Neuroectodermal tumors

ALSO KNOWN AS: Primitive neuroectodermal tumors (PNETs), neuroectodermal neoplasms

RELATED CONDITIONS: Medulloblastomas, peripheral neuroepitheliomas, central neuroblastomas, ependymoblastomas, Gorlin syndrome, nevoid basal cell carcinoma syndrome, Askin tumor (thoracopulmonary PNET), peripheral PNET/Ewing family tumor (pPNET/ESFT), extraosseous Ewing sarcoma

DEFINITION: Neuroectodermal tumors are primary central nervous system (CNS) tumors classified based on genetic and molecular characteristics. This group of tumors was formerly thought to have a common origin in the embryo's neuroectodermal tissue layer cell line (neural crest). The World Health Organization (WHO) began reclassifying central nervous system tumors in 2016, which changed some nomenclature surrounding these conditions.

They possess embryonic cell characteristics of the brain (neuronal), neuronal support (glial), or mesenchymal cells, depending on the degree of differentiation assumed. Neuroectodermal tumors may arise from bone, soft tissue, or other tissues outside the autonomic and central nervous system (peripheral primitive neuroectodermal tumors, pPNETs), they may arise from neurons in the central nervous system (CNS primitive neuroectodermal tumors, PNETs), or they may arise from the autonomic nervous system (neuroblastoma). Medulloblastomas represent the prototype neuroectodermal tumor.

Risk factors: Neuroectodermal tumors have risk factors associated with alterations in the patient’s genome as a sporadic mutation, as part of a syndrome, or as a result of environmental exposure to a mutagen. Syndromes associated with the risk of developing iPNET include multiple-tumor, autosomal dominant diseases such as Gorlin syndrome, Turcot syndrome, and Li-Fraumeni syndrome. Exposure of children to pesticides, particularly organophosphates, has been implicated in several studies as an environmental for the subsequent development of PNET. Organophosphates have been associated in at least one study with a mutation in the PON1 gene, which is responsible for expression of an enzyme that breaks down organophosphates in the liver.

Etiology and the disease process: The genesis of neuroectodermal tumors is associated with chromosomal changes. The most common chromosomal aberration seen in medulloblastomas is the replacement of the short arm of chromosome 17 (17p) with a copy of the long arm (17q), seen in as many as 50 percent of medulloblastoma cases. The Ewing sarcoma family tumor (ESFT) is most often associated with a translocation between chromosomes 11 and 22, resulting in the fusion of the EWSR1 and FLI1 genes.

Incidence: The Swedish Cancer Registry reported that medulloblastomas represented 21 percent of all primary pediatric brain malignancies. The incidence of all neuroectodermal tumors is highest in children, with 0.5 medulloblastoma cases per 100,000 per year reported in the United States. Medulloblastomas represent the most common solid brain tumor found in children (30 percent), with the incidence decreasing to only 1 percent of brain tumors found during adulthood. The majority of medulloblastomas occur in the cerebellum, below the tentorium (extension of the protective tissue covering the brain). Only 4 percent of neuroectodermal tumors occur above the tentorium (midbrain, cerebral cortex). Neuroectodermal tumors outside the central nervous system occur in 1 percent of all sarcomas found.

Symptoms: Usually, the more common signs and symptoms are related to obstruction of cerebrospinal fluid (CSF) flow and subsequent pressure buildup and tissue compression. Symptoms of increased pressure include nausea, vomiting, morning headache, and vision changes. Brain stem compression or encroachment can manifest as irritability, lethargy, and decreased social interaction. Cerebellar signs of involvement include frequent loss of balance. Physical examination findings may consist of papilledema (swelling of both optic nerves); abnormal eye movements; gaze, gait, and limb incoordination; deficits in affected cranial nerves, especially those going to the throat, mouth, shoulders, and tongue; and an increase in head circumference in babies less than two years old. In other sites, neuroectodermal tumors such as pPNET/ESFT can manifest as localized bone pain, a soft-tissue mass located along the middle of long bones with fever and weight loss.

Screening and diagnosis: The final diagnosis of a neuroectodermal tumor is mainly pathological when a tissue sample is examined microscopically and with immunohistochemistry (tests determining cell markers). However, the neuroanatomical location of the tumor, as suggested by clinical history, physical examination, and neuroimaging tests such as magnetic resonance imaging (MRI), can suggest a medulloblastoma. Alternatively, a computed tomography (CT) scan may reveal the tumor but has significantly less resolution than an MRI. There are no screening tests available for neuroectodermal tumors. X-rays and CT of the affected limb may reveal signs of simultaneous bone destruction and remodeling (“sunburst sign”) and a periosteal reaction (disruption in the continuity of the outer bone), as well as bone infiltration. X-rays and a chest CT should also help to find metastases.

Treatment and therapy: Treatment of a neuroectodermal tumor in any location includes surgical removal, radiation therapy, and chemotherapy. Surgical removal must be able to extract the entire primary tumor and probable areas of spread and restore normal cerebral spinal fluid circulation. The latter may be achieved by adding a device diverting excess cerebral spinal fluid to the abdominal cavity (ventriculoperitoneal shunt). For other neuroectodermal tumors outside the nervous system, the same therapeutic principles apply. In children with limb involvement, amputation may be done because of the stunting effect of therapeutic radiation levels on growth plates.

Prognosis, prevention, and outcomes: The prognosis of neuroectodermal tumors after therapy completion is good. Five-year survival rates for central nervous system tumors approach 75 percent with aggressive surgical removal, radiotherapy, and chemotherapy. pPNET/ESFT exhibits similar survival rates with the same treatment, as opposed to radiotherapy and alone (50 percent). Prevention of recurrence includes interval imaging and “second look” surgeries when residual disease is present.

Bibliography

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