Benign and malignant neural tumors .pptx

Peripheral nerve tumors are a heterogeneous group of mostly benign tumors that are rare in the general population. Certain types, including neurofibromas and schwannomas, may occur sporadically or in association with neurofibromatosis (NF).The nerve sheath is a layer of myelin and connective tissue that surrounds and insulates nerve fibers. A nerve sheath tumor is a growth within the cells of this covering.
Nerve sheath tumors form in these layers of insulation. These layers include:

Schwann cells: Cells that wrap around the long area of the nerve cell called the axon, or fiber.
Endoneurium: Connective tissue that surrounds each nerve fiber, like the coating around a wire.
Perineurium: Connective tissue that surrounds bundles of nerve fibers.
Your nervous system is made up of your:

Central nervous system: Your brain and spinal cord.
Peripheral nervous system: A network of nerves that branch off to the rest of your body.
Nerve sheath tumors usually affect your peripheral nervous system.
What are the types of nerve sheath tumors?

The most common types of nerve sheath tumors are:

Schwannomas

These occur in Schwann cells. About 60% of Schwannomas affect the vestibular nerve in your inner ear. Others form under your skin or deeper in your tissues and organs. Common locations of nerve sheath tumors include:

Arms and legs.
Head.
Torso (between your shoulders and hips).
Schwannomas are encapsulated — meaning, contained; covered with a thin layer of tissue — and are almost always noncancerous (benign). Very rarely, long-lasting tumors can become cancerous (malignant).

Neurofibromas

These tumors involve several types of tissue in the nerve sheath, including Schwann cells, endoneurium and perineurium. They usually appear under your skin as nodules or masses, but can also affect deeper nerves.

Neurofibromas aren’t encapsulated, or contained, like schwannomas, and penetrate between bundles of nerves. Plexiform neurofibromas are web-like and surround multiple nerve bundles. They can extend into nearby tissues.

Most neurofibromas are noncancerous. Approximately 5% to 10% become cancerous tumors called malignant peripheral nerve sheath tumors. In about half of people with malignant tumors, cancer has spread to other parts of their body at the time of diagnosis.

How common are nerve sheath tumors?

Benign nerve sheath tumors are relatively rare. Schwannomas are most common in people between the ages of 50 and 60. Neurofibromas most often occur in people between the ages of 20 and 40. Plexiform neurofibromas usually develop before age 5.

Malignant peripheral nerve sheath tumors are extremely rare, affecting about 1 out of every 10 million people each year.
Genetic changes play an important role in the development of nerve sheath tumors. Alteration of the NF2 gene is linked to schwannomas, while the NF1 gene is associated with neurofibromas.
What are the symptoms of nerve sheath tumors?

People with nerve sheath tumors often have no pain or other sympto

1. Neural tumors by swathi .A

2. INTRODUCTION Peripheral nerve tumors are a heterogeneous and complex group of lesions and reflects the intricate structure of peripheral nerves The range of structure and cell types from which the nerve sheath tumors may either arise, or differentiate toward, is quite broad Majority of tumors of PNS are derived from Schwann cells and their peripheral nerve elements In the oral region, neural tumors occur both in the soft tissues and in jaw bones. They occur as painless, smooth surface swelling in the soft tissues, with tongue being the most common site. Within the jaw bones they exhibit a slow rate of growth and mild expansion of the cortical plates Majority are benign and the malignant neoplasms generally have a propensity for local invasion rather than regional or distant metastasis.

3. Classification Benign Tumours: (1) Traumatic Neuroma (2) Palisaded encapsulated neuroma (3) Hamartomas — (a) Mucosal neuroma (B) Neuromuscular hamartoma (4) Neurofibroma/ Neurofibromatosis (5) Schwannoma (6) Granular cell tumor (7) Nerve Sheath Myxoma (8) Pigmented Neuroectodermal Tumor of Infancy Malignant Tumours: Malignant peripheral nerve sheath tumor Olfactory Neuroblastoma Malignant granular cell tumor Peripheral neuroectodermal tumour.

4. Traumatic Neuroma Occurs in response to injury(lacerating/penetrating) Benign non neoplastic overgrowth of nerve fibres & schwann cells. Traumatic injury - swelling, fragmentation, disintegration of nerves at distal ends debris cleared by macrophages shrinkage of neural sheaths »proliferation of axis cylinders, schwann cells, endoneurium from proximal end neural reinnervation usually occurs If proliferating proximal end meets some obstruction, such as scar tissue/mal aligned bone. continuous proliferation Traumatic Neuroma Clinical features. They are mostly diagnosed in young and middle aged adults with a predilection for women at ratio of 2:1 against men. small, firm, slow growing often painful nodules. Oral lesions-near mental foramen, alveolar ridge, lips, tongue May occur centrally in association with nerve trunk Pain on digital pressure/reflex neuralgia

5. histological features Shows a mass of irregular and often interlacing neurofibrils and Schwann cells situated in a connective tissue stroma of either scanty or plentiful proportion. The proliferating nerve fibers themselves may occur either in small discrete bundles or spread diffusely throughout the tissue ’

6. Differential diagnosis Neurofibroma Mucosal neuroma treatment: complete excision Other treatment includes stereotactic radiosurgery, Steroid infiltration Sympathetic ganglion block Percussion and ultrasonic therapy Re occurance is not common

7. MULTIPLE ENDOCRINE NEOPLASIA TYPE 2B (MULTIPLE ENDOCRINE NEOPLASIA TYPE 3; MULTIPLE MUCOSAL NEUROMA SYNDROME The multiple endocrine neoplasia (MEN) syndromes are a group of rare conditions characterized by tumors or hyperplasia of the neuroendocrine tissues. For example, patients with MEN type 1 have benign tumors of the pancreatic islets, adrenal cortex, parathyroid glands, and pituitary gland. MEN type 2A, also known as Sipple syndrome. includes the development of adrenal pheochromocytomas and medullary thyroid carcinoma. patients with MEN type 2B have mucosal neuromas that especially involve the oral mucous membranes. Because oral manifestations are most prominent in MEN type 2B. MEN type 2B is inherited as an autosomal dominant trait. The condition is caused by a mutation of the RET protooncogene on chromosome 10, which has been detected in 95% of affected individuals

8. Clinical features Patients with MEN type 2B usually have a marfanoid body build characterized by thin, elongated limbs with muscle wasting. The face is narrow, but the lips are characteristically thick and protuberant because of the diffuse proliferation of nerve bundles. The upper eyelid sometimes is everted because of thickening of the tarsal plate. Small, pedunculated neuromas may be observable on the conjunctiva, eyelid margin, or cornea. Oral mucosal neuromas are usually the first sign of the condition. These neuromas appear as soft, painless papules or nodules that principally affect the lips and anterior tongue but also may be seen on the buccal mucosa, gingiva, and palate Bilateral neuromas of the commissural mucosa are highly characteristic.

9. These neuroendocrine tumors are frequently bilateral or multifocal. The tumor cells secrete catecholamines, which result in symptoms such as profuse sweating, intractable diarrhea , head aches, flushing, heart palpitations, and severe hypertension . The most significant aspect of this condition is the development of medullary carcinoma of the thyroid gland, which occurs in more than 90% of cases. Medullary carcinoma most often is diagnosed in patients between the ages of 18 and 25 LABORATORY VALUES If medullary carcinoma of the thyroid gland is present, then serum or urinary levels of calcitonin are elevated. Pheochromocytomas may result in increased levels of urinary vanillylmandelic acid (VMA) and increased epinephrine-to-norepinephrine ratios.

10. HISTOPATHOLOGIC FEATURES The mucosal neuromas are characterized by marked hyperplasia of nerve bundles in an otherwise normal or loose connective tissue background. Prominent thickening of the perineurium is typically seen.

11. Multiple endocrine neoplasia (MEN) type 2B. Low-power view of an oral mucosal neuroma showing marked hyperplasia of nerve bundles Multiple endocrine neoplasia (MEN) type 2B. High-power view of the same neuroma as depicted in Note the prominent thickening of the perineurium.

12. TREATMENT AND PROGNOSIS The prognosis for patients with MEN type 2B centers on early recognition of the oral features, given the serious nature of the medullary thyroid carcinoma. prophylactic removal of the thyroid gland at an early age because medullary carcinoma is almost certain to occur. Once it has developed, this tumor often exhibits an aggressive behavior with a poor prognosis. The patient also should be observed for the development of pheochromocytomas because they may result in a life-threatening hypertensive crisis, especially if surgery with general anesthesia is performed.

13. Solitary Circumscribed/ Palisaded Encapsulated Neuroma Benign neoplasm/primary hyperplasia of nerve fibres, axons &Schwann cells 90% are facial lesions. Clinical features 5th-7th dec Limited to areas bordering mucocutaneous junctions of face Intra oral — hard palate Solitary sessile well circumscribed papule on the nose, cheek, and perioral skin less than 1 cm diameter Rubbery feel on palpation

14. NEUROFIBROMA Is a BENIGN TUMOUR OF NERVE TISSUE ORIGIN, DERIVED from the cells that constitute the nerve sheath The neurofibroma is the most common type of peripheral nerve neoplasm. It arises from a mixture of cell types, including Schwann cells and perineural fibroblasts Based on their growth pattern neurofibromas are typed into (a ) localized neurofibroma: these are often sporadic lesions in a non –NF1 (neurofibromatosis type 1) clinical features: no gender predilection , occurs between 20- 30 years of age. Occur anywhere on body, superficially in the dermis and subcutis. The lesion is Painless, tan white colored and fusiform in shape

15. Histological features the lesion consist of wavy elongated cells with dark staining nuclei in a collagenous stroma. They appear like wire like strands or shredded carrot like appearance that are separated from the cells by mucoid material. The cells may be arranged in fascicles, whorls or stipiform patterns. Neurofibromas are nonencapsulated, less cellular although cellular lesions resemble Antoni A areas of schwannoma.

16. (b ) diffuse neurofibroma : Commonly occur in children and young adults in the head and neck region. Appears elevated, plaque like lesion. Histologic features : these lesions have the tendency to spread through the connective tissue septa and between fat cells enveloping the normal structure. uniform matrix made up of fibrillary collagen. Schwann cells are elongated, fusiform or round shaped Presence of pseudo- meiss - nerian body like structures. The lesional tissue may be admixed with mature fat and large ecstatic vessels

17. Plexiform neurofibroma Lesions Occur in early childhood and The lesions of the extremities are enlarged and are termed as elephantiasis neurofibromatosis. Skin appears loose and redundant and hyperpigmented. The gross appearance of plexiform neurofibroma affecting a large segment of nerve resembles a “ bag of worms” appearance Histologic features: Plexiform neurofibromas Are highly cellular and reveal nuclear atypia. Such lesions require regular follow up to identify malignant transformation.

18. Pigmented neurofibroma . Pigmented cells containing melanin are present in about 1% of neurofibromas They are mostly associated with NF1 and diffuse neurofibroma although occasionally seen in the plexiform type. Histologic feature: dendritic or epithelioid shaped pigmented cells are presented dispersed throughout the tumor mass although cluster formation are present in the superficial portion of the lesion. Chances of recurrence are high due to the diffuse growth pattern of the lesion.

19. neurofibromatosis type I (NF1 This form of the disease, also known as “ von Recklinghausen’s ” disease of the skin, accounts for 85% to 97% of cases and is inherited as an autosomal dominant trait. It is caused by a variety of mutations of the NF1 gene, which is located on chromosome region 17q11.2 and is responsible for a tumor suppressor protein product known as neurofibromin. Clinical features: The clinical appearance can vary from small papules to larger soft nodules to massive baggy, pendulous masses (elephantiasis neuromatosa ) on the skin Another highly characteristic feature is the presence of café au lait (coffee with milk) pigmentation on the skin (Fig. 12-65). These spots are smooth-edged, yellow tan to dark-brown macules that vary in diameter from 1 to 2 mm to several centimeters.

20. They are usually present at birth or may develop during the first year of life. Axillary freckling ( Crowe’s sign ) is also a highly suggestive sign. The growth may be accelerated during pregnancy and puberty and malignancy can cause abrupt increase in size. Lisch nodules, translucent brown-pigmented spots on the iris, are found in nearly all affected individuals. Other possible abnormalities include CNS tumors, macrocephaly, mental deficiency, seizures, short stature, and scoliosis.

21. Oral manifestation may occur in about 25% patients. Discrete, nonulcerated nodules Usually noted on the buccal mucosa, palate, alveolar ridge, vestibule, and tongue. In addition macroglossia. Located centrally within the jaw are seen in the mandible, associated with the mandibular nerve. Radiographic findings may include enlargement of the mandibular foramen, enlargement or branching of the mandibular canal, increased bone density, concavity of the medial surface of the ramus, and increase in dimension of the coronoid notch. In addition, several patients with NF1 have been described with associated Noonan syndrome or with central giant cell granulomas of the jaw Treatment: surgical excision, depending on the extent and site. Surgical removal may result in recurrence. Genetic counseling and evaluation of other family members should be performed for those suspected to be affected by a syndrome.

22. Neurofibromatosis Type I (NF1) The diagnostic criteria are met if a patient has two or more of the following features: 1. Six or more café au lait macules more than 5 mm in greatest diameter in prepubertal persons and more than 15 mm in greatest diameter in post pubertal persons 2. Two or more neurofibromas of any type or one plexiform neurofibroma 3. Freckling in the axillary or inguinal regions 4. Optic glioma 5. Two or more Lisch nodules (iris hamartomas) 6. A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex with or without pseudoarthrosis 7. A first-degree relative (parent, sibling, or offspring) with NF1, based on the previously mentioned criteria

23. Neurilemmoma (perineural fibroblastoma , schwannoma, neurinoma) The neurilemoma is a benign neural neoplasm of Schwann cell origin. It is relatively uncommon, although 25% to 48% of all cases occur in the head and neck region. Bilateral neurilemomas of the auditory vestibular nerve are a characteristic feature of the hereditary condition, neurofibromatosis type II (NF2) Clinical features: Neurilemmoma is a slow-growing lesion is usually long durationat the time of presentation by patient, encapsulated tumor the mass is asymptomatic, although tenderness or pain may occur in some instances. The lesion is most common in young and middle-aged adults and can range from a few millimeters to several centimeters in size.

24. Oral manifestations Single, circumscribed nodule of varying size presents Includes tongue, palate, floor of mouth, buccal mucosa, gingiva, lip and vestibule. Other areas involving maxillary sinus and salivary glands. The tongue is the most common location for oral neurilemomas. Radiographic features: the tumor arises centrally within bone and may produce bony expansion. Intraosseous examples are most common in the posterior mandible and usually appear as either unilocular or multilocular radiolucencies on radiographs. Pain and paresthesia are not unusual for intrabony tumors.

25. Histologic features: demonstrates two microscopic patterns in varying amounts: ( 1) Antoni A and (2) Antoni B. Streaming fascicles of spindle-shaped Schwann cells characterize Antoni A tissue. These cells often form a palisaded arrangement around central acellular, eosinophilic areas known as Verocay bodies Verocay bodies consist of reduplicated basement membrane and cytoplasmic processes. Antoni B tissue is less cellular and less organized; the spindle cells are randomly arranged within a loose, myxomatous stroma. Treatment: surgical excision. Stereotactic radiosurgery may be considered for older adult or frail patients, as well as for individuals who decline traditional surgery.

26. Low-power view showing well-organized Antoni A tissue (right) with adjacent myxoid and less organized Antoni B tissue (left). B, The Schwann cells of the Antoni A tissue form a palisaded arrangement around acellular zones known as Verocay bodies.

27. Melanotic neuroectodermal tumour of infancy rare pigmented neoplasm that usually occurs during the first year of life. It is generally accepted that this lesion is of neural crest origin . In the past, however, a number of tissues were suggested as possible sources of this tumor. These included odontogenic epithelium and retina, which resulted in various older terms for this entity, such as pigmented ameloblastoma, retinal anlage tumor, and melanotic progonoma . Because these names are inaccurate, however, they should no longer be used

28. Clinical feature: Melanotic neuroectodermal tumor of infancy almost always develops in young children during the first year of life; only 9% of cases are diagnosed after the age of 12 months. the anterior region of the maxilla, where it classically appears as a rapidly expanding non ulcerated mass that is frequently blue or black. There is a striking predilection for the maxilla, which accounts for 61% of reported cases. Less frequently reported sites include the skull (16%), epi didymis and testis (9%), mandible (6%), and brain (6%). A slight male predilection has been noted.

29. Radiographic features: unilocular or rarely as multiloculated radiolucency. The tumor often destroys the underlying bone and may be associated with displacement of the developing teeth. there may be an associated osteogenic reaction, which exhibits a “sun ray” radiographic pattern that can be mistaken for osteosarcoma.

30. LABORATORY VALUES High urinary levels of vanillylmandelic acid (VMA) often are found in patients with melanotic neuro ectodermal tumor of infancy. This finding supports the hypothesis of neural crest origin because other tumors from this tissue (e.g., pheochromocytoma, neuroblastoma) often secrete norepinephrine-like hormones that are metabolized to VMA and excreted in the urine. HISTOPATHOLOGIC FEATURES: The tumor consists of a biphasic population of cells that form nests, tubules, or alveolar structures within a dense, collagenous stroma. The alveolar and tubular structures are lined by cuboidal epithelioid cells that demonstrate vesicular nuclei and granules of dark-brown melanin pigment. Central portion of the alveolar spaces contain many small round neuroblast like cells consists of small, round cells with hyperchromatic nuclei and little cytoplasm These cells grow in loose nests and are frequently surrounded by the larger pigment-producing cells. Mitotic figures are rare.

31. treatment Surgical removal Some clinicians prefer simple curettage, although others advocate that a 5-mm margin of normal tissue be included with the specimen. potentially serious nature of this tumor and the need for careful clinical evaluation and follow-up of affected patients

32. Malignant tumors of nerve tissue origin “malignant peripheral nerve sheath tumor (“ neuro fibrosarcoma; malignant schwannoma ), which has been reported to occur in about 5% of cases. These tumors are most common on the trunk and lower extremities, although head and neck involvement is occasionally seen. Especially the trigeminal nerve. Clinical features : It represents approx 10% of all soft tissue sarcoma and this diagnosis called one of the most difficult and elusive diagnosis in soft tissue disease. 20-50 years of age . Slightly male predilection( 80% ) Mandible is more frequently affected than the maxilla. When it occurs in the oral cavity it is usually seen arising from the tongue or soft palate. The lip gingiva, palate and buccal mucosa have been sites of involvement. Presence of mass, pain, paraesthesia, muscle weakness are present .

33. Radiographic features : diffuse radiolucency characteristic of a malignant infiltrating neoplasm. It appears smooth radiolucency such as dilatation of mandibular canal when the tumor is originating from this nerve.

34. Histologic features: spindled lesional cells demonstrate the wavy or comma shaped outline and nuclear contour of schwann cells. Cytoplasm is usually indistinct and slightly eosinophilic. Classified into 3 major categories . Epithelioid: demonstrates plump and rounded or ovoid epithelioid cells scattered through out the spindled lesion cells and hyperchromatic nuclei. Spindles cells with large, plump, rounded or strap cells with eosinophilic, fibrillar cytoplasm. Mesenchymal or glandular : usually well differentiated ductal structures lined by simple, stratified, cuboidal/columnar epithelial cells with occasional goblet cells. The lumen may contain pas-positive, diastase-resistant mucous.

35. Differential diagnosis Fibrosarcoma Leiomyosarcoma Treatment: wide surgical excision Radiotherapy & chemotherapy Is not associated with the syndrome

36. (2)Olfactory neuroblastoma Rare tumour originating from the olfactory apparatus. Most frequently in the nasal cavity and nasopharynx. Seen in less than 6%of all malignancies of the nasal cavity. They are neuroectodermal in origin arising from basal cells of the olfactory epithelium. Clinical features: painfull swelling in the area of the nasal fossa resulting in nasal obstruction and epistaxis. Invasive, destructive tumour and rarely metastasizes. Adults between 40-70 years of age. Kadish clinical staging system : Stage a: tumor confined to the nasal cavity Stage b: tumor involving one or more paranasal sinuses Stage c: tumor extending beyond the nasal cavity and paranasal sinuses Stage d: tumor with lymph node or distant metastasis

37. Histologic features: The appearance of the tumor characteristically is one of the densely packed masses of small darkly staining cells each with a poorly defined eosinophilic cytoplasm and a regular round vesicular nuclei, sometimes with stippled chromatin. Rosette formation is common. This is a pseudo glandular structure lined by a single layer of non ciliated columnar cells with a basal nucleus and a circular border at the apex of the cell These resemble the subtentacular and olfactory cells of the olfactory mucosa. Eosinophilic neurofibrils extend into the lumen from the cell borders.

38. Treatment: generally surgery, radiation or both in combination. Although reoccurance of the lesion is rather common 5 year survival rate is 65% for the combined treatment and less than 50% following surgical treatment or radiotherapy used alone.