2 connectivetissueneoplasms-130212174141-phpapp02

Who appreciates ART is NO LESS than who creates it

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Connective tissue neoplasms

Connective tissue neoplasms:

Clinically, most of the benign connective tissue tumors present as swellings which maybe

indistinguishable from hyperplastic lesions

Histologically, oral connective tissue tumors resemble their counterparts occurring at other sites in the body

Classification of connective tissue neoplasms according to the tissue of origin:

1. Tumors of fibrous tissue

2. Tumors of adipose tissue

3. Tumors of vascular tissue

4. Tumors of peripheral nerves

5. Granular cell tumor

6. Tumors of muscles

7. Malignant lymphoma

Tumors of fibrous tissue

True benign neoplastic overgrowths of fibrous tissue (true fibroma) in the oral cavity are rare since

clinically and histologically they can't reliably be distinguished from hyperplasias

** The term fibroma has been used inappropriately to describe reactive lesions (such as fibrous epulis

and Fibroepithelial polyp) but to avoid confusion the term is best avoided except for specific entities

such as the peripheral odontogenic fibroma (which is a true benign tumor)

Malignant tumors (fibrosarcoma) are also rare in the oral cavity and they have a relatively good

prognosis {5 year survival rate is 70%}

** Sarcoma = cancer of bone, cartilage, fat, muscles or blood vessels

** Sarcomas show the cytological malignant features of cellular and nuclear pleomorphism,

mitotic figures and Hyperchromatism

Other lesions of fibrous tissue:

Fibrous histiocytoma There is disagreement amongst pathologists as to whether this benign soft

tissue lesion represents a true neoplasm, a developmental defect, or a reactive process. Cells in

here show fibroblastic and histiocytic differentiation. These tumors have unpredictable behavior

from locally aggressive to malignant. They are rare in the oral cavity and if they occur, they arise

on the buccal mucosa and vestibule


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Nodular fasciitis This benign soft tissue lesion represents a reactive non-neoplastic process

BUT the cause is still unknown. It is rapidly-growing but self-limiting and it may be mistaken

for a fibrosarcoma histologically. It is rare in the oral cavity

Peripheral odontogenic fibroma It is an uncommon gingival mass. It can be confused

with peripheral ossifying fibroma (fibrous epulis). In contrast to the peripheral ossifying

fibroma, the peripheral odontogenic fibroma is a rare lesion. It present clinically as slowly

growing, solid, firmly attached gingival mass sometimes arising between teeth and sometimes

displacing teeth. It consists of cellular fibrous connective tissue with non-neoplastic islands of

odontogenic epithelium

Fibromatosis This term refers to a group of non-neoplastic infiltrating fibrous proliferations

with a biologic behavior and microscopic appearance intermediate between those of true

fibromas and fibrosarcomas. They have certain characteristics in common, including: absence of

cytological & clinical malignant features, histological proliferation of well-

differentiated fibroblasts, an infiltrative growth pattern, and aggressive clinical behavior with

frequent local recurrence

** Aggressive fibromatosis: it is a rare slowly growing proliferation that is locally aggressive and

doesn't show any metastatic potential. It can damage nearby structures causing organ dysfunction.

Approximately 10% of individuals with Gardner's syndrome have such tumors. Histologically it

resembles low-grade fibrosarcomas but it is very locally aggressive and tends to recur even after

complete resection

** Hereditary gingival fibromatosis (e.g. gingival

overgrowth, gingival hyperplasia): it develops as a

slowly growing, non-neoplastic, localized or

generalized enlargement of gingiva that, in severe

cases, may cover the crowns of the teeth. Enlarged

gingiva may be normal in color or erythematous,

and consists of dense fibrous tissue that feels firm

on palpation. Gingival excess results in pocketing

and periodontal problems (due to difficulties in

daily oral hygiene). The overgrowth may also result

in functional and esthetic concerns, create

Diastema, impede or delay tooth eruption, impede

speech & mastication and can prevent normal closure of lips

http://en.wikipedia.org/wiki/Sarcoma


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** Causes of localized fibrous overgrowths of the oral mucosa:

A. Hyperplastic lesions:

- Epulides (fibrous, vascular, giant cell)

- Pyogenic granuloma

- Fibroepithelial polyp

- Denture irritation hyperplasia

- Papillary hyperplasia of the palate

B. Neoplastic and neoplastic-like lesions:

- Peripheral odontogenic fibroma

- Fibrous histiocytoma

- Nodular fasciitis

- Fibromatosis

- Fibrosarcoma

Tumors of adipose tissue:

True benign neoplastic overgrowths of adipose tissue (lipoma) present clinically as soft yellowish

swelling, most commonly in the cheek and tongue

Histologically, lipoma is composed of circumscribed mass of mature adipose tissue supported with

stroma which varies in amount considerably

Lipoma can be histologically in the form of:

*Fibrolipoma Lipoma and fibrous tissue stroma

*Angiolipoma Lipoma and vascular tissue stroma

*Myxolipoma Lipoma and connective tissue stroma

** A typical feature of lipoma is that it floats when it is dropped in the fixative solution (e.g. formalin)

** Some infants and young children are presented to the clinic with ulcerated tumor-like masses of fat

in the buccal mucosa which aren't actually tumors but traumatic herniation of the buccal pad of fat


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Malignant tumors (liposarcoma) are uncommon,

most arise in cheeks, floor of the mouth or the base

of the tongue, they generally have good prognosis.

They show the cytological malignant features of

cellular and nuclear pleomorphism, mitotic figures

and Hyperchromatism

Tumors of vascular tissue:

2. Hemangioma:

It is a benign proliferation of endothelial cells

It is a common lesion, generally accepted to be hamartomatous rather than true neoplasm

** Hamartoma = a benign focal malformation where there's abnormal and excessive formation

of normal tissues

Hemangiomas commonly arise in the head and neck area, involving the mucosa, muscles, bone,

or major salivary gland (e.g. juvenile Hemangioma in parotid gland which is the commonest

salivary gland tumor occurring in infants and children)

Most of them present at birth or arise during early childhood

Clinical presentation:

- Dark red-purple in color

- Elevated lesion that is either smooth or globular (resembling

punch of grapes), soft or hard

- Varies in size

- Most of them arise on the lips, tongue, cheeks and palate

- Typically, they blanch on pressure (get white when

pressurized with a glass plate), however some lesions have

thrombosis or calcifications (which may be detected

radiographically) and get hard and so they don't blanch

- The lesion is usually asymptomatic and it is solitary BUT if

multiple then we might think of something systemic like

generalized angiomatous syndrome

- Some patients report recent increase in size but this may be a

result of hemorrhage,

thrombosis or inflammation

- The lesion may occur

intrabony and it presents as

radiolucent like cyst

radiographically that is filled

with blood histologically

Histopathological presentation:

- According to the size of vascular spaces, hemangiomas may be classified into capillary,

cavernous or mixed type


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- Vascular spaces are lined by endothelium and filled with red blood cells

- Some lesions show evidence of thrombosis or calcification

** Capillary Hemangioma a type of blood

vessel malformation that has relatively small blood-

filled spaces (increased number of blood vessels). It

is the most common variant of Hemangioma which

appears as a raised red area of flesh anywhere on

the body and usually starts at birth, increase in size

rapidly in the first few months, then decrease in

size with age & mostly resolve at the age of 9 years

** Cavernous Hemangioma a type of blood

vessel malformation that has relatively large blood-

filled spaces (increased size of blood vessels). They

can arise virtually anywhere in the body and unlike

the capillary hemangiomas; they can be disfiguring

and do not tend to regress. They may also lead to

spontaneous or traumatic bleeding and ulcerations

** Cellular Hemangioma some lesions

(particularly in infants) may be more solid, highly

cellular with little evidence of canalization, and thus

they are considered as immature stage of capillary

or cavernous Hemangioma, and it is difficult to

distinguish them from Pyogenic granuloma

(lobular capillary Hemangioma) clinically

3. Arteriovenous malformation:

Abnormal connection between arteries and veins, bypassing the capillary system. This vascular

anomaly occurs in the central nervous system, but can appear in any other location

4. Sublingual varicosities:

A condition where ranine veins get dilated and enlarged

Varicosities starts at old age, its size increases with age and it doesn't tend to regress

5. Malignant vascular lesions:

Kaposi sarcoma and angiosarcoma are rare but common in AIDS patients

6. Generalized angiomatous syndromes that may have oral lesions include:

Sturge-weber syndrome:

- This is a congenital disorder in which the patient has:

1. Hemangioma of the face (port-wine stain) extending over one or more branches of

trigeminal nerve

2. Ipsilateral hemangiomas in the meninges over cerebral cortex

3. Contralateral convulsions affecting the limbs

** Hemangioma may also occur in the oral mucosa


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Hereditary hemorrhagic telangiectasia:

- An autosomal disorder characterized by multiple knots

of dilated malformed and fragile capillaries in skin,

mucous membranes and may be the internal organs

- Frequent nose bleeding (epistaxis) is the commonest

presenting symptom

8. Lymphangioma:

It is again generally accepted to be hamartomatous rather

than true neoplasm

It is less common than Hemangioma

It arises at birth or during early childhood

It can occur anywhere in the oral cavity but are most

frequently seen on the tongue causing Macroglossia

It is NOT red in color

The surface of superficially located lesions shows numerous papillary projections or small

nodular masses

If lesions get traumatized, it may undergo inflammation, calcification, or sudden increase in size


Consists of capillary or more common cavernous

endothelial lined spaces that contain lymph

Superficially located lesions have the lymphatic spaces

extended close up to the overlying epithelium causing

it to bulge

Cystic hygroma:

It is a Lymphangiomatous malformation that occur early

in development of lymphatic system

Lesions are detected at birth and present as large

fluctuant swelling often up to 10 cm in diameter

They most frequently affect the head & neck region,

but may extend to involve the base of the tongue, the

floor of the mouth, and less commonly buccal mucosa


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Tumors of peripheral nerves:

1. Nerve sheath tumors:

1. Neurofibroma

- Solitary

- Multiple (neurofibromatosis)

2. Neurilemmoma (shwannoma)

2. Traumatic neuroma

3. Multiple mucosal neuroma

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1. Neurofibroma:

It is a benign Schwann cell tumor arising from either

small cutaneous nerves (subcutaneous

Neurofibroma), or within larger nerves (Plexiform

Neurofibroma)

It is a benign nerve sheath tumor in the peripheral

nervous system that arise either sporadically or in

association with neurofibromatosis type I (formerly

known as Von Recklinghausen’s disease)

Neurofibromas arise from Schwann cells that

exhibit inactivation of the NF1 gene that codes for the

protein neurofibromin

Neurofibroma is usually solitary BUT if it is associated

with neurofibromatosis type I then it is multiple

Malignant transformation is a well-recognized

complication of multiple neurofibromas associated with

neurofibromatosis type I (5-15% of cases) but for the

solitary Neurofibroma it is rare


Neurofibroma shows considerable variation, but it

consists basically of Schwann cells and fibroblasts

with varying amount of collagen and mucoid tissue

A few nerve fibers run through the lesion

The lesion may be circumscribed or diffuse

Plexiform neurofibromas:

- They are large cluster or mass of tumors arising

within or around the nerve trunk surrounded

by proliferation of Schwann cells & fibroblasts

- They are characteristic feature of

Neurofibromatosis type I


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- These lesions are difficult and sometimes impossible to routinely resect without causing

any significant damage to surrounding nerves and tissues

- About 10% of Plexiform neurofibromas undergo transformation into a malignant

peripheral nerve sheath tumor

Neurofibromatosis type I (Von Recklinghausen’s disease):

This genetic disease is either inherited (as familial condition or autosomal dominant) or

sporadic and occurs due to mutation in tumor suppressor gene (NF1)


- Multiple neurofibromas of cutaneous nerves

resulting in considerable disfigurement, the so-called

“Elephantiasis Neuromatosa”

- Intraorally: mucosal swellings (involving the

tongue or gingiva) and bone involvement (affecting

mental and inferior dental nerves in the mandible)

- “Café-au-lait” melanin pigmentation on the skin that

usually precede the neural

lesions

- Axillary freckling (axilla is a

non-sun exposed site!)

** Neurofibromas in here

transform into malignancy in

5-15% of cases

** Neurofibromas carry

increased incidence of malignant transformation upon surgical removal thus NO

surgery should be done!

** If there's multiple giant cell lesions suspect neurofibromatosis type I or primary

hyperparathyroidism

2. Neurilemmoma (Schwannoma):

It is a benign Schwann cell tumor that is an encapsulated

It is a benign nerve sheath tumor that is very homogeneous and consisting only of Schwann cells

Nerve fibers don’t pass through the lesion BUT may be found over the capsule

Within the lesion, spindle-shaped cells are often arranged in parallel bundles with palisaded nuclei


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3. Traumatic neuroma:

It is a non-neoplastic disorganized mass consisting of

nerve fibers, Schwann cells and scar tissue that arise at the

end of a severed nerve

It is an exaggerated nerve regeneration process which

usually presents as a small nodule


Slowly growing

Firm in consistency

Fixed to surrounding structures

Painful to palpation

** It is uncommon in the oral cavity although nerves

are frequently traumatized or severed following

extractions or minor surgery (usually occurs in relation

to large nerves, such as the ones related to the mental

foramen)

4. Multiple mucosal nueroma:

Multiple neuromas of peripheral nerves in oral mucosa are a feature of multiple endocrine

neoplasia syndrome type III (also referred to as Type IIb) in which patients have:

Multiple mucosal neuromas

- These neuromas are clinically and histologically similar to traumatic neuromas

- These neuromas may be the first presenting sign and may precede thyroid cancer

Phaecromocytoma (tumor of adrenal gland cortex)

Medullary thyroid carcinoma (the most important feature since this carcinoma is

aggressive and fatal!)

** The tumor is due to RET oncogene mutation, and those who have family history of the

syndrome may be tested for RET oncogene mutation, and if the result is positive this indicates

the need for prophylactic thyroidectomy

Granular cell tumor:

Was previously called {granular cell myoblastoma}, because it was thought to be of muscle origin.

BUT nowadays it is accepted to be of neural origin

Etiology: it is a benign neoplasm probably due to proliferation of Schwann cells


Slowly growing swelling

Firm in consistency

Fixed to the overlying mucosa and deep structures

Painless

Arises most commonly in the tongue

Multiple tumors may occur


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Non encapsulated

Composed of sheets and strands of large cells with

granular eosinophilic cytoplasm

** Granules represent Lysosomes, vacuoles, or residual

bodies

The surface epithelium commonly shows may show

Psuedo-epitheliomatous hyperplasia that may be

mistaken with malignancy

The presence of striated muscle fibers between the granular cells may suggest invasion but the

lesion is entirely benign

Tumors of muscles:

The following tumors have been reported in the oral cavity but they are rare:

Of smooth muscles: Leiomyoma (benign), leiomyomatous hamartoma, leiomyosarcoma (malignant)

Of skeletal muscles: Rhabdomyoma (benign) , rhabdomyosarcoma (malignant)

Malignant lymphoma:

It is a neoplastic proliferation of the cells of the lymphoreticular system

The majority of malignant lymphomas in the head and neck arise in lymphoid tissue, the cervical lymph

nodes are most often affected followed by the lymphoid structures of Waldeyers' ring

Lymphomas are usually classified into:

Hodgkin’s lymphoma (characterized by Reed Sternberg cells)

Non-Hodgkin’s lymphoma (B cell types, T and NK cell types)

A. Hodgkin’s lymphoma:

Accounts for 30% of all malignant lymphomas

Affects young age group

Distribution: almost nodal and cervical lymph nodes are involved in about 75% of the cases

Etiology: is unknown but genetic factors and viral infection (EBV) have been suggested

Lesions are mostly part of disseminated malignancy

Prognosis: depends on the clinical staging and histological grading and it decreases as the

lesion proceeds from lymphocyte-predominant to lymphocyte-depleted

Overall survival rate is 50-70%


- Progressive painless enlargement of lymph nodes

Histological presentation:

- Histological diagnosis depends on identification of

Reed- Sternberg cells which are regarded as the

neoplastic component

- Reed Sternberg cell is a large cell with either a

double or bilobed nucleus, the two nuclei lying

side by side to produce a “mirror image” effect


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- Histopathological types of Hodgkin’s lymphoma:

Lymphocyte predominant Few Reed-Sternberg cells and many lymphocytes

good prognosis

Mixed cellularity

Nodular sclerosis

Lymphocyte depletion Numerous Reed-Sternberg cells and extensive fibrosis

poor prognosis

B. Non-Hodgkin’s lymphoma:

Much less common

Lesions may remain solitary or they may disseminate

Increased incidence reported in AIDS patients

Divided into two main groups depending on the cells of origin:

1. B cell malignant lymphoma (the majority of malignant lymphoma cases are of this group)

2. T / NK cell lymphoma

Non-Hodgkin’s lymphomas arising in lymphoid tissues other than lymph nodes (extra-nodal

lymphomas) are much less common than nodal tumors, but may arise in the oral soft tissues,

salivary glands, and jaw bones, e.g.:

– MALT lymphoma have better prognosis than nodal lymphomas and lesions remain

localized for long periods and disseminate only late in the course of the disease

– Salivary gland associated lymphoma this arise in the gland lymphoid tissue, or as a

result of malignant transformation in Sjögren Syndrome & myoepithelial Sialadenitis

– Bone

** Mucosal lesions present as soft, fleshy, often ulcerated swellings

** Burkitt's lymphoma is of particular interest since this type of malignant lymphoma

commonly presents as a jaw tumor

Burkitt’s Lymphoma:

- It is a malignant lymphoma of B-cell type that is either endemic or sporadic, and in both

cases there is activation of an oncogene

** The Chromosomal abnormality in Burkitt’s lymphoma is reciprocal translocation of

chromosome 8 with chromosome 14, which may results in activation c-myc oncogene

** Without treatment, Burkitt's lymphoma is a rapidly fatal condition


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- Endemic cases:

In Africa and affects mainly children between 2-14 yrs

There is strong evidence that infection with the (EBV) is a causal factor and that

malaria is a cofactor

The disease is usually multifocal, but a jaw tumor is the presenting symptom in over

half the cases

In the jaws, lesions usually arise posteriorely and are more frequent in the maxilla

than the mandible, but more than one quadrant maybe involved

Tumors are rapidly growing, and are often of massive size, producing gross facial

disfigurement

In the maxilla, tumors extend into sinuses, nose, naso-pharynx and orbit

Teeth in the area are loosened, displaced, and maybe exfoliated

- Sporadic cases:

In non-African countries

No (EBV) association

Abdominal lesions predominate and jaws lesions are uncommon

- Histological presentation:

A tumor of B-cell type

Consists of small, darkly-staining

malignant lymphoid cells scattered amongst

pale-staining non-neoplastic macrophages

producing a "starry sky" pattern

NK/T cell lymphoma:

- It is an uncommon condition

- The nasal NK/T cell lymphoma is a distinct entity and it may cause extensive

destruction of mid-facial structures and can extend into adjacent structures, including the

oral cavity

** Nasal NK/T cell lymphoma was reported

under a variety of terms in the past, including:

Angiocentric T cell lymphoma and lethal

midline granuloma

- It arises in nose/paranasal sinuses and presents

with nasal obstruction, epistaxis, and progresses

to extensive necrosis

- EBV is found in some neoplastic cells which

indicates that it may have a role in the

pathogenesis of the disease

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