Neuronal & Glioneuronal Tumors:

 
Dr. A. Vincent Thamburaj,   
Neurosurgeon, Apollo Hospitals,  Chennai , India.

These rare tumors have both glial and neuronal elements.

They usually occur in children and the young, and present with seizures.

They may mimic a low grade glioma, radiologically.

Surgery is the primary treatment. The overall prognosis is favorable.

 

WHO includes the following in this  group:

 

Gangliocytoma,

Ganglioglioma (grade I or II), & Anaplastic Ganglioglioma (grade III),

Dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos),

Desmoplastic infantile astrocytoma/Ganglioglioma (grade I),

Dysembryoplastic neuroepithelial tumor (DNT) (grade I),

Central Neurocytoma (grade III),

Cerebellar Liponeurocytoma (grade I or III), and

Paraganglioma of the filum terminale (grade I)

 

Ganglioglioma:

 

This is an appropriate designation, first introduced by Courville in 1930, as it describes the most frequent form of this rare tumor group which constitute less than 1% of primary brain tumors. They form 1% of all intramedullary spinal cord tumors.

The mean age at diagnosis ranges from 16 to 25 years, with highest incidence in children, where they constitute 4% to 10% of primary brain tumors. It has been reported in a 70years old.

 

Temporal and frontal lobes are the favored sites. The spinal cord and the brain stem are next commonly involved. Other less common sites are, optic nerve, chiasma, and tract. An increased incidence in association with congenital anomalies, such as, agenesis of corpus callosum and Down's syndrome is noted.

Although metastasis is rare, leptomeningeal and subarchnoid spread have been reported.

 

Symptoms are related to the location, with seizures and focal neurological deficits. Focal neurological deficits with hydrocephalus occur in midline lesions. It is one of the common causes of intractable epilepsy.

 

CT reveals an iso to hypodense mass, with varying degree and calcifications and cystic changes.

MRI reveals a well circumscribed mass that is iso to hypodense on T1 and hyperdense on T2 images. There is variable contrast enhancement.

Ganglioglioma-contrast CT

Grossly, They are firm grayish, avascular tumor with cystic components.

 

Histologically, glial and neuronal elements are present in varying proportions. Glial elements are mostly astrocytic.

In addition to anaplastic gangliogliomas, other variants include, melanotic astrocytes, neurocytoma, and pleomorphic xanthoastrocytoma.  

 

Immunohistochemical staining for synaptophysin, a neuronal cell membrane glycoprotein, helps in diagnosis.

 

When a ganglion cell tumor contains populations of small round cells with nuclear hyperchromasia, it is labelled a ganglioneuroblastoma. These small cells proliferate rapidly,

Ganglioglioma (H&E): spindle shaped glial (open arrows) and

ganglion (black arrows) elements.

making the prognosis worse. This tumor represents an intermediate step on a spectrum from ganglioglioma to neuroblastoma.

 

Adenohypophyseal neuronal choristoma arise from Ganglion cells within the anterior pituitary gland (hence, it is not a brain tumor), most often within the substance of a growth hormone producing pituitary adenoma. Such neural choristomas (or pituicytomas) have been shown to elaborate growth hormone releasing hormone (GRH).

 

Surgical resection is the mainstay of treatment.

Post operative radiation is reserved for lesions at eloquent areas, recurrence, and by some for anaplastic variants. There is no substantial benefit with chemotherapy.

 

The prognosis is favorable with 10 year survival rate in excess of 90% of cases. Location of the tumor is found to be a significant factor. Anaplasia, although debatable, does not alter the prognosis significantly.

Recurrence rate is reported to be about 30%.The recurrence rate, reportedly, is 5 fold and 3.5 fold higher for the brainstem and the spinal cord, respectively, compared with the risk of recurrence for cerebral hemispheric tumors.

 

Desmoplastic Infantile Ganglioglioma (DIGs):

 

These rare tumors, first described by Vandenberg et al in 1987. Typically, they are supratentorial and detected in infants with macrocrania and increased ICT and new onset seizures. They may reach impressively large sizes and are characteristically found to have contiguous leptomeningeal involvement, as reflected by the presence of desmoplasia.

 

Imaging of these neoplasms typically reveals a large, superficially located, supratentorial mass with both solid and cystic components. On CT, the solid component of a DIG is seen as an avidly enhancing, iso to hyperdense region that is contiguous with the meninges.

 

Cystic components underlie solid tumor components. On MRI, enhancement with gadolinium is seen within the solid regions, which appear hypodense on T1 weighted images, and of variable density on T2 weighted images. Cystic areas appear hypodense and hyperdense on T1 and T2weighted images, respectively.

 

Grossly, it is a firm large avascular mass with leptomenigeal extension.

Histologically, both ganglionic and astrocytic neoplastic elements are present with dense desmoplasia.

 

Surgery is the primary form of treatment, with post operative radiation, as advocated by some, in subtotal resections.

They generally have favorable prognosis even in subtotal resection.

 

Gangliocytoma or Ganglioneuroma:

 

Benign, circumscribed, slowly expanding lesion that produces only local signs. The majority of patients are under 30 and the temporal lobe is the favored site.  It may be solid or cystic and may show focal calcification. 

Microscopically, it consists of mature but architecturally abnormal neurons, the glial component being only sufficient as a stroma.

 

Hypothalamic Neuronal Harmartoma: It is a specialized form of gangliocytoma, first reported in 1934.

Clinically symptomatic tumors may largely replace the hypothalamus and usually occur together with endocrinopathy, e,g, obesity, diabetes insipidus or precocious puberty. Most children present with precocious puberty before the age of 3 years.

 

MRI is the imaging of choice. T1 images show good resolution of the hamartoma from the surrounding brain with no contrast enhancement. T2 may show an iso or hyperdense lesion. They may be associated with midline deformities including callosal agenesis, optic malformations, and hemispheric dysgenesis.

 

Grossly, the majority are pedunculated; some are sessile with a wider attachment to the ventral hypothalamus.

Microscopically, they consist of hypothalamic-type neurons, interspersed with glial cells. 

Treatment consists of hormonal management similar to hormonally active pituitary tumors and surgery. A pedunculated tumor is ideal for surgery, by a subtemporal approach. Radiotherapy has not added to survival.

The outcome is generally good, even with partial excision.

 

Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos): It was first reported in 1920 by Lhermitte & Duclos. It is am extremely rare posterior fossa hamartomatous lesion, detected in the 3rd and 4th decades of life, and occasionally in infancy. Although, usually involving the cerebellar hemipheres, vermian involvement has been reported.

Familial affliction, and the presence of coexisting congenital anomalies, such as megalencephaly, heterotopias, and polydactylia, has been described. An association of has been made between dysplastic gangliocytoma and Cowden's syndrome, an autosomal dominant disease, is characterized by the presence of multiple hamartomas.

 

Clinically they present with signs and symptoms of cerebellar dysfunction, or increased intracranial pressure secondary to hydrocephalus.

 

CT reveals an hypodense, nonenhancing enlargement of cerebellar folia and coexistent hydrocephalus. There may be calcifications. MRI reveals the characteristic striated pattern of dysplastic gangliocytoma. These striations consist of alternating bands of hypo and isodense striations.

 

Grossly, it is a mass composed of hypertrophied folia with myelination evident to the eye in the outer part of the molecular layer.

Histologically, there is disruption of cerebellar architecture with proliferation of ganglion cells in the granule cell layer. There is thickening of the molecular layer, widening of the granule cell layer, disappearance of Purkinje cell layer. Neovascular proliferation may be present in areas with the highest neuronal concentration.

 

Surgical resection, and if necessary CSF diversion is the line of treatment. Some recommend radiation in recurrence.

Dysembryoplastic neuroepithelial tumor - DNT/DNET:

This rare tumor was described by Daumas-Duport et al in 1988.

The histogenesis uncertain. It is hypothesized to arise from external granular layer of the cortex.

The common Locations are cortical, and temporal lobe, followed by frontal.

 

They  are most common in children and young adults, but can occur at any age.

Clinical Presentation is usually with partial complex seizures, especially beginning before age 20 years.

 

Histological diagnosis is based on presence of a specific glioneuronal element, consisting of oligodendrocytes in a mucinous matrix in which neurons appear to float or glial nodules associated with cortical dysplasia. Neuronal markers (synaptophysin, neuronal

specific enolase) and glial markers (GFAP, S-100) positive.

CT and MRI reveals a nodular cortical lesion without edema. They may have megagyric or multicystic appearance. Occasionally may enhance or contain calcifications. CT may show calvarial remodeling.

 

Along with low grade gliomas, and gangliogliomas they are grouped as a surgically curable cause of intractable seizures.

 

Despite benign behavior, may have high MIB-1 labeling index.

They are usually stable, even over long periods, even after subtotal excision. Radiotherapy does not appear to be of benefit. no data is available on chemotherapy.

Central Neurocytoma:

DNET-CT

These are rare intraventricular tumors that occur in young adults with a male preponderance. They, probably, represent a relatively well differentiated form of neuronal tumor. They are frequently attached to the septum pellucidum or the walls of the lateral ventricles. Extension through the foramen of monro into the third ventricle is commonly noted. Extraventricular locations have been reported.

 

The patients present with features of hydrocephalus, and seizures in extraventricular ones. Spontaneous hemorrhage may be the presenting feature in some.

 

CT and MRI typically reveal a variably enhancing iso to hyperdense intraventricular mass with calcification and associated hydrocephalus. Differential diagnosis include oligodendroglioma, ependymoma, choroid plexus papilloma, subependymoma, and intraventricular meningioma.

 

Histologically, they appear as sheets of uniform cells in a streaming or 'Indian file' arrangement.

Electron microscopy reveals neurosecretory dense core granules, neuritic processes, and areas resembling synaptic junctions.

Immuno histochemistry is often necessary for diagnosis. Synatophysin and neuron specific enolase reactivity is detected.

 

Complete excision is the main stay of the treatment. Role of radiation is debated.

Although thought to be benign, the natural history is not clear.

 

Paraganglioma of filum terminale:

 

It is a disease of adults, unlike other neuronal tumors, and unlike other paragangliomas (Paraganglia, elsewhere, have been shown to have chemoreceptor roles with modulation of respiratory and cardiovascular function), they are non functional. There is male preponderance.  They are rare. Almost always, the location is at L2/3, just distal to conus. They are slow growing and expand in all directions involving multiple roots at cauda equine.

 

Clinical presentation is like any other degenerative multiple disc degenerative diseases. They may present with cauda equine syndrome.  Diagnosis is usually made after MRI.  It is intradural hyperdense lesion with dural attachment.

 

Surgery is the treatment, with careful protection of rootlets. The tumor is very vascular. Invariably, the tumor is suspended by a feeding artery and its accompanying vein at the cephalic pole of the tumor. Once this artery is secured, the tumor becomes avascular. Piecemeal excision is not advised. Few rootlets need to be sacrificed.

 

Histologically, there are uniform polygonal cells with pale eosinophilic granular cytoplasm. All reported intradural cases are benign.

 

Prognosis is good, with no recurrence after total excision. Role of radiotherapy, in subtotal excisions, is not clear.

 
 
 

 

 

 

 

 

 
 

 

 

 
 

 

 
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 

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