Medulloepithelioma
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.
- 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.
- The resemblance between the tumors refers to the neuroepithelium of the embryonic neural tube.

# Classification
Medulloepitheliomas are classified as embryonal tumors in the WHO classification of CNS tumors.
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.
- 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.

## 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.
- It is possible to identify chalky gray-white deposits within the tumor; they are histologically composed of hyaline cartilage or bone.

## 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
- Resembling embryonic neural tube, with papillary, tubular and trabecular arrangements
- Sheets of poorly differentiated cells
With hyperchromatic nuclei and high nuclear to chromatin  ratio
- 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:
- 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:
- CNS tumors
- Retinoblastoma
Shares radiologic features with medulloepithelioma
- 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.
- The median age at diagnosis is 5 years old.

## 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.
- 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
- CNS dissemination

## Prognosis
The prognosis of medulloepithelioma is generally poor; the median survival time of patients with medulloepithelioma is approximately 5 - 10 months.

# Diagnosis

## Diagnostic Study of Choice
The diagnosis of medulloepithelioma is based on immunhistochemistry, which reveals an over-expression of LIN28A protein.
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.

## History & Symptoms
Medulloepithelioma is usually asymptomatic; however, signs and symptoms of increased intracranial pressure may be sign upon presentation.
Symptoms of medulloepithelioma may include:
- Headache
- Visual disturbances
- Fatigue
- Tinnitus
- Focal neurologic signs
Ataxia
Weakness
- Ataxia
- Weakness

## 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:
- Cystic lesions
With an irregular surface in 60% of cases
- With an irregular surface in 60% of cases
- Spherical free-floating cysts
Containing hyaluronic acid
- Containing hyaluronic acid
- Calcification with chalky opacity
Confined to the ciliary body
- 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.

## 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.

## Prevention
There are no primary preventive measures available for medulloepithelioma.