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.  


=Normal=
The [[cytopathology]] of the salivary glands is covered in the ''[[Head and neck cytopathology]]'' article.
 
=Normal salivary glands=
==Types of salivary glands==
==Types of salivary glands==
Types of glands:<ref>[http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Oral/oral.htm#LABSALIVA http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Oral/oral.htm#LABSALIVA]</ref>
Types of glands:<ref>[http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Oral/oral.htm#LABSALIVA http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Oral/oral.htm#LABSALIVA]</ref>
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==Benign tumours==
==Benign tumours==
'''Tabular form - adapted from Thompson<ref>{{Ref HaNP|295-319}}</ref>'''
'''Tabular form - adapted from Thompson<ref>{{Ref HaNP|295-319}}</ref>'''
{| class="wikitable"
{| class="wikitable sortable"
|
! Entity
| '''Architecture'''
! Architecture
| '''Morphology'''
! Morphology
| '''Cell borders'''
! Cell borders
| '''Cytoplasm'''
! Cytoplasm
| '''Nucleus'''
! Nucleus  
| '''DDx'''
! DDx
| '''Other'''
! Other
| '''Image'''
! Image
|-
|-
|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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| [[adenoid cystic carcinoma]]
| [[adenoid cystic carcinoma]]
| occ. encapsulated, <br>mixed pop. of glandular, <br>myoepithelial and mesenchymal cells
| occ. encapsulated, <br>mixed pop. of glandular, <br>myoepithelial and mesenchymal cells
| [http://en.wikipedia.org/wiki/File:Pleomorphic_adenoma_(1)_parotid_gland.jpg (WP)]
| [[Image:Pleomorphic_adenoma_(1)_parotid_gland.jpg | thumb | center |150px| PA. (WP)]]
|-
|-
|Warthin tumour
|[[Warthin tumour]]
| papillary, <br>'''bilayer'''  
| papillary, <br>'''bilayer'''  
| cuboid (basal), columnar (apical)  
| cuboid (basal), columnar (apical)  
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| [[sebaceous lymphadenoma]]  
| [[sebaceous lymphadenoma]]  
| AKA ''papillary cystadenoma lymphomatosum''
| AKA ''papillary cystadenoma lymphomatosum''
| [http://en.wikipedia.org/wiki/File:Papillary_cystadenoma_lymphomatosum2.jpg (WP)], [http://commons.wikimedia.org/wiki/File:Papillary_cystadenoma_lymphomatosum3.jpg (WP)]  
| [[Image:Papillary_cystadenoma_lymphomatosum2.jpg| thumb| center | 150px| PCL. (WP/Nephron)]]
|-
|-
|Basal cell adenoma
|[[Basal cell adenoma]]
| var., '''islands surrounded'''<br>'''by hyaline bands'''
| var., '''islands surrounded'''<br>'''by hyaline bands''', lesion encapsulated
| basaloid
| basaloid
| subtle
| subtle
| scant,<br>hyperchromatic
| scant,<br>hyperchromatic
| granular
| granular
| basal cell adenocarcinoma
| [[basal cell adenocarcinoma]]
| -
| -
| -  
| -  
|-
|-
|Canalicular adenoma
|[[Canalicular adenoma]]
| '''chains of cells'''
| '''chains of cells'''
| cuboid or columnar
| cuboid or columnar
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| scant,<br>hyperchromatic  
| scant,<br>hyperchromatic  
| granular
| granular
| basal cell adenoma
| [[basal cell adenoma]]
| exclusively oral cavity, 80% in upper lip; IHC: p63-
| exclusively oral cavity, 80% in upper lip; IHC: p63-
| -
| [[Image:Canalicular_adenoma_--_high_mag.jpg | thumb | center |150px| CA. (WC)]]
|-
|-
|Sialoblastoma
|[[Sialoblastoma]]
| var., '''islands surrounded'''<br>'''by loose fibrous stroma'''
| var., '''islands surrounded'''<br>'''by loose fibrous stroma'''
| basaloid
| basaloid
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| scant, hyperch.
| scant, hyperch.
| granular
| granular
| basal cell adenoca
| [[basal cell adenocarcinoma]]
| -
| -
| -
| -
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==Malignant tumours==
==Malignant tumours==
'''Tabular form - adapted from Thompson<ref>{{Ref HaNP|325-357}}</ref>'''
'''Tabular form - adapted from Thompson<ref>{{Ref HaNP|325-357}}</ref>'''
{| class="wikitable"
{| class="wikitable sortable"
|
! Entity
| '''Architecture'''
! Architecture
| '''Morphology'''
! Morphology
| '''Cell borders'''
! Cell borders
| '''Cytoplasm'''
! Cytoplasm
| '''Nucleus'''
! Nucleus  
| '''DDx'''
! DDx
| '''Other'''
! Other
| '''Image'''
! Image
|-
|-
|Mucoepidermoid carcinoma  
|[[Mucoepidermoid carcinoma]]
| cystic & solid
| cystic & solid
| epithelioid
| epithelioid
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| SCC (?)
| SCC (?)
| IHC: p63+
| IHC: p63+
| [http://commons.wikimedia.org/wiki/File:Mucoepidermoid_carcinoma_%282%29_HE_stain.jpg (WC)]
| [[Image:Mucoepidermoid_carcinoma_%282%29_HE_stain.jpg |thumb| center| 150px | MEC. (WC)]]
|-
|-
|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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| [[pleomorphic adenoma]], [[PLGA]]  
| [[pleomorphic adenoma]], [[PLGA]]  
| Stains: PAS+ (pseudocyst material), CD117+, cyclin D1+
| Stains: PAS+ (pseudocyst material), CD117+, cyclin D1+
| [http://commons.wikimedia.org/wiki/File:Adenoid_cystic_carcinoma_-_high_mag.jpg (WC)]  
| [[Image:Adenoid_cystic_carcinoma_-_high_mag.jpg|thumb|center|150px| AdCC. (WC/Nephron)]]  
|-
|-
|Acinic cell adenocarcinoma (AcCC)  
|[[Acinic cell carcinoma]] (AcCC)  
| sheets, acinar (islands)
| sheets, acinar (islands)
| epithelioid
| epithelioid
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| '''granular abundant'''
| '''granular abundant'''
| '''stippled''', +/-occ. nucleoli
| '''stippled''', +/-occ. nucleoli
| ?
| adenocarcinoma not otherwise specified, [[oncocytoma of salivary gland]]
| Stains: PAS +ve, PAS-D +ve; [[IHC]]: S-100 -ve, p63 -ve
| Stains: PAS +ve, PAS-D +ve; [[IHC]]: S-100 -ve, p63 -ve
| [http://www.brown.edu/Courses/Digital_Path/systemic_path/hn/acinic.html (brown.edu)]
| [[Image:Acinic_cell_carcinoma_-_high_mag.jpg | thumb| center|150px| AcCC. (WC/Nephron)]]
|-
|-
|Salivary duct carcinoma  
|[[Salivary duct carcinoma]]
| glandular, cribriform  
| glandular, [[cribriform]]
| columnar  
| columnar  
| subtle/clear  
| subtle/clear  
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| metastatic breast carcinoma  
| metastatic breast carcinoma  
| similar to ductal<br>breast carcinoma; male>female
| similar to ductal<br>breast carcinoma; male>female
| [http://commons.wikimedia.org/wiki/File:Salivary_duct_carcinoma_-a-_low_mag.jpg (WC)]
| [[Image:Salivary_duct_carcinoma_-a-_low_mag.jpg | thumb| center|150px | SDC. (WC/Nephron)]]
|-
|-
|Polymorphous low-grade adenocarcinoma  
|[[Polymorphous low-grade adenocarcinoma]]
| variable, often small<br>nests, may be targetoid  
| variable, often small<br>nests, may be targetoid  
| epithelioid  
| epithelioid  
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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+/-
| [http://commons.wikimedia.org/wiki/File:Polymorphous_low-grade_adenocarcinoma_-_very_low_mag.jpg (WC)]
| [[Image:Polymorphous_low-grade_adenocarcinoma_-_very_low_mag.jpg|thumb|center|150px|PLGA. (WC/Nephron)]]
|-
| [[Epithelial-myoepithelial carcinoma]]
| '''nests (myoepithelial) with tubules (epithelial)'''
| epithelioid
| not distinct
| eosinophilic cytoplasm; epithelial: scant; myoepithelial: moderate
| focal clearing
| [[AdCC]], [[pleomorphic adenoma]]
| rare
| [[Image:Epithelial-myoepithelial_carcinoma_-_high_mag.jpg |thumb|center|150px|EMCa. (WC/Nephron)]]
|-
|-
| [[Basal cell adenocarcinoma]]
| var., '''islands surrounded'''<br>'''by hyaline bands''', lesion '''not''' encapsulated
| basaloid
| subtle
| scant,<br>hyperchromatic
| granular
| [[basal cell adenoma]]
| rare, usu. parotid gland, may arise from a basal cell adenoma
| [[Image:Basal_cell_adenocarcinoma_-_parotid_gland_-_high_mag.jpg|thumb|center|150px|BCA. (WC/Nephron)]]
|}
|}


==DDx==
==DDx==
Palate:
===Palate===
*Polymorphous low-grade adenocarcinoma.
*[[Polymorphous low-grade adenocarcinoma]].
*Adenoid cystic carcinoma.
*[[Adenoid cystic carcinoma]].
*Pleomorphic adenoma.
*[[Pleomorphic adenoma]].
 
===Benign parotid tumours===
*[[Pleomorphic adenoma]].
*[[Warthin tumour]].
 
===Oncocytic tumours===
*Benign:
**Oncocytoma.
**[[Warthin tumour]].
*Malignant:
**[[Mucoepidermoid carcinoma]], oncocytic variant.
**[[Salivary duct carcinoma]].
**[[Carcinoma ex pleomorphic carcinoma]] with a salivary duct carcinoma component.
**[[Apocrine carcinoma]].
**Oncocytic carcinoma.
**[[Acinic cell carcinoma]], oncocytic variant.
 
===Clear cell tumours===
*[[Mucoepidermoid carcinoma]], clear cell variant.
*[[Acinic cell carcinoma]], clear cell variant.
*[[Hyalinizing clear cell carcinoma]].
*[[Epithelial-myoepithelial carcinoma]].
*Metastatic [[clear cell carcinoma]].
**Metastatic [[clear cell renal cell carcinoma]].


Parotid (benign):
===Basaloid neoplasms===
*Pleomorphic adenoma.
*[[Basal cell adenoma]].
*Warthin tumour.
*[[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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*Ductal obstrution.
*Ductal obstrution.


==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===
==Salivary gland mucocele==
Features:
{{Main|Salivary gland mucocele}}
*Fibrosis.
*Non-neoplastic mononuclear inflammatory infiltrate.
 
Image:
*[http://commons.wikimedia.org/wiki/File:Chronic_sialadenitis.jpg Chronic sialadenitis (WC)].
 
==Mucocele==
===General===
*Benign.
 
===Microscopic===
Features:
*Ball of mucous.


==Pleomorphic adenoma==
==Pleomorphic adenoma==
*Abbreviated ''PA''.
{{Main|Pleomorphic adenoma}}


===General===
==Myoepithelioma==
Features:
{{Main|Myoepithelioma}}
*Very common - approx. 60% of parotid gland tumours.<ref name=Ref_HaNP295>{{Ref HaNP|295}}</ref>
*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====
#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===
*May be cartilaginous appearing.
 
===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>IW. 10 January 2011.</ref>
*Mesenchymal stroma - '''important feature'''.
**May be any of following: myxoid, mucochondroid, hyalinized, osseous, fatty.
***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>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.
 
===IHC===
*S-100 +ve, SMA +ve, GFAP +ve.


==Basal cell adenoma==
==Basal cell adenoma==
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*~2% of salivary gland tumours.
*~2% of salivary gland tumours.
*May be multifocal.
*May be multifocal.
*Usu. parotid gland, occasionally submandibular gland.
*Usually parotid gland, occasionally submandibular gland.
*Female:male = ~2:1.
*Female:male = ~2:1.
*May be seen in association with dermal cylindromas in the context of a genetic mutation.
*May be seen in association with [[dermal cylindroma]]s in the context of a genetic mutation.<ref name=pmid12023583>{{Cite journal  | last1 = Choi | first1 = HR. | last2 = Batsakis | first2 = JG. | last3 = Callender | first3 = DL. | last4 = Prieto | first4 = VG. | last5 = Luna | first5 = MA. | last6 = El-Naggar | first6 = AK. | title = Molecular analysis of chromosome 16q regions in dermal analogue tumors of salivary glands: a genetic link to dermal cylindroma? | journal = Am J Surg Pathol | volume = 26 | issue = 6 | pages = 778-83 | month = Jun | year = 2002 | doi =  | PMID = 12023583 }}</ref>
*Malignant transformation - rarely.
*Malignant transformation - rarely.


===Microscopic===
===Microscopic===
Features:
Features:
*Basophilic cells.
#Basal component.
*Usu. nests; may be bilayered tubules ''or'' [[trabeculae]].
#*Basophilic cells - '''key feature'''.
#*Usu. 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 - '''distinguishing feature'''.
#**Stromal cell nuclei width ~= diameter [[RBC]].
#*Dense hyaline stroma.
#Tubular component.
#*Within basal component, may be minimal.
#Lesion is encapsulated - '''key feature'''.


Notes:
Notes:
*No chondromyxoid stroma.
*No chondromyxoid stroma.
**Chondromyxoid stroma present -> pleomorphic adenoma.
**Chondromyxoid stroma present -> [[pleomorphic adenoma]].
*Neoplastic cells embeded in stroma ("stromal invasion") = basal cell adenocarcinoma.
*Neoplastic cells embedded in stroma ("stromal invasion") = basal cell adenocarcinoma.
**Basal cell adenocarcinoma may be cytologically indistinguishable from basal cell adenoma, i.e. "bad" architecture makes it a basal cell adenocarcinoma.
**Basal cell adenocarcinoma may be cytologically indistinguishable from basal cell adenoma, i.e. "bad" architecture makes it a basal cell adenocarcinoma.
DDx:
*[[Adenoid cystic carcinoma]] - not encapsulated.
*[[Basal cell adenocarcinoma]] - not encapsulated.
*[[Canalicular adenoma]] - different site; canalicular adenoma is the in oral cavity, usually upper lip.
Images:
*[http://moon.ouhsc.edu/kfung/jty1/Com/ComImage/Com304-3-LM1.gif BCA (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com/Com304-3-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com/Com304-3-Diss.htm]. Accessed on: 25 October 2011.</ref>
*[http://www.webpathology.com/image.asp?n=1&Case=115 BCA (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=4&Case=115 BCA (webpathology.com)].
*[http://www.flickr.com/photos/euthman/5691555734/in/set-72057594114099781/ BCA (flickr.com/euthman)].


===IHC===
===IHC===
*Luminal stains +ve: CK7 +ve, CAM5.2 +ve.
*Luminal stains +ve: CK7 +ve, CAM5.2 +ve.
*p63 +ve -- basal component.
*[[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.
 
===IHC===
*p63 -ve.
**Basal cell adenoma p63 +ve.
 
==Papillary cystadenoma lymphomatosum==
*[[AKA]] '''Warthin tumour'''.
 
===General===
Epidemiology:
*May be multicentric ~ 15% of the time.
*May be bilateral ~10% of the time.
*Classically: male > female -- changing with more women smokers.
*Smokers.
*Old - usu. 60s, very rarely < 40 years old.
 
Notes:
*No malignant transformation.
*Not in submandibular gland.
*Not in sublingual gland.
*Not in children.
 
===Gross===
*Motor-oil like fluid.
*Cystic component larger in larger lesions.
**Small lesions may be solid.
 
===Microscopic===
Features:
* Papillae (nipple-shaped structures) with a two rows of pink (eosinophilic) epithelial cells (with cuboidal basal cells and columnar luminal cells) -- '''key feature'''.
* Fibrous capsule - pink & homogenous on [[H&E stain]].
* Cystic space filled with debris ''in situ'' (not [[necrosis]]).
* Lymphoid stroma.


Notes:
==Warthin tumour==
*+/-Squamous differentiation.
{{Main|Warthin tumour}}
*+/-Goblet cell differentiation.
 
DDx:
*Lymphoepithelial cyst.
**Cyst within a lymph node.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Papillary_cystadenoma_lymphomatosum3.jpg Warthin tumour - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Papillary_cystadenoma_lymphomatosum2.jpg Warthin tumour - intermed. mag. (WC)].


==Sebaceous adenoma==
==Sebaceous adenoma==
===Microscopic===
{{Main|Sebaceous adenoma}}
Features:
*Benign counterpart of ''[[sebaceous carcinoma]]''.
*Benign counterpart of ''sebaceous carcinoma''.


==Sebaceous lymphadenoma==
==Sebaceous lymphadenoma==
===General===
{{Main|Sebaceous lymphadenoma}}
*Rare salivary gland tumour.<ref name=pmid21393895/>
*Benign.


===Microscopic===
==Oncocytoma of the salivary gland==
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>
*[[AKA]] ''salivary gland oncocytoma''.
*Sebaceous glands within lymphoid tissue - '''key feature'''.
{{Main|Oncocytoma of the salivary gland}}
 
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:
*[http://commons.wikimedia.org/wiki/File:Sebaceous_lymphadenoma_-_low_mag.jpg Sebaceous lymphadenoma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Sebaceous_lymphadenoma_-_high_mag.jpg Sebaceous lymphadenoma - high mag. (WC)].
 
==Oncocytoma==
===General===
*No risk of malignant transformation.
*~1% of all salivary gland tumours.
*Typical age: 60s-80s.
*Associated with radiation exposure.
*Major salivary glands - usu. parotid gland.
 
===Gross===
*Golden brown appearance.
 
===Microscopic===
Features:
*Like [[oncocytoma]]s elsewhere.
**Eosinophilic cytoplasm (on [[H&E stain]]).
***Due to increased number of mitochrondria.
**Fine capillaries.
 
Notes:
*May have clear cell change.
*Multiple small incidental lesions = oncocytosis - ''not'' oncocytoma.
 
===IHC===
*p63 +ve 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.
*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>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:
*[http://commons.wikimedia.org/wiki/File:Mucoepidermoid_carcinoma_%282%29_HE_stain.jpg Mucoepidermoid carcinoma 2 (WC)].
*[http://commons.wikimedia.org/wiki/File:Mucoepidermoid_carcinoma_%283%29_HE_stain.jpg Mucoepidermoid carcinoma 3 (WC)].
*[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.
 
===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==
*Abbreviated ''AcCC''.
{{Main|Acinic cell carcinoma}}
*[[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 cytoplasm.
**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.
 
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>IW. 11 January 2011.</ref>
 
Memory device:
*AcCC - lots of "C"s - '''c'''hromatin stipled, '''c'''ytoplasm generous.
 
Images:
*[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>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/IHC===
*PAS +ve.
*PAS-D +ve.
 
*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 they are not helpful.<ref>IW. 11 January 2011.</ref>


==Adenoid cystic carcinoma==
==Adenoid cystic carcinoma==
===General===
{{Main|Adenoid cystic carcinoma}}
*Common malignant neoplasm of salivary gland.
Note: The [[breast]] tumour is dealt with in ''[[adenoid cystic carcinoma of the breast]]''.
*AKA ''cylindroma''.<ref>Chest. May 1957. Vol. 31. No. 5. PP. 493-511. [http://www.chestjournal.org/content/31/5/493.abstract http://www.chestjournal.org/content/31/5/493.abstract]</ref>
**Should ''not'' be confused with ''[[dermal cylindroma]]'' (a benign skin tumour).
*Composed of ductal cells and myoepithelial cells; '''myoepithelial cells''' > ductal cells.
 
===Microscopic===
Features:
*Cribriform architecture ''or'' pseudoglandular spaces (classic pattern) - '''important feature'''.
**Other patterns: solid, cords, (bilayered) tubules.
**Cystic spaces filled with basophilic material (that is PAS +ve) - '''key feature'''.
*Scant cytoplasm in most cells (myoepithelial cells) - clear/eosinophilic.
**Moderate eosinophilic cytoplasm in the (rare) ductal cells.
*Nucleus - small.
**May be angulated (carrot-shaped) - myoepithelial cells; round/ovoid in ductal cells.
*Hyaline stroma.
 
Memory device:
*A'''d'''CC - mostly '''D'''NA (scant cytoplasm), distinct nucleus (carrot-shaped).
 
Notes:
*Squamous differentiation is extremely rare.  It presence should prompt consideration of:
**Basaloid [[squamous cell carcinoma]], [[basal cell carcinoma]] (BCC).
 
Images:
*[http://commons.wikimedia.org/wiki/File:Adenoid_cystic_carcinoma_-_intermed_mag.jpg AdCC - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Adenoid_cystic_carcinoma_-a-_very_high_mag.jpg AdCC - very high mag. (WC)].
*[http://www.nature.com/modpathol/journal/v16/n12/fig_tab/3880915f2.html Adenoid cystic carcinoma (nature.com)].
 
 
====Grading====
Based on solid component:
*Low grade = tubules and cribriform structures only; no solid component.
*Intermediate grade = solid component <30%.
*High grade = solid component >=30%
 
===Stains===
Special stains:
*PAS +ve material - cystic spaces.<ref name=pc_add>URL: [http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970070-5 http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970070-5]. Accessed on: 12 May 2011.</ref>
 
IHC:<ref name=pmid19360297>{{Cite journal  | last1 = Sequeiros-Santiago | first1 = G. | last2 = García-Carracedo | first2 = D. | last3 = Fresno | first3 = MF. | last4 = Suarez | first4 = C. | last5 = Rodrigo | first5 = JP. | last6 = Gonzalez | first6 = MV. | title = Oncogene amplification pattern in adenoid cystic carcinoma of the salivary glands. | journal = Oncol Rep | volume = 21 | issue = 5 | pages = 1215-22 | month = May | year = 2009 | doi =  | PMID = 19360297 }}</ref>
*CD117 +ve.
*Cyclin D1 +ve.
*Myoepithelial markers (e.g. calponin, actin) +ve.
**Typically -ve in PLGA.


==Salivary duct carcinoma==
==Salivary duct carcinoma==
===General===
{{Main|Salivary duct carcinoma}}
*Malignant counterpart of ''salivary duct adenoma''.
*Male:female ~= 4:1.
*Dismal prognosis.<ref name=pmid21393874>{{Cite journal  | last1 = Rajesh | first1 = NG. | last2 = Prayaga | first2 = AK. | last3 = Sundaram | first3 = C. | title = Salivary duct carcinoma: correlation of morphologic features by fine needle aspiration cytology and histopathology. | journal = Indian J Pathol Microbiol | volume = 54 | issue = 1 | pages = 37-41 | month =  | year =  | doi = 10.4103/0377-4929.77321 | PMID = 21393874 | url = http://www.ijpmonline.org/text.asp?2011/54/1/37/77321 }}</ref>
*Typically >50 years old.
*Mostly in the parotid.
 
===Microscopic===
Features - resembles ductal breast carcinoma:<ref name=pmid21393874/>
*Architecture: sheets, nests, cords, cribriform, micropapillary.
*Neoplastic cells line-up around cystic spaces "Roman bridges".
*Nuclear atypia (variation in size, shape, staining).
*Apocrine snouts - pseudopod-like/lollipop-like undulations of the cell membrane.
*Decapitation secretions - apocrine snouts (membrane bound blobs of cytoplasm) that have separated from its mother cell.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Salivary_duct_carcinoma_-a-_low_mag.jpg SDC - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Salivary_duct_carcinoma_-_low_mag.jpg SDC - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Salivary_duct_carcinoma_-_high_mag.jpg SDC - high mag. (WC)].
*[http://www.webpathology.com/image.asp?case=122&n=2 Salivary duct carcinoma (webpathology.com)].
 
Notes:
*Similar to ductal breast carcinoma - '''key to remember'''.
 
====Subtypes====
*Conventional.
*Mucinous - worse prognosis; opposite of what would one expect from the outcomes in [[breast cancer]].
*Micropapillary - assoc. with a poor prognosis.
*Sarcomatoid/spindle cell.
 
===IHC===
*LMWK, EMA, CK7, CK19 +ve.
*p63 -ve.
*Androgen receptor +ve.
*BRST2 (GCDFP-15) +ve.
*HER2 +ve ~21%; use of [[trastuzumab]] (Herceptin) not systematically studied.
 
Curiosity:
*PSA +/-.
*PSAP +/-.
 
==Polymorphous low-grade adenocarcinoma==
*Abbreviated ''PLGA''.


===General===
==Intraductal carcinoma of the salivary gland==
*Almost exclusively in the oral cavity.
{{Main|Intraductal carcinoma of the salivary gland}}
**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===
==Polymorphous adenocarcinoma==
Features:<ref name=Ref_WMSP74>{{Ref WMSP|74}} <!-- Mike S. --></ref>
*Abbreviated ''PAC''.
*Architecture: often small nests, may be targetoid.
*Previously known as ''polymorphous low-grade adenocarcinoma'', abbreviated ''PLGA''.
**Classically has whorling with '''eye-of-storm''' & '''single file'''.  
{{Main|Polymorphous adenocarcinoma}}
*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]].
 
Images:
*[http://commons.wikimedia.org/wiki/File:Polymorphous_low-grade_adenocarcinoma_-_very_low_mag.jpg PLGA - very low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Polymorphous_low-grade_adenocarcinoma_high_mag.jpg PLGA - high mag. (WC)].
 
===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====
#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===
==Basal cell adenocarcinoma==
*Rare.
{{Main|Basal cell adenocarcinoma}}
*Female:male = 2:1.
*Usu. old 50-60s.
*Usu. parotid gland.
*Prognosis: usu. good.
 
===Microscopic===
Features:
*Biphasic tumour:
*#Epithelial layer.
*#Myoepithelial layer - '''key feature'''.
*Architecture: variable (solid, cystic, tubular, papillary).
*+/-Spindle cells.
*Basement membrane-like material; may mimic adenoid cystic carcinoma.
 
DDx:
*Adenoid cystic carcinoma.
*Pleomorphic adenoma.
 
Notes:
*Usu. few mitoses.
 
Images:
*[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)].


==Sebaceous carcinoma==
==Sebaceous carcinoma==
{{Main|Sebaceous carcinoma}}
{{Main|Sebaceous carcinoma}}
It is similar to the tumour found in the skin.
It is similar to the tumour found in the skin.
==Hyalinizing clear cell carcinoma==
{{Main|Hyalinizing clear cell carcinoma}}


=See also=
=See also=
Line 742: Line 370:
*[[Breast]].
*[[Breast]].
*[[Head and neck cytopathology]].
*[[Head and neck cytopathology]].
*[[Lacrimal gland]].


=References=
=References=
Line 747: Line 376:


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