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L12 Connective Tissue disorders_annotated_formatted_text

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Oral Pathology module: Connective Tissue disorders1

DENT4217

Acknowledgement of country2

The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritual and cultural custodians of their land, and continue to practise their values, languages, beliefs and knowledge.

Artist: Dr Richard Barry Walley OAM

Introduction: Histology of the Oral Mucosa3

The oral mucosa is composed of three layers:

  1. ==Epithelium: A covering of stratified squamous epithelium, which can be keratinized or non-keratinized. Many previously discussed disorders, like leukoplakia, originate here.==
  2. ==Lamina Propria: This is the fibrous connective tissue layer beneath the epithelium. Its main components are:==
    • ==Fibroblasts: Spindle-shaped cells.==
    • ==Collagen fibers: Abundant fibrous protein.==
    • Blood vessels and nerves.
    • This lecture focuses on disorders originating in the lamina propria.
  3. ==Submucosa: The deepest layer, which can contain muscle, adipose tissue, and minor salivary glands. It may be attached directly to bone (e.g., gingiva, hard palate) or other soft tissues (e.g., soft palate, buccal mucosa).==

Learning outcomes3

  • To develop a basic knowledge of reactive, benign and malignant connective tissue lesions that may occur in the oral cavity.

  • To recognise the common causes of various types of localised gingival lesions

  • To understand the etiology and causes relevant to the development of these disorders.

Soft-tissue tumours derived from mesenchymal components of connective tissue

Classification of Connective Tissue Disorders45

Pathogenesis

Connective tissue disorders are broadly categorized based on their pathogenesis:

  • Reactive/Congenital:
    • Reactive: A response to a stimulus (e.g., chemical, mechanical, physical trauma). These are very common in dental practice.
    • Congenital: Present from birth, often related to hereditary genetic mutations.
  • Neoplastic: Triggered by genetic mutations. Risk factors include environmental factors (smoking, alcohol, pollution), aging, and systemic medical conditions.
GroupReactive/congenitalNeoplasms
Fibrous•Fibroma /fibroepithelialpolyp
•Peripheral giant cell granuloma
•Peripheral ossifying fibroma
•Epulis fissuratum (inflammatory fibrous hyperplasia)
•Inflammatory papillary hyperplasia
•Generalized gingival hyperplasia		•Giant cell fibroma
•Myofibroma
•Aggressive Fibromatosis
•Solitaryfibrous tumor
•Fibrosarcoma
•Fibrous histiocytoma, benign and malignant
•Nodular fasciitis
Vascular•Pyogenic granuloma
•Varix; other acquired malformations
•Benign vascular malformation
•Lymphangioma		•Hemangioma
•Angiosarcoma
•Kaposi’s sarcoma
•Hemangiopericytoma
Neural•Traumatic neuroma•Neurofibroma
•Granular cell tumor
•Schwannoma (neurilemoma)
•Mucosal neuromas of MEN III
•Palisaded encapsulated neuroma
•Malignant peripheral nerve sheath tumor
Adipose tissue•Herniated fat pad•Lipoma and Liposarcoma
Muscle•Smooth muscle
•Striated muscle		•Leiomyoma and Leiomyosarcoma
•Rhabdomyoma and Rhabdomyosarcoma

Fibroma (“Bite” or “Irritation” Fibroma, Fibroepithelial or Fibrovascular Polyp), and Giant Cell Fibroma6

Aetiology

  • A reaction to chronic, low-grade irritation or physical trauma, such as cheek biting, lip biting (a stress-relief habit for some), or sharp edges on teeth or restorations.

  • This occurs at any age group without sex predilection and consists of a dome-shaped nodule or papule that may be white/keratotic, mucosa-colored, or ulcerated. It is located in areas readily traumatized by biting (i.e., buccal mucosa, lateral tongue, and lower lip mucosa) or on the gingiva where plaque accumulates.

  • It can be sessile (broad-based) or pedunculated (attached by a stalk).

  • It is less common on the hard or soft palate, where a similar-looking lesion is more likely to be neoplastic.

  • A nodular mass of dense fibrous connective tissue

  • Normal, hyperkeratotic, or ulcerated surface epithelium

Treatment78

  • Simple surgical excision.
  • ==Crucially, the causative factor (irritant) must be identified and removed to prevent recurrence. If the trauma is not eliminated, the lesion will likely return.==

Ossifying fibrous epulis (peripheral ossifying fibroma)9

  • A common, swelling of the gingiva characterized by a core of fibrous connective tissue exhibiting the formation of variable amounts of amorphous deposits of calcifications
  • Mostly seen in children and young adults
  • A reactive lesion to local irritation

Clinically:

  • Red to pink, firm gingival nodule

  • typically arise from the interdental papilla

  • smooth surfaced, can be ulcerated

  • 1 cm in diameter; can be larger

  • Often shows calcification on radiograph

  • ==Imaging (e.g., OPG or periapical X-ray) is essential to rule out a central lesion (i.e., a lesion originating within the bone, like central ossifying fibroma, which can be destructive).==

  • A nodular mass of cellular fibrous connective tissue

  • contains bone, or cementum-like material

  • covered by normal or ulcerated surface epithelium

Treatment78

  • Surgical excision down to the periosteum.
  • The origin is thought to be related to cells of the periodontal ligament, so thorough scaling and root planing of the adjacent teeth is recommended to reduce the risk of recurrence.

A microscopic image showing a fibrous mass.

Angiogranuloma (pyogenic granuloma)10

  • A common reactive vascular lesion

Aetiology

  • A reactive lesion to local irritation or trauma
  • Some are attributed to the effect of female hormones
  • Tumour-like overgrowth of granulation tissue

Misnomer

The term

Clinical features11

  • F>M; the prevalence is higher in women during pregnancy

  • Most common on the gingiva (75% of all oral cases)

  • tongue, lips, and buccal mucosa

  • Bright-red to dark-red, soft nodule

    • smooth or lobulated surface; often ulcerated
    • often bleeds easily
    • <1 cm in diameter, can be larger

  • Pregnancy tumour (granuloma gravidarum): a pyogenic granuloma that develops on the gingiva during pregnancy

  • Epulis Granulomatosa: a pyogenic granuloma that develop in a healing extraction socket

  • Nodular mass of granulation tissue

  • dilated blood vessels in a loose fibrous stroma, with acute and chronic inflammatory infiltrate

  • normal or ulcerated overlying surface epithelium

Peripheral Giant Cell Granuloma (Giant Cell Epulis)1213

  • A relatively common growth on the gingiva or the alveolar ridge characterized by a proliferation of multinucleated giant cells that resemble osteoclasts.

Aetiology

  • A reactive lesion to local irritation or trauma

Clinical features11

  • Exclusively on the gingiva or edentulous alveolar ridge

    • Red to blue-purple, firm gingival nodule
    • typically arise from the interdental papilla
    • smooth surface; may or may not be ulcerated
    • typically <1 cm in diameter; can be larger
    • may cause cupping resorption of the underlying alveolar bone

  • ==Imaging is important to differentiate it from a central giant cell granuloma, a more significant lesion that originates within the jawbone. Central lesions can be destructive and are sometimes associated with hyperparathyroidism (in which case they are called ‘brown tumors’).==

Microscopy14

  • A nodular proliferation composed of osteoclast-like multinucleated giant cells in a cellular and haemorrhagic background
  • osteoclast-like multinucleated giant cells // multinucleated giant cells b/fsen monocytes
  • cellular fibrous stroma
  • extravasated RBCs, and haemosiderin pigmentation

(a brownish pigment from broken-down blood), which contributes to the lesion's clinical color

  • normal or ulcerated overlying surface epithelium

Epulis Fissuratum (Inflammatory fibrous hyperplasia; denture epulis)15

A reactive overgrowth of fibrous connective tissue in response to an ill-fitting denture

Aetiology

  • Trauma from an overextended or ill-fitting denture

Clinical features11

  • In the alveolar vestibule adjacent to a denture flange
  • more frequently along the anterior vestibule

Histopathology16

  • A hyperplasic mass of fibrous connective tissue
  • often with folds and grooves
  • Hyperplastic, hyperkeratotic, or ulcerated surface epithelium

Treatment78

  • Surgical excision of the excess tissue.
  • Fabrication of a new, properly fitting denture is required to prevent recurrence. In some cases, pre-prosthetic surgery to improve the bone contour may be needed.

Reactive Gingival Nodules17

Differential Diagnosis by Appearance

The microscopic composition of these nodules directly influences their clinical appearance (color, consistency), which aids in differential diagnosis.

Diagnosis

Fibroma (inflammatory fibrous hyperplasia)

  • ==Appearance: Pink, pale, and firm.==

  • Nodule of densely collagenous fibrous tissue with scattered vessels and variable edema and inflammation; crevicular epithelium with underlying plasma cells are often seen; when uninflamed, it is indistinguishable from a traumatic fibroma (see Fig. 5.12A-C)

Pyogenic granuloma (lobular capillary hemangioma) (see also Chapter 6)

  • ==Appearance: Red/purple, soft, and bleeds easily.==

  • Lobular or more frequently, nonlobular proliferation of endothelial cells and small, dilated capillaries; often ulcerated and inflamed (see Figs. 5.13A)

  • Endothelial cells show reactive atypia sometimes with a focal “hobnail” pattern and hyperchromatic nuclei (see Fig. 5.13B-C); mitotic figures are often present

  • May see fibrosis depending on stage of organization (Fig. 5.13D-E)

Peripheral ossifying fibroma (fibroma with osseous metaplasia)

  • ==Appearance: Pink or red and firm.==

  • Cellular proliferation of spindled fibroblast-like cells with deposition of osteoid, woven bone with variable osteoblastic rimming, cementum droplets or cementicles (psammoma body-like) (see Figs. 5.14 and 5.15); sometimes lamellar bone is present

  • Spindle cells have ovoid nuclei, dispersed chromatin, and inconspicuous nucleoli and the spindle cell proliferation may have a storiform pattern (Fig. 5.16); the amount of calcified material is variable (Fig. 5.17)

  • There may be clusters of multinucleate giant cells similar to peripheral giant cell granuloma (see Fig. 5.18)

  • Bone morphogenetic protein has been identified in the spindled fibroblast-like cells

Peripheral giant cell granuloma

  • ==Appearance: Reddish-purple or blue and firm.==

  • Proliferation of monocytic and multinucleate giant cells (osteoclast-like or foreign body type) usually in sheets; giant cells contain 20-30 evenly distributed nuclei; mitoses may be seen in monocytic cells; fresh hemorrhage and hemosiderin deposits are usually present especially beneath the grenz zone (see Figs. 5.19 and 5.20)

  • May see concomitant osseous metaplasia similar to peripheral ossifying fibroma

  • Giant cells are positive for TRAP, RANK, and osteoprotegrin

Inflammatory Papillary Hyperplasia (Denture Papillomatosis)18

  • A pebbly overgrowth of the oral mucosa, usually occurs beneath a denture

Aetiology

  • Ill-fitting denture, a denture that is worn 24 hours a day, or denture stomatitis

Clinical features11

  • Multiple, pink to red, edematous or fibrous papules

  • On the hard palate beneath a denture base

    • mainly the palatal vault

  • ==It has a

Microscopy14

  • Multiple papules of edematous fibrous connective tissue
  • Normal or hyperplastic surface epithelium

Treatment78

  • Improving denture hygiene, removing the denture at night, and treating any fungal infection.
  • In advanced cases, surgical removal of the hyperplastic tissue is necessary before fabricating a new denture.

Epulis19

  • Epulis = a growth arising from the gingiva
  • it means “on the gum”
  • Often used to describe localized hyperplastic gingival lesions
  • Fibrous epulis (firm mass on the gingiva)
  • Vascular epulis (angiogranuloma on the gingiva)
  • Fibrous epulis with calcification (peripheral ossifying fibroma)
  • Giant-cell epulis (peripheral giant cell granuloma)
  • Denture epulis (epulis fissuratum)

Outdated Theory

An old, unsupported theory suggested that these lesions could progress from one type to another (e.g., starting as a vascular epulis and becoming more fibrous over time). This hypothesis is not validated by current evidence.

Generalized gingival enlargements

Lesion or conditionSpecial characteristics
Hyperplastic gingivitisExamples: associated with puberty, pregnancy, diabetes
Drug-related gingival hyperplasiaExamples: phenytoin, calcium channel blockers cyclosporine; may be fibrotic
Gingival fibromatosisMay be hereditary; onset in childhood
Leukemic infiltrateGingival swelling and bleeding
Wegener’s granulomatosis (granulomatosis with polyangitis)‘Strawberry gingivitis’; may have palatal ulceration and destruction of kidney, lung or nasal septum involvement; often with a skin rash, conjunctivitis or hearing loss
ScurvyVitamin C deficiency

Giant Cell Fibroma20

  • A variant of fibroma with distinctive features

Nature

This is considered a benign neoplasm, not a reactive lesion.

  • Compared to the common “irritation” fibroma:

    • does not appear to be caused by trauma
    • occurs most frequently on the gingiva
    • many demonstrate rough, papillary surface
      • can be mistaken for a papilloma
    • large stellate, multinucleated fibroblasts microscopically

  • These are distinct from the osteoclast-type giant cells seen in a peripheral giant cell granuloma.

Retrocuspid Papilla

  • Small, pink papules on the lingual gingiva of the lower cuspids
    • frequently bilateral lesions
    • microscopic features similar to giant cell fibroma
    • do not require excision

Vascular Anomalies [Hemangiomas and Vascular Malformations]21

Clinical Caution

Lesions with a significant vascular component pose a risk of bleeding. If unsure of the diagnosis or management, it is best to refer the patient to a specialist.

Major types: ▪vascular tumours and vascular malformations

Classification of Vascular Anomalies

Vascular Tumours

  • Infantile Hemangioma
    • Superficial
    • Deep
  • Congenital Hemangioma▪
    • Noninvoluting congenital hemangioma (NICH)
    • Rapidly involuting congenital hemangioma (RICH)

Vascular Malformations

  • Capillary malformation
  • Venous malformation
  • Arteriovenous malformation
  • Lymphatic malformation

Common Malformation: Lingual Varices

These are very common, especially with aging. They appear as dilated, purple veins on the ventral surface of the tongue and can be accidentally lacerated during dental procedures, leading to bleeding.

General Features22

Hemangiomas

  • Benign tumors
    • the most common tumors of infancy
  • Most lesions are not present at birth (arise during the first 8 weeks of life)
    • few present at birth
  • Display a rapid growth phase (endothelial cell proliferation)
    • typically followed by gradual involution
    • some show rapid involution or do not undergo involution

Vascular Malformations

  • Hamartomatous growths composed of blood or lymphatic vessels with normal endothelial cell turnover
  • Present at birth and persist throughout life
  • Categorized according to the type of vessel involved into:
    • capillary, venous, or arteriovenous, or lymphatic
  • Categorized according to the hemodynamic features into:
    • low-flow vs. high-flow

Congenital Hemangioma23

Info

This is a type of vascular tumor (hamartoma) that can be superficial or deep and appears as red plaques.

The given image contains two microscopic images with labels, with the context of Congenital Hemangioma.

  • Present at birth
  • Subtypes:
    • Rapidly involuting congenital hemangioma (RICH)
      • shows rapid regression, with full involution by 9 to 14 months of age
    • Noninvoluting congenital hemangioma (NICH)
      • does not undergo involution

Microscopy

  • Early phase – a proliferation of plump endothelial cells forming indistinct vascular lumina
  • Mature phase – capillary-sized vascular spaces lined by flattened endothelial cells
  • Involution phase – get replaced by fibrous connective tissue

Venous Malformation24

  • Low-flow anomaly

Clinical features

  • Blue-purple mass

    • present at birth
    • thrombi and phleboliths can form within (because of slow blood flow)

  • ==A common example is lingual varices, which appear as dilated, tortuous, purple veins on the ventral (underside) and lateral borders of the tongue.==

  • They are considered a variation of normal anatomy that becomes more prominent with age.

  • ==Clinical Significance: Dentists should be aware of their presence to avoid accidental laceration during procedures, which can cause significant bleeding.==

Microscopy

  • Dilated thin-walled veins

Treatment

  • Observation, sclerotherapy, or surgical excision
  • Sclerotherapy: injection of sclerosing agents into the lesion to induce fibrosis

Kaposi Sarcoma25

  • A vascular malignancy caused by human herpes virus 8

Clinical Significance

It is highly relevant in dentistry as it can be an early oral sign of HIV/AIDS. A patient may present with this lesion before they are aware of their HIV status.

Etiology

  • Human herpesvirus 8 (HHV-8)/Kaposi sarcoma-associated herpesvirus (KSHV)

Subtypes

I. Classic II. Endemic III. Iatrogenic (transplant-associated) IV. Epidemic (AIDS-related)

Clinical

  • Mainly manifests as multiple lesions on the skin or oral mucosa
    • oral lesions are seen in more than 50% of patients
  • Predilection for adult homosexual males
  • Considered as an AIDS-defining cancer

Oral lesions26

  • strong predilection for the palate and gingiva

  • early lesions appear as purple macules ↔︎ plaques and nodules

  • ==Classically, the lesion is described as raised, velvety, and black, blue, or purple.==

Microscopy14

  • A cellular proliferation of spindle cells surrounding slit-like vascular spaces

Treatment78

  • Often regresses with combined antiretroviral therapy (cART)
  • Other options include surgery, irradiation, intralesional chemotherapeutic agents (e.g. vinblastine), intralesional sclerosing agents (sodium tetradecyl sulfate), and systemic chemotherapy

References27

  • Odell E. 2018. Cawson’s Essentials of Oral Pathology and Oral Medicine
  • Woo SB. 2023. Oral Pathology. A Comprehensive Atlas and Text
  • Sapp JP, Eversole LR, Wysocki GP. 2004. Contemporary oral and maxillofacial pathology.

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