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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#**Serous ~90% of gland.
#**Serous ~90% of gland.
#**Mucinous ~10% of gland.
#**Mucinous ~10% of gland.
#*Serous demilunes = mucinous gland with "cap" consisting of a serous glandular component.
#**Demilune = crescent.<ref>URL: [http://dictionary.reference.com/browse/demilune http://dictionary.reference.com/browse/demilune]. Accessed on: 19 August 2011.</ref>
#**Image: [http://pathology.mc.duke.edu/research/histo_course/demilunes.jpg Serous demilunes (duke.edu)].<ref>URL: [http://pathology.mc.duke.edu/research/pth225.html http://pathology.mc.duke.edu/research/pth225.html]. Accessed on: 19 August 2011.</ref>
# Sublingual:
# Sublingual:
#*Mucinous glands.
#*Mucinous glands.
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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.
| (1) plasmacytoid
| (1) plasmacytoid
| adenoid cystic c.
| [[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]
| [[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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| '''eosinophilic, abundant'''  
| '''eosinophilic, abundant'''  
| unremarkable  
| unremarkable  
| sebaceous lymphadenoma  
| [[sebaceous lymphadenoma]]
| AKA ''papillary cystadenoma lymphomatosum''
| AKA ''papillary cystadenoma lymphomatosum''
| [http://en.wikipedia.org/wiki/File:Papillary_cystadenoma_lymphomatosum2.jpg], [http://commons.wikimedia.org/wiki/File:Papillary_cystadenoma_lymphomatosum3.jpg]  
| [[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 adenoca
| [[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
|-
|-
|Mucoepidermoid carcinoma  
|[[Mucoepidermoid carcinoma]]
| cystic & solid
| cystic & solid
| epithelioid
| epithelioid
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| SCC (?)
| SCC (?)
| IHC: p63+
| IHC: p63+
| [[Image:Mucoepidermoid_carcinoma_%282%29_HE_stain.jpg |thumb| center| 150px | MEC. (WC)]]
|-
|[[Adenoid cystic carcinoma]] (AdCC)
| pseudocysts,<br>'''[[cribriform]]''', solid,<br>hyaline stroma
| epithelioid
| subtle
| '''scant''',<br>hyperchromatic
| '''small'''<br>+/-"carrot-shaped"
| [[pleomorphic adenoma]], [[PLGA]]
| Stains: PAS+ (pseudocyst material), CD117+, cyclin D1+
| [[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
| clear
| clear
| '''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
| [[Image:Acinic_cell_carcinoma_-_high_mag.jpg | thumb| center|150px| AcCC. (WC/Nephron)]]
|-
|-
|Adenoid cystic carcinoma (AdCC)
|[[Salivary duct carcinoma]]
| pseudocysts,<br>cribriform, solid,<br>hyaline stroma
| glandular, [[cribriform]]
| epithelioid
| subtle
| scant,<br>hyperchromatic
| '''small<br>"carrot-shaped"'''
| PLGA
| IHC: C-kit+, cyclin D1+
|-
|Salivary duct carcinoma  
| 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
| [[Image:Salivary_duct_carcinoma_-a-_low_mag.jpg | thumb| center|150px | SDC. (WC/Nephron)]]
|-
|-
|Polymorphous low-grade adenocarcinoma  
|[[Polymorphous adenocarcinoma]] (previously 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+/-
| [[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 adenocarcinoma]].
*Adenoid cystic carcinoma.
*[[Adenoid cystic carcinoma]].
*Pleomorphic adenoma.
*[[Pleomorphic adenoma]].


Parotid (benign):
===Benign parotid tumours===
*Pleomorphic adenoma.
*[[Pleomorphic adenoma]].
*Warthin tumour.
*[[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]].
 
===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>
*Most salivary gland tumours are p40 positive and p63 positive; [[polymorphous adenocarcinoma]] is p63 positive and p40 negative.<ref name=pmid34518135>{{cite journal |authors=Sivakumar N, Narwal A, Pandiar D, Devi A, Anand R, Bansal D, Kamboj M |title=Diagnostic utility of p63/p40 in the histologic differentiation of salivary gland tumors: A systematic review |journal=Oral Surg Oral Med Oral Pathol Oral Radiol |volume=133 |issue=2 |pages=189–198 |date=February 2022 |pmid=34518135 |doi=10.1016/j.oooo.2021.07.010 |url=}}</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===
Features:
*Fibrosis.
*Non-neoplastic mononuclear inflammatory infiltrate.
 
Image:
*[http://commons.wikimedia.org/wiki/File:Chronic_sialadenitis.jpg Chronic sialadenitis (WC)].


==Mucocele==
==Salivary gland mucocele==
===General===
{{Main|Salivary gland mucocele}}
*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===
==Warthin tumour==
Features:
{{Main|Warthin tumour}}
*Channels - "beading of cell".
*Mucoid/hemorrhagic stroma.
 
DDx:
*Basal cell adenoma.
 
===IHC===
*p63 -ve.
**Basal cell adenoma p63 +ve.
 
==Papillary cystadeoma 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.
 
===Microscopy===
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:
*+/-Squamous differentiation.
*+/-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''.


==Oncocytoma==
==Sebaceous lymphadenoma==
===General===
{{Main|Sebaceous lymphadenoma}}
*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===
==Oncocytoma of the salivary gland==
*Golden brown appearance.
*[[AKA]] ''salivary gland oncocytoma''.
 
{{Main|Oncocytoma of the salivary gland}}
===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===
==Acinic cell carcinoma==
*Most common malignant neoplasm of salivary gland in all age groups.
{{Main|Acinic cell carcinoma}}
*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.
*Epidermoid cells:
**Non-keratinized, polygonal squamoid cell with clear or oncocytic cytoplasm.
***Clear cells contain glycogen ([[PAS]] +ve, [[PAS-D]] -ve).
 
Notes:
*Mucin vacuoles may be rare; in a superficial glance -- it may mimic squamous cell carcinoma.
*"Intermediate cells" are described in textbooks. Weinreb thinks they are a pretty much a myth.<ref>IW. 10 January 2011.</ref>
*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 adenocarcinoma==
*Abbreviated ''AcCC''.
 
===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).
 
===Microscopic===
Features:
*Cribriform architecture.
*Scant cytoplasm.
*Carrot-shaped nucleus.
*Hyaline stroma.
 
Images: [http://www.nature.com/modpathol/journal/v16/n12/fig_tab/3880915f2.html Adenoid cystic carcinoma - Mod. Pathol.]
 
Memory device:
*A'''d'''CC - mostly '''D'''NA (scant cytoplasm), distinct nucleus (carrot-shaped).
 
====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%
 
===IHC===
Features:<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.


==Salivary duct carcinoma==
==Salivary duct carcinoma==
===General===
{{Main|Salivary duct carcinoma}}
*Malignant counterpart of ''salivary duct adenoma''.
*Male:female ~= 4:1.
*Typically >50 years old.
*Mostly in the parotid.


===Microscopic===
==Intraductal carcinoma of the salivary gland==
Features:
{{Main|Intraductal carcinoma of the salivary gland}}
*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.


Image:
==Polymorphous adenocarcinoma==
*[http://www.webpathology.com/image.asp?case=122&n=2 Salivary duct carcinoma (webpathology.com)].
*Abbreviated ''PAC''.
 
*Previously known as ''polymorphous low-grade adenocarcinoma'', abbreviated ''PLGA''.
Notes:
{{Main|Polymorphous adenocarcinoma}}
*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===
*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.
 
===Microscopy===
Features:
*Cytologically monotonous (uniform) with variable architecture - '''key feature'''.
**Architecture: often small nests, may be targetoid.
*Nucleus: ovoid & small with small nucleoli.
*Indistinct cell borders.
*Eosinophilic cytoplasm.
 
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===
==Epithelial-myoepithelial carcinoma==
Definition:
{{Main|Epithelial-myoepithelial carcinoma}}
*Malignant transformation of a ''pleomorphic adenoma''.


Diagnosis (either 1 or 2):
==Basal cell adenocarcinoma==
#History of a pleomorphic adenoma at the same site.
{{Main|Basal cell adenocarcinoma}}
#Features of a pleomorphic adenoma and a carcinoma.


Epidemiology:
==Sebaceous carcinoma==
*Rare.
{{Main|Sebaceous carcinoma}}
It is similar to the tumour found in the skin.


===Microscopy===
==Hyalinizing clear cell carcinoma==
Features:
{{Main|Hyalinizing clear cell carcinoma}}
*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.
 
==Sebaceous carcinoma==
*Arises from ''sebaceous glands''
*Sebaceous glands are serous glands and clear on H&E.


=See also=
=See also=
Line 655: Line 371:
*[[Breast]].
*[[Breast]].
*[[Head and neck cytopathology]].
*[[Head and neck cytopathology]].
*[[Lacrimal gland]].


=References=
=References=
Line 660: Line 377:


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

Latest revision as of 20:36, 2 June 2024

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

Types of salivary glands

Types of glands:[1]

  1. Serrous - eosinophilic cytoplasmic granules, acinar arrangement - vaguely resembles the acinar morphology of the pancreas.
  2. Mucinous - light eosinophilic staining.

Identifying the glands

The three main glands:

  1. Parotid:
    • Serous glands - lower viscosity, acini (lobules).[2]
    • Most tumours in this gland are benign.
  2. Submandibular:
    • Serous and mucinous glands.
      • Serous ~90% of gland.
      • Mucinous ~10% of gland.
    • Serous demilunes = mucinous gland with "cap" consisting of a serous glandular component.
  1. Sublingual:
    • Mucinous glands.

Other:

  • Adipose tissue is found between the glands.
    • It increases with age.

Images:

Memory devices:

  • The parotid gland vaguely resembles the pancreas.
  • Submandibular = glands are mixed.

Overview

Benign tumours

Tabular form - adapted from Thompson[5]

Entity Architecture Morphology Cell borders Cytoplasm Nucleus DDx Other Image
Pleomorphic adenoma var. mixed pop.; must include: (1) myoepithelium, (2) mesenchymal stroma, and (3) epithelium (ductal cells) or chondromyxoid stroma var. var. (1) plasmacytoid adenoid cystic carcinoma occ. encapsulated,
mixed pop. of glandular,
myoepithelial and mesenchymal cells
PA. (WP)
Warthin tumour papillary,
bilayer 		cuboid (basal), columnar (apical) clearly seen eosinophilic, abundant unremarkable sebaceous lymphadenoma AKA papillary cystadenoma lymphomatosum
PCL. (WP/Nephron)
Basal cell adenoma var., islands surrounded
by hyaline bands, lesion encapsulated 		basaloid subtle scant,
hyperchromatic 		granular basal cell adenocarcinoma - -
Canalicular adenoma chains of cells cuboid or columnar subtle scant,
hyperchromatic 		granular basal cell adenoma exclusively oral cavity, 80% in upper lip; IHC: p63-
CA. (WC)
Sialoblastoma var., islands surrounded
by loose fibrous stroma 		basaloid subtle scant, hyperch. granular basal cell adenocarcinoma - -

Malignant tumours

Tabular form - adapted from Thompson[6]

Entity Architecture Morphology Cell borders Cytoplasm Nucleus DDx Other Image
Mucoepidermoid carcinoma cystic & solid epithelioid distinct fuffy, clear,
abundant 		nuclei sm. SCC (?) IHC: p63+
MEC. (WC)
Adenoid cystic carcinoma (AdCC) pseudocysts,
cribriform, solid,
hyaline stroma 		epithelioid subtle scant,
hyperchromatic 		small
+/-"carrot-shaped" 		pleomorphic adenoma, PLGA Stains: PAS+ (pseudocyst material), CD117+, cyclin D1+
AdCC. (WC/Nephron)
Acinic cell carcinoma (AcCC) sheets, acinar (islands) epithelioid clear granular abundant stippled, +/-occ. nucleoli adenocarcinoma not otherwise specified, oncocytoma of salivary gland Stains: PAS +ve, PAS-D +ve; IHC: S-100 -ve, p63 -ve
AcCC. (WC/Nephron)
Salivary duct carcinoma glandular, cribriform columnar subtle/clear hyperchromatic columnar metastatic breast carcinoma similar to ductal
breast carcinoma; male>female
SDC. (WC/Nephron)
Polymorphous adenocarcinoma (previously polymorphous low-grade adenocarcinoma) variable, often small
nests, may be targetoid 		epithelioid indistinct eosinophilic ovoid & small with
small nucleoli 		AdCC minor salivary gland tumour,
often in palate,
cytologically monotonous; IHC: S-100+, CK+, vim.+, GFAP+/-, BCL2+/-
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
EMCa. (WC/Nephron)
Basal cell adenocarcinoma var., islands surrounded
by hyaline bands, lesion not encapsulated 		basaloid subtle scant,
hyperchromatic 		granular basal cell adenoma rare, usu. parotid gland, may arise from a basal cell adenoma
BCA. (WC/Nephron)

DDx

Palate

Benign parotid tumours

Oncocytic tumours

Clear cell tumours

Basaloid neoplasms

IHC overview

General:

  • Usually has limited value.

Overview:

  • Luminal markers: CK7, CK19, CAM5.2 (LMWK).
  • Basal markers: p63, HMWK, CK14.
  • Myoepithelial markers: calponin, actin.
  • Uncommitted: S-100.

Notes:

  • p63 and S-100 are sometimes call myoepithelial.

Specifics:

  • Calponin, S-100, Ki-67 may be useful as per Nagao et al.[8]
  • Most salivary gland tumours are p40 positive and p63 positive; polymorphous adenocarcinoma is p63 positive and p40 negative.[9]

Benign

General DDx:

  • Inflammation.
  • Neoplasm.
  • Ductal obstrution.

Chronic sialadenitis

Main article: Chronic sialadenitis

Salivary gland mucocele

Main article: Salivary gland mucocele

Pleomorphic adenoma

Main article: Pleomorphic adenoma

Myoepithelioma

Main article: Myoepithelioma

Basal cell adenoma

General

  • ~2% of salivary gland tumours.
  • May be multifocal.
  • Usually parotid gland, occasionally submandibular gland.
  • Female:male = ~2:1.
  • May be seen in association with dermal cylindromas in the context of a genetic mutation.[10]
  • Malignant transformation - rarely.

Microscopic

Features:

  1. Basal component.
    • Basophilic cells - key feature.
    • Usu. in nests.
    • Large basophilic nucleus.
    • Minimal-to-moderate eosinophilic cytoplasm.
  2. Stromal cells.
    • Plump spindle cells without significant nuclear atypia - distinguishing feature.
      • Stromal cell nuclei width ~= diameter RBC.
    • Dense hyaline stroma.
  3. Tubular component.
    • Within basal component, may be minimal.
  4. Lesion is encapsulated - key feature.

Notes:

  • No chondromyxoid stroma.
  • 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.

DDx:

Images:

IHC

  • Luminal stains +ve: CK7 +ve, CAM5.2 +ve.
  • p63 +ve -- basal component.
  • S-100 +ve -- spindle cells in the stroma.

Canalicular adenoma

Main article: Canalicular adenoma

Warthin tumour

Main article: Warthin tumour

Sebaceous adenoma

Main article: Sebaceous adenoma

Sebaceous lymphadenoma

Main article: Sebaceous lymphadenoma

Oncocytoma of the salivary gland

  • AKA salivary gland oncocytoma.
Main article: Oncocytoma of the salivary gland

Malignant

One approach:

  • Differentiate -- luminal vs. myoepithelial vs. basal (mucoepideroid).

Mucoepidermoid carcinoma

Main article: Mucoepidermoid carcinoma

Acinic cell carcinoma

Main article: Acinic cell carcinoma

Adenoid cystic carcinoma

Main article: Adenoid cystic carcinoma

Note: The breast tumour is dealt with in adenoid cystic carcinoma of the breast.

Salivary duct carcinoma

Main article: Salivary duct carcinoma

Intraductal carcinoma of the salivary gland

Main article: Intraductal carcinoma of the salivary gland

Polymorphous adenocarcinoma

  • Abbreviated PAC.
  • Previously known as polymorphous low-grade adenocarcinoma, abbreviated PLGA.
Main article: Polymorphous adenocarcinoma

Carcinoma ex pleomorphic adenoma

  • Abbreviated Ca ex PA.
Main article: Carcinoma ex pleomorphic adenoma

Epithelial-myoepithelial carcinoma

Main article: Epithelial-myoepithelial carcinoma

Basal cell adenocarcinoma

Main article: Basal cell adenocarcinoma

Sebaceous carcinoma

Main article: Sebaceous carcinoma

It is similar to the tumour found in the skin.

Hyalinizing clear cell carcinoma

Main article: Hyalinizing clear cell carcinoma

See also

References

  1. ↑ http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Oral/oral.htm#LABSALIVA
  2. ↑ http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Epithelia/Epithel.htm
  3. ↑ URL: http://dictionary.reference.com/browse/demilune. Accessed on: 19 August 2011.
  4. ↑ URL: http://pathology.mc.duke.edu/research/pth225.html. Accessed on: 19 August 2011.
  5. ↑ Thompson, Lester D. R. (2006). Head and Neck Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 295-319. ISBN 978-0443069604.
  6. ↑ Thompson, Lester D. R. (2006). Head and Neck Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 325-357. ISBN 978-0443069604.
  7. ↑ 7.0 7.1 7.2 Chhieng, DC.; Paulino, AF. (Dec 2002). "Basaloid tumors of the salivary glands.". Ann Diagn Pathol 6 (6): 364-72. doi:10.1053/adpa.2002.37013. PMID 12478487.
  8. ↑ Nagao, T.; Sato, E.; Inoue, R.; Oshiro, H.; H Takahashi, R.; Nagai, T.; Yoshida, M.; Suzuki, F. et al. (Oct 2012). "Immunohistochemical analysis of salivary gland tumors: application for surgical pathology practice.". Acta Histochem Cytochem 45 (5): 269-82. doi:10.1267/ahc.12019. PMID 23209336.
  9. ↑ Sivakumar N, Narwal A, Pandiar D, Devi A, Anand R, Bansal D, Kamboj M (February 2022). "Diagnostic utility of p63/p40 in the histologic differentiation of salivary gland tumors: A systematic review". Oral Surg Oral Med Oral Pathol Oral Radiol 133 (2): 189–198. doi:10.1016/j.oooo.2021.07.010. PMID 34518135.
  10. ↑ Choi, HR.; Batsakis, JG.; Callender, DL.; Prieto, VG.; Luna, MA.; El-Naggar, AK. (Jun 2002). "Molecular analysis of chromosome 16q regions in dermal analogue tumors of salivary glands: a genetic link to dermal cylindroma?". Am J Surg Pathol 26 (6): 778-83. PMID 12023583.
  11. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/Com/Com304-3-Diss.htm. Accessed on: 25 October 2011.
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