GINGIVAL PIGMENTATION

Dr Nida Sumra

CONTENTS

• Introduction • Historical aspects • Physiology of pigmentation• Normal racial variations • Classification of oral pigmentation• Pigmented lesions of the oral mucosa • Methods of depigmentation • Conclusion • References

INTRODUCTION

Historical aspects

• 1912 - Bonnet and Laboef described physiologic pigmentation of oral mucosa.

• 1914 - Brault and Monpellier and in 1923 - Lortat – Jacob & Solente also reported the normal occurance of pigmentation in the French people and fillipinos.

• 1924 - Reiche described the occurance of oral pigmentation in Arabian, Chinese and East Indians.

• 1945 – Dummet C.O. reported pigmentation variations in healthy oral tissues of more than 600 negros.

Physiology of pigmentation• Melanocytes • These are specialized unicellular dendritic cells residing in the

basal cell layer of the epidermis and oral epithelium.• Primitive melanocytes originate from neural crest of ectoderm.• In the epithelium they divide and maintain themselves as a

self- reproducing population

Structure

• Round cells with pale-staining cytoplasm.

• Lack desmosomes and tonofilaments but possess long dendritic processes.

• Melanosomes.

• Melanocytes are cells capable of synthesizing tyrosinase, which, when incorporated within specialized organelles, the melanosomes, initiates events leading to the synthesis and deposition of melanin.

• Routine hematoxylin and eosin (H&E) preparations

• Replicate throughout their life, although at a much slower rate

• According to the degree of maturation, melanosomes are classified in 4 stages.

• Stage I. Membrane delinated vesicles containing tyrosinase and a proteinateous matrix.

• Stage II. Oval organels with numerous membrane filaments distinctive periodicity.

• Stage III. Less periodicity and melanin deposition.• Stage IV. A dense uniform particle without any

distinguishable internal structure.

Melanin

Structure• The exact structure of melanin has not been

determined.• Melanin is defined as a biochrome of high

molecular weight formed by the enzymatic oxidation of phenyl alanine.

• Insoluble polymer of tyrosine derivative formed from tyrosine by the action of copper.

• The first step of the biosynthetic pathway for both eumelanins and pheomelanins is catalysed by tyrosinase:

• Tyrosine → DOPA → dopaquinone

Dopaquinone can combine with cysteine - pheomelanins• Dopaquinone + cysteine → benzothiazine intermediate →

pheomelanin

Also, dopaquinone can be converted to leucodopachrome - eumelanins

• Dopaquinone → leucodopachrome → dopachrome  → quinone → eumelanin

Regulation of melanin synthesis

• Melanin synthesis can be controlled by three major determinants:

Genes

Hormones

U-V Radiation

Endocrine control

• Melanocyte stimulating harmone (MSH)• Adrenocorticotropic hormone (ACTH)• Androgens

Normal racial variations

• Common characteristic of the darker races including Caucasian brunettes.

• Most usual cases of brown oral pigmentation are ethnic.• The pigmentation is usually symmetrically distributed

over the gingiva and palatal mucosa.

• Dumett examined 600 negroes of varying shades of complexion to determine the relationship of oral to cutaneous pigmentation and found that gingival pigmentation was directly proportional to skin pigmentation

• Erica Amir et al (1991) studied the oral physiologic pigmentation and found that it varied, according to the intensity of the skin pigmentation.

• Patsakas et al (1991) conducted a study to determine the distribution of melanin granules in different anatomical areas of the gingiva and to relate the melanin granules to the degree of gingival inflammation. The results showed positive correlation between the density of melanin granules of the vestibular epithelium and the severity of inflammation.

CLASSIFICATION OF ORAL PIGMENTATION

• Endogenous pigmentation

• Exogenous pigmentation

PIGMENTED LESIONS OF ORAL MUCOSA

Blue / purple vascular lesions

Brown melanotic lesions

Brown heme Associated lesions

Gray / black pigmentation

VASCULAR LESIONS.

Kaposi’s sarcoma • Tumor of putative vascular origin • Described by Morietz Kaposi (1872) • Slow progressive growth.• Diagnostic sign for AIDS

Clinical Appearance• The oral mucosa is red, blue and purple and hard palate is

most favored site. • Multifocal with numerous isolated and coalescing plaques.

Some will involve entire palate.• Facial gingiva second most favored oral site

Management Early plaque or macular lesions no treatment. Nodular lesions are surgically excised. Intra lesions injection of 1% sodium, tetradecyl sulfate.

BROWN MELANOTIC LESIONS

NEVOCELLULAR AND BLUE NEVI

• Nevi are benign proliferation of melanocytes.

Nevo cellular nevi • Arise from basal cell layer melanocyte early in life• Called as junctional nevi when macular. • Flat, brown and have a regular round or oval out line. • Dome shaped navei

Blue nevus

• Not derived from basal layer melanocytes

• Blue in color on the skin • Biopsy necessary for

diagnostic confirmation.

Treatment • Simple excision

• Dyer et al (1993) reported a case of pigmented naevus of the gingiva which was a recurrent lesion. The histological examination confirmed the presence of junctional activity of melanocytes at the epithelio mesenchymal interface.

MALIGNANT MELANOMA

Melanoma may arise from neoplastic transformation of either melanocytes or nevus cells.

Clinical features • Melanomas of oral mucosa less common than cutaneous. • Oral lesions mainly in hard palate and gingiva followed by lips

and buccal mucosa.• Mixture of color such as brown, black, blue and red • Can be asymmetrical or irregular margins. • Depending on radial and vertical growth sub classified

Nodular melanoma – Superficial spreading melanoma – Lentigo malignant melanoma – Acral lentiguous melanoma

• Management – Oral melanomas highly malignant and have high

mortality. – Biopsy essential for diagnosis. – Destruction of underlying bone or metastasis

indicate poor outcome. – Excision with centimeter wide margins followed by

radical radiotherapy. – Immunotherapy with interferon and gene therapy

is also under trial.

DRUG INDUCED MELANOSIS

• A variety of drugs can induce oral mucosal pigmentation.

• May be localized usually to the hard palate or multifocal throughout the mouth.

• Lesions are flat without any evidence of nodularity or swelling.

• Antimalarial therapy, tricyclic antidepressants, Busulfan, cyclophosphamide, bleomycin and fluoracil

• Birek et al (1988) reported two cases of pigmentation of the palatal mucosa due to quindine therapy both the clinical appearances were those of melanin pigmentation and had characteristic bluish black color.

• Siller et al (1994) reported oral mucosal pigmentation in two patients taking the drug minocycline and demonstrated minocycline deposition within teeth and bone by fluorescence microscopy.

• Meyerson et al (1995) reported acquired isolated lingual hyperpigmentation caused by minocycline in two women .They had been receiving oral minocycline for approximately 4 weeks to 4 months.

SMOKING ASSOCIATED MELANOSIS

Clinical features • Diffuse macular melanosis

• Seen on the buccal mucosa, lateral tongue, palate and floor of the mouth.

• Lesions are brown, flat and irregular.

• Hedin et al (1993) compared the frequency of oral melanin pigmentation in a large number of former smokers with that of non smokers. Results showed that although clinically pigment free, the oral mucosa may have elevated melanin content for a period of time until the melanocyte activity declines.

• Brown et al (1991) found smoker’s melanosis to be secondary to tobacco smoking as described by Hedin and as such has an identifiable etiologic agent or factor.

ENDOCRINOPATHIC PIGMENTATION

• Addison’s disease

• Cushings syndrome

Bronzing of the skin and patchy melanosis, of the gingiva, palate and buccal mucosa are classical signs

Oral melanotic pigmentation accompanied by cutaneous bronzing.

Serum steroid and ACTH determination will aid in the diagnosis

Treatment • The pigment will disappear once

appropriate therapy for the endocrine problem is initiated.

GENO DERMATOSES

• Peutz–Jeghers syndrome. • Albright’s syndrome. • Neurofibromatosis.

PEUTZ – JEGHERS SYNDROME

CLINICAL FEATURES Melanin pigmentation of the

lips and oral mucosa is usually present from birth.

Buccal mucosa more frequently involved followed by gingiva and hard palate.

Facial pigmentation tends to fade later on, the mucosa pigmentation persists.

ALBRIGHTS SYNDROME • It is also called polyostotic fibrous dysplasia . • Associated with skin lesions and endocrine

dysfunction

Clinical Features • Bowing or thickening of long bones – unilateral /

bilateral• Bone of face and skull are frequently involved.• Skin lesions described as “Café au-lait” spots

NEUROFIBROMATOSIS (Von- Reckling hausen’s Disease)

– Multiple neural tumors

Clinical Features – “Café au-lait” spots. – Oral lesions present as discrete nodules, which tend to be of

same colour as the oral mucosal,– Palate, alveolar ridges, vestibules and tongue.

• Most sero positive patients present with diffuse, multifocal macular, brown pigmentation of the buccal mucosa

• Gingiva, palate and tongue may also be involved.

Histologically • Characterized by basilar melanin pigment.• Alangford et al (1989) reported six cases of oral

hyperpigmentation in HIV infected patients. The lesions could be related to systemic clofazimine or ketoconazole therapy.

HIV ORAL MELANOSIS

BROWN HEME ASSOCIATED LESIONS

HEMOCHROMATOSIS• Deposition of hemosiderin

pigment in multiple organs and tissue

• Primary heritable disease or secondary to variety of disease

• Clinical features – Mucosal lesions appear

brown to gray diffuse macules.

– Seen on the palate and gingiva.

GRAY BLACK PIGMENTATIONS

AMALGAM TATTOO

• The lesions are macular and bluish gray or even black.

• Buchner and Hansen (1990) evaluated series of cases of amalgam tattoo, which were analyzed clinically and histologically. The most common location was the gingiva and alveolar mucosa followed by the buccal mucosa. Histologically the amalgam was present in the tissues as discrete fine, dark granules and as irregular solid fragments.

GRAPHIC TATTOO • Graphic tattoo occur on

the palate representing traumatic implantation from a lead pencil.

• The lesions are usually macular, focal and gray or black in colour.

Microscopically • Graphite resembles

amalgam in tissue although special stains can segregate the two.

HEAVY METAL INGESTION

• Ingestion of heavy metals or metal salts can be occupational hazard.

• In oral cavity found along the free marginal gingiva

• Metallic line is gray or black in colour.

• Bismuth, lead, mercury, silver.

DEPIGMENTATION

Hanioka T et al. Association of melanin pigmentation in the gingiva of children with parents who smoke. Pediatrics Aug 2005;116(2):186-90.

- Santosh Kumar et al

Oral Pigmentation Index –Dummett et al 1964

0: No clinical pigmentation (pink gingiva)

1: Mild clinical pigmentation (mild light brown color)

2: Moderate clinical pigmentation (medium brown or mixed pink and brown color)

3: Heavy clinical pigmentation (deep brown or bluish black color)

METHODS OF DEPIGMENTATION 1. De-epithelization

• a. Scalpel technique

• b. Gingival abrasion technique using diamond bur

• c. Combination of the scalpel and bur

2. Gingivectomy

3. Free gingival autografting

4. Acellular dermal matrix allograft (ADMA)

5. Electrosurgery

6. Cryosurgery• a. Using liquid nitrogren• Using a gas expansion system

7. Chemical agents• a. 90% phenol and 95% alcohol• b. Ascorbic acid

8. Laser[• a. Nd:YAG• b. Semiconductor diode laser• c. CO2 laser• d. Argon laser

SURGICAL METHODS

Criteria for patient selection • Skin shade not very dark toned, but gingiva is deeply

pigmented. • Periodontal health not compromised or is pretreated. • Adequate thickness of the periodontal tissues.

Scalpel

• The procedure essentially involves surgical removal of the gingival epithelium along with a layer of the underlying connective tissue under adequate local anesthesia and allowing the denuded connective tissue to heal by secondary intention.

Split thickness epithelial excision technique

Gingival abrasion technique using diamond bur

• Similar to the scalpel technique.• Comparatively simple, safe and non-aggressive method

that can be easily performed and readily repeated, if necessary, to eradicate any residual repigmentation.

• Extra care should be taken to control the speed and pressure of the handpiece bur so as not to cause unwanted abrasion or pitting of the tissue.

• Minimum pressure with feather light brushing strokes with copious saline irrigation should be used without holding the bur in one place to perceive excellent results

Gingivo abrasion technique

Gingivectomy• Removing the gingival margin by gingivectomy or the entire attached

gingiva by the “push back” procedure may also be used.

• However, these procedures are associated with alveolar bone loss, prolonged healing by secondary intention and excessive pain and discomfort caused by exposure and denudation of the underlying bone.

• Oswaldo Bergamaschi et al (1993) treated five patients with gingival pigmentation by gingivectomy to remove band like melanin pigmentation. They concluded that gingival resective procedure is not of permanent value, because pigmentation tends to return to baseline values.

Free gingival graft

• Tamizi et al (1996) used free gingival auto graft treatment of pigmentation and obtained successful results.

• Nicholas (1981) reported a case of amalgam tattoo of the labial gingiva in the maxillary anterior region treated by palatal gingival auto graft successfully.

• Esthetic result was not always satisfactory due to color differences between the palatal tissues and the gingiva

• The presence of a demarcated line commonly observed around the graft in the recipient site may itself pose an esthetic problem.

Acellular dermal matrix allograft

• Novaes et al. reported the use of ADMA for elimination of the gingival pigmentation.

• These studies demonstrated the efficacy of the ADMA, with the advantages of reduced surgical time, decreased postoperative complications, unlimited amount of graft material and a predictable and satisfactory esthetic result.

• However, it is expensive and requires clinical expertise.

Electrosurgery• According to Oringer’s “Exploding cell theory, it is predicted

that electrical energy leads to the molecular disintegration of melanin cells of the operated and surrounding sites.

• Thus, electrosurgery has a strong influence in retarding migration of melanin cells.

• However, it requires more expertise. • Prolonged or repeated application of current to the tissues

induces heat accumulation and undesired tissue destruction.• Contact of current with the periosteum and vital teeth should be

avoided.• Hence, it is to be used in light brushing strokes and the tip has

to be kept moving.

CRYOSURGICAL DEPIGMENTATION

• It is a method of tissue destruction by rapid freezing• The cytoplasm of the cells freezes, leading to

denaturation of proteins and cell death. It does not require use of local anesthesia or periodontal dressing, is relatively painless and has shown excellent results lasting for several years.

• The cryotherapy procedure requires a special container for storage of liquid nitrogen.

• The depth of penetration is difficult to control and prolonged freezing may cause excessive tissue destruction.

• The Dip-stick method utilizes a small cotton bud/swab dipped in LN, which can be applied on the pigmented area and maintained in contact for around 20–30 s as described by Tal et al.

• It requires a separate sitting after about 5 days, during which the residual pigmentation, if any, may be removed.

• It is followed by considerable swelling and accompanied by increased soft tissue destruction

• Spray technique is the most popular method using open end cryoprobes i.e. spray tip cone or cylinder.

• In this method, the cryogen is sprayed directly on to the lesion. The spray tip is held 1 cm away from the lesion and a steady spray of liquid nitrogen is directed at the centre of the lesion.

• In the cryoprobe technique, liquid nitrogen is circulated so as to cool the tip of the cryoprobe, which is to be applied on to the lesion.

• It will be not possible to observe immediate tissue changes after application of the cryogen

CRYOSURGERY

Pre-op

Post-op

Liq. N2O

Chemical agents (chemoexfoliation)

• It is a treatment method that destroys the epidermis and/or dermis using a chemical peeling agent.

• A variety of chemical peeling agents are available; phenols, salicylic acid, glycolic acid, trichloracetic acid, etc.

• These agents have been classified into four types: Very superficial, superficial, medium depth and deep, based on their penetration

• Phenol penetrates the subepithelial connective tissue and causes necrosis or apoptosis of melanocytes. It result in incapacity of melanocytes to normally synthesize melanin.

• Phenol does not seem to determine melanocyte destruction; rather, it compromises its activity.

• Hirschfeld reported a series with 20 cases that were treated for melanin pigmentation with the phenol–alcohol method.

• It requires the area to be air-dried before application The phenol pellet is applied and maintained for 1 min and the area needs to be rinsed with 99% alcohol.

ASCORBIC ACID

• Ascorbic acid significantly inhibits tyrosinase activity

LASERS• Lasers combine the advantages of rapid healing of the

scalpel surgery and the minimal bleeding of electrosurgery.• A one-step laser treatment is usually sufficient to eliminate

the pigmented gingiva and does not require a periodontal dressing.

• Easy handling, short treatment line, hemostasis, sterilization effects and excellent coagulation.

• The treated area should be left exposed in the mouth. Few myofibroblasts present in the base of the wound cause minimal contraction and scarring, with little restriction in movement of the soft tissues.

• Emin Essen et al (2004) used CO2 laser for gingival depigmentation. Ablation of the hyperpigmented gingiva was accomplished with minimal carbonization and almost no bleeding and concluded that CO2 laser appears to be safe and effective procedure.

• Yousuf et al (2000) - a semiconductor diode laser and it was effective in removing melanin. Post operative reevaluation showed continuous healing process with the proliferation of squamous epithelial cells.

• Ishikawa et al (2004) The Er. YAG laser -possesses suitable characteristics for oral soft and hard tissue ablation. It had been applied for effective elimination of granulation tissue and gingival melanin pigmentation.

REPIGMENTATION• Repigmentation is described as "spontanoues" and has been

attributed to the activity and migration of cells from surrounding areas..

• Although the exact mechanism of repigmetnation is not known, it is suggested that the melanocytes from normal skin proliferate and migrate into the depigmented areas.

• Further research is needed on gingival repigmentation to study factors affecting the rate and length of time required for reappearance of the pigmented areas.

• It should be noted, however, that the simplicity of the technique prevents permanent damage, unlike many other periodontal treatments, hence deepithelialization can be done repeatedly in the same areas for a number of times.

 

CONCLUSION.

• Gingival melanin pigmentations can occur as a consequence of local, systemic, environmental or genetic factors.

• To ensure treatment success, the potential causative or aggravating agent of the pigmentation should be identified and eliminated, if possible, before the surgical treatment.

• Various techniques are available with some advantages and some drawbacks.

• However, choice of the technique should be dependent on individual preference, clinical expertise and patient affordability.

• More data is required on comparative techniques to ensure the long-term predictability and success.

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