What Are Neurogenic Tumors?
These are tumors that can originate from any nervous structure within the body. They account for twelve percent of all benign and eight percent of all malignant soft tissue tumors. They can form at any location innervated by the peripheral nervous system, the most common location being the mediastinum (space in the chest that holds the heart and other important structures).
Neurogenic tumors can be divided based on their origin cells into the following:
Ganglion Cells - These tumors are derived from the neural crest cells, a temporary group of cells that give rise to most of the peripheral nervous system, and several non-neural cells (like smooth muscle cells seen in the cardiovascular system) and are known as peripheral neuroblastic tumors.
Based on the International Neuroblastoma Pathology Classification (1999), these peripheral neuroblastic tumors are divided into four types:
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Neuroblastoma - It commonly affects children aged five or younger and is generally considered malignant (cancerous). Signs and symptoms vary depending on the part of the being affected; the most common ones are abdominal pain, mass under the skin that is not tender when touched, chest pain, proptosis (protrusion of the eyeballs), unexplained weight loss, etc.
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Ganglioneuroblastoma - It is an intermediate tumor that arises from the nerve tissues. An intermediate tumor is one that is in between benign (slow-growing and unlikely to spread) and malignant (fast-growing, aggressive, and likely to spread). They are often found in children older than ten years of age.
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Ganglioneuroblastoma Nodular- It is a rare subtype of neurogenic tumor that represents a prototypic example of a biological and clinically non-aggressive component (like ganglioneuroblastoma) combined with biologically and clinically aggressive nodular component (like neuroblastoma).
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Ganglioneuroma- They are considered benign and composed of gangliocytes (a nerve cell whose body is outside the central nervous system) and mature stroma. Compared to neuroblastoma and ganglioneuroblastoma, these are often seen in older children, ranging from the first to fifth decade of life. They are sporadic but can be associated with endocrinologic neoplasia. They can arise independently or be derived from neuroblastoma or ganglioneuroblastoma. In some cases, they have been found after radiation, too. The most common locations are the posterior mediastinum (a portion of the mediastinum located posterior to the pericardium) and the retroperitoneum (area in the back of the abdomen behind the peritoneum).
Paraganglion Cells - Paraganglion cells are cells that can make neurohormones (chromaffin paraganglion) or act as neurohormones' receptors (nonchromaffin paraganglion). They can give rise to two types of neurogenic tumors:
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Pheochromocytomas - This is a rare benign tumor that develops in the adrenal glands. They are a pair of glands on top of each kidney and produce hormones like epinephrine and norepinephrine. The tumor formed in them also releases the same hormones, leading to symptoms like irregular heartbeat, headache, profuse sweating, nervousness, etc. If left untreated, a pheochromocytoma can lead to life-threatening damage to the body.
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Paragangliomas - They can occur at any age, although most of them arise in the fourth or fifth decade of life. If the tumors are biologically active (functioning paraganglioma), they can present clinically with hypertension, blushing, and headaches. They are often associated with multiple endocrine neoplasias or von Hippel-Lindau disease (a hereditary condition associated with tumors arising in multiple organs). Most tumors are rubbery, firm, and usually well-demarcated with expansile borders, sometimes with hemorrhage and cystic degeneration. They can be located in any of the three mediastinal compartments- chemoreceptor tissue along the paravertebral area or around the aortic arch, vagus nerves (tenth cranial nerve), and sympathetic nerves within the middle, superior, and anterior mediastinum.
Nerve Sheath Cells- A nerve sheath is a layer of myelin (a combination of protein and fatty substances) and connective tissue that surrounds and insulates nerve fibers. Any tumor that arises from this layer is considered to be a neurogenic tumor of nerve sheath origin.
Three types of tumors arise from the nerve sheath cells; they are:
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Neurofibromas - This tumor is a proliferation of nerve sheath cells interspersed with thick, wavy collagen bundles. Neurofibromas can be classified into three categories - solitary, diffuse, and plexiform. Solitary neurofibromas present as small polyploid masses, diffuse neurofibromas have a plaque-like appearance, and plexiform neurofibromas are large and complex, with a bag-of-worms appearance. They affect individuals during the second to the fourth decade of life.
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Neurofibromatosis - These tumors are poorly circumscribed and locally invasive and contain a heterogeneous mix of Schwann cells, fibroblasts, and other cell types. There are two types of neurofibromatosis - neurofibromatosis type 1 (also known as von Recklinghausen's disease) and neurofibromatosis type 2. The former is characterized by neurofibromas, cafe-au-lait spots, freckling, and optic gliomas, and the latter presents as bilateral vestibular schwannomas and meningiomas.
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Schwannomas - These are the most common nerve sheath tumors, originating from the spinal root and extending along the intercostal nerve. They are usually marginated, spherical, and lobulated or dumbbell-shaped para spinous masses that span 1-2 posterior rib interspaces but can attain large size.
How Are Neurogenic Tumors Diagnosed?
Most neurogenic tumors originate in the thoracic region, and evaluation should be done by a thoracic surgeon experienced in the most modern, safe, and minimally invasive techniques. The first step is a thorough physical examination, followed by medical history. Some individuals have a family history of neurogenic tumors, which plays an important role during diagnosis.
After the examination, the thoracic surgeon will request any of the following investigations based on the type and location of the tumor:
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Computed Tomographic (CT) Scan - It is a specialized X-ray technology that can differentiate different types of neurogenic tumors. For example, the CT of a ganglioneuroma will show low internal attenuation relative to skeletal muscle, whereas the CT of a paraganglioma will show a soft tissue mass with marked enhancement, with or without extensive hemorrhage and cystic degeneration.
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Magnetic Resonance Imaging (MRI) - Also an imaging modality that uses radio waves and magnetic fields to produce detailed images. Similar to a CT, an MRI will show tumor-specific features that aid in diagnosis.
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M-iodobenzylguanidine (MIBG) Imaging - It is a scanning technique in which a radioactive compound will be injected into the individual. Pheochromocytomas, paragangliomas, and other neurogenic tumors will take up this compound, and the resultant image will reflect this.
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Positron Emission Tomography (PET) Scan - Also a scanning technique that detects radioactive compounds the tumor picks up.
How Are Neurogenic Tumors Treated?
Most of the neurogenic tumors will be treated with a combination of surgery and concurrent therapy. Surgery can be either a video-assisted thoracic surgery (VATS) or an open surgery (like median sternotomy). Concurrent therapy includes chemo and radiation therapy, both of which shrink the tumor so that it can be surgically removed. Chemotherapy uses medication to destroy cancer cells, whereas radiation uses high-energy rays to kill them.
Conclusion
Neurogenic tumors are complicated lesions that can be managed only with the help of a multidisciplinary team. The team should comprise neuro-spine surgeons, oncologists, radiation oncologists, anesthesiologists, radiologists, pathologists, nurses, and physician assistants. Any delay in the diagnosis will have a poor prognosis because most tumors tend to metastasize.
