDx:
*[[Adenoid cystic carcinoma]] (tubular variant).
*[[Pleomorphic adenoma]], tubular variant.
**Has focal epithelial-myoepithelial carcinoma-like areas.
 
====Images====
<gallery>
Image:Epithelial-myoepithelial_carcinoma_-_intermed_mag.jpg | EMCa - intermed. mag. (WC/Nephron)
Image:Epithelial-myoepithelial_carcinoma_-_high_mag.jpg | EMCa - high mag. (WC/Nephron)
Image:Epithelial-myoepithelial carcinoma - very high mag.jpg | EMCa - very high mag. (WC/Nephron)
</gallery>
www:
*[http://www.pathologyimagesinc.com/sgt-cytopath/epith-myoepith-ca/cytopathology/images-features/emc-rev-cyto1-18.jpg EMCa  (pathologyimagesinc.com)].<ref>{{cite web |url=http://www.pathologyimagesinc.com/sgt-cytopath/epith-myoepith-ca/cytopathology/fs-emc-cytopath-feat.html |title=Cytopathologic Features of
Epithelial-myoepithelial Carcinoma |last1= |first1= |last2= |first2= |date= |work= |publisher= |accessdate=January 18, 2011}}</ref>
*[http://www.headandneckoncology.org/content/2/1/4 EMCa (headandneckoncology.org)].
 
===IHC===
*CAM5.2 +ve -- epithelial component.
*p63 +ve -- myoepithelial component.


==Basal cell adenocarcinoma==
==Basal cell adenocarcinoma==
*Abbreviated ''BCAC''.
{{Main|Basal cell adenocarcinoma}}
===General===
*Very rare.
*Malignant.
*Good prognosis.
*May arise from a ''[[basal cell adenoma]]''.<ref name=pmid8952553/>
 
===Gross===
*Usually in the parotid gland ~90% of cases.<ref name=pmid8952553>{{Cite journal  | last1 = Muller | first1 = S. | last2 = Barnes | first2 = L. | title = Basal cell adenocarcinoma of the salivary glands. Report of seven cases and review of the literature. | journal = Cancer | volume = 78 | issue = 12 | pages = 2471-7 | month = Dec | year = 1996 | doi =  | PMID = 8952553 }}</ref>
 
===Microscopic===
Features:
#Lesion is '''not''' encapsulated - '''key feature'''.
#Basal-like cells:
#*Basophilic cells - '''key feature'''.
#*Usually in nests.
#**May be bilayered tubules ''or'' [[trabeculae]].
#*Large basophilic nucleus.
#*Minimal-to-moderate eosinophilic cytoplasm.
#Stromal cells.
#*Plump spindle cells without significant nuclear atypia.
#**Stromal cell nuclei width ~= diameter [[RBC]].
#*Dense hyaline stroma.
#Tubular component.
#*Within basal component, may be minimal.
 
DDx:
*[[Adenoid cystic carcinoma]].
*[[Basal cell adenoma]] - encapsulated.
*Basaloid [[squamous cell carcinoma]].
 
====Images====
<gallery>
Image:Basal_cell_adenocarcinoma_-_parotid_gland_-_intermed_mag.jpg | BCAC - intermed. mag. (WC/Nephron)
Image:Basal_cell_adenocarcinoma_-_parotid_gland_-_high_mag.jpg | BCAC - high mag. (WC/Nephron)
Image:Basal_cell_adenocarcinoma_-_2_-_parotid_gland_-_high_mag.jpg | BCAC - high mag. (WC/Nephron)
</gallery>
www:
*[http://www.webpathology.com/image.asp?n=5&Case=115 Basal cell adenocarcinoma - intermed. mag. (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=6&Case=115 Basal cell adenocarcinoma - high mag. (webpathology.com)].
 
===IHC===
Features:<ref name=pmid17922602>{{Cite journal  | last1 = Farrell | first1 = T. | last2 = Chang | first2 = YL. | title = Basal cell adenocarcinoma of minor salivary glands. | journal = Arch Pathol Lab Med | volume = 131 | issue = 10 | pages = 1602-4 | month = Oct | year = 2007 | doi = 10.1043/1543-2165(2007)131[1602:BCAOMS]2.0.CO;2 | PMID = 17922602 }}</ref>
*CK7 +ve (strong).
*S100 +ve/-ve.


==Sebaceous carcinoma==
==Sebaceous carcinoma==
Line 896: Line 406:


==Hyalinizing clear cell carcinoma==
==Hyalinizing clear cell carcinoma==
*Abbreviated ''HCCC''.
{{Main|Hyalinizing clear cell carcinoma}}
 
===General===
*Rare.
*Good prognosis.<ref name=pmid21393908>{{Cite journal  | last1 = Masilamani | first1 = S. | last2 = Rao | first2 = S. | last3 = Chirakkal | first3 = P. | last4 = Kumar | first4 = AR. | title = Hyalinizing clear cell carcinoma of the base of tongue: a distinct and rare entity. | journal = Indian J Pathol Microbiol | volume = 54 | issue = 1 | pages = 167-9 | month =  | year =  | doi = 10.4103/0377-4929.77393 | PMID = 21393908 }}</ref>
*Typically palate or tongue.<ref name=pmid21669357>{{Cite journal  | last1 = Kauzman | first1 = A. | last2 = Tabet | first2 = JC. | last3 = Stiharu | first3 = TI. | title = Hyalinizing clear cell carcinoma: a case report and review of the literature. | journal = Oral Surg Oral Med Oral Pathol Oral Radiol Endod | volume = 112 | issue = 1 | pages = e26-34 | month = Jul | year = 2011 | doi = 10.1016/j.tripleo.2011.02.041 | PMID = 21669357 }}</ref>
 
===Microscopic===
Features:<ref name=pmid20596970>{{Cite journal  | last1 = O'Sullivan-Mejia | first1 = ED. | last2 = Massey | first2 = HD. | last3 = Faquin | first3 = WC. | last4 = Powers | first4 = CN. | title = Hyalinizing clear cell carcinoma: report of eight cases and a review of literature. | journal = Head Neck Pathol | volume = 3 | issue = 3 | pages = 179-85 | month = Sep | year = 2009 | doi = 10.1007/s12105-009-0124-3 | PMID = 20596970 }}</ref>
*Groups of cells with abundant clear cytoplasm.
**Arranged in cords, trabeculae or clusters.
**Minimal [[nuclear pleomorphism]].<ref name=pmid7506496/>
*Hyalinized stroma.
 
Notes:
*Clear cytoplasm due to glycogen.<ref name=pmid7506496>{{Cite journal  | last1 = Milchgrub | first1 = S. | last2 = Gnepp | first2 = DR. | last3 = Vuitch | first3 = F. | last4 = Delgado | first4 = R. | last5 = Albores-Saavedra | first5 = J. | title = Hyalinizing clear cell carcinoma of salivary gland. | journal = Am J Surg Pathol | volume = 18 | issue = 1 | pages = 74-82 | month = Jan | year = 1994 | doi =  | PMID = 7506496 }}</ref>
*Low mitotic rate.
 
DDx:
*[[Mucoepidermoid carcinoma]], clear cell variant.
*[[Acinic cell carcinoma]], clear cell variant.
*Metastatic [[clear cell renal cell carcinoma]].
**Classically have hemorrhage & [[necrosis]].
*[[Epithelial-myoepithelial carcinoma]].
 
====Images====
<gallery>
Image:Hyalinizing_clear_cell_carcinoma_-_intermed_mag.jpg | HCCC - intermed. mag. (WC/Nephron)
Image:Hyalinizing_clear_cell_carcinoma_-_very_high_mag.jpg | HCCC - very high mag. (WC/Nephron)
</gallery>
www:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811632/figure/Fig2/ HCCC (nlm.nih.gov)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811632/figure/Fig5/ HCCC (nlm.nih.gov)].<ref name=pmid20596970/>
===Stains/IHC===
*PAS +ve.
*AE1/AE3 +ve.
*EMA +ve.<ref name=pmid7506496/>
 
Others:
*Desmin -ve.
*SMA -ve.<ref name=pmid7506496/>
*S-100 -ve.<ref name=pmid7506496>{{Cite journal  | last1 = Milchgrub | first1 = S. | last2 = Gnepp | first2 = DR. | last3 = Vuitch | first3 = F. | last4 = Delgado | first4 = R. | last5 = Albores-Saavedra | first5 = J. | title = Hyalinizing clear cell carcinoma of salivary gland. | journal = Am J Surg Pathol | volume = 18 | issue = 1 | pages = 74-82 | month = Jan | year = 1994 | doi =  | PMID = 7506496 }}</ref>
 
===Molecular===
Recurrent [[translocation]]:<ref name=pmid21484932>{{Cite journal  | last1 = Antonescu | first1 = CR. | last2 = Katabi | first2 = N. | last3 = Zhang | first3 = L. | last4 = Sung | first4 = YS. | last5 = Seethala | first5 = RR. | last6 = Jordan | first6 = RC. | last7 = Perez-Ordoñez | first7 = B. | last8 = Have | first8 = C. | last9 = Asa | first9 = SL. | title = EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. | journal = Genes Chromosomes Cancer | volume = 50 | issue = 7 | pages = 559-70 | month = Jul | year = 2011 | doi = 10.1002/gcc.20881 | PMID = 21484932 }}</ref>
*t(12;22) -- EWSR1/ATF1.
**Same translocation as in ''[[clear cell sarcoma]]''.


=See also=
=See also=
Line 955: Line 419:


[[Category:Head and neck pathology]]
[[Category:Head and neck pathology]]
[[Category:Salivary gland|Salivary gland]]
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