Neurinoma (schwannoma): causes, symptoms, diagnosis, treatment

Neurilemoma (syn.: neurinoma, schwannoma) is a benign tumor of neurolemmocytes of cranial or spinal peripheral nerves. It is localized in the subcutaneous tissue of the head, trunk and limbs along the nerve trunks. The tumor is usually solitary, round or oval in shape, often of a dense consistency, pinkish-yellow in color, no more than 5 cm in diameter. It can be painful, sometimes with pain irradiation along the corresponding nerve.

Originates from Schwann structures that form the nerve myelin sheath. Otherwise, the disease is called neurinoma, or a tumor of the nerve sheath.

The appearance of a schwannoma is a round, dense node surrounded by a capsule. It is characterized by mainly slow growth, about 1-2 mm per year, although cases of intensive-aggressive development and malignancy are known. [ 1 ]

[ 2 ]

Epidemiology

Schwannoma can be both benign and malignant. The neoplasm is diagnosed relatively rarely - approximately in 7% of patients with soft tissue sarcomas. The pathology is detected mainly in middle-aged people, and in women - somewhat more often than in men.

Intracranial schwannoma occurs in 9-13% of all tumor processes in the brain. If we talk about cerebral neurinoma, we usually mean schwannoma of the auditory nerve (other names are acoustic, vestibular neurinoma), since other cranial nerves are affected much less often. Multiple pathology (including bilateral) is more typical for neurofibromatosis.

Organ schwannoma can occur in the nasopharyngeal region and nasal cavity, as well as in the stomach and lungs, larynx, tongue, palatine tonsil, in the retroperitoneal space and mediastinum.

Malignancy of schwannoma is possible, although in practice it is relatively rare.

Causes neurinomas (schwannomas)

The exact causes of the formation of schwannoma, like many other nerve neoplasms, are currently not fully understood. The node occurs through the proliferation of Schwann structures from myelinated nerve fibers.

It has been proven that the tumor is associated with a mutation of individual genes of chromosome 22, which are responsible for the production of a protein that restrains the growth of Schwann cells. Incorrect protein synthesis leads to excessive growth of such structures. At the same time, the causes of mutational failures in chromosome 22 have not yet been determined. The influence of large doses of radiation or prolonged chemical intoxication, as well as the involvement of other benign tumors (including those that are inherited) are not excluded. [ 3 ]

Risk factors

The main risk factor for the development of schwannoma is neurofibromatosis type 2. This is a relatively rare genetic pathology, which is characterized by an increased tendency to benign tumors, mainly bilateral schwannomas of the 8th pair of cranial nerves. The disease is transmitted by an autosomal dominant type of inheritance and has no connection with gender.

Hereditary schwannoma is unilateral, sometimes combined with neurofibromas or meningiomas, neuromas of other cranial nerves, astrocytomas and spinal ependymomas.

Other possible risk factors include:

• radiation effects;
• chemical influences;
• burdened hereditary history (there were or are relatives in the family who suffer from neuromas or other tumor processes).

Pathogenesis

Schwannoma is a neoplasm, usually benign, less often malignant, which develops on the basis of Schwann structures of the nervous membrane. The lesion has a general histogenetic nature and is distinguished by its location. Macroscopically, schwannoma is a clearly defined rounded nodular element surrounded by a fibrous capsule. In section, yellowish inclusions may be detected, which is especially noticeable in intracranial neurinomas. Often, there are zones of angiomatosis and cystic transformation in the form of parallel rows of spindle-shaped cells that surround the acellular region of the fibrous matrix. Such cell rows are called Verocai bodies; they are more typical of spinal schwannoma.

The fascicular variety of schwannoma is distinguished by its reticular structure. The lesion is formed by loosely arranged cells with lymphocyte-like nuclei. The cellular cytoplasm is visually not filled due to xanthomatosis.

Intracranial schwannoma combines reticular structures and Verocai bodies.

Microscopically, the neoplasm may have a different structure, which depends on the presence of connective tissue, the degree of serous fluid penetration, the presence of cystic cavities, the presence of tissue degeneration, and the development and type of the vascular network. Some schwannomas are supplied with numerous vessels, sometimes with thickenings and vascular lacunae.

Schwannomas can be intracranial, spinal, soft tissue (intradermal), organ and peripheral nerve. [ 4 ]

Pathomorphology of neuroma

The tumor is encapsulated and, according to its histological structure, is divided into Antoni types A and B.

In the first type, the tumor consists of intertwined thin fibrous structures that stain yellow with picro-fuchsin, grouped in the form of bundles that are random or form rhythmic structures. Between the fibers, oval or elongated cells are located, forming palisade-like structures. In some parts of the tumor, Verocai bodies are found, which are areas without nuclei, around which the cells are arranged in a palisade, which is pathognomonic for the Antoni type A. In the Antoni type B, a parallel arrangement of tumor elements predominates in the form of thin-fibrous bundles surrounded by connective tissue with a large number of tissue basophils. Mucoid transformation of the tumor stroma is noted, sometimes with the formation of small pseudocysts. There may be intermediate types between these types of neurilemoma.

Histogenesis of neuroma

Electron microscopy revealed that the tumor elements are typical neurolemmocytes, the cytoplasmic membrane of which is closely adjacent to the basement membrane. In Antoni type B, there are dystrophic changes in neurolemmocytes, in the cytoplasm of which massive vacuoles are detected, sometimes with myelin structures. These cells, as a rule, do not have a basement membrane.

Symptoms neurinomas (schwannomas)

The clinical picture depends on the location and size of the neoplasm. Schwannoma of the brain is accompanied by craniocerebral symptoms, schwannoma of the spinal cord - signs of cerebrospinal damage, and neuroma of the peripheral nerves is manifested by a disorder of sensitivity of the extremities. As the tumor grows and deepens into the tissue, compression begins, which is accompanied by corresponding symptoms.

Vestibular schwannoma manifests itself with symptoms of nerve damage, cerebellar disorders and brainstem manifestations. In most cases, the auditory nerve is affected unilaterally (90%). The first signs may be as follows:

• noise and ringing in the ear;
• hearing loss;
• vestibular disorders.

As the acoustic schwannoma grows, it compresses nearby nerves, particularly the trigeminal nerve. Sensory disturbances and dull, constant pain on the affected side (similar to a toothache) are noted. Late stages are accompanied by weakness and atrophy of the masticatory muscles.

Signs of compression of the abducens and facial nerves are:

• loss of taste;
• salivary disorders;
• changes in facial sensitivity;
• double vision, strabismus, lacrimation or dry eyes (which is typical for a situation when a schwannoma of the oculomotor nerve develops).

If facial nerve schwannoma occurs in a patient with neurofibromatosis, the clinical picture is expanded by the symptoms of this disease. Skin hyperpigmentation, the appearance of brownish spots, and bone pathologies can be observed.

Trigeminal schwannoma is the second most common neuroma. The first signs appear depending on the size of the tumor. Most often, we are talking about the following symptoms:

• changes in facial sensitivity (feeling of cold, goosebumps, appearance of areas of numbness);
• weakness, paresis of the masticatory muscles;
• dull pain in the face on the affected side;
• change in taste;
• hallucinations of taste and smell, which can also affect the quality of appetite.

Although virtually any cranial nerve can be affected, schwannomas of the optic nerve and olfactory nerve are not common. These nerves do not contain sheaths made up of Schwann cells.

Spinal neurinoma is diagnosed mainly in the cervical and thoracic spine. Lumbar schwannoma is much less common. In all cases, the pathological formation surrounds the spinal cord, exerting pressure on it from all sides. This is manifested by the following clinical symptoms:

• radicular pain syndrome;
• vegetative disorders;
• signs of damage to the spinal cord.

The patient complains of numbness, increased temperature sensitivity, and a crawling sensation in the area of innervation by the affected nerve. Schwannoma of the soft tissues of the neck is accompanied by unpleasant sensations in the occipital, cervical, shoulder, and elbow areas. The pain is usually acute, may resemble an attack of angina, and radiate to the upper limb or shoulder blade.

Nerves that extend from the spinal cord (nerve roots) are an extension of the spinal cord responsible for the transport of impulses to various structures in the body. The spinal cord ends at the level of the first lumbar vertebra, where the so-called conus medullaris is formed. The nerve-root bundle below this cone is called the equine tail. Schwannoma of the equine tail is accompanied by pain in the corresponding localization, changes in reflexes, decreased muscle strength and sensitivity. In some cases, patients lose their ability to work, although a neurinoma of this localization usually responds well to surgical treatment. The operation is mandatory and urgent, since often, in the absence of treatment, patients experience bladder dysfunction and paresis of the lower extremities.

Soft tissues include not only muscles, but also nerve endings, which can also be affected by a benign tumor process. Thus, schwannoma of the soft tissues of the thigh is often diagnosed. The disease manifests itself as pain when pressed, as well as other symptoms, the severity of which depends on the size of the neoplasm. In some cases, edema, local sensitivity disorder, paresis and paresthesia are detected.

Mediastinal schwannoma, another less common type of this neoplasm, has the following symptomatic characteristics:

Chest pain, possibly radiating to the shoulder girdle, neck and shoulder blade area;

• heart rhythm disturbance;
• cough, difficulty breathing;
• general weakness, fatigue;
• headache and dizziness;
• facial flushing.

Schwannoma of the small pelvis is accompanied by dysfunction of the organs located in this area. Retention or incontinence of urine and/or stool, disruptions in the digestive system, and disorders of reproductive and sexual function are possible.

Schwannoma of the brachial plexus is a malignant pathology and often results from malignization of neurinoma. Patients complain of characteristic pain in the area between the shoulder and neck. The pain appears or intensifies when bending, turning, or moving the head.

Schwannoma of the sciatic nerve manifests itself as constant pain in the lower limb while walking, as well as when bending and unbending the affected leg at the knee joint. It is possible to develop paresthesia in the foot, weakness, especially noticeable when walking. During diagnostic measures, signs of sciatic nerve neuropathy are detected. [ 5 ]

Stages

Schwannoma of the auditory nerve (also known as acoustic or vestibular neuroma) goes through four stages in its development.

1. The pathological focus does not leave the boundaries of the internal auditory canal; the diametrical size of the extracanal part is from 1 mm to 1 cm.
2. The tumor process expands the internal auditory canal and spreads into the cerebellopontine angle, and the diameter expands to 11-20 mm.
3. The tumor reaches the brainstem, but does not compress it. The diameter expands to 21-30 mm.
4. The brain stem is compressed, the diameter of the formation exceeds 3 cm.

Benign schwannoma

Soft tissue schwannoma rarely metastasizes in a benign course, but often reaches large sizes and grows deeply. However, some such tumors tend to grow aggressively, so it is recommended to remove them at the earliest opportunity.

In general, the tumor process affects mainly the head and spine, neck and upper limbs, can be single or multiple, and often grows slowly in the form of a clear node of dense consistency. One of the characteristic signs is the appearance of pain when pressing.

Often, such schwannomas do not manifest themselves in any way and are detected by chance. However, even in this case, specialists recommend removing the pathological focus without waiting for the development of neurological symptoms and other adverse effects and complications.

Malignant schwannoma

Malignant transformation of schwannoma occurs in isolated cases, but the probability of malignancy should not be completely ignored. During malignancy, clearly defined areas with increased cellularity and numerous mitoses, anaplastic polygonal and round epithelial structures appear against the background of benign zones. There are borderline changes in the transition areas. Cystic changes are visualized in approximately 75% of cases of malignant schwannomas.

Complications and consequences

A large number of schwannomas have a benign course and grow quite slowly, without causing significant neurological deficit. Therefore, in some cases, doctors suggest that patients choose a wait-and-see approach, without radical removal of the neoplasm. At the same time, doubts arise: could any adverse complications arise during this time?

Risks do exist, so "waiting" is not recommended for all patients, but only for those who have severe decompensated somatic pathology that prevents surgery. This includes elderly patients.

In general, the choice of active surgical treatment is more justified. [ 6 ]

Possible complications of further growth of schwannoma include:

• paresis, paralysis;
• disorders of the digestive and pelvic organs;
• hearing and vision impairments;
• increased intracranial pressure;
• cardiac and respiratory dysfunction;
• malignancy (malignancy).

Diagnostics neurinomas (schwannomas)

The most informative diagnostic procedure for acoustic schwannoma is magnetic resonance imaging with contrast in T1 and T2 modes. This method helps to determine the size of the neoplasm, the presence of peritumorous edema and signs of occlusive hydrocephalus, which occurs as a result of compression of the fourth ventricle. Computer tomography and hardware audiography are also performed.

The main diagnostic methods, including instrumental diagnostics, include:

• neurological examination for damage to the cranial and spinal nerves;
• audiogram (determines the degree of hearing loss in acoustic-vestibular schwannoma);
• computed tomography, magnetic resonance imaging, nuclear magnetic resonance.

Rounded schwannomas are well visualized by nuclear resonance. In some cases, the neoplasm has the appearance of a drop. During contrast MRI, the tumor actively accumulates contrast and demonstrates high intensity, which is visualized on the image as a white round element.

In spinal schwannoma, a rounded neoplasm is also determined. If the tumor grows through the intervertebral foramen, it takes on the appearance of an hourglass, which is clearly visible on the CT picture. [ 7 ]

Laboratory tests are non-specific and are carried out as part of general clinical studies.

Radiographic characteristics of schwannoma:

• a well-defined pathological area, with displacement of adjacent structures without growth into them;
• signs of cystic and fatty degeneration;
• rarity of calcifications and hemorrhages (up to 5% of cases).

MRI characteristics of schwannoma:

• T1 hypotensive or isometric;
• T1 with contrast – intense signal enhancement;
• T2 – heterogeneous hyperintensity, with possible cystic changes;
• T2 – large neoplasms have areas of hemorrhage.

Differential diagnosis

Differential diagnostics in the preoperative period is quite difficult. Differences should be sought between sarcomas (liposarcomas and fibrosarcomas), ganglioneuromas and other tumor processes of connective tissue.

Existing preoperative diagnostic methods are not generally accepted, procedures are prescribed individually. Magnetic resonance imaging with the introduction of a contrast agent is often the most informative.

According to statistics, only in 10-15% of cases the doctor manages to make a correct diagnosis of schwannoma before performing surgery. This mainly concerns cases associated with the presence of neurofibromatosis.

Treatment neurinomas (schwannomas)

Depending on the clinical characteristics and size of the schwannoma, the patient's condition and age, the doctor may resort to one of three types of treatment:

• dynamic control (waiting tactics);
• surgical treatment (surgical tactics);
• stereotactic radiosurgery.

If the schwannoma is benign, small, does not cause neurological deficits and does not have a high growth rate, the doctor may resort to watchful waiting. Such tactics are appropriate for elderly patients who have somatic diseases in the decompensation stage.

However, in the vast majority of cases, given the risk of further growth of the neoplasm, it is more advisable to choose an active approach - in particular, removal of the schwannoma.

Medicines

Chemotherapy is used for malignant schwannomas, although the tumor is often resistant to it and it is necessary to individually select suitable and effective drugs. Chemotherapy is also prescribed for metastasis. The treatment is long-term, intravenous, and the dosage is determined specifically for each patient. The most commonly prescribed chemotherapeutic drugs are Vincristine, Doxorubicin, platinum agents, Etoposide and Cyclophosphamide.

Possible treatment regimens:

• Vindesine 3 mg per m² intravenously/drip. for 1-4 days in courses of 21 days + Cisplatin 40 mg per m² intravenously/drip. for 1-4 days + Etoposide 100 mg per m² intravenously/drip. in courses of 21 days.
• Vincristine 0.75 mg/m² intravenously/drip on the first, third and fifth day + Doxorubicin 15 mg/m² intravenously/drip on the first, third and fifth day + Cyclophosphamide 300 mg/m² intravenously/drip on the first through fifth day. Courses in periods of 21 days.
• Topotecan 1 mg per m² intravenously/drip from day 1 to day 7 + Cyclophosphamide 100 mg per m² intravenously/drip from day 1 to day 7 + Etoposide 100 mg per m² intravenously/drip from day 8 to day 10 in 21-day courses.

The patient's condition is constantly monitored by a specialist. If necessary, he urgently replaces the drug or adjusts the dose. The most common side effects during chemotherapy are: constipation, abdominal pain, numbness and tingling in the feet and hands, muscle and bone-joint pain, nausea and vomiting, muscle weakness.

Surgical treatment

Schwannoma is an indication for surgery for most patients. Patients with large and giant schwannomas, as well as with pronounced neurological deficit, are operated on without fail. Small neoplasms can be removed using radiosurgery.

To eliminate vestibular (acoustic) schwannomas, one of three basic types of surgical access is used. Most often, retrosigmoid access is used, somewhat less often - translabyrinthine and through the middle cranial fossa. All of these methods have their "pros" and "cons", based on which the doctor makes a decision on the type of operation to be performed.

Over the past few years, specialists have been actively using microsurgical instruments in surgical practice, which has increased the percentage of relapse-free and successful removal of schwannomas. The development of postoperative complications occurs relatively rarely: we are talking about disorders of nerve innervation and neurological functions, cerebrospinal fluid leakage and hemorrhages, edema of brain structures, inflammatory processes, wound infection, paresis and paralysis.

The goal of radiosurgical treatment, which is used primarily for small tumors, is to establish control over the growth of schwannoma. Often, the use of this method allows stabilizing the development of the pathological focus and reducing its volume - in more than 80% of cases. Gamma knife is indicated for the treatment of schwannomas up to 35 mm in size. [ 8 ]

Prevention

Specific preventive measures to prevent schwannoma have not been developed, since modern medicine does not have sufficient information about the nature of the disease.

People at risk should be especially attentive to their health, regularly visit doctors for preventive examinations. This applies to people who have previously been exposed to radiation, or have a burdened heredity for other tumor processes in the nervous system, nephrofibromatosis, etc. In addition to examination by a neurologist, it is recommended to periodically perform computed tomography or magnetic resonance imaging. The need for other auxiliary diagnostic procedures is determined individually.

Forecast

Surgery is the preferred and recommended treatment method, successfully used for schwannoma. Recurrences are extremely rare, as is malignancy.

In general, schwannomas are mostly benign, but can reach large sizes - 10-20 cm in diameter, which is mainly due to late diagnosis. Late referral to doctors can be explained by the scarcity of initial clinical manifestations, long asymptomatic course, non-specific symptoms. The most common reason for seeking medical help is a situation when the tumor begins to press and displace nearby structures and organs.

The prognosis after surgical removal of a benign neoplasm is considered favorable: patients have an almost 100% five-year survival rate. After removal of the malignant lesion, the five-year survival rate is about 50%. Schwannoma in the form of a relapse develops mainly with its incomplete removal, which is observed in 5-10% of cases.