ONCO | Finals | Topic 1

NEURAL LESION
I. Reactive Lesions
a. Traumatic Neuroma
II. Neoplasms
a. Schwannoma
b. Neurofibroma
c. MEN Syndrome
d. Malignant Peripheral Nerve Sheath Tumor (Neurogenic Sarcoma)

I. Reactive Lesions
a) TRAUMATIC NEUROMA

Etiology Clinical Fx Histopath Fx Txt & Prognosis

 Caused by injury to a  (+) Associated pain - occasional  Bundles of nerves in  Surgical
peripheral nerve tenderness to constant, severe pain haphazard or tortuous excision
 May occur with trauma from a  (+) Radiating facial pain arrangement are found curettage
surgical procedure such as:  Injection of LA into the area of admixed with dense  Recurrences
o Tooth extraction tumescence relieves pain collagenous fibrous tissue are infrequent
o LA injection  Wide age range, mostly adults  Chronic inflammatory cell
o Accident  Most common location : mental infiltrate may be seen,
 Transection of a sensory nerve foramen particularly those that are
—> inflammation and scarring  Followed by : extraction sites in the symptomatic
in the area of injury anterior maxilla and posterior mandible
 As the proximal nerve segment  Common soft tissue locations : lower lip,
proliferates in an attempt to tongue, buccal mucosa, palate
regenerate into the distal
segment, it becomes
entangled and trapped in the
developing scar, resulting in a
disorganized composite mass
of fibrous tissue, Schwann cells
and axons.

STACEY MENDOZA
II. Neoplasms
a) SCHWANNOMA (Neurilemmomma)
Etiology
 Benign neoplasm that is
derived from a proliferation
of Schwann cells of the
neurilemma, or nerve sheath
 As the lesion grows, the
nerve is pushed aside and
does not become enmeshed
within the tumor
Clinical Fx
 Encapsulated submucosal
mass that presents typically as
an asymptomatic lump in
patients of any age
 Tongue - favored location
 May be found throughout the
mouth
 Well defined radiolucent
pattern with a corticated
periphery
 May cause pain or paresthesia
 Slow growing, but may undergo
a sudden increase in size
(sometimes thought as due to
intralesional hemorrhage)
 Solitary schwannoma —> not
found in neurofibromatosis (with
clinical significance)
STACEY MENDOZA
Histopath Fx Txt & Prognosis
 Spindle cells assume 2 different  Surgical excision
patterns:  Recurrence -
1. Antoni a areas - palisaded whorls unlikely
and waves, surround acellular  Prognosis -
eosinophilic zone (verocay body) excellent
2. Antoni b tissue - spindle cells
haphazardly distributed in a
delicate fibrillar microcystic matrix,
by immunohistochemistry, tumor
strongly expresses s-100 protein, (-)
stains for actin and desmin
 Ancient Schwannoma (microscopic
variant) has been described to
designate degenerative changes in
long-standing schwannoma
 (+) Fibrosis, inflammatory cells and
hemorrhage
 b) NEUROFIBROMA
 May appear as solitary lesions or as multiple lesions as part of the syndrome Neurofibromatosis (Von Recklinghausen’s disease of
the skin)

Etiology  Neurofibromatosis - inherited as an autosomal-dominant trait; has variable expressivity and often appears after
spontaneous mutation
 2 subsets have been defined : associated with NF1 gene and the other with NF2 gene
Clinical Fx Solitary Neurofibroma
o Presents at any age  Malignant transformations of Neurofibroma —> Malignant
o An uninflammed asymptomatic, submucosal mass Peripheral Nerve Sheath Tumor (Neurogenic Sarcoma) = 5-
o Tongue, buccal mucosa, and vestibule - most 15%
commonly affected  6 > (+) café-au-lait macules at any location > 1.5cm in
diameter = suggestive of neurofibromatosis other
 Oral lesions are typically associated with important diagnostic signs of the syndrome
Neurofibromatosis 1 o Crowe’s sign - axillary freckling
o Multiple Neurofibromas, cutaneous o Lisch spots - iris freckling
o Café-au-lait macules
o Bone abnormalities,  Bone changes may be seen
o CNS changes,  Cortical erosion from adjacent soft tissue tumors
o and other stigmata  Medullary resorption from intraosseous lesions

 Neurofibromas range clinically from discrete, superficial
nodules —> deep, diffuse masses
 Lesions may be so numerous and prominent —>
cosmetically significant
 I/O Neurofbromas may be seen in 25% of patients with
neurofibromatosis
 When other stigmata (enlarged fungiform papillae and
bone abnormalities), oral manifestations may be seen in
70% of NF cases
 Mandibular nerve - most common in the mandible
 May result to pain or paresthesia
 In cases of mandibular involvement, an accompanying
radiographic sign may be the formation of a flaring of the
inferior alveolar foramen, the so-called “BLUNDERBUSS
FORAMEN”

STACEY MENDOZA
Histopath  Solitary and multiple - same microscopic features
 Contain spindle-shaped cells, with fusiform or wavy nuclei found in a delicate ct matrix
 This matrix may be myxoid in character
 May be well circumscribed or may blend with the surrounding ct

 Mast cells are scattered throughout the lesion

 Plexiform Neurofibroma - histologic subtype highly characteristic of neurofibromatosis
 Collagen matrix supports extensive interlacing masses of nerve tissue
 Small axons may be seen among proliferating Schwann cells and perineurial cells

 Demonstration of S-100 protein and neurofilaments by immunohistochemistry may be useful in confirming the Dx for
neurofibroma
 S-100 protein - once thoght to be unique in the CNS
 May also be found outside the CNS including Schwann cells, chondrocytes, Langerhans cells, and nevus cells
 Antibody to S-100 protein stains a wide array of unrelated neoplasms, including tumors, paranganglioma, some salivary
gland tumors, granular cell tumor, Langerhans cell dose (LCD), chondrosarcoma, some muscle tumors and 95% of
melanomas
Diff Dx  Solitary Neurofibroma
o Traumatic Fibroma
o Granular Cell Tumor
o Lipoma
 Diffuse Neurofibroma - resulting into Macroglossia
o Lymphangioma
o Amyloidosis
Txt & Prog  Solitary Neurofibroma
 Surgical excision
 Little chance of recurrence
 Multiple Lesions
 Surgical excision but impractical
 Prognosis for a pt who has had a neurosarcomatous change in a preexisting lesion is poor

STACEY MENDOZA
 c) Mucosal Neuroma of Multiple Endocrine Neoplasia Syndrome Type III (MEN SYNDROME)

Etiology Clinical Fx Histopath Fx Txt & Prognosis

 MEN Syndrome - comprise a MEN III consists of :  Serpiginous bands of  Mucosal neuromas
group of conditions o Medullary Carcinoma Of The nerve tissue o Surgical excision,
characterised by neoplasms Thyroid surrounded by o No recurrence
arising in several endocrine o Pheochromocytoma Of The normal connective expected
organs Adrenal tissue  Significance of
 Only MEN type III a.k.a. MEN 2b o Mucosal Neuromas  Axons have been neuromas : may be the
has oral manifestations o Café-Au-Lait Macules found in the first sign of a potentially
 Autosomal dominant trait o Neurofibromas Of The Skin proliferating nerve fatal syndrome
 MEN III is caused by a mutation in tissue  Medullary Carcinoma of
the RET oncogene resulting in a  MEN I and MEN II are related to MEN the Thyroid - progressive
single amino acid substitution of III in that pt with types I and II have malignancy that invades
a single methionine to threonine neoplasms of various endocrine locally and has the
that affects a critical region of organs, but they do not have oral ability to metastasize to
the tyrosine kinase catalytic core manifestations of mucosal neuromas local lymph nodes and
 Mucosal neuromas appear early in distant organs
life  Pheochromocytoma -
 Small, discrete nodules on the benign neoplasm that
conjunctiva, labia or larynx or in the produces
oral cavity catecholamines that
 Oral lesions are seen on the tongue, may cause significant
lips and buccal mucosa HPN and other CV
abnormalities
 Early detection of
mucosal neuromas —>
establishing dx or calling
attention to other
components of the
syndrome

STACEY MENDOZA
d) Malignant Peripheral Nerve Sheath Tumor (MPNST)
 Rare malignancy that may develop from preexisting neurofibroma or de novo
 Can complicate neurofibromatosis
 Cell of origin : schwann cells, and possibly other nerve sheath cells

Clinical Fx Histopath Fx Txt & Prognosis

 In soft tissues:  May be seen arising from a  Surgical excision
 Appears as an expansile mass that is neurofibroma or from a nerve trunk  Recurrence is common
usually asymptomatic  Composed of abundant spindle cells  Metastases are frequently seen
 In bone: with variable numbers of abnormal  Prognosis : fair to good
 Believed to arise from the IAN mitotic figures
 Dilation of the mandibular canal or as a  Streaming and palisading of nuclei are
diffuse radiolucecny often seen
 Pain or paresthesia  Nuclear pleomorphism may be
 Microscopic separation from
fibrosarcoma and leiomyosarcoma may
be difficult —> immunohistochemistry an
important dx adjunct

STACEY MENDOZA
LESIONS OF MUSCLE AND FAT

I. Neoplasms
 Benign Tumors
 Leiomyoma
 Rhabdomyoma
 Lipoma
 Granular Cell Myoblastoma
 Congenital Epulis of the Newborn
 Malignant Tumors
 Leiomyosarcoma
 Rhabdomyosarcoma
 Liposarcoma

LEIOMYOMA & LEIOMYOSARCOMA

 Smooth muscle neoplasms
 Relatively uncommon, may arise anywhere in the body

Clinical Fx Histopath Fx Txt & Prognosis

 Leiomyoma - commonly arise in the muscularis
layer of the gut and in the body of the uterus
 Leiomyosarcoma - commonly arise in the
retroperitoneum, mesentery, omentum,
subcutaneous and in deep tissues of the limb
 Both are rare in the oral cavity
 Oral leiomyomas - slow-growing, asymptomatic
submucosal masses
 Oral Leiomyosarcoma
 All age groups
 Found in most intraoral regions
 Usually in the tongue, hard palate or buccal
mucosa
 May be seen at any age
 Usually discovered when they are 1 - 2 cm in
diameter
 Microscopic dx may be difficult —  Leiomyomas - surgical excision,
> spindle cell proliferation shares recurrence unexpected
many similarity with neurofibroma,  Oral Leiomyosarcoma
or schwannoma, fibrzomatosis and  Wide surgical excision
myofibroma  Metastasis to lymph nodes or
 Special stains that identify lung is not uncommon
collagen may be helpful in
distinguishing these lesions
 Immunohistochemical demo of
actin can confirm dx
 Vascular Leiomyoma - a.k.a.
Angioleiomyoma microscopic
subtypehas numerous thick-walled
vessels associated with well-
differentiated smooth muscle cells
 Oral Leiomyosarcoma
 Microscopic dx is a challenge

STACEY MENDOZA
RHABDOMYOMA
 Rare lesions with a predilection for the soft tissues of the head and the neck
Clinical Fx Histopath Fx Txt & Prognosis
 Oral sites : floor of the mouth, soft palate, tongue,  2microscopic variants are  Fetal type may be confused with
buccal mucosa recognised: Rhabdomyosarcoma
 Mean age : 50 years  Adult Type - neoplastic cells mimic  Treatment : Excision
 Children to older adults their normal counterparts  Recurrence : Unlikely
 Asymptomatic, well-defined submucosal mass  Fetal Type - neoplastic cells are
elongated, and less differentiated
and exhibit fewer cross striations

RHABDOMYSARCOMA
Clinical Fx
 Head and neck —> found primarily in
children
 Outside the head and neck —>
adults presents as a rapidly growing
mass
 May cause pain or paresthesia if jaw
involvement occurs
 Most commonly affected oral sites :
tongue and soft palate
 Embryonal type: most commoly seen
in head and neck
Histopath Fx Txt & Prognosis
Subdivided into 3 principal microscopic forms:  Combination of surgery, radiation
 Embryonal - children and chemotherapy —> better
 Alveolar - children clinical results
 Pleomorphic – adults  Survival rates increased from 10% to
better than 70%
 Embryonal type
 consist of primitive round cells in which
striations are rarely found
 2 subtypes: (1) spindle cell type (2) botryoid
type; both confer excellent prognosis
 Because of the relatively undifferentiated
nature of this microscopic subtype,
immunohistochemistry to demonstrate
muscle- associated proteins ( desmin, actin,
myogenic, myoD1) is typically used to
support light microscopic interpretations
 Alveolar Type - composed of round cells but in
a compartmentalized pattern
 Pleomorphic Type - best differentiated,
contains strap or spindle cells that often exhibit
cross striations

STACEY MENDOZA
LIPOMA
 Uncommon neoplasms that may occur in any region of the oral cavity
Clinical Fx Histopath Fx Diff Dx Txt & Prognosis
 Buccal mucosa, tongue, floor  Numerous microscopic subtype  Granualr Cell Tumor  Surgical excision
of the mouth  All types have adipocytes of various  Neurofibroma  Recurrence not expected
 Asymptomatic, yellowish degrees of maturity  Traumatic Fibroma
submucosal mass  Well-circumscribed, lobulated mass of  Salivary Gland Lesions
 Overlying epithelium is intact mature fat cells (mucocele, mixed
 Superficial blood vessels are tumor)
usually evident over the tumor

LIPOSARCOMA
 Rarely encountered in soft tissues of head and neck

Clinical Fx Histopath Fx Txt & Prognosis

 May potentially occur at any site
 Adults
 Slow-growing —> mistaken as
benign process
4 Subclassifications :  Surgical or radiation
 well-differentiated  Prognosis= fair to good
 myxoid
 round cell
 pleomorphic
 Expression of CD34
 Degree of tumor cell differentiation +
identification of microscopic subtype — >
predict clinical behavior

STACEY MENDOZA
GRANULAR CELL MYOBLASTOMA
 Uncommon benign tumor of unknown cause
 Granular cells make up the lesions, and are believed to be of neural (schwann cell) origin
 Origins from skeletal muscle, macrophages, undifferentiated mesenchymal cells, and parasites have been suggested but unproven
 Related lesion known as Congenital gingival granular cell tumor —> cells identical microscopically
 Slight differences have been noted suggesting that congenital gingival tumors have a different histogenesis

Clinical Fx Histopath Fx Diff Dx Txt & Prognosis

 Children to elderly  Clinical tumescence of granular cell tumors Tongue Lesions  Surgical
 Mean : middle adult life is due to the presence of unencapsulated  Neurofibroma Excision in a
 Predilection for females sheets of large polygonal cells with pale  Schwannoma conservative
 Common location in granular or grainy cytoplasm  Palisaded Encapsulated fashion
h&n : tongue  Nuclei are small, compact, and Neuroma  No
 Uninflammed morphologically benign recurrence
asymptomatic mass,  Mitotic figures are rare  Intraoral Lesions -
 Smaller than 2cm in  Pseudoepitheliomatous hyperplasia of oral Asymptomatic lumps
diameter epithelium - 50% of cases  Salivary gland tumors
 Yellowish surface  Overlooked granular cells —>  LIpoma
coloration overdiagnosis of scca  Benign mesenchymal
 Overlying epithelium is  Benign process neoplasms
intact  (+) Autophagic vacuoles
 Congenital Gingival  (-) Angulate bodies in the gingival lesion — Reactive Lesions
granular cell tumors difference with congenital counterpart  Focal Fibrous Hyperplasia
 Anterior gingiva of  (+) Microfilaments with fusiform dense  a.k.a. Traumatic Fibroma
newborns bodies, pinocytic vesicles, and basement
 Uninflammed, membrane —> gingival lesions Submucoal Masses
pedunculated, or  Granular cell tumors express:  Gingival Cysts
broad-based masses o S-100 protein (neural tumors)  Neuroectodermal Tumor of
 Maxillary gingiva > o CD57 Infancy
mandibular gingiva o type IV collagen  Rhabdomyosarcoma
 Girls > boys  Express carcinoembryonic antigens ad
 (-) Recurrence human leukocyte antigens (HLA-DR) biopsy with histopathologic analysis
 Negative for alpha-1-antichymotrypsin and to achieve a definite dx
muscle actin

STACEY MENDOZA
STACEY MENDOZA