Craniopharyngioma pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
Craniopharyngiomas are [[Epithelial|epithelial tumors]] that usually arise in the [[pituitary stalk]] adjacent to the [[optic chiasm]]. On [[gross pathology]], craniopharyngiomas are [[Cystic|cystic or partially cystic]] with solid areas.The cyst is filled with a turbid, [[Protein|proteinaceous material]] of brownish-yellow color that glitters and sparkles because of a high content of floating cholesterol crystals. On microscopic [[histopathology]], it is categorized into two subtypes: Adamantinomatous and papillary. | Craniopharyngiomas are [[Epithelial|epithelial tumors]] that usually arise in the [[pituitary stalk]] adjacent to the [[optic chiasm]]. On [[gross pathology]], craniopharyngiomas are [[Cystic|cystic or partially cystic]] with solid areas.The [[cyst]] is filled with a [[Turbidity|turbid]], [[Protein|proteinaceous material]] of brownish-yellow color that glitters and sparkles because of a high content of floating [[Cholesterol|cholesterol crystals]]. On microscopic [[histopathology]], it is categorized into two subtypes: Adamantinomatous and papillary. | ||
==Pathophysiology== | ==Pathophysiology== | ||
*Craniopharyngioma is a [[Glial|nonglial]] [[Brain tumor|intracranial tumor]] derived from a [[Congenital disorder|malformation]] of [[Embryonic|embryonic tissue]]. <ref name="pmid1260697">{{cite journal |vauthors=Petito CK, DeGirolami U, Earle KM |title=Craniopharyngiomas: a clinical and pathological review |journal=Cancer |volume=37 |issue=4 |pages=1944–52 |date=April 1976 |pmid=1260697 |doi= |url=}}</ref> | *Craniopharyngioma is a [[Glial|nonglial]] [[Brain tumor|intracranial tumor]] derived from a [[Congenital disorder|malformation]] of [[Embryonic|embryonic tissue]]. <ref name="pmid1260697">{{cite journal |vauthors=Petito CK, DeGirolami U, Earle KM |title=Craniopharyngiomas: a clinical and pathological review |journal=Cancer |volume=37 |issue=4 |pages=1944–52 |date=April 1976 |pmid=1260697 |doi= |url=}}</ref> | ||
*There are differing hypotheses on its embryonic origin. | *There are differing [[hypotheses]] on its [[Embryonic|embryonic origin]]. | ||
*[[Pathogenesis]] of craniopharyngioma is not completely understood. | *[[Pathogenesis]] of craniopharyngioma is not completely understood. | ||
*Some authorities advocate that it originates from [[Ectodermal dysplasia|ectodermal]] remnants of [[Rathke's pouch]]. <ref name="pmid6818504">{{cite journal |vauthors=Rush JA, Younge BR, Campbell RJ, MacCarty CS |title=Optic glioma. Long-term follow-up of 85 histopathologically verified cases |journal=Ophthalmology |volume=89 |issue=11 |pages=1213–9 |date=November 1982 |pmid=6818504 |doi= |url=}}</ref> | *Some authorities advocate that it originates from [[Ectodermal dysplasia|ectodermal]] [[Ectoderm|remnants]] of [[Rathke's pouch]]. <ref name="pmid6818504">{{cite journal |vauthors=Rush JA, Younge BR, Campbell RJ, MacCarty CS |title=Optic glioma. Long-term follow-up of 85 histopathologically verified cases |journal=Ophthalmology |volume=89 |issue=11 |pages=1213–9 |date=November 1982 |pmid=6818504 |doi= |url=}}</ref> | ||
*Few [[Pathology|pathologists]] believe that it originates from residual embryonal epithelium of the [[Anterior pituitary|anterior pituitary gland]] and of the [[Infundibulum|anterior infundibulum]]. | *Few [[Pathology|pathologists]] believe that it originates from residual [[Embryo|embryonal epithelium]] of the [[Anterior pituitary|anterior pituitary gland]] and of the [[Infundibulum|anterior infundibulum]]. | ||
===Embryonic theory=== | ===Embryonic theory=== | ||
*According to this theory, craniopharyniomas arise from [[Neoplastic|neoplastic transformation]] of [[Squamous epithelium|embryonic squamous]] cell nests of [[Rathke's pouch]] with the [[stomodeum]].<ref name="pmid9761047">{{cite journal |vauthors=Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, Bruner JM |title=The descriptive epidemiology of craniopharyngioma |journal=J. Neurosurg. |volume=89 |issue=4 |pages=547–51 |date=October 1998 |pmid=9761047 |doi=10.3171/jns.1998.89.4.0547 |url=}}</ref> | *According to this theory, craniopharyniomas arise from [[Neoplastic|neoplastic transformation]] of [[Squamous epithelium|embryonic squamous]] [[Cell (biology)|cell nests]] of [[Rathke's pouch]] with the [[stomodeum]].<ref name="pmid9761047">{{cite journal |vauthors=Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, Bruner JM |title=The descriptive epidemiology of craniopharyngioma |journal=J. Neurosurg. |volume=89 |issue=4 |pages=547–51 |date=October 1998 |pmid=9761047 |doi=10.3171/jns.1998.89.4.0547 |url=}}</ref> | ||
*Cell remnants of the [[Craniopharyngeal canal|craniopharyngeal duct]] are spread through the intrasellar and [[Sella turcica|suprasellar region]]. | *Cell remnants of the [[Craniopharyngeal canal|craniopharyngeal duct]] are spread through the [[intrasellar]] and [[Sella turcica|suprasellar region]]. | ||
*The rotation of the [[Anterior pituitary|adenohypophysis]] is caused by different rates of cellular multiplication. | *The rotation of the [[Anterior pituitary|adenohypophysis]] is caused by different rates of [[Cellular|cellular multiplication]]. | ||
*Different rates of cellular multiplication results in a spread of cells of the [[Craniopharyngeal canal|craniopharyngeal]] duct to the [[Sella turcica|suprasellar region]]. | *Different rates of cellular multiplication results in a spread of cells of the [[Craniopharyngeal canal|craniopharyngeal]] duct to the [[Sella turcica|suprasellar region]]. | ||
*The rare location at the cerebellopontine angle could fit with this hypothesis. | *The rare location at the [[Cerebellum|cerebellopontine angle]] could fit with this [[hypothesis]]. | ||
===Metaplastic theory=== | ===Metaplastic theory=== | ||
*Papillary craniopharyngiomas are the result of [[metaplasia]] of the [[Pituitary gland|adenohypophyseal]] cells in the [[anterior pituitary]]. | *Papillary craniopharyngiomas are the result of [[metaplasia]] of the [[Pituitary gland|adenohypophyseal]] cells in the [[anterior pituitary]]. | ||
*This theory is supported by the presence of [[Metaplasticity|metaplastic]] nests in the gland. <ref name="pmid6818504">{{cite journal |vauthors=Rush JA, Younge BR, Campbell RJ, MacCarty CS |title=Optic glioma. Long-term follow-up of 85 histopathologically verified cases |journal=Ophthalmology |volume=89 |issue=11 |pages=1213–9 |date=November 1982 |pmid=6818504 |doi= |url=}}</ref> | *This theory is supported by the presence of [[Metaplasticity|metaplastic]] [[Gland|nests in the gland]]. <ref name="pmid6818504">{{cite journal |vauthors=Rush JA, Younge BR, Campbell RJ, MacCarty CS |title=Optic glioma. Long-term follow-up of 85 histopathologically verified cases |journal=Ophthalmology |volume=89 |issue=11 |pages=1213–9 |date=November 1982 |pmid=6818504 |doi= |url=}}</ref> | ||
===Gross Pathology=== | ===Gross Pathology=== | ||
*On [[Macroscopic|macroscopic examination]], craniopharyngiomas are cystic or partially cystic with solid areas. <ref name="pmid7885544">{{cite journal |vauthors=Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, Shiminski-Maher T, Flamm ES, Epstein FJ, Miller DC |title=Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome |journal=Neurosurgery |volume=35 |issue=6 |pages=1001–10; discussion 1010–1 |date=December 1994 |pmid=7885544 |doi= |url=}}</ref> | *On [[Macroscopic|macroscopic examination]], craniopharyngiomas are [[Cystic|cystic or partially cystic with solid areas]]. <ref name="pmid7885544">{{cite journal |vauthors=Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, Shiminski-Maher T, Flamm ES, Epstein FJ, Miller DC |title=Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome |journal=Neurosurgery |volume=35 |issue=6 |pages=1001–10; discussion 1010–1 |date=December 1994 |pmid=7885544 |doi= |url=}}</ref> | ||
*Craniopharyngiomas can arise anywhere along the [[craniopharyngeal canal]]. | *Craniopharyngiomas can arise anywhere along the [[craniopharyngeal canal]]. | ||
*It occur most often in [[Sella turcica|sellar]] or [[Sella turcica|suprasellar region]] but can have anterior extension to the [[Cistern|prechiasmatic cistern]] and [[Paranasal sinus|subfrontal spaces]].<ref name="pmid7885544">{{cite journal |vauthors=Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, Shiminski-Maher T, Flamm ES, Epstein FJ, Miller DC |title=Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome |journal=Neurosurgery |volume=35 |issue=6 |pages=1001–10; discussion 1010–1 |date=December 1994 |pmid=7885544 |doi= |url=}}</ref> | *It occur most often in [[Sella turcica|sellar]] or [[Sella turcica|suprasellar region]] but can have [[Anterior|anterior extension]] to the [[Cistern|prechiasmatic cistern]] and [[Paranasal sinus|subfrontal spaces]].<ref name="pmid7885544">{{cite journal |vauthors=Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, Shiminski-Maher T, Flamm ES, Epstein FJ, Miller DC |title=Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome |journal=Neurosurgery |volume=35 |issue=6 |pages=1001–10; discussion 1010–1 |date=December 1994 |pmid=7885544 |doi= |url=}}</ref> | ||
*Posterior extension into the [[Pontine|prepontine]] , [[third ventricle]], [[posterior fossa]], and [[foramen magnum]]; and laterally toward the subtemporal spaces. | *[[Posterior|Posterior extension]] into the [[Pontine|prepontine]] , [[third ventricle]], [[posterior fossa]], and [[foramen magnum]]; and [[External rotation|laterally]] toward the [[Temporal|subtemporal spaces]]. | ||
*Rare locations of craniopharyngiomas are; the [[nasopharynx]] , [[Paranasal sinus|paranasal area]] , [[sphenoid bone]], [[ethmoid sinus]], [[Chiasmatic cistern|intrachiasmatic area]], [[temporal lobe]]. | *Rare locations of craniopharyngiomas are; the [[nasopharynx]] , [[Paranasal sinus|paranasal area]] , [[sphenoid bone]], [[ethmoid sinus]], [[Chiasmatic cistern|intrachiasmatic area]], [[temporal lobe]]. | ||
*Craniopharyngiomas are supplied with blood coming from the [[Cerebral circulation|anterior cerebral circulation]].<ref name="pmid10690718">{{cite journal |vauthors=Duff J, Meyer FB, Ilstrup DM, Laws ER, Schleck CD, Scheithauer BW |title=Long-term outcomes for surgically resected craniopharyngiomas |journal=Neurosurgery |volume=46 |issue=2 |pages=291–302; discussion 302–5 |date=February 2000 |pmid=10690718 |doi= |url=}}</ref> | *Craniopharyngiomas are supplied with [[blood]] coming from the [[Cerebral circulation|anterior cerebral circulation]].<ref name="pmid10690718">{{cite journal |vauthors=Duff J, Meyer FB, Ilstrup DM, Laws ER, Schleck CD, Scheithauer BW |title=Long-term outcomes for surgically resected craniopharyngiomas |journal=Neurosurgery |volume=46 |issue=2 |pages=291–302; discussion 302–5 |date=February 2000 |pmid=10690718 |doi= |url=}}</ref> | ||
*Several [[Cytokines|inflammatory cytokines]] have been shown to be elevated in the craniopharyngioma cyst fluid compared with cerbrospinal fluid ([[CSF|CSF)]].<ref name="pmid17630614">{{cite journal |vauthors=Garrè ML, Cama A |title=Craniopharyngioma: modern concepts in pathogenesis and treatment |journal=Curr. Opin. Pediatr. |volume=19 |issue=4 |pages=471–9 |date=August 2007 |pmid=17630614 |doi=10.1097/MOP.0b013e3282495a22 |url=}}</ref> | *Several [[Cytokines|inflammatory cytokines]] have been shown to be elevated in the craniopharyngioma [[Cyst|cyst fluid]] compared with [[CSF|cerbrospinal fluid]] ([[CSF|CSF)]].<ref name="pmid17630614">{{cite journal |vauthors=Garrè ML, Cama A |title=Craniopharyngioma: modern concepts in pathogenesis and treatment |journal=Curr. Opin. Pediatr. |volume=19 |issue=4 |pages=471–9 |date=August 2007 |pmid=17630614 |doi=10.1097/MOP.0b013e3282495a22 |url=}}</ref> | ||
*Tumor adhesion is the result of local inflammation. | *[[Tumor]] adhesion is the result of [[Inflammation|local inflammation]]. | ||
===Microscopic pathology=== | ===Microscopic pathology=== | ||
*The [[histologic]] pattern consists of nesting of [[squamous]] [[epithelium]] bordered by radially arranged cells. | *The [[histologic]] pattern consists of [[Nestin (protein)|nesting]] of [[squamous]] [[epithelium]] bordered by radially arranged cells. | ||
*Tumor is frequently accompanied by calcium deposition and have a microscopic [[papillary]] architecture.<ref name="pmid9761047">{{cite journal |vauthors=Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, Bruner JM |title=The descriptive epidemiology of craniopharyngioma |journal=J. Neurosurg. |volume=89 |issue=4 |pages=547–51 |date=October 1998 |pmid=9761047 |doi=10.3171/jns.1998.89.4.0547 |url=}}</ref> | *[[Tumor]] is frequently accompanied by [[Calcium|calcium deposition]] and have a [[microscopic]] [[papillary]] architecture.<ref name="pmid9761047">{{cite journal |vauthors=Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, Bruner JM |title=The descriptive epidemiology of craniopharyngioma |journal=J. Neurosurg. |volume=89 |issue=4 |pages=547–51 |date=October 1998 |pmid=9761047 |doi=10.3171/jns.1998.89.4.0547 |url=}}</ref> | ||
*Two distinct types are recognized:<ref name="pmid12466115">{{cite journal |author=Sekine S, Shibata T, Kokubu A, ''et al'' |title=Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations |journal=Am. J. Pathol. |volume=161 |issue=6 |pages=1997–2001 |year=2002 |month=December |pmid=12466115 |pmc=1850925 |doi= |url=http://ajp.amjpathol.org/cgi/pmidlookup?view=long&pmid=12466115}}</ref><ref name="pmid15569047">{{cite journal |author=Sekine S, Takata T, Shibata T, ''et al'' |title=Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma: evidence for its odontogenic epithelial differentiation |journal=Histopathology |volume=45 |issue=6 |pages=573–9 |year=2004 |month=December |pmid=15569047 |doi=10.1111/j.1365-2559.2004.02029.x |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0309-0167&date=2004&volume=45&issue=6&spage=573}}</ref> | *Two distinct types are recognized:<ref name="pmid12466115">{{cite journal |author=Sekine S, Shibata T, Kokubu A, ''et al'' |title=Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations |journal=Am. J. Pathol. |volume=161 |issue=6 |pages=1997–2001 |year=2002 |month=December |pmid=12466115 |pmc=1850925 |doi= |url=http://ajp.amjpathol.org/cgi/pmidlookup?view=long&pmid=12466115}}</ref><ref name="pmid15569047">{{cite journal |author=Sekine S, Takata T, Shibata T, ''et al'' |title=Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma: evidence for its odontogenic epithelial differentiation |journal=Histopathology |volume=45 |issue=6 |pages=573–9 |year=2004 |month=December |pmid=15569047 |doi=10.1111/j.1365-2559.2004.02029.x |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0309-0167&date=2004&volume=45&issue=6&spage=573}}</ref> | ||
#Adamantinomatous craniopharyngioma | #Adamantinomatous craniopharyngioma | ||
#Papillary craniopharyngioma | #Papillary craniopharyngioma | ||
*In the adamantinomatous type, [[Calcification|calcifications]] are visible on neuroimaging and are helpful in diagnosis. | *In the adamantinomatous type, [[Calcification|calcifications]] are visible on [[neuroimaging]] and are helpful in [[diagnosis]]. | ||
*The papillary type rarely calcifies. On [[Microscopy|light microscopy]], the [[Cyst|cysts]] are seen to be lined by [[Squamous epithelium|stratified squamous epithelium]]. | *The papillary type rarely calcifies. On [[Microscopy|light microscopy]], the [[Cyst|cysts]] are seen to be lined by [[Squamous epithelium|stratified squamous epithelium]]. | ||
*[[Keratin|Keratin pearls]] may also be seen. | *[[Keratin|Keratin pearls]] may also be seen. | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]
Overview
Craniopharyngiomas are epithelial tumors that usually arise in the pituitary stalk adjacent to the optic chiasm. On gross pathology, craniopharyngiomas are cystic or partially cystic with solid areas.The cyst is filled with a turbid, proteinaceous material of brownish-yellow color that glitters and sparkles because of a high content of floating cholesterol crystals. On microscopic histopathology, it is categorized into two subtypes: Adamantinomatous and papillary.
Pathophysiology
- Craniopharyngioma is a nonglial intracranial tumor derived from a malformation of embryonic tissue. [1]
- There are differing hypotheses on its embryonic origin.
- Pathogenesis of craniopharyngioma is not completely understood.
- Some authorities advocate that it originates from ectodermal remnants of Rathke's pouch. [2]
- Few pathologists believe that it originates from residual embryonal epithelium of the anterior pituitary gland and of the anterior infundibulum.
Embryonic theory
- According to this theory, craniopharyniomas arise from neoplastic transformation of embryonic squamous cell nests of Rathke's pouch with the stomodeum.[3]
- Cell remnants of the craniopharyngeal duct are spread through the intrasellar and suprasellar region.
- The rotation of the adenohypophysis is caused by different rates of cellular multiplication.
- Different rates of cellular multiplication results in a spread of cells of the craniopharyngeal duct to the suprasellar region.
- The rare location at the cerebellopontine angle could fit with this hypothesis.
Metaplastic theory
- Papillary craniopharyngiomas are the result of metaplasia of the adenohypophyseal cells in the anterior pituitary.
- This theory is supported by the presence of metaplastic nests in the gland. [2]
Gross Pathology
- On macroscopic examination, craniopharyngiomas are cystic or partially cystic with solid areas. [4]
- Craniopharyngiomas can arise anywhere along the craniopharyngeal canal.
- It occur most often in sellar or suprasellar region but can have anterior extension to the prechiasmatic cistern and subfrontal spaces.[4]
- Posterior extension into the prepontine , third ventricle, posterior fossa, and foramen magnum; and laterally toward the subtemporal spaces.
- Rare locations of craniopharyngiomas are; the nasopharynx , paranasal area , sphenoid bone, ethmoid sinus, intrachiasmatic area, temporal lobe.
- Craniopharyngiomas are supplied with blood coming from the anterior cerebral circulation.[5]
- Several inflammatory cytokines have been shown to be elevated in the craniopharyngioma cyst fluid compared with cerbrospinal fluid (CSF).[6]
- Tumor adhesion is the result of local inflammation.
Microscopic pathology
- The histologic pattern consists of nesting of squamous epithelium bordered by radially arranged cells.
- Tumor is frequently accompanied by calcium deposition and have a microscopic papillary architecture.[3]
- Two distinct types are recognized:[7][8]
- Adamantinomatous craniopharyngioma
- Papillary craniopharyngioma
- In the adamantinomatous type, calcifications are visible on neuroimaging and are helpful in diagnosis.
- The papillary type rarely calcifies. On light microscopy, the cysts are seen to be lined by stratified squamous epithelium.
- Keratin pearls may also be seen.
- The cysts are usually filled with a yellow, viscous fluid which is rich in cholesterol crystals.
- Islands of densely packed cells merge with loosely cohesive aggregates of squamous cells known as stellate reticulum.
- Nodules of “wet keratin” representing remnants of pale nuclei embedded within an eosinophilic keratinous mass may be found.
- Cystic cavities containing squamous debris are lined by flattened epithelium.
- Granulomatous inflammation associated with cholesterol clefts and giant cells may be detectable, but this is more typical for xanthogranuloma.[2]
- Piloid gliosis with abundant Rosenthal fibers is often seen at the infiltrative interface of the tumor and should not be mistaken for pilocytic astrocytoma.
- Malignant transformation” of craniopharyngioma appears to be very rare.
Genetics
- Multiple chromosomal abnormalities have been reported by classic cytogenetic analysis.
- Most tumors had abnormalities involving chromosomes 2 and 12.
- More than 70% of adamantinomatous craniopharyngiomas harbor a mutation of the β-catenin gene.
- Most of the mutations affect exon 3, which encodes the degradation targeting box of β-catenin.
- No mutations have been demonstrated in papillary craniopharyngioma.
- Comparative genomic hybridization studies on two large series of craniopharyngiomas have failed to show significant chromosomal imbalances.
- The mutations of genes encoding β-catenin (CTNNB1 and APC) are an exclusive characteristic of adamantinomatous craniopharyngioma.
- Few researchers demonstrated a causative effect of mutant β-catenin in the etiology of human adamantinomatous craniopharyngioma.
References
- ↑ Petito CK, DeGirolami U, Earle KM (April 1976). "Craniopharyngiomas: a clinical and pathological review". Cancer. 37 (4): 1944–52. PMID 1260697.
- ↑ 2.0 2.1 2.2 Rush JA, Younge BR, Campbell RJ, MacCarty CS (November 1982). "Optic glioma. Long-term follow-up of 85 histopathologically verified cases". Ophthalmology. 89 (11): 1213–9. PMID 6818504.
- ↑ 3.0 3.1 Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F, Bruner JM (October 1998). "The descriptive epidemiology of craniopharyngioma". J. Neurosurg. 89 (4): 547–51. doi:10.3171/jns.1998.89.4.0547. PMID 9761047.
- ↑ 4.0 4.1 Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, Shiminski-Maher T, Flamm ES, Epstein FJ, Miller DC (December 1994). "Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome". Neurosurgery. 35 (6): 1001–10, discussion 1010–1. PMID 7885544.
- ↑ Duff J, Meyer FB, Ilstrup DM, Laws ER, Schleck CD, Scheithauer BW (February 2000). "Long-term outcomes for surgically resected craniopharyngiomas". Neurosurgery. 46 (2): 291–302, discussion 302–5. PMID 10690718.
- ↑ Garrè ML, Cama A (August 2007). "Craniopharyngioma: modern concepts in pathogenesis and treatment". Curr. Opin. Pediatr. 19 (4): 471–9. doi:10.1097/MOP.0b013e3282495a22. PMID 17630614.
- ↑ Sekine S, Shibata T, Kokubu A; et al. (2002). "Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations". Am. J. Pathol. 161 (6): 1997–2001. PMC 1850925. PMID 12466115. Unknown parameter
|month=ignored (help) - ↑ Sekine S, Takata T, Shibata T; et al. (2004). "Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma: evidence for its odontogenic epithelial differentiation". Histopathology. 45 (6): 573–9. doi:10.1111/j.1365-2559.2004.02029.x. PMID 15569047. Unknown parameter
|month=ignored (help)