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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|[[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]]
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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]]
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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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| 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 carcinoma]] (AcCC)  
|[[Acinic cell carcinoma]] (AcCC)  
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| adenocarcinoma not otherwise specified, [[oncocytoma of salivary gland]]
| 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://commons.wikimedia.org/wiki/File:Acinic_cell_carcinoma_-_high_mag.jpg (WC)]
| [[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 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+/-
| [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]]
| [[Epithelial-myoepithelial carcinoma]]
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| [[AdCC]], [[pleomorphic adenoma]]
| [[AdCC]], [[pleomorphic adenoma]]
| rare
| rare
| [http://commons.wikimedia.org/wiki/File:Epithelial-myoepithelial_carcinoma_-_high_mag.jpg (WC)]
| [[Image:Epithelial-myoepithelial_carcinoma_-_high_mag.jpg |thumb|center|150px|EMCa. (WC/Nephron)]]
|-
|-
| [[Basal cell adenocarcinoma]]
| [[Basal cell adenocarcinoma]]
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| [[basal cell adenoma]]
| [[basal cell adenoma]]
| rare, usu. parotid gland, may arise from a basal cell adenoma
| rare, usu. parotid gland, may arise from a basal cell adenoma
| [http://commons.wikimedia.org/wiki/File:Basal_cell_adenocarcinoma_-_parotid_gland_-_high_mag.jpg (WC)]
| [[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]].
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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>
*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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==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 cells).
 
DDx:
*[[Lymphoma]] - especially [[MALT lymphoma]].<ref>{{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:
*[http://commons.wikimedia.org/wiki/File:Chronic_sialadenitis.jpg Chronic sialadenitis (WC)].


==Salivary gland mucocele==
==Salivary gland mucocele==
*[[AKA]] ''salivary mucocele''.
{{Main|Salivary gland mucocele}}
*May be referred to as ''[[mucocele]]''.
===General===
*Benign.
*Infected [[mucocele]] = mucopyocele.
 
===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/1076717-workup http://emedicine.medscape.com/article/1076717-workup]. Accessed on: 6 March 2012.</ref>
*Granulation tissue-like and pseudocyst-like.
**Granulation tissue-like:
***Fibroblasts.
***Small caliber blood vessels.
***Histocytes.
***Neutrophils.
**Pseudocyst:
***No epithelial lining.
***Poorly circumscribed.
*Pale pink extracellular material (mucous) - '''key feature'''.
*+/-[[Granuloma]]s.<ref name=pmid7251405>{{Cite journal  | last1 = Seifert | first1 = G. | last2 = Donath | first2 = K. | last3 = von Gumberz | first3 = C. | title = [Mucoceles of the minor salivary glands. Extravasation mucoceles (mucus granulomas) and retention mucoceles (mucus retention cysts) (author's transl)]. | journal = HNO | volume = 29 | issue = 6 | pages = 179-91 | month = Jun | year = 1981 | doi =  | PMID = 7251405 }}</ref>
 
DDx:
*[[Granulation tissue]].
*[[Signet ring cell carcinoma]] - muciphages may mimic signet ring cells.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Mucocele_of_lower_lip_%281%29.JPG Mucocele - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Mucocele_of_lower_lip_%282%29.JPG Mucocele - high mag. (WC)].
*[http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=292590975 Mucocele (dermatlas.med.jhmi.edu)].


==Pleomorphic adenoma==
==Pleomorphic adenoma==
*Abbreviated ''PA''.
{{Main|Pleomorphic adenoma}}
 
===General===
Features:
*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 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.
 
===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:
*[http://commons.wikimedia.org/wiki/File:Myoepithelioma_-_intermed_mag.jpg Myoepithelioma - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Myoepithelioma_-_very_high_mag.jpg Myoepithelioma - very high mag. (WC)].
 
===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==
*[[AKA]] ''papillary cystadenoma lymphomatosum''.
{{Main|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.
 
Image:
*[http://www.flickr.com/photos/bc_the_path/2510239905/in/photostream/ Warthin tumour (flickr.com)].
 
===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:
*+/-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==
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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:
*[[WC]]:
**[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)].
*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:
*[http://commons.wikimedia.org/wiki/File:Oncocytoma_of_the_Salivary_Gland.jpg Salivary gland oncocytoma (WC/euthman)].
 
===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/>
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Parotid_gland_oncocytoma_-_intermed_mag.jpg Parotid gland oncocytoma - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Parotid_gland_oncocytoma_-_very_high_mag.jpg Parotid gland oncocytoma - very high mag. (WC)].
 
===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:
*[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.
 
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==
*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 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:
*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.
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Acinic_cell_carcinoma_-_intermed_mag.jpg AcCC - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Acinic_cell_carcinoma_-_very_high_mag.jpg AcCC - very high mag. (WC)].
 
====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>


==Adenoid cystic carcinoma==
==Adenoid cystic carcinoma==
:See: ''[[Adenoid cystic carcinoma of the breast]]'' for the [[breast]] tumour.
{{Main|Adenoid cystic carcinoma}}
===General===
Note: The [[breast]] tumour is dealt with in ''[[adenoid cystic carcinoma of the breast]]''.
*Common malignant neoplasm of salivary gland.
*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).
 
DDx:
*[[Pleomorphic adenoma]], esp. if encapsulated.
 
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===
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.
*Myoepithelial markers (e.g. calponin, actin) +ve.
**Typically -ve in PLGA.
 
===Molecular===
Features:<ref>{{Cite journal  | last1 = Mitani | first1 = Y. | last2 = Rao | first2 = PH. | last3 = Futreal | first3 = PA. | last4 = Roberts | first4 = D. | last5 = Stephens | first5 = P. | last6 = Zhao | first6 = YJ. | last7 = Zhang | first7 = L. | last8 = Mitani | first8 = M. | last9 = Weber | first9 = RS. | title = Novel Chromosomal Rearrangements and breakpoints at the t(6;9) in Salivary Adenoid Cystic Carcinoma: association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome. | journal = Clin Cancer Res | volume =  | issue =  | pages =  | month = Oct | year = 2011 | doi = 10.1158/1078-0432.CCR-11-1870 | PMID = 21976542 }}</ref>
*t(6;9) MYB-NFIB. 
**Seen in ~50% of cases.
**Worse prognosis if present, esp. if fusion assoc. with transcription.


==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'''.


DDx:
==Intraductal carcinoma of the salivary gland==
*[[Carcinoma ex pleomorphic adenoma]] with SDC component.
{{Main|Intraductal carcinoma of the salivary gland}}


====Subtypes====
==Polymorphous adenocarcinoma==
*Conventional.
*Abbreviated ''PAC''.
*Mucinous - worse prognosis; opposite of what would one expect from the outcomes in [[breast cancer]].
*Previously known as ''polymorphous low-grade adenocarcinoma'', abbreviated ''PLGA''.
*Micropapillary - assoc. with a poor prognosis.
{{Main|Polymorphous adenocarcinoma}}
*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 +/-.
*ER-beta +ve.<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: 3 April 2012.</ref>
*ER-alpha -ve (the common ''ER'' stain).
 
==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.
 
===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:
*[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====
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:
*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)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Epithelial-myoepithelial_carcinoma_-_intermed_mag.jpg EMCa - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Epithelial-myoepithelial_carcinoma_-_high_mag.jpg EMCa - high mag. (WC)].
 
===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:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Basal_cell_adenocarcinoma_-_parotid_gland_-_intermed_mag.jpg BCAC - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Basal_cell_adenocarcinoma_-_parotid_gland_-_high_mag.jpg BCAC - high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Basal_cell_adenocarcinoma_-_2_-_parotid_gland_-_high_mag.jpg BCAC - high mag. (WC)].
*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 981: Line 364:


==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:
*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/>
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Hyalinizing_clear_cell_carcinoma_-_intermed_mag.jpg HCCC - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Hyalinizing_clear_cell_carcinoma_-_very_high_mag.jpg HCCC - very high mag. (WC)].
 
===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 1,040: 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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