CONNECTIVE TISSUE TUMORS

Introduction
Mesenchymal or mesodermal in origin Intercellular substance(matrix), collagen fiber, cells Cells- Cells are endothelial cells , pericytes, fibroblasts, smooth muscle cells , fat (adipocyte) cells, blood forming cells

Classification
Based on the origin of tissue Mostly based on the type of tissue like fibrous, skeletal or smooth muscle , blood cells, endothelial cell , neural cells etc

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Fibrous and myofibroblastic tumours Tumours included in the fibrohistocytic category Lipomatous tumours Smooth muscle tumours Skeletal muscles tumours Vascular tumours Perivascular tumours Synovial tumours Neural tumours Extra skeletal osseous & cartilaginous tumours Miscellaneous tumours unclassified

 Benign and malignant morphologically

Tumors which will be discussed

Benign connective tissue tumors are 1. Fibroma /Fibromatosis 2. Myofibroma 3. Lipoma /Lipoblastoma 4. Oral hemangioma 5. Lymphangioma 6. Myxoma 7. Chondroma 8. Benign chondromablastoma 9. Chondromyxoid Fibroma 10. Osteom /osteoid osteoma 11. Benign osteoblastoma

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 Malignant connective tissue tumors are 1. Fibrosarcoma 2. Fibrous histocytoma(malignant) 3. Hemangioendothelioma 4. Hemagiopericytoma 5. Kaposi's sarcoma(AIDS related ) 6. Ewings sarcoma 7. Chondrosarcoma 8. Osteosarcoma 9. Malignant lymphoma(Hodgkins lymphoma) 10. Non- Hodgkin's lymphoma 11. Burkitts lymphoma 12. Hodgkin disease 13. Plasmacytoma
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 Benign and malignant tumors of muscle tissue tumors 1. Leimyoma 2. Rhabdomyosarcoma 3. Granular cell myoblastoma 4. Leimyosarcoma 5. Rhabdomyosarcoma 6. Alveolar soft Part sarcoma Benign and malignant tumors of nerve tissue 1. Traumatic neuroma 2. Neurofibroma 3. Neurolemmoma 4. Melanotic neuroectodermal tumors of infancy
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Fibroma
Fibroblastic tumours

Fibroma
Tumors arising from connective tissue fibroblast Benign tumor of fibroblast and most common tumor of oral cavity. < 1.5 cm in size Most of them are associated with irritation and trauma. Solitary
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 It is true neoplasm of connective tissue origin Most of reactive and inflammatory focal/localized hyperplasia are diagnosed as fibroma True fibroma are rare in oral cavity ( most of them are reactive in nature). Long standing pyogenic granuloma may undergo healing by sclerosis will then resemble fibroma.

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 It may be confused with pyogenic granuloma and peripheral giant cell granuloma if prominent vascular component is missing. Most of fibroma are peripheral ,central variety is rare in oral cavity. It may hard and soft fibroma depending upon consistency Less cellular or highly cellular depending upon cellularity.

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Pyogenic granuloma

Fibroma

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 PGCG and POF occur exclusively in gingiva Fibroma and pyogenic granuloma can occurs in any site in oral cavity All these entities thought to represent spectrum of one disease processes.

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PGCG

Peripheral Ossifying Fibroma

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FIBROMATOSIS

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Fibromatosis
Benign fibroblastic proliferation Infiltrative Tendency towards recurrence

Never metastasize
Superficial Small , slowly growing and arise from the fascia or aponeurosis and only rarely involve deeper structure Deep large , more rapidly growing , more aggressive, high recurrence rate, involve deeper structure.
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Fibromatosis
Uncommon and usually extension of lesion arising primarily in neck and submental areas. Mandible is most often involved. Submandibular soft tissue, floor of mouth, parotid region, tongue and gingiva or alveolar mucosa are also involved. Primary intraoral lesion - rare Represent infiltrating fibrous proliferations with a biological behavior and microscopic appearance intermediate between benign fibroma and fibrosarcoma.
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Histological photo
Bland sheets of spindle cells in dense collagen stroma. Slitlike vessel is seen with minor perivascular edema and chronic inflammatory cells including lymphocytes and mast cells. Note also absence of mitoses or nuclear atypia

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FIBROSARCOMA

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Fibrosarcoma
Malignant tumor of fibroblast Uncommon only 10 % occur in head and neck region

The tissue of origin seems to be the periosteum rather than mucosal connective tissue (J Laryng Otol 1986;100:1417-20.)
Tends to arise from preexisting lesion such as fibrous dysplasia, chronic osteomyelitis, pagets disease, post radiation cases.
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 Solitary palpable mass ranging from 3 to 8 cm in greatest diameter.

Duration range from few weeks to 20 years. Most arise in deeper part of soft tissue, intramuscular and intermuscular fibrous soft tissue, fascial envelope , aponeurosis, tendons. Radiologically shows periosteal and cortical thickening ( D/D parosteal osteosarcoma? )

Gross- solitary , soft , firm, fleshy , rounded to lobulated mass that is grossly white to tan yellow. Small tumours may be well circumscribed, partly or completely encapsulated.
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 Fibrosarcoma can arise in soft tissues or within bone Intra-osseous fibrosarcomas may develop endosteally or possibly periosteally, Slow growing mass, painless ( D/D synovial sarcoma/ MPNST) Occurs any where in head and neck region. Most common in mandible

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 Well circumscribed mass.

Adult fibrosarcomas are almost always deep seated. There may be areas of necrosis or hemorrhage 'malignant tumor of fibroblasts that shows no other evidence of cellular differentiation and is capable of recurrence and metastasis.' Lymph node metastasis rare Lung is principle site for metastasis.
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Variants Sclerosing epitheliod type Myxoid type Fibromyxoid

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Fibromatosis Cellularity Nuclear overlap Hyperchromasia Nucleoli Mitotic activity Necrosis Vessel wall infiltration Low to mod Absent Absent Inconspicuous 1+ Absent Absent

Low grade Fibrosarcoma Low to mod Present Present Prominent 1+ to 3 + Rare Rare

High grade Fibrosarcoma Mod to severe Absent Present More prominent and pleomorphic More than 3+ Present (Hemorrhage) Present

Herring bone pattern

Collagen fibres bundles

Absent
Abundant

Present
Abundant

Present ( less distinct)

Less collagen fibres

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Fibrosarcoma

Hard Palate

Anterior tongue

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Microphotograph
Monomorphic population of spindle cells arranged in fascicles and intersect at acute angles resulting in herringbone appearance.

Mitoses are common.

Pleomorphism is minimal.

The reticulin stain demonstrate abundant fibers wrapped around each cell.
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Tumour cells demonstrate positivity for vimentin and are negative for EMA (epithelial membrane antigen), cytokeratin, S100 protein, smooth muscle actin and desmin.

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DD of fibrosarcoma
Fibrous dysplasia Osteosarcoma Pagets sarcoma Malignant fibrous histiocytoma

Malignant neurosarcoma

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Lipoma/ Lipoblastoma/ Liposarcoma

Adipocytic tumours

LIPOMA
Primary malignant tumor arising from fat. Most common soft-tissue tumor Lipomas are adipose tumors that are often located in the subcutaneous tissues of the head, neck, shoulders, and back 40-60 yrs; M>F Thigh and retroperitoneum; Rare in bone

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 Most lipomas are asymptomatic, can be diagnosed with clinical examination and do not require treatment. found in deeper tissues such as the intermuscular septa, the abdominal organs, the oral cavity, the internal auditory canal, the cerebellopontine angle and the thorax Lipomatosis may also be associated with Gardners syndrome

Hereditary multiple lipomatosis, an autosomal dominant condition.

Madelungs disease, or benign symmetric lipomatosis, refers to lipomatosis of the head, neck, shoulders, and proximal upper extremities

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 usually present as non-painful, round, mobile masses, with a characteristic soft, doughy feel. Overlying skin is normal

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Lipoma

Soft ,well circumscribed, thinly encapsulated, rounded mass varying in size from few millimetre to 5 cm or more Cut section pale ,yellow to orange and has a uniform greasy surface & MESENCHYMAL TUMORS irregular lobular pattern.

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Painless, well-delimited, yellowish nodule located on the tongue.

Adipose neoplastic cells surrounded by dense fibrous connective tissue characterizing a fibrolipoma (hematoxylin eosin, original magnification 100).
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Types ( histological)
Angiolipomas - painful and usually arise shortly after puberty

Pleomorphic lipomas - bizarre, multinucleated giant cells are admixed with normal adipocytes
spindle cell lipomas - slender spindle cells admixed in a localized portion of regular- appearing adipocytes superficial lipoma, adenolipoma - characterized by the presence of eccrine sweat glands in the fatty tumor; (often located on the proximal parts of the limbs)

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D/D: Epidermoid cyst Nodular fasciitis Liposarcoma Sarcoidosis Hematoma

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Lipoblastoma/ Lipoblastomatosis
The term lipoblastoma first used by Jaffe in 1926. Less than 1% of head and neck cancers lipoblastoma and Lipoblastomatosis are rare benign neoplasms of foetal white fat tissue that occurs almost exclusively in infants and children younger than 3 years of age. Histologic type - well differentiated, myxoid, pleomorphic, and round cell

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Histologic type of Lipoblastoma

Classic type- characterized by a minimal myxoid component consisting of intercellular mucin, spindle cells, and stellate primitive mesenchymal cells together with adipocytic component Myxoid lipoblastomas - contained abundant interstitial mucin, which comprised more than 50% of the specimen.

Lipoma-like lipoblastomas - lacked a myxoid component and are composed predominantly of mature adipocytes with scattered monovacuolated and multivacuolated lipoblasts; and
Hibernoma -like lipoblastomas lacked a myxoid component and are composed predominantly of multivacuolated lipoblasts, some of which had central nuclei and granular eosinophilic cytoplasms.

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Gross specimen

Circumscribed lipoblastoma. Cut surface shows myxomatous lobulated appearance

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Microphotograph

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Oral hemangioma Hemangioendothelioma Hemagiopericytoma Kaposi's sarcoma

Vascular tumours

 Benign vascular tumors are very common and most frequently occur in the skin

It is often difficult to determine whether benign vascular lesions are malformations, true neoplasms or, in some cases, reactive processes.
Essentially impossible to reliably distinguish blood vessel endothelium from lymphatic endothelium, which probably reflects the close functional and embryogenetic relationship between these cell types

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Oral hemangioma
Benign tumor of vascular tissue

Common on skin and mucous membrane

Most of are developmental anomalies

Not true neoplasm

Capillary or cavernous type

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Clinical presentation : Hemangiomas

On examination, the superficial hemangioma usually consists of a raised, reddish to purple tumor with a distinct margin. In contrast, deep subcutaneous hemangiomas often have a deep bluish hue with normal overlying skin, making diagnosis more difficult. Both the lesions are firm to palpation and do not pulsate or exhibit any thrills or bruits. Intraoral site tongue and cheek
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Pathophysiology /Histology
Arrested development in mesenchymal vascular primordia 3 stages of development capillary stage Early=superficial Late=deeper, subcutaneous Retiform stage Mature, end stage Capillary stage

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Pathophysiology /Histology
2 phases of growth 1) Proliferating phase endothelial hyperplasia with thymidine incorporation rapid growth during infancy hormone response-estradiol-17 beta receptors 2) Involutional phase fibrosis and fat deposition low to absent thymidine incorporation rapid growth with regression
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well-defined borders and is primarily composed of large vessels lined by flattened endothelial cells (hematoxylin eosin, 100). Inset, Solid focal areas composed of spindle and epithelioid cells with irregular nuclei were also observed

Photomicrograph of cavernous hemangioma demonstrating large blood-filled vascular channels in the underlying connective tissue

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Differential diagnosis of hemangioma:

1) Vascular malformation - present at birth; persists throughout life Varix dilated vein 2) Hematoma 3) Lymphangioma - proliferation of lymphatic endothelial cells - often combined with hemangioma 4) Pyogenic granuloma 5) Mucocele; salivary gland tumor

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Hemangioendothelioma (HE)
Epithelioid hemangioendothelioma (EHE) is an angiocentric vascular tumor with metastatic potential (Weiss and Bridge, 2002)

The term epithelioid hemangioendothelioma was originally

described by Weiss and Enzinger (1982) to classify a vascular tumor with borderline biological properties intermediate between hemangioma and angiosarcoma.
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 This tumor was described by WHO as an intermediate malignant neoplasm (Weiss and Bridge, 2002) HE are extremely rare in the oral cavity. The most common intraoral sites were the gingival / alveolar mucosa and tongue

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 Grossly , the tumours were firm and rubbery, most with a grayish-tan cut surface, and only one with hemorrhagic foci.

Clinical photo

an incidental finding, of a painless oral mass,

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Non-encapsulated, with ill-defined margins, and infiltrating Tongue muscles (Original magnification 0.8 2.0

Tumour composed of nests or cords proliferating epithelioid endothelial cells

Tumour cells with intracytoplasmic Lumina with red blood cells (arrow)

Tumour composed of multiple spindle-shape epithelioid cells and mitosis MESENCHYMAL TUMORS (arrow) are easily found (H&E)

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D/D
Vascular tumours showing epithelioid characteristics, Including Epithelioid angiosarcoma - an infiltrative, destructive vascular tumour,
composed of pleomorphic cells, associated with numerous often atypical mitosis, and frequently with necrosis

Epithelioid hemangioma- For its prominent inflammatory process permits its

distinction from HE

Spindle cell hemangioma- benign lesion in older patients with a predilection for the limbs, and characterized by cavernous vascular spaces, with papillary structures, thrombi and phleboliths, associated with a focal solid spindled vascular tumour Kaposiform hemangioendothelioma (KHE) - vascular tumour of infancy Epithelioid angiomatous nodule- usually confined to the dermis with only
infrequent extension into the superficial subcutaneous tissue and rarely in the sub mucosa.
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Histology
Involves three stage : Patch stage- proliferation of miniature vessels resulting in irregular , jagged vascular network around existing vessels

Plaque stage further proliferation with significant spindle cell component. Nodular stage spindle cells increase to form a nodular mass that resemble fibrosarcoma
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Microphotograph

Spindle cells arranged in short fascicles and numerous erythrocytes typical of Kaposi's sarcoma
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Differential diagnosis
Hemangioma Erythroplakia Melanoma Pyogenic granuloma Pericytoma Angiosarcoma Bacillary angiomatosis , mimics KS clinically and microscopically caused by Bartonella henselae or B. quintana.

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