Medulloepithelioma: Difference between revisions
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==Overview== | ==Overview== | ||
'''Medulloepithelioma''' is a rare, primitive, fast-growing [[brain tumor]] | '''Medulloepithelioma''' is a rare, primitive, fast-growing [[brain tumor]] that usually originates from [[cell (biology)|cell]]s of the [[embryonic]] [[medullary cavity]]. On the other hand, [[tumors]] originating in the [[ciliary body]] of the [[human eye|eye]] are referred to as [[Embryo|embryonal]] medulloepitheliomas or diktyomas. Medulloepithelioma was first discovered by Bailey and Cushing in 1926. The [[pathogenesis]] of medulloepithelioma is characterized by highly malignant undifferentiated primitive [[Neuroepithelial cell|neuroepithelial]] [[tumor]]. It most commonly manifests in the [[cerebral hemispheres]], [[brainstem]], [[cerebellum]], and in peripheral sites. Medulloepithelioma arises from primitive [[medulla oblongata|medullary]] [[epithelium]], which is normally involved in the [[embryonic]] formation of [[CNS]]. Medulloepithelioma commonly affects individuals younger than 10 years of age. [[CT scan]] findings of medulloepithelioma, include an isodense or hypodense lesion with variable [[heterogeneity]] and [[calcification]]. Complete [[surgical resection]] is the mainstay of treatment for medulloepithelioma. Adjuvant radiochemotherapy is often indicated. | ||
==Historical Perspective== | ==Historical Perspective== | ||
* Intracerebral medulloepithelioma was first discovered by Bailey and Cushing in 1926.<ref name="pmid23248698">{{cite journal| author=Chakrabarti I, Majumdar K, Giri A| title=Infratentorial medulloepithelioma with divergent differentiation: Possibly a predictor of poor outcome. | journal=J Pediatr Neurosci | year= 2012 | volume= 7 | issue= 2 | pages= 142-5 | pmid=23248698 | doi=10.4103/1817-1745.102581 | pmc=3519076 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23248698 }}</ref> | |||
The resemblance between the tumors refers to the neuroepithelium of the embryonic neural tube. | * Intraocular medulloepithelioma was first named by Grinker in 1930; the name derives from its [[histopathological]] resemblance to an even rarer form of medulloeptihelioma of the brain described by Bailey and Cushing.<ref name="Grinker1931">{{cite journal|last1=Grinker|first1=Roy R.|title=GLIOMAS OF THE RETINA|journal=Archives of Ophthalmology|volume=5|issue=6|year=1931|pages=920|issn=0093-0326|doi=10.1001/archopht.1931.00820060088009}}</ref> | ||
* The resemblance between the [[tumors]] refers to the neuroepithelium of the [[Embryo|embryonic]] [[neural tube]].<ref name="Grinker1931" /> | |||
==Classification== | ==Classification== | ||
Medulloepitheliomas are classified as embryonal tumors in the [[World Health Organization|WHO]] classification of [[Brain tumor|CNS tumors]].<ref name="pmid27157931">{{cite journal| author=Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK et al.| title=The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal=Acta Neuropathol | year= 2016 | volume= 131 | issue= 6 | pages= 803-20 | pmid=27157931 | doi=10.1007/s00401-016-1545-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27157931 }}</ref> | Medulloepitheliomas are classified as [[Embryo|embryonal]] [[tumors]] in the [[World Health Organization|WHO]] classification of [[Brain tumor|CNS tumors]].<ref name="pmid27157931">{{cite journal| author=Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK et al.| title=The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal=Acta Neuropathol | year= 2016 | volume= 131 | issue= 6 | pages= 803-20 | pmid=27157931 | doi=10.1007/s00401-016-1545-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27157931 }}</ref> | ||
In 2016, the [[WHO]] classification system was reviewed and identified the [[tumors]] that were previously labeled [[Embryo|embryonal]] [[tumor]] with abundant [[neutrophils]] and true rosettes, [[ependymoblastoma]], and medulloepithelioma and included them in embryonal tumor with multilayered rosettes (ETMR) group; provided they have evidence of ''C19MC'' amplification.<ref name="pmid24337497">{{cite journal| author=Korshunov A, Sturm D, Ryzhova M, Hovestadt V, Gessi M, Jones DT et al.| title=Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity. | journal=Acta Neuropathol | year= 2014 | volume= 128 | issue= 2 | pages= 279-89 | pmid=24337497 | doi=10.1007/s00401-013-1228-0 | pmc=4102829 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24337497 }}</ref> | |||
* ETMR are highly [[malignant]] pediatric tumors with varied embryonal histology but shared genetic alterations in the ''C19MC'' [[gene]]. | |||
==Pathophysiology== | ==Pathophysiology== | ||
===Pathogenesis=== | ===Pathogenesis=== | ||
The pathogenesis of medulloepithelioma is characterized by highly malignant undifferentiated primitive neuroepithelial tumor. | |||
* The pathogenesis of medulloepithelioma is characterized by highly malignant undifferentiated primitive neuroepithelial tumor. | |||
* It most commonly manifests in the cerebral hemispheres, [[brainstem]], [[cerebellum]], and in peripheral sites. | |||
* Intraocular medulloepithelioma arises from the primitive medullary epithelium, which is normally involved in the [[embryonic]] formation of [[CNS]] and is a derivative of the inner layer of the optic cup. Rarely, it can also originate from the retina or optic nerve.<ref name="pmid3056510">{{cite journal| author=Canning CR, McCartney AC, Hungerford J| title=Medulloepithelioma (diktyoma). | journal=Br J Ophthalmol | year= 1988 | volume= 72 | issue= 10 | pages= 764-7 | pmid=3056510 | doi=10.1136/bjo.72.10.764 | pmc=1041579 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3056510 }}</ref> | |||
===Genetics=== | ===Genetics=== | ||
For embryonal tumor with multilayered rosettes (ETMR) | For embryonal tumor with multilayered rosettes (ETMR) | ||
* LIN28A immunohistochemistry | * LIN28A [[immunohistochemistry]] | ||
* FISH analysis of the 19q13.42 | *[[FISH]] analysis of the 19q13.42 | ||
===Gross Pathology=== | ===Gross Pathology=== | ||
It is possible to identify chalky gray-white deposits within the tumor; they are histologically composed of hyaline cartilage or bone.<ref name="VajaranantMafee2005">{{cite journal|last1=Vajaranant|first1=Thasarat S.|last2=Mafee|first2=Mahmood F.|last3=Kapur|first3=Rashmi|last4=Rapoport|first4=Mark|last5=Edward|first5=Deepak P.|title=Medulloepithelioma of the Ciliary Body and Optic Nerve: Clinicopathologic, CT, and MR Imaging Features|journal=Neuroimaging Clinics of North America|volume=15|issue=1|year=2005|pages=69–83|issn=10525149|doi=10.1016/j.nic.2005.02.008}}</ref> | * Intraocular medulloepithelioma most commonly appears as a white, gray, or yellow-colored [[ciliary body]] [[tumor]].<ref name="pmid655220">{{cite journal| author=Broughton WL, Zimmerman LE| title=A clinicopathologic study of 56 cases of intraocular medulloepitheliomas. | journal=Am J Ophthalmol | year= 1978 | volume= 85 | issue= 3 | pages= 407-18 | pmid=655220 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=655220 }}</ref> | ||
* It is possible to identify chalky gray-white deposits within the [[tumor]]; they are [[histologically]] composed of [[hyaline cartilage]] or [[bone]].<ref name="VajaranantMafee2005">{{cite journal|last1=Vajaranant|first1=Thasarat S.|last2=Mafee|first2=Mahmood F.|last3=Kapur|first3=Rashmi|last4=Rapoport|first4=Mark|last5=Edward|first5=Deepak P.|title=Medulloepithelioma of the Ciliary Body and Optic Nerve: Clinicopathologic, CT, and MR Imaging Features|journal=Neuroimaging Clinics of North America|volume=15|issue=1|year=2005|pages=69–83|issn=10525149|doi=10.1016/j.nic.2005.02.008}}</ref> | |||
===Microscopic Pathology=== | ===Microscopic Pathology=== | ||
On '''microscopic histopathological analysis''', characteristic findings of medulloepithelioma may include: | On '''microscopic [[histopathological]] analysis''', characteristic findings of medulloepithelioma may include: | ||
*Small round blue cell tumor | *Small round blue cell [[tumor]] | ||
*Focal differentiation into [[astrocytic]], [[neuronal]] or [[glial cell|ependymal]] phenotypes possible | *Focal [[differentiation]] into [[astrocytic]], [[neuronal]] or [[glial cell|ependymal]] [[phenotypes]] possible | ||
*Multilayered rosettes may be seen | *Multilayered rosettes may be seen | ||
*Growth in streams or palisades | *Growth in streams or palisades | ||
| Line 47: | Line 49: | ||
*Fibrillary background in tumors with advanced [[neuronal]] maturation | *Fibrillary background in tumors with advanced [[neuronal]] maturation | ||
*Variable [[mitotic]] activity | *Variable [[mitotic]] activity | ||
*Neoplastic pseudostratified neuroepithelium | *[[Neoplastic]] [[Pseudostratified epithelium|pseudostratified]] neuroepithelium | ||
**Resembling embryonic neural tube, with papillary, tubular and trabecular arrangements | **Resembling [[Neural tube|embryonic neural tube]], with papillary, tubular and trabecular arrangements | ||
*Sheets of poorly differentiated cells | *Sheets of poorly [[Differentiation|differentiated]] [[cells]] | ||
**With hyperchromatic nuclei and high | **With [[Hyperchromicity|hyperchromatic]] [[nuclei]] and high [[nuclear]] to [[chromatin]] ratio | ||
*Periodic acid-Schiff positive external limiting membrane | *[[Periodic acid-Schiff]] positive external limiting [[membrane]] | ||
*No cilia or blepharoplasts on luminal surface of tubules | *No [[cilia]] or blepharoplasts on [[Luminal|luminal surface]] of [[tubules]] | ||
On '''immunohistopathological analysis''', characteristic findings of medulloepithelioma may include: | On '''[[Immunohistochemistry|immunohistopathological analysis]]''', characteristic findings of medulloepithelioma may include: | ||
*Positive [[S-100]] | *Positive [[S-100]] | ||
*Positive INI1 | *Positive INI1 | ||
*Positive LIN28 | *Positive [[LIN28]] | ||
==Causes== | ==Causes== | ||
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==Differentiating Medulloepithelioma from Other Diseases== | ==Differentiating Medulloepithelioma from Other Diseases== | ||
Medulloepithelioma must be differentiated from other diseases that cause vision loss, ocular mass, and headache such as: | Medulloepithelioma must be differentiated from other diseases that cause vision loss, ocular mass, and headache such as: | ||
*CNS tumors | *[[CNS]] tumors | ||
*Retinoblastoma | *[[Retinoblastoma]] | ||
**Shares radiologic features with medulloepithelioma | **Shares [[radiologic]] features with medulloepithelioma | ||
*Intraocular [[lymphoma]] | *Intraocular [[lymphoma]] | ||
*[[Anterior chamber]] [[cyst]] | *[[Anterior chamber]] [[cyst]] | ||
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Medulloepithelioma is a rare disease. | Medulloepithelioma is a rare disease. | ||
===Age=== | ===Age=== | ||
The median age at diagnosis is 5 years old.<ref name="pmid25136238">{{cite journal| author=Peshtani A, Kaliki S, Eagle RC, Shields CL| title=Medulloepithelioma: A triad of clinical features. | journal=Oman J Ophthalmol | year= 2014 | volume= 7 | issue= 2 | pages= 93-5 | pmid=25136238 | doi=10.4103/0974-620X.137171 | pmc=4134557 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25136238 }}</ref> | * Medulloepithelioma commonly affects individuals younger than 10 years of age.<ref name="Russel">Russel DS, Rubinstein LJ. Pathology of tumors the nervous system, 5th ed. Baltimore: Williams & Wilkins 1989; pp. 247-51.</ref> | ||
* The median age at diagnosis is 5 years old.<ref name="pmid25136238">{{cite journal| author=Peshtani A, Kaliki S, Eagle RC, Shields CL| title=Medulloepithelioma: A triad of clinical features. | journal=Oman J Ophthalmol | year= 2014 | volume= 7 | issue= 2 | pages= 93-5 | pmid=25136238 | doi=10.4103/0974-620X.137171 | pmc=4134557 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25136238 }}</ref> | |||
===Gender=== | ===Gender=== | ||
Medulloepithelioma affects men and women equally. | Medulloepithelioma affects men and women equally. | ||
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There is no racial predilection for medulloepithelioma. | There is no racial predilection for medulloepithelioma. | ||
==Risk Factors== | ==Risk Factors== | ||
There are no known associated risk factors in the development of medulloepithelioma. | There are no known associated [[risk factors]] in the development of medulloepithelioma. | ||
== Screening == | == Screening == | ||
There is insufficient evidence to recommend routine screening for medulloepithelioma. | There is insufficient evidence to recommend routine [[screening]] for medulloepithelioma. | ||
== Natural History, Complications and Prognosis== | == Natural History, Complications and Prognosis== | ||
===Natural History=== | ===Natural History=== | ||
*Patients with medulloepithelioma may be initially asymptomatic. | *Patients with medulloepithelioma may be initially [[asymptomatic]]. | ||
*Early clinical features include vision loss, irritability, and neurological deficit. If left untreated, patients with medulloepithelioma may progress to death.<ref name="pmid25136238" /> | *Early clinical features include [[vision loss]], [[irritability]], and [[neurological]] deficit. If left untreated, patients with medulloepithelioma may progress to death.<ref name="pmid25136238" /> | ||
*Medulloepithelioma have been reported to occur in the cerebral hemispheres, brainstem, cerebellum, and peripheral sites. | *Medulloepithelioma have been reported to occur in the [[cerebral hemispheres]], [[brainstem]], [[cerebellum]], and peripheral sites. | ||
===Complications=== | ===Complications=== | ||
Common complications of medulloepithelioma include:<ref name="pmid25136238" /> | Common complications of medulloepithelioma include:<ref name="pmid25136238" /> | ||
| Line 97: | Line 100: | ||
*CNS dissemination<ref name="pmid8609554">{{cite journal| author=Molloy PT, Yachnis AT, Rorke LB, Dattilo JJ, Needle MN, Millar WS et al.| title=Central nervous system medulloepithelioma: a series of eight cases including two arising in the pons. | journal=J Neurosurg | year= 1996 | volume= 84 | issue= 3 | pages= 430-6 | pmid=8609554 | doi=10.3171/jns.1996.84.3.0430 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8609554 }}</ref> | *CNS dissemination<ref name="pmid8609554">{{cite journal| author=Molloy PT, Yachnis AT, Rorke LB, Dattilo JJ, Needle MN, Millar WS et al.| title=Central nervous system medulloepithelioma: a series of eight cases including two arising in the pons. | journal=J Neurosurg | year= 1996 | volume= 84 | issue= 3 | pages= 430-6 | pmid=8609554 | doi=10.3171/jns.1996.84.3.0430 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8609554 }}</ref> | ||
===Prognosis=== | ===Prognosis=== | ||
The prognosis of medulloepithelioma is generally poor; the median survival time of patients with medulloepithelioma is approximately 5 - 10 months.<ref name="pmid8609554" /> | The [[prognosis]] of medulloepithelioma is generally poor; the median survival time of patients with medulloepithelioma is approximately 5 - 10 months.<ref name="pmid8609554" /> | ||
== Diagnosis == | == Diagnosis == | ||
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The diagnosis of medulloepithelioma is based on immunhistochemistry, which reveals an over-expression of LIN28A protein.<ref name="pmid28971535" /> | The diagnosis of medulloepithelioma is based on immunhistochemistry, which reveals an over-expression of LIN28A protein.<ref name="pmid28971535" /> | ||
Previously, the diagnosis of medulloepithelioma required only morphological analysis; however, the World Health Organization classification of central nervous system tumors was revised, and now genetic analysis is necessary.<ref name="pmid28971535">{{cite journal| author=Kusakabe K, Kohno S, Inoue A, Seno T, Yonezawa S, Moritani K et al.| title=Combined morphological, immunohistochemical and genetic analyses of medulloepithelioma in the posterior cranial fossa. | journal=Neuropathology | year= 2018 | volume= 38 | issue= 2 | pages= 179-184 | pmid=28971535 | doi=10.1111/neup.12431 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28971535 }}</ref> | Previously, the diagnosis of medulloepithelioma required only morphological analysis; however, the [[World Health Organization]] classification of [[central nervous system]] tumors was revised, and now [[genetic analysis]] is necessary.<ref name="pmid28971535">{{cite journal| author=Kusakabe K, Kohno S, Inoue A, Seno T, Yonezawa S, Moritani K et al.| title=Combined morphological, immunohistochemical and genetic analyses of medulloepithelioma in the posterior cranial fossa. | journal=Neuropathology | year= 2018 | volume= 38 | issue= 2 | pages= 179-184 | pmid=28971535 | doi=10.1111/neup.12431 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28971535 }}</ref> | ||
=== History & Symptoms=== | === History & Symptoms=== | ||
Medulloepithelioma is usually asymptomatic; however, signs and symptoms of increased intracranial pressure may be sign upon presentation.<ref name="pmid25136238" /> | Medulloepithelioma is usually [[asymptomatic]]; however, signs and symptoms of increased [[intracranial pressure]] may be sign upon presentation.<ref name="pmid25136238" /> | ||
Symptoms of medulloepithelioma may include:<ref name="pmid25136238" /> | [[Symptom|Symptoms]] of medulloepithelioma may include:<ref name="pmid25136238" /> | ||
*[[Headache]] | *[[Headache]] | ||
*Visual disturbances | *[[Visual disturbance|Visual disturbances]] | ||
*[[Fatigue]] | *[[Fatigue]] | ||
*[[Tinnitus]] | *[[Tinnitus]] | ||
*Focal neurologic signs | *[[Focal neurologic signs]] | ||
**Ataxia | **[[Ataxia]] | ||
**Weakness | **[[Weakness]] | ||
=== Physical Examination === | === Physical Examination === | ||
Patients with medulloepithelioma usually are well-appearing. Physical examination may be remarkable for: | Patients with medulloepithelioma usually are well-appearing. [[Physical examination]] may be remarkable for: | ||
*Paralysis of a | *Paralysis of a [[limb]] (monoparesis) or [[hemiparesis]] | ||
*Paralysis of the head and eye movements | *Paralysis of the head and eye movements | ||
*Total loss of vision | *Total [[loss of vision]] | ||
Patients with medulloepithelioma of the ciliary body present with some findings on clinical examination that are suggestive of the diagnosis, including:<ref name="pmid159278612">{{cite journal| author=Vajaranant TS, Mafee MF, Kapur R, Rapoport M, Edward DP| title=Medulloepithelioma of the ciliary body and optic nerve: clinicopathologic, CT, and MR imaging features. | journal=Neuroimaging Clin N Am | year= 2005 | volume= 15 | issue= 1 | pages= 69-83 | pmid=15927861 | doi=10.1016/j.nic.2005.02.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15927861 }}</ref> | Patients with medulloepithelioma of the [[ciliary body]] present with some findings on [[clinical examination]] that are suggestive of the [[diagnosis]], including:<ref name="pmid159278612">{{cite journal| author=Vajaranant TS, Mafee MF, Kapur R, Rapoport M, Edward DP| title=Medulloepithelioma of the ciliary body and optic nerve: clinicopathologic, CT, and MR imaging features. | journal=Neuroimaging Clin N Am | year= 2005 | volume= 15 | issue= 1 | pages= 69-83 | pmid=15927861 | doi=10.1016/j.nic.2005.02.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15927861 }}</ref> | ||
* Cystic lesions | * Cystic [[lesions]] | ||
** With an irregular surface in 60% of cases | ** With an irregular surface in 60% of cases | ||
* Spherical free-floating cysts | * Spherical free-floating [[cysts]] | ||
** Containing hyaluronic acid | ** Containing [[hyaluronic acid]] | ||
* Calcification with chalky opacity | * [[Calcification]] with chalky opacity | ||
** Confined to the ciliary body | ** Confined to the [[ciliary body]] | ||
=== Laboratory Findings === | === Laboratory Findings === | ||
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===CT Findings=== | ===CT Findings=== | ||
Brain CT scan may be helpful in the diagnosis of medulloepithelioma. | [[Brain]] [[CT scan]] may be helpful in the [[diagnosis]] of medulloepithelioma. | ||
Findings on CT scan suggestive of medulloepithelioma include isodense or hypodense [[lesions]] with variable [[heterogeneity]] and [[calcification]]. | Findings on CT scan suggestive of medulloepithelioma include isodense or hypodense [[lesions]] with variable [[heterogeneity]] and [[calcification]]. | ||
The tumor enhances with contrast. | The [[tumor]] enhances with contrast. | ||
=== MRI Findings === | === MRI Findings === | ||
MRI may be helpful in the diagnosis of medulloepithelioma. Findings on MRI suggestive of medulloepithelioma | MRI may be helpful in the diagnosis of medulloepithelioma. Findings on [[MRI]] suggestive of medulloepithelioma | ||
== Treatment == | == Treatment == | ||
=== Medical Therapy === | === Medical Therapy === | ||
There is no standard regimen for medulloepithelioma due to its rarity, although craniospinal radiation, high dose chemotherapy with stem cell rescue has been used. | There is no standard regimen for medulloepithelioma due to its rarity, although craniospinal [[Radiation therapy|radiation]], high dose [[chemotherapy]] with [[stem cell]] rescue has been used. | ||
=== Surgery === | === Surgery === | ||
Complete surgical resection is the mainstay of treatment for medulloepithelioma. | Complete [[surgical resection]] is the mainstay of treatment for medulloepithelioma. | ||
Adjuvant | Adjuvant radio and chemotherapy is often indicated.<ref name="OumgharHazmiri2017">{{cite journal|last1=Oumghar|first1=Nezha|last2=Hazmiri|first2=Fatima Ezzahra|last3=El Omrani|first3=Abdelhamid|last4=Rais|first4=Hanane|last5=Khouchani|first5=Mouna|title=Posterior cerebral fossa medulloepithelioma: report of a case|journal=BMC Clinical Pathology|volume=17|issue=1|year=2017|issn=1472-6890|doi=10.1186/s12907-017-0064-x}}</ref> | ||
=== Prevention === | === Prevention === | ||
Latest revision as of 04:34, 17 September 2019
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2] Roukoz A. Karam, M.D.[3]
Synonyms and keywords: Medullary epithelioma, Diktyoma
Overview
Medulloepithelioma is a rare, primitive, fast-growing brain tumor that usually originates from cells of the embryonic medullary cavity. On the other hand, tumors originating in the ciliary body of the eye are referred to as embryonal medulloepitheliomas or diktyomas. Medulloepithelioma was first discovered by Bailey and Cushing in 1926. The pathogenesis of medulloepithelioma is characterized by highly malignant undifferentiated primitive neuroepithelial tumor. It most commonly manifests in the cerebral hemispheres, brainstem, cerebellum, and in peripheral sites. Medulloepithelioma arises from primitive medullary epithelium, which is normally involved in the embryonic formation of CNS. Medulloepithelioma commonly affects individuals younger than 10 years of age. CT scan findings of medulloepithelioma, include an isodense or hypodense lesion with variable heterogeneity and calcification. Complete surgical resection is the mainstay of treatment for medulloepithelioma. Adjuvant radiochemotherapy is often indicated.
Historical Perspective
- Intracerebral medulloepithelioma was first discovered by Bailey and Cushing in 1926.[1]
- Intraocular medulloepithelioma was first named by Grinker in 1930; the name derives from its histopathological resemblance to an even rarer form of medulloeptihelioma of the brain described by Bailey and Cushing.[2]
- The resemblance between the tumors refers to the neuroepithelium of the embryonic neural tube.[2]
Classification
Medulloepitheliomas are classified as embryonal tumors in the WHO classification of CNS tumors.[3]
In 2016, the WHO classification system was reviewed and identified the tumors that were previously labeled embryonal tumor with abundant neutrophils and true rosettes, ependymoblastoma, and medulloepithelioma and included them in embryonal tumor with multilayered rosettes (ETMR) group; provided they have evidence of C19MC amplification.[4]
- ETMR are highly malignant pediatric tumors with varied embryonal histology but shared genetic alterations in the C19MC gene.
Pathophysiology
Pathogenesis
- The pathogenesis of medulloepithelioma is characterized by highly malignant undifferentiated primitive neuroepithelial tumor.
- It most commonly manifests in the cerebral hemispheres, brainstem, cerebellum, and in peripheral sites.
- Intraocular medulloepithelioma arises from the primitive medullary epithelium, which is normally involved in the embryonic formation of CNS and is a derivative of the inner layer of the optic cup. Rarely, it can also originate from the retina or optic nerve.[5]
Genetics
For embryonal tumor with multilayered rosettes (ETMR)
- LIN28A immunohistochemistry
- FISH analysis of the 19q13.42
Gross Pathology
- Intraocular medulloepithelioma most commonly appears as a white, gray, or yellow-colored ciliary body tumor.[6]
- It is possible to identify chalky gray-white deposits within the tumor; they are histologically composed of hyaline cartilage or bone.[7]
Microscopic Pathology
On microscopic histopathological analysis, characteristic findings of medulloepithelioma may include:
- Small round blue cell tumor
- Focal differentiation into astrocytic, neuronal or ependymal phenotypes possible
- Multilayered rosettes may be seen
- Growth in streams or palisades
- Vascular endothelial proliferations
- Fibrillary background in tumors with advanced neuronal maturation
- Variable mitotic activity
- Neoplastic pseudostratified neuroepithelium
- Resembling embryonic neural tube, with papillary, tubular and trabecular arrangements
- Sheets of poorly differentiated cells
- With hyperchromatic nuclei and high nuclear to chromatin ratio
- Periodic acid-Schiff positive external limiting membrane
- No cilia or blepharoplasts on luminal surface of tubules
On immunohistopathological analysis, characteristic findings of medulloepithelioma may include:
Causes
The cause of medulloepithelioma is unknown.
Differentiating Medulloepithelioma from Other Diseases
Medulloepithelioma must be differentiated from other diseases that cause vision loss, ocular mass, and headache such as:
- CNS tumors
- Retinoblastoma
- Shares radiologic features with medulloepithelioma
- Intraocular lymphoma
- Anterior chamber cyst
Epidemiology and Demographics
Medulloepithelioma is a rare disease.
Age
- Medulloepithelioma commonly affects individuals younger than 10 years of age.[8]
- The median age at diagnosis is 5 years old.[9]
Gender
Medulloepithelioma affects men and women equally.
Race
There is no racial predilection for medulloepithelioma.
Risk Factors
There are no known associated risk factors in the development of medulloepithelioma.
Screening
There is insufficient evidence to recommend routine screening for medulloepithelioma.
Natural History, Complications and Prognosis
Natural History
- Patients with medulloepithelioma may be initially asymptomatic.
- Early clinical features include vision loss, irritability, and neurological deficit. If left untreated, patients with medulloepithelioma may progress to death.[9]
- Medulloepithelioma have been reported to occur in the cerebral hemispheres, brainstem, cerebellum, and peripheral sites.
Complications
Common complications of medulloepithelioma include:[9]
- Optic nerve injury
- Increased intracranial pressure
- CNS dissemination[10]
Prognosis
The prognosis of medulloepithelioma is generally poor; the median survival time of patients with medulloepithelioma is approximately 5 - 10 months.[10]
Diagnosis
Diagnostic Study of Choice
The diagnosis of medulloepithelioma is based on immunhistochemistry, which reveals an over-expression of LIN28A protein.[11]
Previously, the diagnosis of medulloepithelioma required only morphological analysis; however, the World Health Organization classification of central nervous system tumors was revised, and now genetic analysis is necessary.[11]
History & Symptoms
Medulloepithelioma is usually asymptomatic; however, signs and symptoms of increased intracranial pressure may be sign upon presentation.[9]
Symptoms of medulloepithelioma may include:[9]
Physical Examination
Patients with medulloepithelioma usually are well-appearing. Physical examination may be remarkable for:
- Paralysis of a limb (monoparesis) or hemiparesis
- Paralysis of the head and eye movements
- Total loss of vision
Patients with medulloepithelioma of the ciliary body present with some findings on clinical examination that are suggestive of the diagnosis, including:[12]
- Cystic lesions
- With an irregular surface in 60% of cases
- Spherical free-floating cysts
- Containing hyaluronic acid
- Calcification with chalky opacity
- Confined to the ciliary body
Laboratory Findings
There are no specific laboratory findings associated with medulloepithelioma.
Imaging Findings
CT and MR imaging findings can be helpful, especially if the mass is confined in an area of the ciliary body without involvement of the retina.[13]
X-ray Findings
There are no x-ray findings associated with medulloepithelioma.
CT Findings
Brain CT scan may be helpful in the diagnosis of medulloepithelioma.
Findings on CT scan suggestive of medulloepithelioma include isodense or hypodense lesions with variable heterogeneity and calcification.
The tumor enhances with contrast.
MRI Findings
MRI may be helpful in the diagnosis of medulloepithelioma. Findings on MRI suggestive of medulloepithelioma
Treatment
Medical Therapy
There is no standard regimen for medulloepithelioma due to its rarity, although craniospinal radiation, high dose chemotherapy with stem cell rescue has been used.
Surgery
Complete surgical resection is the mainstay of treatment for medulloepithelioma.
Adjuvant radio and chemotherapy is often indicated.[14]
Prevention
There are no primary preventive measures available for medulloepithelioma.
References
- ↑ Chakrabarti I, Majumdar K, Giri A (2012). "Infratentorial medulloepithelioma with divergent differentiation: Possibly a predictor of poor outcome". J Pediatr Neurosci. 7 (2): 142–5. doi:10.4103/1817-1745.102581. PMC 3519076. PMID 23248698.
- ↑ 2.0 2.1 Grinker, Roy R. (1931). "GLIOMAS OF THE RETINA". Archives of Ophthalmology. 5 (6): 920. doi:10.1001/archopht.1931.00820060088009. ISSN 0093-0326.
- ↑ Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK; et al. (2016). "The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary". Acta Neuropathol. 131 (6): 803–20. doi:10.1007/s00401-016-1545-1. PMID 27157931.
- ↑ Korshunov A, Sturm D, Ryzhova M, Hovestadt V, Gessi M, Jones DT; et al. (2014). "Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity". Acta Neuropathol. 128 (2): 279–89. doi:10.1007/s00401-013-1228-0. PMC 4102829. PMID 24337497.
- ↑ Canning CR, McCartney AC, Hungerford J (1988). "Medulloepithelioma (diktyoma)". Br J Ophthalmol. 72 (10): 764–7. doi:10.1136/bjo.72.10.764. PMC 1041579. PMID 3056510.
- ↑ Broughton WL, Zimmerman LE (1978). "A clinicopathologic study of 56 cases of intraocular medulloepitheliomas". Am J Ophthalmol. 85 (3): 407–18. PMID 655220.
- ↑ Vajaranant, Thasarat S.; Mafee, Mahmood F.; Kapur, Rashmi; Rapoport, Mark; Edward, Deepak P. (2005). "Medulloepithelioma of the Ciliary Body and Optic Nerve: Clinicopathologic, CT, and MR Imaging Features". Neuroimaging Clinics of North America. 15 (1): 69–83. doi:10.1016/j.nic.2005.02.008. ISSN 1052-5149.
- ↑ Russel DS, Rubinstein LJ. Pathology of tumors the nervous system, 5th ed. Baltimore: Williams & Wilkins 1989; pp. 247-51.
- ↑ 9.0 9.1 9.2 9.3 9.4 Peshtani A, Kaliki S, Eagle RC, Shields CL (2014). "Medulloepithelioma: A triad of clinical features". Oman J Ophthalmol. 7 (2): 93–5. doi:10.4103/0974-620X.137171. PMC 4134557. PMID 25136238.
- ↑ 10.0 10.1 Molloy PT, Yachnis AT, Rorke LB, Dattilo JJ, Needle MN, Millar WS; et al. (1996). "Central nervous system medulloepithelioma: a series of eight cases including two arising in the pons". J Neurosurg. 84 (3): 430–6. doi:10.3171/jns.1996.84.3.0430. PMID 8609554.
- ↑ 11.0 11.1 Kusakabe K, Kohno S, Inoue A, Seno T, Yonezawa S, Moritani K; et al. (2018). "Combined morphological, immunohistochemical and genetic analyses of medulloepithelioma in the posterior cranial fossa". Neuropathology. 38 (2): 179–184. doi:10.1111/neup.12431. PMID 28971535.
- ↑ Vajaranant TS, Mafee MF, Kapur R, Rapoport M, Edward DP (2005). "Medulloepithelioma of the ciliary body and optic nerve: clinicopathologic, CT, and MR imaging features". Neuroimaging Clin N Am. 15 (1): 69–83. doi:10.1016/j.nic.2005.02.008. PMID 15927861.
- ↑ Vajaranant TS, Mafee MF, Kapur R, Rapoport M, Edward DP (2005). "Medulloepithelioma of the ciliary body and optic nerve: clinicopathologic, CT, and MR imaging features". Neuroimaging Clin N Am. 15 (1): 69–83. doi:10.1016/j.nic.2005.02.008. PMID 15927861.
- ↑ Oumghar, Nezha; Hazmiri, Fatima Ezzahra; El Omrani, Abdelhamid; Rais, Hanane; Khouchani, Mouna (2017). "Posterior cerebral fossa medulloepithelioma: report of a case". BMC Clinical Pathology. 17 (1). doi:10.1186/s12907-017-0064-x. ISSN 1472-6890.