Ameloblastoma pathophysiology: Difference between revisions

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{{CMG}}{{SM}}
 
{{CMG}}; {{AE}} {{SM}}, {{VKG}}
{{Ameloblastoma}}
{{Ameloblastoma}}
==Overview==
==Overview==
On gross pathology, the characteristic findings of ameloblastoma may include solid and cystic, mulitcystic and intraosseous or extraosseous, or rarely unicystic.
[[Ameloblastoma]] arise from remnants of ameloblast or [[dental lamina]], dentigerous cysts, or basal layer of oral [[mucosa]]. There is evidence that suppression of matrix [[metalloproteinase]]-2 may inhibit the local invasiveness of [[ameloblastoma]]. On gross [[pathology]], the characteristic findings of [[ameloblastoma]] may include [[solid]] and [[cystic]], multicystic and [[intraosseous]] or extraosseous, or rarely unicystic. On microscopic histopathological analysis, stellate reticulum, [[giant cells]], subepithelial hyalinization, and columnar [[Basal cell|basal]] cells in palisading arrangement with vacuolated [[cytoplasm]] are characteristic findings of [[ameloblastoma]]. The exact [[pathophysiology]] of [[ameloblastoma]] is not fully understood. It is thought that [[ameloblastoma]] is the result of either suppression of matrix [[metalloproteinase]]-2 that may inhibit the local invasiveness of [[ameloblastoma]], or there is also some research suggesting that α5β1 [[integrin]] may participate in the local invasiveness of [[ameloblastoma]]. [[Genes of the liver, gallbladder, and biliary tract|Genes]] involved in the [[pathogenesis]] of ameloblastoma include ''[[BRAF]] V600E''.
On microscopic histopathological analysis, stellate reticulum, giant cells, subepithelial hyalinization, and columnar basal cells in palisading arrangement with vacuolated cytoplasm are characteristic findings of ameloblastoma. The exact pathophysiology of ameloblastoma is not fully understood. It is thought that ameloblastoma is the result of either suppression of matrix metalloproteinase-2 that may inhibit the local invasiveness of ameloblastoma, or there is also some research suggesting that α5β1 integrin may participate in the local invasiveness of ameloblastomas. Genes involved in the pathogenesis of ameloblastoma include ''BRAF V600E''.<ref name="wiki">  Ameloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Ameloblastoma Accessed on December 25, 2015</ref ><ref name="librepathology">  Ameloblastoma. Libre pathology(2015) http://librepathology.org/wiki/index.php/Ameloblastoma Accessed on December 25, 2015</ref>
==Pathophysiology==
==Pathophysiology==
The pathophysiology of ameloblastoma depends on the histological subtype: Histopathological variants of ameloblastoma can be found [[Ameloblastoma classification|'''here''']].
===Pathogenesis===
===Pathology===
* [[Ameloblastoma]] arise from remnants of ameloblast or [[dental lamina]], dentigerous cysts, or basal layer of [[oral mucosa]].<ref name="wiki">Ameloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Ameloblastoma Accessed on December 25, 2015</ref><ref name="librepathology">Ameloblastoma. Libre pathology(2015) http://librepathology.org/wiki/index.php/Ameloblastoma Accessed on December 25, 2015</ref><ref name="pmid4115148">{{cite journal| author=Pandya NJ, Stuteville OH| title=Treatment of ameloblastoma. | journal=Plast Reconstr Surg | year= 1972 | volume= 50 | issue= 3 | pages= 242-8 | pmid=4115148 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4115148  }} </ref><ref name="pmid26015700">{{cite journal |vauthors=Masthan KM, Anitha N, Krupaa J, Manikkam S |title=Ameloblastoma |journal=J Pharm Bioallied Sci |volume=7 |issue=Suppl 1 |pages=S167–70 |date=April 2015 |pmid=26015700 |pmc=4439660 |doi=10.4103/0975-7406.155891 |url=}}</ref><ref name="pmid17170964">{{cite journal |vauthors=Brazis PW, Miller NR, Lee AG, Holliday MJ |title=Neuro-ophthalmologic Aspects of Ameloblastoma |journal=Skull Base Surg |volume=5 |issue=4 |pages=233–44 |date=1995 |pmid=17170964 |pmc=1656531 |doi= |url=}}</ref>
Ameloblastomas arise from remnants of ameloblast or dental lamina, dentigerous cysts, or basal layer of oral mucosa. Ameloblasts, which are part of the odontogenic epithelium,  are responsible for enamel production and eventual crown formation. There is evidence that suppression of matrix metalloproteinase-2 may inhibit the local invasiveness of ameloblastoma, however, this was only demonstrated in vitro. There is also some research suggesting that α5β1 integrin may participate in the local invasiveness of ameloblastomas.<ref name="wiki"> Ameloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Ameloblastoma Accessed on December 25, 2015</ref ><ref name="librepathology"> Ameloblastoma. Libre pathology(2015) http://librepathology.org/wiki/index.php/Ameloblastoma Accessed on December 25, 2015</ref>
* [[Ameloblasts]], which are part of the odontogenic [[epithelium]],  are responsible for [[enamel]] production and eventual crown formation.
The ameloblastoma is an ectodermal odontogenic tumor of the jaws which apparently originates from the Malassez rests in the periodontium, from the gingival epithelium, from the enamel organs, or from ordinary dental cysts (dentigerous cysts, follicular cysts, or radicular cysts).<ref name="pmid4115148">{{cite journal| author=Pandya NJ, Stuteville OH| title=Treatment of ameloblastoma. | journal=Plast Reconstr Surg | year= 1972 | volume= 50 | issue= 3 | pages= 242-8 | pmid=4115148 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4115148  }} </ref>
* There is evidence that suppression of matrix [[metalloproteinase]]-2 may inhibit the local invasiveness of [[ameloblastoma]], however, this was only demonstrated in vitro.
===Genetics===
* There is also some research suggesting that α5β1 [[integrin]] may participate in the local invasiveness of ameloblastomas.
A recent study discovered a high frequency of ''BRAF V600E'' mutations in solid/multicystic ameloblastoma. These data suggests drugs targeting mutant ''BRAF'' as potential novel therapies for ameloblastoma.<ref name="wiki"> Ameloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Ameloblastoma Accessed on December 25, 2015</ref >
* The [[ameloblastoma]] is an ectodermal [[odontogenic]] tumor of the [[jaw]] which apparently originates from the Malassez rests in the [[periodontium]], from the [[Gingiva|gingival]] [[epithelium]], from the enamel organs, or from ordinary dental cysts (dentigerous cysts, follicular cysts, or radicular cysts).
 
==Genetics==
Genes involved in the [[pathogenesis]] of ameloblastoma include:
 
* [[BRAF]] V600E <ref name="McClaryWest20152">{{cite journal|last1=McClary|first1=Andrew C.|last2=West|first2=Robert B.|last3=McClary|first3=Ashley C.|last4=Pollack|first4=Jonathan R.|last5=Fischbein|first5=Nancy J.|last6=Holsinger|first6=Christopher F.|last7=Sunwoo|first7=John|last8=Colevas|first8=A. Dimitrios|last9=Sirjani|first9=Davud|title=Ameloblastoma: a clinical review and trends in management|journal=European Archives of Oto-Rhino-Laryngology|volume=273|issue=7|year=2015|pages=1649–1661|issn=0937-4477|doi=10.1007/s00405-015-3631-8}}</ref>


===Gross Pathology===
==Gross Pathology==
On gross pathology the following are the characteristic findings of ameloblastoma:
On gross [[pathology]] the following are the characteristic findings of ameloblastoma:<ref name="pmid18091060">{{cite journal |vauthors=Mendenhall WM, Werning JW, Fernandes R, Malyapa RS, Mendenhall NP |title=Ameloblastoma |journal=Am. J. Clin. Oncol. |volume=30 |issue=6 |pages=645–8 |date=December 2007 |pmid=18091060 |doi=10.1097/COC.0b013e3181573e59 |url=}}</ref><ref name="pmid17102048">{{cite journal |vauthors=Dunfee BL, Sakai O, Pistey R, Gohel A |title=Radiologic and pathologic characteristics of benign and malignant lesions of the mandible |journal=Radiographics |volume=26 |issue=6 |pages=1751–68 |date=2006 |pmid=17102048 |doi=10.1148/rg.266055189 |url=}}</ref><ref name="McClaryWest2015">{{cite journal|last1=McClary|first1=Andrew C.|last2=West|first2=Robert B.|last3=McClary|first3=Ashley C.|last4=Pollack|first4=Jonathan R.|last5=Fischbein|first5=Nancy J.|last6=Holsinger|first6=Christopher F.|last7=Sunwoo|first7=John|last8=Colevas|first8=A. Dimitrios|last9=Sirjani|first9=Davud|title=Ameloblastoma: a clinical review and trends in management|journal=European Archives of Oto-Rhino-Laryngology|volume=273|issue=7|year=2015|pages=1649–1661|issn=0937-4477|doi=10.1007/s00405-015-3631-8}}</ref>
*Solid and cystic
*Solid and [[cystic]]
*Multicystic and intraosseous or extraosseous
*Multicystic and [[intraosseous]] or extraosseous
*Rarely may be unicystic.
*Rarely may be unicystic
*Shown below is the gross specimen of resected left half of mandible initiated at third molar.
[[Image:800px-Ameloblastoma.jpg|400px]]


===Microscopic Pathology===
==Microscopic Pathology==
*Stellate reticulum - star-shaped cells, found in a developing tooth
On microscopic examination, the following characteristic findings of ameloblastoma are present:
*Giant cells may or may not be present
*[[Stellate reticulum]] - star-shaped cells, found in a developing [[tooth]]<ref name="pmid6697311">{{cite journal |vauthors=Gardner DG, Corio RL |title=Plexiform unicystic ameloblastoma. A variant of ameloblastoma with a low-recurrence rate after enucleation |journal=Cancer |volume=53 |issue=8 |pages=1730–5 |date=April 1984 |pmid=6697311 |doi= |url=}}</ref><ref name="McClaryWest20153">{{cite journal|last1=McClary|first1=Andrew C.|last2=West|first2=Robert B.|last3=McClary|first3=Ashley C.|last4=Pollack|first4=Jonathan R.|last5=Fischbein|first5=Nancy J.|last6=Holsinger|first6=Christopher F.|last7=Sunwoo|first7=John|last8=Colevas|first8=A. Dimitrios|last9=Sirjani|first9=Davud|title=Ameloblastoma: a clinical review and trends in management|journal=European Archives of Oto-Rhino-Laryngology|volume=273|issue=7|year=2015|pages=1649–1661|issn=0937-4477|doi=10.1007/s00405-015-3631-8}}</ref>
*[[Giant cells]] may or may not be present
*Subepithelial hyalinization may or may not be present
*Subepithelial hyalinization may or may not be present
*Seen deep to the basement membrane
*Seen deep to the [[basement membrane]]
*Suprabasal cells loosely textured and noncohesive, resembling stellate reticulum
*Suprabasal cells loosely textured and noncohesive, resembling stellate reticulum
*The plexiform type has epithelium that proliferates in a "Fish Net Pattern"
*The plexiform type has [[epithelium]] that proliferates in a "Fish Net Pattern"
*The follicular type will have outer arrangement of columnar or palisaded [[ameloblast]] like cells and inner zone of triangular shaped cells resembling stellate reticulum in bell stage. The central cells sometimes degenerate to form central microcysts
*The follicular type will have outer arrangement of columnar or palisaded [[ameloblast]] like cells and inner zone of triangular shaped cells resembling stellate [[reticulum]] in bell stage. The central cells sometimes degenerate to form central microcysts
*No enamel or dentin formation
*No [[enamel]] or dentin formation
*Tall columnar cells
*Tall columnar cells
**Palisaded nuclei with reverse polarization
**Palisaded [[nuclei]] with reverse [[polarization]]
***Reverse polarization of nuclei = nuclei distant from the basement membrane/nuclei at pole opposite of basement membrane
***Reverse [[polarization]] of [[nuclei]] = nuclei distant from the [[basement membrane]]/nuclei at pole opposite of basement membrane
***Palisaded nuclei = picket fence appearance; columnar-shaped nuclei with long axis perpendicular to the basement membrane -- key feature
***Palisaded nuclei = picket fence appearance; columnar-shaped nuclei with long axis perpendicular to the basement membrane (key feature)
**Subnuclear vacuolization
**Subnuclear vacuolation
*The following are the different histopathological variants of ameloblastoma:<ref name="librepathology"> Ameloblastoma. Libre pathology(2015) http://librepathology.org/wiki/index.php/Ameloblastoma Accessed on December 25, 2015</ref><ref name="wiki"> Ameloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Ameloblastoma Accessed on December 25, 2015</ref >
*The following are the different histopathological variants of [[ameloblastoma]]:<ref name="librepathology">Ameloblastoma. Libre pathology(2015) http://librepathology.org/wiki/index.php/Ameloblastoma Accessed on December 25, 2015</ref><ref name="wiki">Ameloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Ameloblastoma Accessed on December 25, 2015</ref>
**Intraosseous (follicular, plexiform, acanthomatous, multicystic, unicystic, granular cell [lysosomes by EM], basal cell, desmoplastic)
**[[Intraosseous]] (follicular, plexiform, acanthomatous, multicystic, unicystic, [[granular cell]] [lysosomes by EM], [[basal cell]], desmoplastic)
**Extraosseous (follicular, plexiform, basal cell)
**Extraosseous (follicular, plexiform, basal cell)
Histopathological variants of ameloblastoma can be found [[Ameloblastoma classification|'''here''']]<ref name="Gruica">{{cite journal
The image shows the characteristic features:<ref name="Gruica">{{cite journal
|title=Ameloblastoma of the follicular, plexiform, and acanthomatous type in the maxillary sinus: a case report.
|title=Ameloblastoma of the follicular, plexiform, and acanthomatous type in the maxillary sinus: a case report.
|author=Gruica B, Stauffer E, Buser D, Bornstein M.
|author=Gruica B, Stauffer E, Buser D, Bornstein M.
Line 48: Line 52:
|pages=311–4
|pages=311–4
|pmid=12731620}}</ref>
|pmid=12731620}}</ref>
Shown below is a micrograph of ameloblastoma
[[Image:800px-Ameloblastoma_-_high_mag.jpg‎|400px]]
The image shows the characteristic features:


* Islands of [[cells]] with palisaded [[nuclei]] that have reverse polarization.
* Islands of [[cells]] with palisaded [[nuclei]] that have reverse polarization.
* Reverse polarization of nuclei : nuclei distant from the [[basement membrane]]/nuclei at pole opposite of basement membrane.
* Reverse polarization of nuclei : [[nuclei]] distant from the [[basement membrane]]/nuclei at pole opposite of [[basement membrane]]
* Palisaded nuclei :picket fence appearance; columnar-shaped nuclei with long axis perpendicular to the basement membrane.
* Palisaded nuclei: picket fence appearance; columnar-shaped nuclei with long axis perpendicular to the [[basement membrane]]


* Subnuclear [[vacuolization]] in palisading cell - vacuoles at the basement membrane aspect.
* Subnuclear vacuolation in palisading cell - vacuoles at the [[basement membrane]] aspect
* Loose [[stroma]] around the islands of cells.
* Loose [[stroma]] around the islands of cells
* Star-like cells at the centre of the islands of cells (stellate reticulum).
* Star-like cells at the centre of the islands of cells (stellate reticulum)
====Video====
====Video====
{{#ev:youtube|VW5aSalmyF0}}
{{#ev:youtube|VW5aSalmyF0}}
<gallery>
800px-Ameloblastoma - intermed mag (1).jpg|intermediate magnification showing ameloblastoma
</gallery>


==References==
==References==
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shivali Marketkar, M.B.B.S. [2], Vamsikrishna Gunnam M.B.B.S [3]

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Overview

Ameloblastoma arise from remnants of ameloblast or dental lamina, dentigerous cysts, or basal layer of oral mucosa. There is evidence that suppression of matrix metalloproteinase-2 may inhibit the local invasiveness of ameloblastoma. On gross pathology, the characteristic findings of ameloblastoma may include solid and cystic, multicystic and intraosseous or extraosseous, or rarely unicystic. On microscopic histopathological analysis, stellate reticulum, giant cells, subepithelial hyalinization, and columnar basal cells in palisading arrangement with vacuolated cytoplasm are characteristic findings of ameloblastoma. The exact pathophysiology of ameloblastoma is not fully understood. It is thought that ameloblastoma is the result of either suppression of matrix metalloproteinase-2 that may inhibit the local invasiveness of ameloblastoma, or there is also some research suggesting that α5β1 integrin may participate in the local invasiveness of ameloblastoma. Genes involved in the pathogenesis of ameloblastoma include BRAF V600E.

Pathophysiology

Pathogenesis

Genetics

Genes involved in the pathogenesis of ameloblastoma include:

Gross Pathology

On gross pathology the following are the characteristic findings of ameloblastoma:[7][8][9]

Microscopic Pathology

On microscopic examination, the following characteristic findings of ameloblastoma are present:

  • Stellate reticulum - star-shaped cells, found in a developing tooth[10][11]
  • Giant cells may or may not be present
  • Subepithelial hyalinization may or may not be present
  • Seen deep to the basement membrane
  • Suprabasal cells loosely textured and noncohesive, resembling stellate reticulum
  • The plexiform type has epithelium that proliferates in a "Fish Net Pattern"
  • The follicular type will have outer arrangement of columnar or palisaded ameloblast like cells and inner zone of triangular shaped cells resembling stellate reticulum in bell stage. The central cells sometimes degenerate to form central microcysts
  • No enamel or dentin formation
  • Tall columnar cells
    • Palisaded nuclei with reverse polarization
      • Reverse polarization of nuclei = nuclei distant from the basement membrane/nuclei at pole opposite of basement membrane
      • Palisaded nuclei = picket fence appearance; columnar-shaped nuclei with long axis perpendicular to the basement membrane (key feature)
    • Subnuclear vacuolation
  • The following are the different histopathological variants of ameloblastoma:[2][1]
    • Intraosseous (follicular, plexiform, acanthomatous, multicystic, unicystic, granular cell [lysosomes by EM], basal cell, desmoplastic)
    • Extraosseous (follicular, plexiform, basal cell)

The image shows the characteristic features:[12]

  • Subnuclear vacuolation in palisading cell - vacuoles at the basement membrane aspect
  • Loose stroma around the islands of cells
  • Star-like cells at the centre of the islands of cells (stellate reticulum)

Video

{{#ev:youtube|VW5aSalmyF0}}

References

  1. ↑ 1.0 1.1 Ameloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Ameloblastoma Accessed on December 25, 2015
  2. ↑ 2.0 2.1 Ameloblastoma. Libre pathology(2015) http://librepathology.org/wiki/index.php/Ameloblastoma Accessed on December 25, 2015
  3. ↑ Pandya NJ, Stuteville OH (1972). "Treatment of ameloblastoma". Plast Reconstr Surg. 50 (3): 242–8. PMID 4115148.
  4. ↑ Masthan KM, Anitha N, Krupaa J, Manikkam S (April 2015). "Ameloblastoma". J Pharm Bioallied Sci. 7 (Suppl 1): S167–70. doi:10.4103/0975-7406.155891. PMC 4439660. PMID 26015700.
  5. ↑ Brazis PW, Miller NR, Lee AG, Holliday MJ (1995). "Neuro-ophthalmologic Aspects of Ameloblastoma". Skull Base Surg. 5 (4): 233–44. PMC 1656531. PMID 17170964.
  6. ↑ McClary, Andrew C.; West, Robert B.; McClary, Ashley C.; Pollack, Jonathan R.; Fischbein, Nancy J.; Holsinger, Christopher F.; Sunwoo, John; Colevas, A. Dimitrios; Sirjani, Davud (2015). "Ameloblastoma: a clinical review and trends in management". European Archives of Oto-Rhino-Laryngology. 273 (7): 1649–1661. doi:10.1007/s00405-015-3631-8. ISSN 0937-4477.
  7. ↑ Mendenhall WM, Werning JW, Fernandes R, Malyapa RS, Mendenhall NP (December 2007). "Ameloblastoma". Am. J. Clin. Oncol. 30 (6): 645–8. doi:10.1097/COC.0b013e3181573e59. PMID 18091060.
  8. ↑ Dunfee BL, Sakai O, Pistey R, Gohel A (2006). "Radiologic and pathologic characteristics of benign and malignant lesions of the mandible". Radiographics. 26 (6): 1751–68. doi:10.1148/rg.266055189. PMID 17102048.
  9. ↑ McClary, Andrew C.; West, Robert B.; McClary, Ashley C.; Pollack, Jonathan R.; Fischbein, Nancy J.; Holsinger, Christopher F.; Sunwoo, John; Colevas, A. Dimitrios; Sirjani, Davud (2015). "Ameloblastoma: a clinical review and trends in management". European Archives of Oto-Rhino-Laryngology. 273 (7): 1649–1661. doi:10.1007/s00405-015-3631-8. ISSN 0937-4477.
  10. ↑ Gardner DG, Corio RL (April 1984). "Plexiform unicystic ameloblastoma. A variant of ameloblastoma with a low-recurrence rate after enucleation". Cancer. 53 (8): 1730–5. PMID 6697311.
  11. ↑ McClary, Andrew C.; West, Robert B.; McClary, Ashley C.; Pollack, Jonathan R.; Fischbein, Nancy J.; Holsinger, Christopher F.; Sunwoo, John; Colevas, A. Dimitrios; Sirjani, Davud (2015). "Ameloblastoma: a clinical review and trends in management". European Archives of Oto-Rhino-Laryngology. 273 (7): 1649–1661. doi:10.1007/s00405-015-3631-8. ISSN 0937-4477.
  12. ↑ Gruica B, Stauffer E, Buser D, Bornstein M. (2003). "Ameloblastoma of the follicular, plexiform, and acanthomatous type in the maxillary sinus: a case report". Quintessence International. 34 (4): 311–4. PMID 12731620. Unknown parameter |month= ignored (help)

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