connective tissue tumors

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. Fibrous and myofibroblastic tumours2. Tumours included in the fibrohistocytic category3. Lipomatous tumours4. Smooth muscle tumours5. Skeletal muscles tumours6. Vascular tumours7. Perivascular tumours8. Synovial tumours9. Neural tumours10. Extra skeletal osseous & cartilaginous tumours11. Miscellaneous tumours12. unclassified

• Benign and malignant morphologically

Tumors which will be discussed

• Benign connective tissue tumors are 1. Fibroma /Fibromatosis2. Myofibroma3. Lipoma /Lipoblastoma4. Oral hemangioma5. Lymphangioma6. Myxoma7. Chondroma8. Benign chondromablastoma9. Chondromyxoid Fibroma10. Osteom /osteoid osteoma11. Benign osteoblastoma

6MESENCHYMAL TUMORS

• Malignant connective tissue tumors are1. Fibrosarcoma2. Fibrous histocytoma(malignant)3. Hemangioendothelioma 4. Hemagiopericytoma5. Kaposi's sarcoma(AIDS related )6. Ewings sarcoma7. Chondrosarcoma8. Osteosarcoma9. Malignant lymphoma(Hodgkin’s lymphoma)10. Non- Hodgkin's lymphoma11. Burkitt’s lymphoma12. Hodgkin disease13. Plasmacytoma

7MESENCHYMAL TUMORS

• Benign and malignant tumors of muscle tissue tumors1. Leimyoma2. Rhabdomyosarcoma3. Granular cell myoblastoma4. Leimyosarcoma5. Rhabdomyosarcoma6. Alveolar soft Part sarcoma

• Benign and malignant tumors of nerve tissue1. Traumatic neuroma2. Neurofibroma3. Neurolemmoma4. Melanotic neuroectodermal tumors of infancy

8MESENCHYMAL TUMORS

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

10MESENCHYMAL TUMORS

• 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.


• 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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FibromaPyogenic granuloma

MESENCHYMAL TUMORS

• 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.


PGCG Peripheral Ossifying Fibroma


FIBROMATOSIS


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.


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.


Histological photo

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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

FIBROSARCOMA


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.


• 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.


• 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


• 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.


Variants

• Sclerosing epitheliod type

• Myxoid type

• Fibromyxoid


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Fibromatosis Low grade Fibrosarcoma

High grade Fibrosarcoma

Cellularity Low to mod Low to mod Mod to severe

Nuclear overlap Absent Present Absent

Hyperchromasia Absent Present Present

Nucleoli Inconspicuous Prominent More prominent and pleomorphic

Mitotic activity 1+ 1+ to 3 + More than 3+

Necrosis Absent Rare Present (Hemorrhage)

Vessel wall infiltration

Absent Rare Present

Herring bone pattern

Absent Present Present ( less distinct)

Collagen fibres bundles

Abundant Abundant Less collagen fibres

MESENCHYMAL TUMORS

Fibrosarcoma

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Hard Palate Anterior tongue

MESENCHYMAL TUMORS

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.


• Tumour cells demonstrate positivity for vimentin and are negative for EMA (epithelial membrane antigen), cytokeratin, S100 protein, smooth muscle actin and desmin.


DD of fibrosarcoma

• Fibrous dysplasia

• Osteosarcoma

• Paget’s sarcoma

• Malignant fibrous histiocytoma

• Malignant neurosarcoma


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


• 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 Gardner’s syndrome

• Hereditary multiple lipomatosis, an autosomal dominant condition.

• Madelung’s disease, or benign symmetric lipomatosis, refers to lipomatosis of the head, neck, shoulders, and proximal upper extremities


• usually present as non-painful, round, mobile masses, with a characteristic soft, doughy feel.

• Overlying skin is normal


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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 & irregular lobular pattern.

Lipoma

MESENCHYMAL TUMORS

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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).

MESENCHYMAL TUMORS

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)


D/D:-

• Epidermoid cyst

• Nodular fasciitis

• Liposarcoma

• Sarcoidosis

• Hematoma


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


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.


Gross specimen

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Circumscribed lipoblastoma. Cut surface shows myxomatous lobulated appearance

MESENCHYMAL TUMORS

Microphotograph


Oral hemangiomaHemangioendothelioma HemagiopericytomaKaposi'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


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


MESENCHYMAL TUMORS 46

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

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


Pathophysiology /Histology2 phases of growth1) 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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Photomicrograph of cavernous hemangioma demonstrating large blood-filled vascular

channels in the underlying connective tissue

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

MESENCHYMAL TUMORS

Differential diagnosis of hemangioma:

1) Vascular malformation - present at birth; persists throughout life Varix – dilated vein2) Hematoma3) Lymphangioma - proliferation of lymphatic endothelial cells - often combined with hemangioma4) Pyogenic granuloma5) Mucocele; salivary gland tumor


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.


• 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


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

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an incidental finding, of a painless oral mass,

Clinical photo

MESENCHYMAL TUMORS

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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

(arrow) are easily found (H&E)MESENCHYMAL TUMORS

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. 56MESENCHYMAL TUMORS

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


Microphotograph

• Spindle cells arranged in short fascicles and numerous erythrocytes typical of Kaposi's sarcoma


Differential diagnosis

• Hemangioma• Erythroplakia• Melanoma

• Pyogenic granuloma• Pericytoma• Angiosarcoma

• Bacillary angiomatosis , mimics KS clinically and microscopically caused by Bartonella henselae or B. quintana.


connective tissue tumors

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