Medulloepithelioma
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]
Synonyms and keywords: Medullary epithelioma
Overview
Medulloepithelioma is a rare, primitive, fast-growing brain tumor thought to stem from cells of the embryonic medullary cavity. Tumors originating in the ciliary body of the eye are referred to as embryonal medulloepitheliomas or diktyomas.[1][2] Medulloepithelioma was first discovered by Bailey and Cushing in 1926. The pathogenesis of medulloepithelioma is characterized by highly malignant undifferentiated primitive neuroepithelial tumor. Tumors generally originate in the ciliary body of the eye. 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 is more commonly observed among patients between 6 months and 5 years old. On CT, findings of medulloepithelioma, include an isodense or hypodense lesion with variable heterogeneity and calcification. Surgery is the mainstay of therapy for medulloepithelioma. Total resection in conjunction with radiation therapy is the most common approach to the treatment of medulloepithelioma.
Historical Perspective
Medulloepithelioma was first discovered by Bailey and Cushing in 1926.
Classification
Medulloepitheliomas are classified as embryonal tumors in the WHO classification of CNS tumors.[3]
Medulloepithelioma may be classified into 3 groups:
- Medulloepithelioma not otherwise specified
- Medulloepithelioma with differentiation into astrocytes, oligodendrocytes; ependymal cells
- Medulloepithelioma with neuronal cells, other cells (melanocytes, mesenchymal cells), and mixed cellular elements
Pathophysiology
Pathogenesis
The pathogenesis of medulloepithelioma is characterized by:
- A highly malignant undifferentiated primitive neuroepithelial tumor
- Tumors generally originate in the ciliary body of the eye
- Located in cerebral hemispheres, brainstem, cerebellum, and peripheral sites
Medulloepithelioma arises from primitive medullary epithelium, which is normally involved in the embryonic formation of CNS.
Genetics
The germline DICER1 gene mutation has been associated with the development of medulloepithelioma.[4]
Gross Pathology
This tumor most commonly appears as a white, gray, or yellow-colored ciliary body tumor.
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 N/C 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:
- Positive S-100
- Positive INI1
- Positive LIN28
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:
- Brain tumors
- Intraocular lymphoma
- Anterior chamber cyst
Epidemiology and Demographics
Medulloepithelioma is a rare disease.
Age
Medulloepithelioma commonly affects individuals younger than 4-5 years of age.[5]
The median age at diagnosis is 5 years old.[4]
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.
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.
- Medulloepithelioma have been reported to occur in the cerebral hemispheres, brainstem, cerebellum, and peripheral sites.
Complications
Common complications of medulloepithelioma include:
- Optic nerve injury
- Increased intracranial pressure
Prognosis
The prognosis of medulloepithelioma is generally poor; the median survival time of patients with medulloepithelioma is approximately 5 months.
Diagnosis
Diagnostic Study of Choice
The diagnosis of medulloepithelioma is based on immunhistochemistry, which reveals an over-expression of LIN28A protein.[6]
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.[6]
History & Symptoms
Medulloepithelioma is usually asymptomatic. Symptoms of medulloepithelioma may include:[4]
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
Laboratory Findings
There are no specific laboratory findings associated with medulloepithelioma.
Imaging Findings
CT Findings
On CT, findings of medulloepithelioma include isodense or hypodense lesions with variable heterogeneity and calcification.
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 radiochemotherapy is often indicated.[7]
Prevention
There are no primary preventive measures available for medulloepithelioma.
References
- ↑ McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.
- ↑ Definition of Medulloepithelioma, from Online Medical Dictionary. Retrieved 7 January 2010.
- ↑ 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.
- ↑ 4.0 4.1 4.2 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.
- ↑ Russel DS, Rubinstein LJ. Pathology of tumors the nervous system, 5th ed. Baltimore: Williams & Wilkins 1989; pp. 247-51.
- ↑ 6.0 6.1 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.
- ↑ 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.