TUMOR OF NERVES AND MUSCLES
DR. SUHASINI GP
SENIOR LECTURER
DEPT. ORAL &MAXILLOFACIAL PATHOLOGY AND MICROBIOLOGY
SUBHARTI DENTAL COLLEGE AND HOSPITAL
SWAMI VIVEKANAND SUBHARTI UNIVERSITY
MEERUT. UP
Subject: Oral Pathology

TUMOR OF NERVES

Epineurium
Perineurium
Endoneurium
Fascicles
Nerve fiber
Node of Ranvier
Schwann cell
Myelin
Axon
From: Møller: Sensory Systems, 2003

TRAUMATIC NEUROMA
(Amputation neuroma)
• Not a true neoplasm
Attempt at repair of damaged nerve trunk i.e.
hyperplasia of nerve fibers and their supporting tissues
• Degeneration of the distal portion of the nerve after
severance NF begins with swelling, fragmentation and
disintegration of axis cylinder and myelin sheaths
• Repair of damaged N begins with proliferation of
neurilemmal sheaths and endoneurium

P.Deb 7

Wallerian degeneration
The degenerative changes the distal segment of a
peripheral nerve fiber (axon and myelin) undergoes
when its continuity with its cell body is interrupted by a
focal lesion.
Syn: orthograde degeneration, secondary degeneration
Interrupted axons regenerate from injury, provided that
endoneural tube is intact

• Repair - proliferation of axis cylinders, cells of
the neurilemmal sheaths and endoneurium
• Occurs unless proliferating proximal end
meets some obstruction

Clinical Features
• Small nodule or swelling of mucosa
• Central lesion
• Slowly growing lesion
• Middle aged adults, more in females
• Pain locally

• Irregular nodular proliferation along mental nerve

Histologic Features
• Mass of irregular interlacing neurofibrils and
Schwann cells in connective tissue stroma
• Proliferative nerve bundles occur as discrete
bundles or spread diffusely
• Mild chronic inflammatory cell infiltrate

Hephazard arrangement of nerve bundles within fibrous CT stroma

PALISADED ENCAPSULATED NEUROMA
(Solitary circumscribed neuroma)
• Benign neoplasm, not a form of traumatic
neuroma
• Trauma- etiology
• Reactive lesion rather than a true neoplasm

Clinical features
• Striking predilection for face-90%
• 5th-7th decade
• Smooth, painless, dome shaped nodule,
usually less than 1cm
• Intraoral- common in hard palate, upper labial
mucosa

• Areas bordering mucocutaneous junctions,
predominantly on face- nose, cheek, upper
eyelid, lip and chin
• Represent hyperplasia of nerve fibers, the
axons and their nerve sheath cells.

Histopathology
• Well circumscribed, incomplete capsule
• Some lesions- lobulated appearance
• Interlacing fascicles of spindle shaped cells-
consistent with Schwann cells (wavy, pointed)
• Nuclei show parallel orientation within
fascicles (more definite palisading and Verocay
bodies typical of the Antoni type A tissue of
neurilemmoma are not seen)

• Solitary circumscribed neuroma- better
descriptive term
(tumor is not always encapsulated and usually
not true palisaded)
• Treatment- local surgical excision

The Elephant Man Mistake
• A popular movie ‘The Elephant Man’ portrayed the
story of an individual (Joseph Merrick) with facial and
scalp tissue proliferations as arising from an extreme
case of Neurofibroma (NF).
• Yet, the study of archived tissue from this man
showed not NF but rather hyalinized C T (Proteus
syndrome).
• Individuals with NF have unnecessarily endured
greater anxiety and a heavier psychologic burden since
this Hollywood mistake.

Neurofibroma
(Neurofibromatosis, Von Recklinghausen’s Disease,
fibroma molluscum, elephant man disease)
• Benign tumor of nerve tissue origin
• Arise from perineural fibroblasts
• Seen either
– As a solitary lesion
– As a part of Neurofibromatosis- Autosomal dominant
– Chromosome Type 1- 17q11.2 (Neurofibromin)
– 22q12.1 (Schwannomin- type 2)

Clinical Features-
• Neurofibromatosis- Hereditary disease, no gender
predilection, cosmetic problems, risk of malignant
transformation
• Oral Manifestations-
– Discrete, non-ulcerated nodules of normal mucosal
colour OR
– Diffuse masses of tissue
– Buccal mucosa, palate, alveolar ridge, tongue
– Macroglossia due to diffuse involvement of tongue
– Occasionally located centrally within jaw bones
Neurofibroma

• Slow-growing, soft, painless, small nodules to larger
masses
• Osseous changes, mental disorders, ocular diseases
• Facial pain or paresthesia
• Mandible- show fusiform enlargement of mand canal
• Plexiform- variant- feels like “bag of worms”-
pathognomonic for neurofibromatosis
• Malignant transformation-
MPNST……

- Crowe’s sign

Café-au-lait spots-
• Neurofibromatosis- smooth borders (coast of
california)
• fibrous dysplasia (irregular- coastline of
Maine)
• Segmental neurofibromatosis- restricted to
one location of the body

NF II (acoustic form)
• Chromosome 22 (Merlin)
• Bilateral acoustic neuroma
• CNS tumors
• Cutaneous neurofibromas
• Cafe-au-lait spots (less frequency)

Histologic Features-
• Solitary neurofibroma may or may not be well
circumscribed
• Interlacing bundles of spindle-shaped cells often with wavy
nuclei
• Cells are associated with delicate collagen bundles and
variable amounts of myxoid matrix
• Numerous mast cells
• In plexiform neurofibroma- distorted masses of
myxomatous peripheral nerve tissue still within perineural
sheath; masses scattered within a collagen-rich matrix

cells with wavy nuclei
intermingled with
neurites in irregular
pattern
Delicate interwining CT
fibrils
Cellular/ myxoid
pattern
Mast cells

Treatment-
• Solitary neurofibroma- surgical excision
• For neurofibromas associated with
Neurofibromatosis- surgical removal only for
functional or cosmetic purpose
Neurofibroma

NEUROLEMMOMA
Neurilemoma, perineural fibroblastoma,
Schwannoma, neurinoma, lemmoma
• Benign neural neoplasm of Schwann cell origin
• Neurites are not a component of tumor as in
neurofibroma
• Composed of Schwann cells in poorly collagenized
stroma
• Proliferation of Schwann cells at one point inside
perineurium

Clinical Features
• Slowly growing lesion
• Any age
• No gender predilection
• Usually painless
• Presence of tumor mass

Oral Manifestations
• Tongue, palate, floor of mouth, buccal mucosa,
gingiva, lip, vestibule
• Maxillary sinus and salivary glands, as well as
retropharyngeal, nasopharyngeal and
retrotonsillar areas
• Mandible, bone destruction, expansion
• Pain, paresthesia

Histologic Features
• Encapsulated
• Antoni type A and Antoni type B
• Antoni type A cells with elongated or spindle shaped nuclei
aligned to form palisading pattern
• Antoni type B does not exhibit palisading, but rather disorderly
arrangement
• Verocay bodies, small hyaline structures (consists of reduplicated
BM & cytoplasmic processes)
• Large irregularly shaped vessels which are characteristic of
Schwannomas

• Neurilemmoma may undergo degenerative
changes (rare- in intraoral lesions).
• When the changes are pronounced, the tumors
have been called ancient Schwannomas (cyst
formation, hyalinization, calcification,
hemorrhage, and nuclear atypism).

Schwannoma with extensive degenerative
changes like hemorrhage, cyst formation & calcification

Schwannoma of Submandibular Gland

MULTIPLE ENDOCRINE NEOPLASIA SYNDROME

MULTIPLE ENDOCRINE NEOPLASIA SYNDROME
(MEN SYNDROME-MEN III, MEN IIb)
• Tumors or hyperplasias of neuroendocrine
tissues
• Autosomal dominant trait
• Adrenal pheochromocytomas, medullary
thyroid carcinoma, submucosal neuroma

• Tall, lanky, marfanoid body type
• Adrenal and thyroid tumors do not present until
after puberty
• oral mucosal neuromas - develop during 1st decade
• Mutations of RET proto-oncogene – regulator of
neural crest development and receptor of glial
derived neurotrophic factor (GDNF)

Clinical Features
• 2-7 mm yellowish-white, sessile, painless nodule of
lips, anterior tongue and buccal commissures
• ‘Bumpy lip'
• Similar lesion on eyelid, producing eversion of lid, &
on the sclera
• Facial skin, around nose, may be involved
• Serum and urinary calcitonin levels elevated
• Increase in serum levels of vanillylmandelic acid
(VMA)
• Altered epinephrine norepinephrine ratio

• Luxol fast blue
• S 100
• Col IV
• Vimentin
• NSE

Histologic Features
• Partially encapsulated aggregation or proliferation
of nerves
• Background of loose endoneurium-like fibrous
stroma
• Occasional hyperplasias and bulbous expansions

Self limiting disease

MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY
Pigmented ameloblastoma
Melanoameloblastoma
Retinal anlage tumor
Melanotic progonoma
Melanotic epithelial odontoma
Pigmented teratoma

• Uncommon osteolyticpigmented neoplasm
• Origin- Odontogenic apparatus, pigmented
anlage of the retina, sensory neuroectodermal
tissues

Clinical Features
• Within first year of life
• Male-to-female ratio of 6:7
• Anterior part of maxillary ridge
• Skull, mandible, epididymis, brain
• Rare lesions have been reported in shoulder, skin,
femur, mediastinum, uterus

• Rapidly growing, nonulcerated, darkly
pigmented lesions
• Displace or destroy developing deciduous and
permanent dentition
• Can present as unilocular, or rarely as
multiloculated radiolucency
• Increase in urinary level of VMA

Histologic Features
• Distinct biphasic pattern
• Cells arranged in alveolus-like spaces lined by cuboidal
or large polygonal cells, which have pale abundant
cytoplasm may contain melanin pigment
• Central portions small round neuroblast like cells which
show little cytoplasm, exhibit round, deeply staining
nucleus

Treatment - Partial maxillectomy
Local recurrence

• Masson’s fontana
• HMB 45
• NSE /Synaptophysin

MALIGNANT PERIPHERAL NERVE SHEATH TUMOR
Malignant Schwannoma, malignant
neurilemoma, neurogenic sarcoma,
neurofibrosarcoma

• MPNST- is preferred name for spindle cell
malignancy of peripheral nerve Schwann cells
• Mostly trigeminal nerve involved.

Neurofibrosarcoma

• 20-50 years people are affected.
• Males
• Persons with NFI typically occur a decade earlier
• most common head and neck area of involvement is
neck, but oral cavity- extremely rare
• Mostly in tongue, soft palate, mandible.
• Pain, paresthesia present.
• Half cases-neurofibromatosis (4% of
neurofibromatosis patients)

Roentgenographic Features
• Diffuse radiolucency -INFILTRATIVE
• Smooth radiolucency

H/P
• SPINDLE CELLS –wavy or comma-shaped outline.
• Arranged in sweeping fascicles pattern.
• Highly pleomorphic cells and mitotic activity
• EPITHELOID, MESENCHYMAL/GLANDULAR
• TRITON TUMOR- rhabdomyoblastic
differentiation
• Treatment- wide surgical excision

Epithelioid
• Plump, rounded or ovoid epithelioid cells scattered in
small numbers & in well defined clusters
• Vesicular or hyperchromatic nuclei
• Rhabdomyoblastic differentiation - Triton tumor
Glandular
• Well-differentiated ductal structures lined by simple,
stratified, cuboidal or columnar epithelial cells with
occasional goblet cells
• The lumina contain PAS-positive, diastase-resistant
mucus
• Multiple sarcomatous tissue types

OLFACTORY NEUROBLASTOMA
Esthesioneuroblastoma, esthesioneuroepithelioma
• Most frequently in nasal cavity and nasopharynx
• Ethmoidal sinus,
• In or invading maxillary sinus
• Neuroectodermal in origin arising from basal cells
of the olfactory epithelium

Clinical Features
• Painful swelling in area of nasal fossa-
nasal obstruction, epistaxis
• Anosmia, pain
• Invasive, destructive tumor, but only
rarely metastasizes

Kadish clinical staging system
• STAGE A- Tumour confined to the nasal cavity
• STAGE B- Tumour involving one or more PNS
• STAGE C- Tumour extending beyond nasal cavity & PNS
• STAGE D- Tumour with lymph node or distant
metastasis

Histologic Features
• Densely packed masses of small darkly staining cells
with poorly defined eosinophilic cytoplasm regular
round vesicular nucleus
• Rosette, pseudorosette formation common
• Eosinophilic neurofibrils extend into lumen from cell
borders
• Stroma has fibrillar neuroid pattern

Rx- surgical excision+ radiotherapy, chemotherapy)

• Rosettes

Thank You