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__NOTOC__
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{{SI}}
{{Pineocytoma}}
{{Pineocytoma}}
{{CMG}}{{AE}}{{SR}}
{{CMG}}{{AE}}{{SR}} {{ADG}}


{{SK}} Pineocytomas; Pinealocytoma; Pinealocytomas; PC; Pineal gland tumor; Brain tumor
{{SK}} [[Pineocytomas]]; [[Pinealocytoma]]; [[Pinealocytomas]]; [[PC]]; [[Pineal gland tumor]]; [[Brain tumor]]


==Overview==
==Overview==
Pineocytoma is a benign, slowly growing [[pineal parenchymal tumors|pineal parenchymal tumor]]. The pineal gland, in the brain secretes melatonin which regulates sleep cycle . Pineocytomas most often occur in adults as a solid mass, although they may appear to have fluid-filled (cystic) spaces on images of the brain. Signs and symptoms of pineocytomas include headaches, nausea, , vision abnormalities, and [[Parinaud syndrome|Parinaud syndrome.]] Pineocytomas are usually slow-growing and rarely spread to other parts of the body. Treatment includes surgery to remove the pineocytoma; most of these tumors do not regrow (recur) after surgery.<ref name="introwiki1">Pineocytoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Pineocytoma. Accessed on November 18, 2015</ref>
Pineocytoma is a [[benign]], slowly growing [[pineal]] [[parenchymal]] [[tumor]]. The [[pineal gland]], in the [[brain]] secretes [[melatonin]] which regulates [[sleep]] cycle . Pineocytomas most often occur in adults as a solid [[mass]], although they may appear to have fluid-filled ([[Cyst|cystic]]) spaces on images of the [[brain]]. [[Signs and Symptoms|Signs and symptoms]] of pineocytomas include [[headaches]], [[nausea]], [[Vision impairment|vision abnormalities]], and [[Parinaud syndrome|Parinaud syndrome.]] Pineocytomas are usually slow-growing and rarely spread to other parts of the body. Treatment includes [[surgery]] to remove the pineocytoma; most of these [[Tumor|tumors]] do not regrow (recur) after [[surgery]].<ref name="introwiki1">Pineocytoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Pineocytoma. Accessed on November 18, 2015</ref>


== Classification ==
== Classification ==
The 2007 WHO classification of central nervous system tumors divides pineal gland tumors into four groups [16]:
The 2007 WHO classification of [[central nervous system]] [[tumors]] divides [[pineal gland]] [[Tumor|tumors]] into four groups:
* Pineocytoma (grade I)
* Pineocytoma (grade I)
* Pineal parenchymal tumors of intermediate differentiation (grade II or III)
*[[Pineal]] [[parenchymal]] [[tumors]] of intermediate differentiation (grade II or III)
* Papillary tumor of the pineal region (grade II or III)
*[[Papillary tumors of the pineal region|Papillary tumor of the pineal region]] (grade II or III)
* Pineoblastoma (grade IV)
*[[Pineoblastoma]] (grade IV)
According to the ''WHO classification of tumors of the central nervous system'', pineocytoma is classified into a WHO grade I tumor.<ref name="WHOgrade">General feature of pineocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015</ref>


==Pathophysiology==
==Pathophysiology==
 
===Pathogenesis===
=== Normal Anatomy ===
* Due to the [[Pineal gland|pineal gland's]] location, any [[tumor]] or [[cyst]] formation would lead to the compression of the [[aqueduct of Sylvius]].
* The pineal gland is a small reddish-brown structure that derives its name from its pinecone-like shape.  
* The [[aqueduct of Sylvius]] allows the [[cerebrospinal fluid]] to circulate out. 
* The pineal ranges in size from 10 to 14 mm; it is located in the midline, above the tentorium and superior colliculi and below the splenium of the corpus callosum and the vein of Galen, and is attached to the superior aspect of the posterior border of the third ventricle.  
* When there is a blockage in [[aqueduct of Sylvius]] by an abnormal [[pineal gland]], the passage of the duct is blocked, and [[CSF]] pressure builds up, leading to [[hydrocephalus]]. 
*  
** Results in [[nausea]], [[vomiting]], visual changes, [[Headache|headaches]], [[Seizure|seizures]], and memory changes. 
 
* Increase in [[intracranial pressure]] can even be life-threatening, prompting emergency treatment. 
=== Embryology ===
* The [[hydrocephalus]] can be relieved by the placement of a [[Ventriculoperitoneal shunt|VP shunt]] or [[ventriculostomy]]. 
* Pineal gland develops as a diverticulum in the diencephalic roof of the third ventricle during the second month of gestation.  
*[[Vision]] changes would also occur due to an involvement of the [[tectal]] region. 
* The mature gland is suspended from the pineal stalk from the posterior roof of the third ventricle.  
** The [[tectal]] region helps dictate [[Eye movement|eye movements]].
* The pineal secretes melatonin, which is involved in diurnal rhythms.
** Fault in the [[tectal]] region causes [[double vision]], an issue with focusing on objects, and [[eye movement]] impairment.
* The [[pineal gland]] can cause [[Parinaud's syndrome|Parinaud syndrome]] due to the increasing size of the [[gland]] compressing the pretectal area and [[Superior colliculus|superior colliculi]] of the [[midbrain]].
**[[Parinaud's syndrome|Parinaud syndrome]] prevents a person from moving his or her [[eyes]] up and down.
* The [[thalamus]] can be affected, and if so, there can be disturbances on that side of the body which would result in [[weakness]] and loss of [[sensation]].
* The tumor's effect on the [[hypothalamus]] will lead to [[weight gain]], disruption of sleep, disruption of temperature control, and water regulation. 
* Cerebellar involvement would result in motor impairment.  
** If the tumor of the pineal gland is present in childhood, then endocrine dysfunctions can also result such as precocious pseudopuberty, [[diabetes insipidus]], and a slowed growth rate.


===Gross Pathology===
===Gross Pathology===
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On microscopic histopathological analysis, pineocytoma is characterized by:<ref name="micro1">Microscopic features of pineocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015</ref>
On microscopic histopathological analysis, pineocytoma is characterized by:<ref name="micro1">Microscopic features of pineocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015</ref>
*Cytologically benign cells (uniform size of nuclei, regular nuclear membrane, light chromatin)
*Cytologically benign cells (uniform size of nuclei, regular nuclear membrane, light chromatin)
*Pineocytomatous/neurocytic rosette, which is an irregular circular/flower-like arrangement of cells with a large meshwork of fibers ([[neuropil]]) at the centre
*Pineocytomatous/neurocytic rosette, which is an irregular circular/flower-like arrangement of cells with a large meshwork of fibers ([[neuropil]]) at the center.
 
[[File:Pineocytoma - intermed mag.jpg|center|thumb|Intermediate magnification micrograph of a pineocytoma. HPS stain.<ref name="micropic1">Microscopic images of pineocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015</ref>]]
According to the ''WHO classification of tumors of the central nervous system'', pineocytoma is classified into a WHO grade I tumor.<ref name="WHOgrade">General feature of pineocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015</ref>


===Immunohistochemistry===
===Immunohistochemistry===
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*[[Ki-67 (Biology)|Ki-67]]
*[[Ki-67 (Biology)|Ki-67]]
*[[TUBB3|Beta tubulin III]]
*[[TUBB3|Beta tubulin III]]
===Gallery===
<gallery>
Image:Pineocytoma - intermed mag.jpg|<sub>Intermediate magnification micrograph of a pineocytoma. HPS stain.<ref name=micropic1>Microscopic images of pineocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015</ref></sub>
Image:Pineocytoma - high mag.jpg|<sub>High magnification micrograph of a pineocytoma. HPS stain.<ref name=micropic1>Microscopic images of pineocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015</ref></sub>
Image:Pineocytoma - very high mag.jpg|<sub>Very high magnification micrograph of a pineocytoma. HPS stain.<ref name=micropic1>Microscopic images of pineocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015</ref></sub>
Image:Ihc1.jpg|<sub>The tumor cells are diffusely positive for synaptophysin and neurofilament.<ref name=ihcpin1>Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file [http://radiopaedia.org/cases/pineocytoma here]). Creative Commons BY-SA-NC</ref></sub>
Image:Ihc2.jpg|<sub>Positivity to Ki-67. The Ki-67 index is 2-3%.<ref name=ihc2>Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file [http://radiopaedia.org/cases/pineocytoma here]). Creative Commons BY-SA-NC</ref></sub>
</gallery>


==Differentiating Pineocytoma from other Diseases==
==Differentiating Pineocytoma from other Diseases==
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*[[Cavernoma|Cavernoma in pineal region]]
*[[Cavernoma|Cavernoma in pineal region]]
*[[Aneurysm|Aneurysm in pineal region]]
*[[Aneurysm|Aneurysm in pineal region]]
For differentiating pineal gland tumors from other cranial tumors click [[Astrocytoma differential diagnosis|here]]


{| class="wikitable"
For differentiating among different types of pineal gland tumors click here
|+
! rowspan="2" |Tumors
! rowspan="2" |Grade
! rowspan="2" |Pathalogic Features
! rowspan="2" |5-year survival
! rowspan="2" |Cerebrospinal fluid (CSF) dissemination
! colspan="2" |Imaging
|-
!CT
!MRI
|-
|Pineocytoma
|
* Grade I lesion
|
* Small, uniform, mature cells that resemble pineocytes
* Lobular architecture and pineocytomatous rosettes
|
* 86%–100%
|
* Rare
|Well demarcated, usually less than 3 cm, and iso- to hyperattenuating.
|
* Hypo- to isointense on T1-weighted images and hyperintense on T2-weighted images.
|-
|Pineal Parenchymal Tumor of Intermediate Differentiation
|
* Grade II or III
|
* Gross inspection, PPTID is similar in appearance to pineocytoma.
* It is a well-circumscribed lesion without evidence of necrosis.
* Histologic evaluation reveals diffuse sheets of uniform cells and the formation of small rosettes, with features intermediate between those of pineocytoma and those of pineoblastoma.
* Low to moderate levels of mitotic activity and nuclear atypia are seen.
|
* 39%–74%
|
* Rare
|
* No specific imaging findings
|
* No specific imaging findings
* Demonstrate high signal intensity on T2-weighted images and enhance on postcontrast images
* Cystic areas may also be seen
|-
|Pineoblastoma
|
* Grade IV
|
* Pineo-blastomas are highly cellular embryonal neoplasms that resemble other primitive neuroectodermal neoplasms of the central nervous system.
* Cells have scant cytoplasm and are arranged in diffuse sheets.
* Homer-Wright rosettes (neuroblastic differentiation) or Flexner-Wintersteiner rosettes (retinoblastic differentiation) may be seen, and hemorrhage or necrosis may be present.
* Infiltration into adjacent structures and craniospinal dissemination commonly occur
|
* 58%
|
* Most common cause of the death
|
* Lobulated, typically hyperattenuating mass, an appearance that reflects its highly cellular histologic features.
|
* Ill-defined enhancing pineal mass with resultant hydrocephalus
|-
|Papillary Tumor of the Pineal Region
|
* Grade II or III
|
* PTPRs are well-circumscribed lesions that can measure up to 5 cm and may have a cystic component.
* At histologic evaluation, they demonstrate an epithelial-like growth pattern, papillary features, rosettes, and perivascular pseudorosettes.
* The immunohistochemical findings help differentiate PTPR from other lesions in the pineal region, especially ependymoma and choroid plexus papilloma.
|
* 73%
|
* 75% times
|
|
* Well-circumscribed lesions with variable signal intensity on T1-weighted images, high signal intensity on T2-weighted images, and enhancement on postcontrast images.
* Cystic areas are commonly present.
* Hyperintensity on T1-weighted images has been described, which is hypothesized to be related to secretory inclusions containing protein or glycoprotein.
|-
|Germinoma
|
* Grade II
|
* Account for 1%–2% of all cranial neoplasms
* 65% of intracranial germinomas occur in the pineal region
|
* >79%
|
* The possibility of CSF seeding necessitates imaging evaluation of the entire neuroaxis
|
* Sharply circumscribed, hyperattenuating mass that engulfs the pineal calcifications
|
* Demonstrates a solid mass that may have cystic components.
* Germinomas are iso- to hyperintense to gray matter on T1- and T2-weighted images 
* Avid, homogeneous enhancement on postcontrast images
|-
|Teratoma
|
* Grade III
|
* Mature teratoma reveals a lobulated neoplasm with a complex mixture of adult-type tissues from all three embryonic germ layers.
* Skin and skin appendages may be seen due to the ectodermal component.
* The mesoderm contributes to the presence of cartilage, bone, fat, and smooth and skeletal muscle.
* Respiratory or enteric epithelium arises from the endodermal component.
* Immature teratomas contain incompletely differentiated tissue elements that resemble fetal tissue.
|
|
|
* Multiloculated, lobulated lesion with foci of fat attenuation, calcification, and cystic regions
|
* T1-weighted MR images may show foci of T1 shortening due to fat and variable signal intensity related to calcification.
* On T2-weighted images, the soft-tissue component is iso- to hypointense.
|-
|Pineal Cyst
|
* Grade II
|
* Pineal cysts occur in all age ranges but are most predominant in adults 40–49 years of age; studies demonstrate a female predominance.
* Their origin is debated, with some suggesting they result from degenerative changes in the gland.
* These lesions are typically asymptomatic and are usually 2–15 mm in size.
* Follow-up studies have indicated that these lesions remain stable in size over time.
* When they exceed 15 mm, patients may become symptomatic, typically with headache or visual changes.
* Intracystic hemorrhage (“pineal apoplexy”) and acute hydrocephalus rarely occur; resultant death has been reported
|
* 75% of pineal cysts remained stable during a period of 0.5–9.1 years.
|
* Rare
|
|
* Round or oval, thin-walled, and well-circumscribed.
* They typically demonstrate signal intensity similar to that of CSF on T1- and T2-weighted images
|-
|Epidermoid and Dermoid Cysts
|
|
* The wall of epidermoid cysts is composed of simple stratified squamous epithelium, and the cyst contents consist of layers of keratinaceous debris, which impart a “pearly” appearance to the gross specimen.
* Dermoid cysts contain dermal appendages (hair follicles, sweat glands.
* Both lesions slowly expand over time and rupture can result in chemical meningitis, which may be fatal.
|
|
|
* Epidermoid cysts have low attenuation, similar to that of CSF.
* Dermoid cysts have a more variable appearance, and areas of low attenuation may be seen due to a lipid component—not due to fat, which is of mesodermal origin.
* Peripheral calcifications may be seen in both lesions.
|
* Epidermoid cysts are hypointense on T1-weighted images and hyperintense on T2-weighted images, with signal intensity similar to that of CSF.
* They insinuate into adjacent structures and encase nerves and blood vessels, making resection difficult.
|-
|Astrocytoma
|
* Grade I II III IV
|
* Uncommon.
* They derive from stromal astrocytes
* In the pineal region they arise from the splenium of the corpus callosum, the thalamus, or the tectum of the midbrain.
* Rarely, they may arise from the neuronal elements within the pineal gland.
|
* Grade 2
** 34% without treatment
** 70% with [[radiation therapy]]
*  The [[prognosis]] is worst for these grade 4 [[glioma]]s.<ref name="pmid15497115">{{cite journal |vauthors=See SJ, Gilbert MR |title=Anaplastic astrocytoma: diagnosis, prognosis, and management |journal=Semin. Oncol. |volume=31 |issue=5 |pages=618–34 |date=October 2004 |pmid=15497115 |doi= |url=}}</ref><ref name="pmid12187956">{{cite journal |vauthors=Korshunov A, Golanov A, Sycheva R |title=Immunohistochemical markers for prognosis of anaplastic astrocytomas |journal=J. Neurooncol. |volume=58 |issue=3 |pages=203–15 |date=July 2002 |pmid=12187956 |doi= |url=}}</ref><ref name="pmid2990664">{{cite journal |vauthors=Burger PC, Vogel FS, Green SB, Strike TA |title=Glioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications |journal=Cancer |volume=56 |issue=5 |pages=1106–11 |date=September 1985 |pmid=2990664 |doi= |url=}}</ref>
**Few patients survive beyond 3 years.
|
* Uncommon
|
*In [[low grade astrocytoma]]:
**Poorly demarcated mass
**Low density
**No inhancement inside the tumor
**In few cases we might see some [[calcification]] and [[Cyst|cystic]] changes inside the mass
*In [[high grade astrocytoma]]:
**Poorly demarcated mass
**Low density
**There are partial enhancement inside the [[tumor]] mass
|
* Bulbous enlargement of the tectal plate is noted.
* The lesion is typically isointense on T1-weighted images
* Hyperintense on T2-weighted images with no to minimal enhancement on postcontrast images
|-
|Lipoma
|
|
* Abnormal differentiation of the meninx primitiva, which is the undifferentiated mesenchyme that surrounds the developing brain and normally develops into the leptomeninges and subarachnoid space.
* Lipomas represent malformations and not neoplasms.
* Blood vessels and nerves course through them, making resection difficult if required.
|
|
|
* Low attenuation, consistent with fat
|
* hyperintense on T1-weighted images with saturation on fat-saturated images
|}


==Epidemiology==
==Epidemiology==
===Prevalence===
===Prevalence===
*Pineocytoma constitutes approximately 45% of the pineal parenchymal tumors.<ref name="HiratoNakazato2001">{{cite journal|last1=Hirato|first1=Junko|last2=Nakazato|first2=Yoichi|journal=Journal of Neuro-Oncology|volume=54|issue=3|year=2001|pages=239–249|issn=0167594X|doi=10.1023/A:1012721723387}}</ref>
*Pineocytoma constitutes approximately 45% of the pineal parenchymal tumors.<ref name="HiratoNakazato2001">{{cite journal|last1=Hirato|first1=Junko|last2=Nakazato|first2=Yoichi|journal=Journal of Neuro-Oncology|volume=54|issue=3|year=2001|pages=239–249|issn=0167594X|doi=10.1023/A:1012721723387}}</ref><ref name="epipineo12" />
*Pineocytoma constitutes approximately 0.4 - 1% of the intracranial neoplasms.<ref name="ClarkSughrue2011">{{cite journal|last1=Clark|first1=Aaron J.|last2=Sughrue|first2=Michael E.|last3=Aranda|first3=Derick|last4=Parsa|first4=Andrew T.|title=Contemporary Management of Pineocytoma|journal=Neurosurgery Clinics of North America|volume=22|issue=3|year=2011|pages=403–407|issn=10423680|doi=10.1016/j.nec.2011.05.004}}</ref>
*Pineocytoma constitutes approximately 0.4 - 1% of the intracranial neoplasms.<ref name="ClarkSughrue2011">{{cite journal|last1=Clark|first1=Aaron J.|last2=Sughrue|first2=Michael E.|last3=Aranda|first3=Derick|last4=Parsa|first4=Andrew T.|title=Contemporary Management of Pineocytoma|journal=Neurosurgery Clinics of North America|volume=22|issue=3|year=2011|pages=403–407|issn=10423680|doi=10.1016/j.nec.2011.05.004}}</ref>


===Age===
===Age===
*Pineocytoma is a rare disease that tends to affect all age groups, most commonly in the second decade of life.<ref name="epipineo12">Epidemiology of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>
*Pineocytoma is a rare disease that tends to affect all age groups, most commonly in the second decade of life.<ref name="epipineo12">Epidemiology of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>
*Pineal tumors are more common in children aged 1 to 12 years where these constitute about 3 percent of brain tumors [2].
===Gender===
*Pineal tumors are substantially more common in males. <ref name="epipineo12">Epidemiology of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>
*In those with germ cell tumors, the male predominance was approximately 12:1.
=== Demographics ===
*In Europe and North America, pineal tumors account for less than 1 percent of all primary brain tumors.
=== Race ===
* Pineal tumors are more common in Asian countries than in Western countries.
* This increased frequency is due largely to an increase in germ cell tumors, which comprise 70 to 80 percent of all pineal region tumors in Japan and Korea.


==Natural History, Complication and Prognosis==
==Natural History, Complication and Prognosis==
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*Clark et al. after performing a systematic review of the literature reported that the 1- and 5-year progression free survival (PFS) rates for patients that underwent resection versus the biopsy group were 97% and 90%, and 89% and 75% respectively. The 1- and 5-year PFS rates for the gross total resection group versus the group undergoing subtotal resection combined with radiation therapy were 100% and 94%, and 100% and 84% respectively.<ref name="Alexiou2012">{{cite journal|last1=Alexiou|first1=George A|title=Management of pineal region tumours in children|journal=Journal of Solid Tumors|volume=2|issue=2|year=2012|issn=1925-4075|doi=10.5430/jst.v2n2p15}}</ref>
*Clark et al. after performing a systematic review of the literature reported that the 1- and 5-year progression free survival (PFS) rates for patients that underwent resection versus the biopsy group were 97% and 90%, and 89% and 75% respectively. The 1- and 5-year PFS rates for the gross total resection group versus the group undergoing subtotal resection combined with radiation therapy were 100% and 94%, and 100% and 84% respectively.<ref name="Alexiou2012">{{cite journal|last1=Alexiou|first1=George A|title=Management of pineal region tumours in children|journal=Journal of Solid Tumors|volume=2|issue=2|year=2012|issn=1925-4075|doi=10.5430/jst.v2n2p15}}</ref>


==History and Symptoms==
== Diagnosis ==
===History===
 
===History ===
When evaluating a patient for pineocytoma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review.
When evaluating a patient for pineocytoma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review.
===Symptoms===
===Symptoms===
*The clinical presentation of pineocytoma is mainly from the [[obstructive hydrocephalus]] secondary to compression of the [[tectum]] of the midbrain and obstruction of the [[Cerebral aqueduct|aqueduct]].<ref name="symptoms1">Clinical presentation of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>
*The clinical presentation of pineocytoma is mainly from the [[obstructive hydrocephalus]] secondary to compression of the [[tectum]] of the midbrain and obstruction of the [[Cerebral aqueduct|aqueduct]].<ref name="symptoms1">Clinical presentation of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>
**Pineal tumors cause neurologic dysfunction by direct invasion, compression, or obstruction of cerebrospinal fluid (CSF) flow.  
**Pineal tumors cause neurologic dysfunction by direct invasion, compression, or obstruction of cerebrospinal fluid (CSF) flow.
**The rate of tumor growth determines the rapidity of symptom onset and is an important prognostic factor.
**The rate of tumor growth determines the rapidity of symptom onset and is an important prognostic factor.
*Pineal gland tumors share some common clinical and radiographic features based upon their anatomic location. Symptoms of pineocytoma include:
*Pineal gland tumors share some common clinical and radiographic features based upon their anatomic location. Symptoms of pineocytoma include:
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|}
|}


==Physical Examination==
===Staging===
The staging work-up for pineal tumors include
*Contrast-enhanced MRI of the brain and the entire spine.
*The cerebrospinal fluid (CSF) for cytological examination.
===Physical Examination===
Compression of the superior colliculi can lead to a characteristic gaze palsy, known as [[Parinaud syndrome]]. Common physical examination findings of pineocytoma include:<ref name="symptoms1">Clinical presentation of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>
Compression of the superior colliculi can lead to a characteristic gaze palsy, known as [[Parinaud syndrome]]. Common physical examination findings of pineocytoma include:<ref name="symptoms1">Clinical presentation of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>


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*[[Loss of bladder control]]
*[[Loss of bladder control]]
*[[Ataxia]]
*[[Ataxia]]
===Laboratory Diagnosis===
There are no specific laboratory findings for pineocytoma. However, the following findings are of significant
*Both serum and CSF should be assayed for alpha-fetoprotein and beta human chorionic gonadotropin (beta-hCG) to help diagnose a germ cell tumor.
*Immunohistochemistry may be of value in detecting these markers or placental alkaline phosphatase.


==CT==
===CT===
*Head CT scan may be diagnostic of pineocytoma.  
*Head CT scan may be diagnostic of pineocytoma.  
*Findings on CT scan suggestive of pineocytoma include a mass of intermediate density similar to the adjacent brain with peripheral calcifications.<ref name="scan1">Radiographic features of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopeadia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>
*Findings on CT scan suggestive of pineocytoma include a mass of intermediate density similar to the adjacent brain with peripheral calcifications.<ref name="scan1">Radiographic features of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopeadia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>
[[File:CT image pineocytoma 2.jpg|center|thumb|300x300px|Case courtesy of A.Prof Frank Gaillard, <a href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/2647">rID: 2647</a>]]


===Gallery===
===MRI===
<gallery>
Image:CT image pineocytoma 1.jpg|<sub>Different patterns of pineal calcification: Exploded calcification of tumors of pineal cell origin and engulfed calcification by germinomas.<ref name=ctradiopaedia1>Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file [http://radiopaedia.org/cases/pineal-tumour-calcification-illustration here]). Creative Commons BY-SA-NC</ref></sub>
Image:CT image pineocytoma 2.jpg|<sub>Single image following biopsy and third ventriculostomy demonstrates a pineal region soft tissue mass. A small amount of blood is seen in the occipital horn on the right. Ventricles remain dilated.<ref name=ctradiopaedia1>Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file [http://radiopaedia.org/cases/pineal-tumour-calcification-illustration here]). Creative Commons BY-SA-NC</ref></sub>
Image:CT image pineocytoma 3.jpg|<sub>A 14 X 13 mm (axial) soft tissue density mass in the pineal region with eccentric peripheral calcification demonstrated. The ventricles are prominent, out of keeping with the degree of sulcal prominence, indicating mild to moderate obstructive hydrocephalus due to the lesion partially obstructing the upper margin of the cerebral aqueduct. Periventricular hypoattenuation is in keeping with chronic small vessel ischaemia +/- transependymal CSF accumulation.<ref name=ct3>Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file [http://radiopaedia.org/cases/pineocytoma here]). Creative Commons BY-SA-NC</ref></sub>
 
 
</gallery>
 
==MRI==
*Brain MRI may be diagnostic of pineocytoma.
*Brain MRI may be diagnostic of pineocytoma.
*Features on MRI suggestive of pineocytoma include:<ref name="scan1">Radiographic features of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopeadia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>
*Features on MRI suggestive of pineocytoma include:<ref name="scan1">Radiographic features of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopeadia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref>
 
[[File:MRI image of pineocytoma 2.jpg|center|thumb|A large and ill-defined mass is present in the region of the pineal gland, demonstrating contrast enhancement.<ref name="mri1">Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file [http://radiopaedia.org/cases/pineocytoma-1 here]). Creative Commons BY-SA-NC</ref>]]
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===Gallery===
=== Other Diagnostic Studies ===
<gallery>
Image:MRI image of pineocytoma 1.jpg|<sub>A large and ill-defined mass is present in the region of the pineal gland, demonstrating contrast enhancement.<ref name=mri1>Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file [http://radiopaedia.org/cases/pineocytoma-1 here]). Creative Commons BY-SA-NC</ref></sub>
Image:MRI image of pineocytoma 2.jpg|<sub>Axial T2 demonstrating a circular mass centered in pineal region measures 12 x 11 x 9 mm and demonstrates homogeneous enhancement (on volumetric sequence for stereotaxis), peripheral calcification, and diffusion restriction.  It has mass effect on the adjacent structures with stenosis of the cerebral aqueduct (some flow still present on cine imaging) and associated non-communicating hydrocephalus affecting the lateral ventricles and 3rd ventricle. Foramina of Monroe are patent. No other suspicious enhancing lesion, including of the leptomeninges. No suprasellar/sellar mass in non-dedicated study.<ref name=mri2>Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file [http://radiopaedia.org/cases/pineocytoma here]). Creative Commons BY-SA-NC</ref></sub>
Image:MRI image of pineocytoma 3.jpg|<sub>T2 MRI image demonstrating a well circumscribed mass is located in the region of the pineal gland. It is a little heterogeneous with multiple small regions of cyst formation (on T2) most marked anteriorly, probably at the site of biopsy.<ref name=mri3>Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file [http://radiopaedia.org/cases/pineocytoma-causing-hydrocephalus here]). Creative Commons BY-SA-NC</ref></sub>
Image:MRI image of pineocytoma 4.jpg|<sub>Axial T1 with contrast demonstrating a large enhancing mass is present in the pineal region compressing the tectum and resulting in obstructive hydrocephalus.<ref name=mri4>Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file [http://radiopaedia.org/cases/pineocytoma-with-astrocytic-differentiation-1 here]). Creative Commons BY-SA-NC</ref></sub>
 


</gallery>
'''Stereotactic biopsy'''
* A direct, visually guided biopsy of the pineal gland mass with open or neuroendoscopic surgery has been preferred due to concerns about injury to the deep cerebral veins.
* An open procedure also allows CSF to be obtained for
** Tumor marker studies
** Permits direct visualization of the third ventricle for staging purposes
** Sllows a third ventriculostomy to be performed for CSF diversion if needed.
* The diagnostic yield of stereotactic biopsy ranges from 94 to 100 percent.
* If the biopsy is nondiagnostic, equivocal, or suggests a benign tumor such as mature teratoma or meningioma, surgery is recommended to establish a definitive diagnosis or to identify focal areas of malignant disease


==Treatment==
==Treatment==
*The mainstay of therapy for pineocytoma is [[surgery]] (gross total or subtotal resection).<ref name="prog1">Treatment and prognosis of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015.http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref><ref name="DeshmukhSmith2004">{{cite journal|last1=Deshmukh|first1=Vivek R.|last2=Smith|first2=Kris A.|last3=Rekate|first3=Harold L.|last4=Coons|first4=Stephen|last5=Spetzler|first5=Robert F.|title=Diagnosis and Management of Pineocytomas|journal=Neurosurgery|volume=55|issue=2|year=2004|pages=349–357|issn=0148-396X|doi=10.1227/01.NEU.0000129479.70696.D2}}</ref><ref name="Alexiou2012">{{cite journal|last1=Alexiou|first1=George A|title=Management of pineal region tumours in children|journal=Journal of Solid Tumors|volume=2|issue=2|year=2012|issn=1925-4075|doi=10.5430/jst.v2n2p15}}</ref>  
*The mainstay of therapy for pineocytoma is [[surgery]] (gross total or subtotal resection).<ref name="prog1">Treatment and prognosis of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015.http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015</ref><ref name="DeshmukhSmith2004">{{cite journal|last1=Deshmukh|first1=Vivek R.|last2=Smith|first2=Kris A.|last3=Rekate|first3=Harold L.|last4=Coons|first4=Stephen|last5=Spetzler|first5=Robert F.|title=Diagnosis and Management of Pineocytomas|journal=Neurosurgery|volume=55|issue=2|year=2004|pages=349–357|issn=0148-396X|doi=10.1227/01.NEU.0000129479.70696.D2}}</ref><ref name="Alexiou2012">{{cite journal|last1=Alexiou|first1=George A|title=Management of pineal region tumours in children|journal=Journal of Solid Tumors|volume=2|issue=2|year=2012|issn=1925-4075|doi=10.5430/jst.v2n2p15}}</ref>
*The treatment of PPTs must be guided by the histologic subtype.  
*The treatment of PPTs must be guided by the histologic sub type can be assessed by tissue diagnosis 
*Empiric therapy is recommended in nongerminomatous GCT in a patient with characteristic neuroimaging studies and elevated serum or CSF levels of the tumor markers alpha-fetoprotein and/or the beta subunit of human chorionic gonadotropin. 
* Empiric therapy for patient with germinoma can be initiated based upon the imaging presence of “bi focal” tumors, CSF beta-hCG <50 mIU/mL, and no elevation of alpha-fetoprotein.  
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Latest revision as of 06:46, 6 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2] Aditya Ganti M.B.B.S. [3]

Synonyms and keywords: Pineocytomas; Pinealocytoma; Pinealocytomas; PC; Pineal gland tumor; Brain tumor

Overview

Pineocytoma is a benign, slowly growing pineal parenchymal tumor. The pineal gland, in the brain secretes melatonin which regulates sleep cycle . Pineocytomas most often occur in adults as a solid mass, although they may appear to have fluid-filled (cystic) spaces on images of the brain. Signs and symptoms of pineocytomas include headaches, nausea, vision abnormalities, and Parinaud syndrome. Pineocytomas are usually slow-growing and rarely spread to other parts of the body. Treatment includes surgery to remove the pineocytoma; most of these tumors do not regrow (recur) after surgery.[1]

Classification

The 2007 WHO classification of central nervous system tumors divides pineal gland tumors into four groups:

According to the WHO classification of tumors of the central nervous system, pineocytoma is classified into a WHO grade I tumor.[2]

Pathophysiology

Pathogenesis

Gross Pathology

On gross pathology, pineocytoma is characterized by solid, sometimes with focal areas of cystic change, gray, well-circumscribed mass with or without hemorrhage.[3][4]

Microscopic Pathology

On microscopic histopathological analysis, pineocytoma is characterized by:[5]

  • Cytologically benign cells (uniform size of nuclei, regular nuclear membrane, light chromatin)
  • Pineocytomatous/neurocytic rosette, which is an irregular circular/flower-like arrangement of cells with a large meshwork of fibers (neuropil) at the center.
Intermediate magnification micrograph of a pineocytoma. HPS stain.[6]

Immunohistochemistry

Pineocytoma is demonstrated by positivity to tumor markers such as:[7][8][9][10]

Differentiating Pineocytoma from other Diseases

Pineocytoma must be differentiated from:[11]

For differentiating pineal gland tumors from other cranial tumors click here

For differentiating among different types of pineal gland tumors click here

Epidemiology

Prevalence

  • Pineocytoma constitutes approximately 45% of the pineal parenchymal tumors.[10][12]
  • Pineocytoma constitutes approximately 0.4 - 1% of the intracranial neoplasms.[13]

Age

  • Pineocytoma is a rare disease that tends to affect all age groups, most commonly in the second decade of life.[12]

Natural History, Complication and Prognosis

Natural History

If left untreated, patients with pineocytoma may progress to develop seizures, obstructive hydrocephalus, local recurrence, and CSF metastasis.[14][15]

Complications

Common complications of pineocytoma include:[15][10]

Prognosis

  • Prognosis is generally excellent, and the 5-year survival rate of patients with pineocytoma is approximately 86%.[15]
  • Pineocytoma has the most favorable prognosis among all the pineal gland tumors.[16]
  • Clark et al. after performing a systematic review of the literature reported that the 1- and 5-year progression free survival (PFS) rates for patients that underwent resection versus the biopsy group were 97% and 90%, and 89% and 75% respectively. The 1- and 5-year PFS rates for the gross total resection group versus the group undergoing subtotal resection combined with radiation therapy were 100% and 94%, and 100% and 84% respectively.[17]

Diagnosis

History

When evaluating a patient for pineocytoma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review.

Symptoms

  • The clinical presentation of pineocytoma is mainly from the obstructive hydrocephalus secondary to compression of the tectum of the midbrain and obstruction of the aqueduct.[14]
    • Pineal tumors cause neurologic dysfunction by direct invasion, compression, or obstruction of cerebrospinal fluid (CSF) flow.
    • The rate of tumor growth determines the rapidity of symptom onset and is an important prognostic factor.
  • Pineal gland tumors share some common clinical and radiographic features based upon their anatomic location. Symptoms of pineocytoma include:
Symtpoms Signs
Headaches Papilledema
Vision abnormalities Ataxia
Nausea and vomiting Loss of upward gaze
Impaired ambulation Tremor
Altered pupillary reflexes
Hyperactive deep tendon reflexes

Staging

The staging work-up for pineal tumors include

  • Contrast-enhanced MRI of the brain and the entire spine.
  • The cerebrospinal fluid (CSF) for cytological examination.

Physical Examination

Compression of the superior colliculi can lead to a characteristic gaze palsy, known as Parinaud syndrome. Common physical examination findings of pineocytoma include:[14]

HEENT

  • Bulging soft spots (fontanelles)
  • Eyes that are constantly looking down (sunsetting sign)
  • Deficiency in upward-gaze
  • Pupillary light-near dissociation (pupils respond to near stimuli but not light)
  • Convergence-retraction nystagmus

Neurological

Laboratory Diagnosis

There are no specific laboratory findings for pineocytoma. However, the following findings are of significant

  • Both serum and CSF should be assayed for alpha-fetoprotein and beta human chorionic gonadotropin (beta-hCG) to help diagnose a germ cell tumor.
  • Immunohistochemistry may be of value in detecting these markers or placental alkaline phosphatase.

CT

  • Head CT scan may be diagnostic of pineocytoma.
  • Findings on CT scan suggestive of pineocytoma include a mass of intermediate density similar to the adjacent brain with peripheral calcifications.[18]
Case courtesy of A.Prof Frank Gaillard, <a href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/2647">rID: 2647</a>

MRI

  • Brain MRI may be diagnostic of pineocytoma.
  • Features on MRI suggestive of pineocytoma include:[18]
A large and ill-defined mass is present in the region of the pineal gland, demonstrating contrast enhancement.[19]
MRI component Findings

T1

  • Isointense to brain parenchyma

T2

  • Solid components are isointense to brain parenchyma
  • Areas of cystic change
  • Sometimes the majority of the tumor is cystic

T1 with gadolinium contrast

  • Solid components vividly enhance

Other Diagnostic Studies

Stereotactic biopsy

  • A direct, visually guided biopsy of the pineal gland mass with open or neuroendoscopic surgery has been preferred due to concerns about injury to the deep cerebral veins.
  • An open procedure also allows CSF to be obtained for
    • Tumor marker studies
    • Permits direct visualization of the third ventricle for staging purposes
    • Sllows a third ventriculostomy to be performed for CSF diversion if needed.
  • The diagnostic yield of stereotactic biopsy ranges from 94 to 100 percent.
  • If the biopsy is nondiagnostic, equivocal, or suggests a benign tumor such as mature teratoma or meningioma, surgery is recommended to establish a definitive diagnosis or to identify focal areas of malignant disease

Treatment

  • The mainstay of therapy for pineocytoma is surgery (gross total or subtotal resection).[15][16][17]
  • The treatment of PPTs must be guided by the histologic sub type can be assessed by tissue diagnosis
  • Empiric therapy is recommended in nongerminomatous GCT in a patient with characteristic neuroimaging studies and elevated serum or CSF levels of the tumor markers alpha-fetoprotein and/or the beta subunit of human chorionic gonadotropin.
  • Empiric therapy for patient with germinoma can be initiated based upon the imaging presence of “bi focal” tumors, CSF beta-hCG <50 mIU/mL, and no elevation of alpha-fetoprotein.
Management Options of Penial Gland tumors
CSF diversion
  • The optimal surgical strategy to treat acute hydrocephalus in patients with pineal tumors is uncertain.
  • CSF diversion (ventriculoperitoneal [VP] shunt or third ventriculostomy may be necessary in symptomatic patients, although debulking surgery may obviate the need for this procedure
  • When CSF diversion is necessary, endoscopic third ventriculostomy can be carried out at the same time as the biopsy and is preferred over VP shunts, which can be complicated by infection, shunt malfunction, subdural hematoma, and rarely, tumor seeding
Surgical resection
  • Some series report long-term survival with surgery alone, even in patients with pineoblastomas.
  • Indeed, for pineoblastomas, gross total surgical resection appears to correlate with improved survival.
  • Patients with symptomatic recurrent pineocytomas should also be considered for surgical resection of the lesion
Radiation
  • Postoperative adjuvant RT is frequently (but not universally) recommended, and local control is dose-dependent.
  • The incidence of leptomeningeal recurrence was significantly lower among patients receiving CSI compared with those who did not.
  • The five-year survival rates were 86 and 49 percent for pineocytomas and non-pineocytoma PPTs, respectively.
  • Adjuvant RT is not universally recommended after gross total resection of a pineocytoma
Stereotactic radiosurgery
  • Stereotactic radiosurgery (SRS) is emerging as a useful treatment alternative for pineocytomas, although experience is limited.
  • The precise radiation fields that are defined by MRI or CT-computerized treatment planning minimize damage to the surrounding brain, and the risks of general anesthesia and craniotomy are avoided.
  • SRS is increasingly being used to treat pineal region tumors, either as an additional therapy after conventional treatments or as a primary treatment.
  • Due to the low rate of side effects, IRS may develop into an attractive alternative to microsurgery in de novo diagnosed pineocytomas. In malignant PPTs, IRS may be routinely applied in a multimodality treatment schedule supplementary to conventional irradiation.
Chemotherapy as part of multimodality therapy
  • The similarity of pineoblastomas to medulloblastomas in terms of their clinical behavior and tendency for leptomeningeal seeding has led to the use of similar chemotherapy regimens in patients with pineoblastoma as part of a multimodality approach.
  • Chemotherapy has been used to delay radiation therapy in very young children, for whom the long-term neurocognitive and developmental side effects of craniospinal irradiation (CSI) are a major concern.
  • The importance of radiation therapy as a component of the initial treatment of supratentorial primitive neuroectodermal tumors (PNETs) is also supported by the German HIT-SKK87 and HIT-SKK92 protocols, as well as the Canadian pediatric brain tumor protocol
  • Successful treatment of pineocytomas requires surgery with or without RT, while the best results with pineoblastomas are seen with multimodality approaches that include chemotherapy.
  • The main goal of open surgery on pineocytoma is the complete tumor removal with minimal morbidity, whenever possible. However, even if gross total excision cannot be achieved, establishment of an accurate diagnosis, maximal cytoreduction, and restoration of the CSF pathway may be achieved.
  • Radiotherapy administration to subtotally resected tumor is not associated with an increase in either tumor control or survival.[17]
  • Stereotactically guided iodine-125 seed implantation has been proposed as a potential alternative to microsurgery in de novo diagnosed pineocytomas, since it was proven efficient and safe.
  • Patients with pineocytoma will develop hydrocephalus in majority of the cases and they will require CSF diversion. Ventriculo-peritoneal (V-P) shunt placement is a viable option with low morbidity and mortality rate. However, shunt malfunction in this population is as high as 20%. In addition, tumor metastasis through a CSF shunt has been reported. Endoscopic third ventriculostomy (ETVC) is an alternative option, which also permits a biopsy of the tumor in the same procedure. Ahn et al. reported that the biopsy samples, obtained in the lateral ventricle or pineal region, were more favorable towards a successful diagnosis than those in the thalamus or tectal region. Neuroendoscopic biopsy procedures have been proven safe with low complication rates.[17]

References

  1. ↑ Pineocytoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Pineocytoma. Accessed on November 18, 2015
  2. ↑ General feature of pineocytoma. Libre pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015
  3. ↑ Pathology and radiographic features of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 18, 2015
  4. ↑ Gross description of pineocytoma. Pathology Outlines 2015. http://pathologyoutlines.com/topic/cnstumorpineocytoma.html. Accessed on November 20, 2015
  5. ↑ Microscopic features of pineocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015
  6. ↑ Microscopic images of pineocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 18, 2015
  7. ↑ Microscopic description of pineocytoma causing hydrocephalus. Dr Frank Gaillard. Radiopaedia 2015. http://radiopaedia.org/cases/pineocytoma-causing-hydrocephalus. Accessed on November 20, 2015
  8. ↑ Histology of pineocytoma. Dr Frank Gaillard. Radiopaedia 2015. http://radiopaedia.org/cases/pineocytoma-with-astrocytic-differentiation-1. Accessed on November 20, 2015
  9. ↑ IHC features of pineocytoma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Pineal_gland#Pineocytoma. Accessed on November 20, 2015
  10. ↑ 10.0 10.1 10.2 Hirato, Junko; Nakazato, Yoichi (2001). Journal of Neuro-Oncology. 54 (3): 239–249. doi:10.1023/A:1012721723387. ISSN 0167-594X. Missing or empty |title= (help)
  11. ↑ Differential diagnosis of pineal region mass. Dr Henry Knipe and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineal-region-mass. Accessed on November 20, 2015
  12. ↑ 12.0 12.1 Epidemiology of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015
  13. ↑ Clark, Aaron J.; Sughrue, Michael E.; Aranda, Derick; Parsa, Andrew T. (2011). "Contemporary Management of Pineocytoma". Neurosurgery Clinics of North America. 22 (3): 403–407. doi:10.1016/j.nec.2011.05.004. ISSN 1042-3680.
  14. ↑ 14.0 14.1 14.2 Clinical presentation of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015
  15. ↑ 15.0 15.1 15.2 15.3 Treatment and prognosis of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015.http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015
  16. ↑ 16.0 16.1 Deshmukh, Vivek R.; Smith, Kris A.; Rekate, Harold L.; Coons, Stephen; Spetzler, Robert F. (2004). "Diagnosis and Management of Pineocytomas". Neurosurgery. 55 (2): 349–357. doi:10.1227/01.NEU.0000129479.70696.D2. ISSN 0148-396X.
  17. ↑ 17.0 17.1 17.2 17.3 Alexiou, George A (2012). "Management of pineal region tumours in children". Journal of Solid Tumors. 2 (2). doi:10.5430/jst.v2n2p15. ISSN 1925-4075.
  18. ↑ 18.0 18.1 Radiographic features of pineocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopeadia 2015. http://radiopaedia.org/articles/pineocytoma. Accessed on November 20, 2015
  19. ↑ Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file here). Creative Commons BY-SA-NC


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