Difference between revisions of "Salivary glands"

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


=Normal salivary glands=
=Normal salivary glands=
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|[[Pleomorphic adenoma]]
|[[Pleomorphic adenoma]]
| var.
| var.
| '''mixed pop.'''; must include: (1) myoepithelium, (2) epithelium (ductal cells), (3) [[chondromyxoid stroma]] 
| '''mixed pop.'''; must include: (1) myoepithelium, (2) mesenchymal stroma, and (3) epithelium (ductal cells) ''or'' [[chondromyxoid stroma]] 
| var.
| var.
| var.
| var.
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| [[basal cell adenoma]]
| [[basal cell adenoma]]
| exclusively oral cavity, 80% in upper lip; IHC: p63-
| exclusively oral cavity, 80% in upper lip; IHC: p63-
| [http://www.webpathology.com/image.asp?n=1&Case=116 (webpathology.com)], [http://www.webpathology.com/image.asp?n=2&Case=116 (webpathology.com)]
| [[Image:Canalicular_adenoma_--_high_mag.jpg | thumb | center |150px| CA. (WC)]]
|-
|-
|[[Sialoblastoma]]
|[[Sialoblastoma]]
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|-
|-
|[[Adenoid cystic carcinoma]] (AdCC)  
|[[Adenoid cystic carcinoma]] (AdCC)  
| pseudocysts,<br>'''cribriform''', solid,<br>hyaline stroma  
| pseudocysts,<br>'''[[cribriform]]''', solid,<br>hyaline stroma  
| epithelioid
| epithelioid
| subtle  
| subtle  
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|-
|-
|[[Salivary duct carcinoma]]  
|[[Salivary duct carcinoma]]  
| glandular, cribriform  
| glandular, [[cribriform]]
| columnar  
| columnar  
| subtle/clear  
| subtle/clear  
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| [[Image:Salivary_duct_carcinoma_-a-_low_mag.jpg | thumb| center|150px | SDC. (WC/Nephron)]]
| [[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)]]
| [[Image:Polymorphous_low-grade_adenocarcinoma_-_very_low_mag.jpg|thumb|center|150px|PLGA. (WC/Nephron)]]
|-
|-
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==DDx==
==DDx==
===Palate===
===Palate===
*[[Polymorphous low-grade adenocarcinoma]].
*[[Polymorphous adenocarcinoma]].
*[[Adenoid cystic carcinoma]].
*[[Adenoid cystic carcinoma]].
*[[Pleomorphic adenoma]].
*[[Pleomorphic adenoma]].
Line 214: Line 217:
*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.
Line 227: Line 237:
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 cell]]s).
Note:
*If the infiltrate is predominantly lymphocytes Sjögren's is a possibility, and reporting a ''[[Focus score]]'' should be considered.
DDx:
*[[Lymphoma]] - especially [[MALT lymphoma]].<ref name=pmid22475637>{{Cite journal  | last1 = Beasley | first1 = MJ. | title = Lymphoma of the Thyroid and Head and Neck. | journal = Clin Oncol (R Coll Radiol) | volume =  | issue =  | pages =  | month = Apr | year = 2012 | doi = 10.1016/j.clon.2012.02.010 | PMID = 22475637 }}</ref>
====Image====
<gallery>
Image:Chronic_sialadenitis.jpg | Chronic sialadenitis. (WC/Nephron)
</gallery>
==Salivary gland mucocele==
==Salivary gland mucocele==
*[[AKA]] ''salivary mucocele''.
{{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====
<gallery>
Image:Mucocele_of_lower_lip_%281%29.JPG | Mucocele - low mag. (WC/KGH)
Image:Mucocele_of_lower_lip_%282%29.JPG | Mucocele - high mag. (WC/KGH)
Image:Mucocele_-_low_mag.jpg | Mucocele - low mag. (WC/Nephron)
Image:Mucocele_-_high_mag.jpg | Mucocele - high mag. (WC/Nephron)
</gallery>
www:
*[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.
 
Image:
*[http://screening.iarc.fr/atlasoral_detail.php?flag=1&lang=1&Id=C0100002&cat=C1 PA in situ (iarc.fr)].
 
===Microscopic===
Features:<ref name=Ref_HaNP295>{{Ref HaNP|295}}</ref>
*Proliferation of myoepithelium and epithelium (ductal cells) in mesenchymal stroma.
**Cells in ducts = epithelial.
**Cells not in ducts = myoepithelial.<ref name=IW_10jan2011>IW. 10 January 2011.</ref>
*Mesenchymal stroma - '''important feature'''.
**May be any of following: [[myxoid stroma|myxoid]], mucochondroid, hyalinized, osseous, fatty.
***[[chondromyxoid stroma|Chondroid]] = specific for PA; can diagnose PA without an epithelial (ductal) component if chondroid is present.
***Myxoid = not specific for PA.
 
Notes:
*Mesenchymal stroma not required for diagnosis -- if >5% ducts.<ref name=IW_10jan2011>IW. 10 January 2011.</ref>
**No chondroid stroma ''and'' <5% ductal cells = '''[[myoepithelioma]]'''.
*Complete excision is often elusive; stating "completely excised" on a surgical pathology report is unwise.
*Look for, i.e. rule-out, poorly differentiated carcinoma: ''carcinoma ex pleomorphic adenoma''.
 
Memory device: '''MEC''' = '''m'''yoepithelium, '''e'''pithelium, '''c'''hondromyxoid stroma.
 
DDx:
*[[Myoepithelioma]].
*[[Carcinoma ex pleomorphic adenoma]].
*[[Epithelial-myoepithelial carcinoma]].
 
====Images====
<gallery>
Image:Pleomorphic_adenoma_%281%29_parotid_gland.jpg | PA. (WC)
Image:Pleomorphic_adenoma_%282%29_parotid_gland.jpg | PA. (WC)
Image:Pleomorphic_adenoma_%283%29_parotid_gland.jpg | PA. (WC)
Image:Pleomorphic_adenoma_%284%29_parotid_gland.jpg | PA. (WC)
</gallery>
www:
*[http://www.webpathology.com/image.asp?n=7&Case=111 PA - myxoid stroma (webpathology.com)].
 
===IHC===
*S-100 +ve, SMA +ve, GFAP +ve.


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


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


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


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


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


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


==Acinic cell carcinoma==
==Acinic cell carcinoma==
Line 637: Line 335:


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


==Salivary duct carcinoma==
==Salivary duct carcinoma==
{{Main|Salivary duct carcinoma}}
{{Main|Salivary duct carcinoma}}


==Polymorphous low-grade adenocarcinoma==
==Intraductal carcinoma of the salivary gland==
*Abbreviated ''PLGA''.
{{Main|Intraductal carcinoma of the salivary gland}}
 
===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====
==Polymorphous adenocarcinoma==
<gallery>
*Abbreviated ''PAC''.
Image:Polymorphous_low-grade_adenocarcinoma_-_very_low_mag.jpg | PLGA - very low mag. (WC/Nephron)
*Previously known as ''polymorphous low-grade adenocarcinoma'', abbreviated ''PLGA''.
Image:Polymorphous_low-grade_adenocarcinoma_high_mag.jpg | PLGA - high mag. (WC/Nephron)
{{Main|Polymorphous adenocarcinoma}}
</gallery>
===IHC===
*S100 +ve, CK +ve, vimentin +ve.
*GFAP +ve/-ve.
*BCL2 +ve/-ve.
*Generally negative for myoepithelial markers (calponin, actin) - '''useful if negative'''.


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


==Epithelial-myoepithelial carcinoma==
==Epithelial-myoepithelial carcinoma==

Latest revision as of 20:36, 2 June 2024

File:Blausen 0780 SalivaryGlands.png
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
Error creating thumbnail:
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-
Error creating thumbnail:
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
Salivary duct carcinoma glandular, cribriform columnar subtle/clear hyperchromatic columnar metastatic breast carcinoma similar to ductal
breast carcinoma; male>female
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
Error creating thumbnail:
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

Salivary gland mucocele

Pleomorphic adenoma

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

Warthin tumour

Sebaceous adenoma

Sebaceous lymphadenoma

Oncocytoma of the salivary gland

  • AKA salivary gland oncocytoma.

Malignant

One approach:

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

Mucoepidermoid carcinoma

Acinic cell carcinoma

Adenoid cystic carcinoma

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

Salivary duct carcinoma

Intraductal carcinoma of the salivary gland

Polymorphous adenocarcinoma

  • Abbreviated PAC.
  • Previously known as polymorphous low-grade adenocarcinoma, abbreviated PLGA.

Carcinoma ex pleomorphic adenoma

  • Abbreviated Ca ex PA.

Epithelial-myoepithelial carcinoma

Basal cell adenocarcinoma

Sebaceous carcinoma

It is similar to the tumour found in the skin.

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.