2. INDEX
• INTRODUCTION
• CLASSIFICATION
• ENDOGENOUS PIGMENTATION
• EXOGENOUS PIGMENTATION
• DRUG RELATED PIGMENTED LESIONS
• ASSOCIATED SYNDROMES
• MISCELLANEOUS
- HIV INFECTIONS
- NEVI OF OTA
• DEPIGMENTATION
• WORKUP
3. PIGMENT
• Color or Coloring Agent
NORMAL MUCOSA
• Pale pink to deep bluish purple
sometimes even blackish
4. NORMAL RANGE DEPENDS UPON
Melanogenesis and distribution of melanin
pigment
Keratinization
Depth of epithelization
Vascularity
5. Melanin
= primary pigment producing brown
coloration
• Tyrosine – tyrosinase –melanin- this occurs
in the melanosomes of melanocytes
• Then the melanosomes are transferred from
the melanocyte to a group of keratinocytes
called the epidermal melanin unit
• Variations in skin color is related to the
number of melanosomes, the degree of
melanization, and the distribution of the
epidermal melanin unit
11. EXOGENOUS PIGMENTATION
SOURCE
COLOR
DISEASE PROCESS
SILVER AMALGAM
GREY/
BLACK
TATTOO, IATROGENIC TRAUMA
GRAPHITE
GREY/
BLACK
TATTOO, IATROGENIC TRAUMA
LEAD, BISMUTH,
MERCURY
GREY
INGESTION OF PAINTS, DRUGS
CHROMOGENIC
BACTERIA
BLACK/
BROWN/
GREEN
SUPERFICIAL COLONIZATION
12. PIGMENTED LESIONS
Focal
Diffuse & bilateral
Early onset
-
Adult onset
Systemic
•Addisons
disease
•Heavy
metal
•Kaposi’s
sarcoma
No
systemic
• Drug
induced
• Post infl
ammatory
• Smokers
melanosis
Red-blue-purple
Blue-grey
Brown
Blanching
•Varix
•Hemagioma
Non
•blanching
•Amalgam
Tattoo
•Foreign
Body tattoo
•Blue nevus
•Melanotic
macule
•Pigmented
nevus
•Melanoma
•Melano
acanthoma
•Thrombus
•Hematoma
Adel Kauzman, Marisa Pavone, Nick Blanas. Pigmented Lesions of the Oral Cavity: Review, Differential Diagnosis, and
Case Presentations. Journal of the Canadian Dental Association.
November 2004, Vol. 70, No. 10
13. DRUG RELATED PIGMENTED LESIONS
QUININE & OTHER ANTIMALARIAL DRUGS
MINOCYLINE
ORAL CONTRACEPTIVES
ASSOCIATED SYNDROMES
PEUTZ JEGHER‘S SYNDROME
ADDISON‘S DISEASE
ALBRIGHT SYNDROME
NEUROFIBROMATOSIS
MISCELLANEOUS LESIONS
HIV INFECTION
HAIRY TONGUE
NEVI OF OTA
14. CLINICAL CLASSIFICATION OF ORAL PIGMENTATION
COLOR
BLUE/
PURPLE
SOLITARY
FOCAL
VARIX,
HEMANGIOMA
DIFFUSE
HEMANGIOMA
BROWN
MELANOTIC
MACULE,
NEVUS
MELANOMA
ECCYMOSIS
MELANOMA
DRUGS
HAIRY TONGUE
GREY/
BLACK
AMALGAM
GRAPHITE
NEVUS
AMALGAM
HAIRY TONGUE
MELANOMA
MULTIFOCAL
KAPOSI‘S SARCOMA
HEREDITARY
HAEMORRAGIC
TELANGIECTASIA
PHYSIOLOGIC
LICHEN PLNUS
DRUG INDUCED
ADDISON‘S
PETECHIAE
PEUTZ JEGHER‘S
ALBRIGHT‘S
HEAVY METAL
INGESTION
15. ENDOGENOUS PIGMENTATION
ORIGINATES FROM WITHIN THE BODY
A) MELANIN PIGMENTATION: ‗MELAS‘– BLACK
Endogenous, non haemoglobin derived brown black pigment
formed when the enzyme tyrosinase mediated by MSH from
anterior pituitary catalyses the oxidation of tyrosine to
dihydroxyphenylalanine in melanocytes that subsequently transfer
the melanin into adjacent cells.
COLOR— Pale Brown to Black depending on the amount of
melanin
•
Number of melanocytes are equal in fair and dark skinned
people, only the level of melanogenesis varies
16. ORAL MELANOACANTHOMA
• It another unusual, benign, melanocytic
lesion that is unique to the mucosal
tissues.
• Its an innocuous melanocytic lesion
that may spontaneously resolve, with
or without surgical intervention.
• Reactive in nature
• Almost exclusively occurs in blacks &
has a female predilection.
18. BROWN MELANOTIC LESIONS
ORAL MELANOTIC MACULE :
Oral counterpart
Usually a solitary lesion occurs mostly in light skinned people
Lesion is well circumscribed and grey, brownish black
Majority being less than 1cm in diameter & remains constant
in size
Most common site is lower lip followed by gingiva, buccal
mucosa and hard palate
Asymptomatic and don't tend to become malignant
Occur equally in men and women, rarely in children
Pigmentation is due to increase in melanin pigment by basal
cell melanocytes without increase in melanocytes
19. HISTOPATHOLOGICALLY :
Normal epithelial layer with basal cell containing numerous melanin
pigment granules without proliferation of melanocytes
DIFFERENTIAL DIAGNOSIS:
Melanoplakia,
Amalgam Tattoo,
Nevi,
Focal
Ecchymosis,
Early superficial spreading melanoma
20. • Biopsy
• melanin-containing dendritic cells are seen to
extend high into a thickened spinous layer.
melanoacanthoma
• Surgery –no predisposition to melanoma
• Myxoma syndrome-soft tissue myxoma +
endocrinopathy (autosomal dominant)
• Laugier –Hunziker syndrome/phenomenonacquired disorder + lips, oral, finger+
subungual melanocytic streaks
21. NEVOCELLULAR AND BLUE NEVI :
Unlike ephelis or melanotic macule, nevi are due to benign
proliferations of melanocytes
Histologically they are of two types
i) NEVOCELLULAR NEVI
JUNCTIONAL NEVI
Resides at the junction of epithelium and basement membrane.
Flat and brown and have regular round or oval outline.
Arises in early in life
INTER MUCOSAL NEVI
Melanocytes lose their continuity with surface epithelium &
become localized to connective tissue.
22. • Benign proliferations of melanocytes
Nevus cells - localized to basal layer- junction of
epithelium and basement membrane+
connective tissue
Minimal proliferation
Macular, flat and brown, regular outline
Junctional nevi
23. Melanocytes form clusters at the
epitheliomesenchymal junction
proliferate down into the connective tissue
Dome shaped appearance
Compound nevi
Lose their continuity with surface epithelium+
cells become localized - deeper connective tissues
Intradermal nevi (skin)
Intramucosal (mouth)
26. II) BLUE NEVI :
Not derived from basal layer.
Blue in color because the melanocytic cells resides deep in connective tissue
and overlying vessels dampens the brown colorations and yield a blue tint.
Differ morphologically from nevocellular by being more spindle shaped.
May be seen at any age
May be macular or nodular.
Both nevocellular and blue nevi are less than 0.5 cm in size.
Occur most commonly on gingiva or hard palate, also on buccal mucosa and
lips.
Biopsy- MUST.
Treatment – Surgical Excision.
27.
28. COMPOUND NEVUS
• Round oval shape, well- demarcated,
• Smooth – bordered,
• May be dome–shaped or papillomatous;
colors range from flesh colored very dark
brown with individual nevi being relatively
homogeneous in color.
31. HISTOPATHOLOGY OF NEVI
Microscopically, the nest of
nevi cells is laden with melanin and
is seen below the basal cell layer
(intramucosal nevus), at the junction
of basal layers (junctional nevus), in
both sites (compound nevus), or
deep in the connective tissue (blue
nevus).
Excision of these lesions is
required to rule out other serious
pigmented lesions.
36. MALIGNANT MELANOMA
Melanomas arises from neoplastic transformation of either
melanocytes or nevus cells
Predisposing factors :
- sunlight, degree of nature pigmentation and precancerous
lesions such as junctional nevi
Clinically appears as macular or nodular,
Coloration varies ranging from brown black to black with zones
of depigmentation with jagged and irregular margins
Commonly occurs on anterior labial gingiva and anterior aspect
of hard palate
39. RISK FACTORS FOR CUTANEOUS
MELANOMA
•
•
•
•
•
•
•
•
•
Large number of typical moles
Atypical moles
Family H/O melanoma
Prior melanoma
Freckling
H/O repeated blistering sunburns
Ease of sunburning
Inability to tan
Light hair and blue eyes
40. Oral melanomas are extremely rare
• May be focal or diffuse
Occur as macular brown or black plaques with
irregular margins
• Biopsy is required for diagnosis
41. SUSPICIOUS CHANGES IN NEVI
SYMMETRY
ORDER IRREGULARITY
OLOR VARIEGATION
IAMETER GREATER THAN 0.6 cm
LEVATION
Gondivkar SM, Indurkar A, Degwekar S, Bhowate R. Primary oral malignant melanoma- A case
report and review of literature. Quitessence International. 2009; 40(1): 41-46.
42.
43. “Lentigo maligna melanoma” or “hutchinson’s
freckle”
Facial skin lesions – atypical melanocytic
hyperplasia /melanoma in situ.
Melanocytic tumor cells spread laterally and
superficially
Radial growth phase
Good prognosis
Nodular-deeper invasion-vertical growth-poor
44. • Breslow method, by which millimeter
depths of invasion are measured (depth
correlating with prognosis
• Oral mucosa -anterior labial
gingiva, anterior hard palate.
• They may be focal or diffuse and mosaic
45.
46. Staging
• Stage I-primary tumor only (T any No Mo)
• Level I- melanoma in situ without evidence of
invasion/microinvasion present
• Level II-invasion upto lamina propria
• Level III- deep skeletal tissue-muscles
• Stage II- metastatic to regional lymph node (T any
N1 Mo)
• Stage III- distant node metastasis (T any Nany M1)
Gondivkar et al. Primary malignant melanoma-case report & review of
literature.quitesscence int vol 7; jan 2009
47. • The American Joint Committee on Cancer does
not have published guidelines for the staging of
oral malignant melanomas. Most practitioners use
general clinical stages in the assessment of oral
mucosal melanoma, as follows:
• Stage I - Localized disease
• Stage II - Regional lymph node metastasis
• Stage III - Distant metastasis
• Tumor thickness and lymph node metastasis are
reliable prognostic indicators. Lesions thinner
than 0.75 mm rarely metastasize, but they do have
metastatic potential. On occasion, a small primary
lesion is discovered after an enlarged lymph node
is found to harbor melanoma.
48. Tumor Depth
<1 mm
1 - 2 mm
2.1 - 4 mm
>4 mm
Approximate 5
year survival
95-100%
80-96%
60-75%
50%
49. DDx
CONDITION
DISTINGUISHING CHARACTERISTICS
Seborrheic keratosis
“Stuck-on appearance”, symmetric often multiple
Traumatized or irritated nevus
Returns to normal appearance within 7-14 days
Pigmented basal cell carcinoma
Waxy appearance, telangiectasias
Lentigo
Prevalent in sun-exposed skin, evenly pigmented,
symmetric
Blue nevus
Darkly pigmented from dermal melanocytes, no h/o
change
Angiokeratoma
Vascular tumors, difficult to distinguish from
melanoma
Traumatic hematoma
May mimic melanoma but resolves in 7-14 days
Venous lake
Blue, compressible, found on ears and lips
Hemangioma
Compressible, stable
Dermatofibroma
Firm growths of fibrous histiocytes, ‘button-hole’
when pinched
Pigmented actinic keratosis
Sandpapery feel; sun-exposed area
51. Treatment protocol for malignant melanoma
Surgery
Radiotherapy
Surgery and combined therapy
Chemotherapy
Curative chemotherapy
Dimethyl triazeno imidazole
carboxamide (DTIC)
Nimustine hydrochloride
(ACNU)
Vincristine (VNC)
Immunotherapy
Others
Cancer/testis antigens
(CTAs) expression
profile for vaccine
development
Gene therapy
OK432 (a biologic
response modifier)
IL-2
Palliative chemotherapy
Dacarbazine
Platinum analogs
Nitrosoureas
Microtubular toxins
Other cytokines
Pai A, Prasad S, Patil BA, Dyasanoor S, Hegde S. Oral pigmentation: Case report and review of
malignant melanoma with flow charts for diagnosis and treatment. General Dentistry. 2012;
410-416.
52. MELANOMA MEDICAL THERAPY
• Medical therapy is not often beneficial for oral melanoma.
Chemotherapeutic medications for the treatment of oral
melanoma do not reliably reduce the tumor volume.
• Aggressive surgery remains the treatment of choice.
• Interferon, dacarbazine, and BCG vaccine have been tried
with marginal and unpredictable results.
• Drug therapy (dacarbazine), therapeutic radiation, and
immunotherapy are used in the treatment of cutaneous
melanoma, but they are of questionable benefit to patients
with oral melanoma. Dacarbazine is not effective in the
treatment of oral melanoma; however, dacarbazine
administration in conjunction with interleukin 2 may have
therapeutic value.
53. Treatment of metastatic melanoma
Single-agent
chemotherapy
Multi-drug
combination
Nitrosourea +
vinca alkaloids
+ platinum
compounds +
dacarbazine
Immunotherapies
INF-α, IL-2,
combination of
INF-α + IL-2
Biochemotherapy
Dacarbazine +
INF-α + IF-2
Others
Cisplatin
Carboplatin
Vinblastine
Vindesine
Pai A, Prasad S, Patil BA, Dyasanoor S, Hegde S. Oral pigmentation: Case report and review of
malignant melanoma with flow charts for diagnosis and treatment. General Dentistry. 2012;
410-416.
Dacarbazine
Temozolomide
(DTIC analog)
Nitrosoureas
Fotemustine
54. Newer agents used for treating melanoma
Lenalidomide (a thalidomide derivative)
Thalidomide + temozolomide
Taxane ABI-007
Sorafenib
Anti-Bcl-2 antisense
Anti-Bcl-2 antisense + dacarbazine
MEDI-522 humanized monoclonal antibody
Cytotoxic T-lymphocyte antigen-4 (CTLA-4)
Ipilimumab with or without dacarbazine combination
Pai A, Prasad S, Patil BA, Dyasanoor S, Hegde S. Oral pigmentation: Case report and review of
malignant melanoma with flow charts for diagnosis and treatment. General Dentistry. 2012;
410-416.
55. PHYSIOLOGICAL PIGMENTATION
Due
to greater melanocyte activity rather than a greater
number of melanocytes.
This
type of pigmentation is symmetric and persistent and
does not alter normal archaistic such as gingival stippling
Blacks,
Asians, dark skinned caucasians most frequently
show diffuse melanosis of facial gingiva
In
addition, lingual gingiva & tongue may exhibit multiple
diffused and reticulated brown macule
Seen in patients at any age, no gender predilection
56.
No further attention is required, in case of
doubt, it should be excised and sent
for histopathological study.
Lingual gingiva & tongue may exhibit multiple, diffuse &
reticulated brown macule
Basilar melanosis, evolves in childhood
Does not alter normal architecture
No change in intensity
Multifocal or diffuse pigmentation
investigated-endocrinopathic disease.
Degree of intraoral
cutaneous coloration
pigmentation
of
–may
recent
not
onset
–
correspond
57. SMOKER’S MELANOSIS
Diffuse
macular melanosis of buccal mucosa, palate, lateral
tongue, floor of the mouth is usually seen among the smokers
Tobacco smoke products stimulates the melanocytes and
causes hyperpigmentetion. increased production of
melanin, which may provide a biologic defence against the
noxious agents present in tobacco smoke.
Clinically
lesions are brown, flat & irregular some are
geographic or map like in configuration
Intensity of pigmentation appears to be time and dose related
Histologically basilar melanosis with melanin is observed
58. • Brown, flat, and irregular, geographic or
maplike
• basilar melanosis with melanin incontinence
• No premalignant potential
• Rx for Cosmetics
59.
60. Drug induced Melanosis
Drugs associated with oral mucosal pigmentation
• Antimalarials: quinacrine, chloroquine,
• hydroxychloroquine
• Quinidine
• Zidovudine (AZT)
• Tetracycline
• Minocycline
• Chlorpromazine
ETIOLOGY
The pathogenesis of drug-induced pigmentation
varies, depending on the causative drug. involve
accumulation of melanin, deposits of the drug or one
of its metabolites, synthesis of pigments under the
influence of the drug or deposition of iron after
damage to the dermal vessels.
• Quinidine: Mucosal discolouration is described as blue–grey or
blue–black in most cases only the hard palate is involved
62. Oral contraceptives &pregnancy are associated
with hyperpigmentation of facial skin- periorbital
& perioral region -melasma or chloasma.
Flat lesions, nail bed & skin
63. ENDOCRINOPATHIC PIGMENTATION
Bronzing of skin
and patchy melanosis of the oral mucosa are signs of
Addison’s Disease and Cushing’s Syndrome
Cause-hyperpigmentation is the oversynthesis of a ACTH hormone with
melanocyte stimulating properties
In both, the skin may appear tanned and buccal mucosa may be
The changes are due to accumulation of melanin granules
Serum steroid and ACTH will aid in diagnosis.
blotchy.
64. Addison’s disease
Granulomatous infection of cortex/ autoimmune cortical
destruction
Adrenocortical insufficiency
Steroid hormones decrease
Feedback loop stimulated
Excess secretion of ACTH
Hypotension and hypoglycemia,stimulation of MSH
67. PEUTZ JEGHER’S SYNDROME
Autosomal
dominant condition associated with intestinal
polyposis and pigmentation of oral mucosa, lips, skin.
Pigmentation
is distinctive with lesions on anterior part of
tongue, buccal mucosa
Lesions are focal, multiple, melanotic brown macules less than
0.5cm in diameter
68. Peutz-Jeghers
• Characterized by
hyperpigmented macules
on the lips and oral
mucosa and polyposis of
the small intestine
• Dark brown or black
macules appear typically
on the lips, especially the
lower lip, in infancy or
childhood
• Similar lesions may appear
on buccal mucosa, tongue,
gingiva, and genital
mucosa
• Macules may also occur around
the mouth, on the central face,
backs of the hands, especially
the fingers, and on the toes and
tops of the feet.
• Associated polyposis involves
the small intestine preferentially.
• But, hamartomatous polyps of
the stomach and colon may
occur.
• Symptoms of hamartomas of the
small intestine may cause
repeated bouts of abdominal
pain and vomiting, and
intussusception
69. Peutz-Jeghers Syndrome
• Cosmetic Rx of labial
macules has been
accomplished with the
use of a 694-mm ruby
laser
• incidence of
malignancy within the
polyps is 2-3%
• Incidence of GI
malignancy is low, but
increased incidence of
other kinds of cancerbreast, and gynecologic
malignancies in women
• Syndrome is inherited
and transmitted as a
simple mendelian
dominant trait
• Sporadic noninherited
cases may occur
• The gene (STK11/LKB1)
has been localized to
19p13.3
• 19p13.3 is believed to
be a tumor suppressor
gene
70. Peutz-Jeghers Syndrome
• Cronkhite-Canada
syndrome should be
considered in DDx
• Characterized by
melanotic macules on the
fingers and
gastrointestinal polyposis
• Also generalized , uniform
darkening of the
skin, extensive
alopecia, and
onychodystrophy
• The polys that occur are
usually benign adenomas
and may involve the whole
GI tract
• A protein-losing
enteropathy may develop
and is associated with the
degree of intestinal
polyposis
• Onset is after age 30 yrs
• Sporadically occurring,
benign condition
• Hypogeusia is the
dominant initial symptom
• Diarrhea and ectodermal
changes may follow
• 75% of cases have been
reported in Japan
74. •
•
•
•
Café au Lait Pigmentation
Color of coffee with cream
Small ephelis-like macules to broad diffuse
Late childhood and multiple
Neurofibromatosis- nodular and diffuse
pendulous neurofibromas - skin and (rarely)
in the oral cavity
• Basilar melanosis without melanocyte
proliferation
• McCune Albright syndrome
75. DISEASES COMMONLY ASSOCIATED WITH CAFÉ AU LAIT PIGMENTATION
Ataxia-telangiectasia
Neurofibromatosis type 1, Noonan’s
syndrome
Familial café au lait spots
Neurofibromatosis type 2
Familial cavernous malformation
Nijmegen breakage syndrome
Fanconi’s anemia
Noonan’s syndrome
Hereditary nonpolyposis colorectal
cancer
Ring chromosome 7 syndrome
Idiopathic epilepsy
Ring chromosome 15 syndrome
Johanson-Blizzard syndrome
Ring chromosome 17 syndrome
McCune-Albright syndrome
Russell-Silver syndrome
Microcephalic osteodysplastic
primordial dwarfism
Tuberous sclerosis
Neurofibromatosis type 1
Turcot’s syndrome
76. ALBRIGHT’S SYNDROME/CAFE AU LAIT PIGMENTATION
Polyostotic fibrous dysplasia of bone is of two
types
i) Albright‘s Syndrome
- Fibrous dysplasia
- Café au lait spots
- Endocrinal disturbances
ii) Fibrous
Dysplasia with CAFE AU LAIT spots
(Jaffe‘s spots)
- irregular, pigmented melanotic spots varies from small
macule to broad diffuse lesions
- light brown in color and occur rarely in oral cavity
•
Microscopically Café au lait spots represents with basilar
melanosis without melanotic proliferation
77. NEUROFIBROMATOSIS
• Individuals with 6 or more large (>1.5 cm in
diameter) café-au-lait macules should be
suspected of possibly having
neurofibromatosis.
• 2 forms- NF1 (von recklinghausen’s disease),
NF2 (acoustic neurofibromatosis).
• Axillary freckling (Crowe’s sign) accompanied
by p/o 6 or more macules is pathognomonic
for NF 1.
78. Pigmented Lichen Planus
• Erosive lichen planus + diffuse melanosis
• Increased production of melanin by the
melanocytes
• Accumulation of melanin laden macrophages
in the superficial connective tissue
79. PIGMENTED BASAL CELL CARCINOMA
Papular border
may have central ulceration.
Usually solar exposed surface in older patients
Patients
usually has dark brown eyes and dark
brown or black hair.
80. NEUROECTODERMAL TUMOUR
OF INFANCY
Benign neoplasm composed of premature pigment producing
cells which have their origin in neural crest
Infants under 6 years of age
Occurs mainly in maxilla
Lesions present as non-ulcerated darkly pigment mass
TREATMENT—Surgical Excision
81. Laugier-Hunziker Pigmentation
• Acquired, idiopathic, macular
hyperpigmentation of the oral mucosal tissues
specifically involving the lips and buccal
mucosae.
• Up to 60% of affected patients also may have
nail involvement, usually in the form of
longitudinal melanotic streaks w/o incidence
of dystrophic change.
82. Laugier-Hunziker Pigmentation
• Patients typically present with
multiple, discrete, irregularly shaped brown or
dark brown oral macules.
• Individual macules are usually no more than 5
mm in diameter.
• In rare instances, the lesions may coalesce to
produce a diffuse area of involvement.
83. Laugier-Hunziker Pigmentation
• Diagnosis of exclusion
• The pigmentation may be esthetically
unpleasing, but it is otherwise innocuous.
• Rx is not indicated but laser and cryotherapy
have been used with some success.
86. • HAEMANGIOMA
Raised, nodular, sometimes flat,
macular & diffuse particularly on the
facial skin and are called as
PORT WINE STAINS
Most commonly tongue and lip mucosa
On tongue they are multinodular & bluish red in color
May occur in childhood, adults or elderly persons
Depending on the depth of vascular proliferation
within the oral sub mucosa, the color of lesion varies.
- If close to overlying epithelium- Reddish Blue
- If deeper in connective tissues - Deep Blue
87. Port wine stain involves facial skin is flat &magenta I
colour.
Skull radiograph: vessel wall calcification yield
bilamellar radiopaque tracks
“Tram line calcification”
• Bubbly or honeycomb trabeculated appearance
• Overlying cortex is expanded and thinned, but
complete cortical disruption and invasion into soft
tissue are not present
Diascopy
Intraluminal clots form- palpable and do not blanch
89. • Calcified nodules/phleboliths- radiographically
evident
• 85% of childhood-onset hemangiomas
spontaneously regress after puberty
90. TREATMENT
• Conventional surgery, laser surgery, cryosurgery
• Sclerosing agents - 1% sodium tetradecyl sulfate
(intralesional injection)- .05 to 0.15 ml/cm3
• Absolute ethanol has also been used
• Cutaneous port-wine stains - subcutaneous tattooing or by
argon laser
• If larger feeder vessels are present, embolization using
metal coils may significantly reduce arterial blood flow.
92. Histopathology
• Cavernous -large dilated vascular channels
lined by endothelial cells without a muscular
coat
• Cellular/capillary-endothelial
proliferation, vascular lumina are very small
• Intramuscular –deep lesions
93. Sturge Weber syndrome
• Encephalotrigeminal angiomatosis
• Port wine stain (nevus flammeus) –
leptomeninges of cerebral cortex
• Mental retardation, hemiparesis, seizures
• Ocular lesions
• Calcification
• d/d- angioosteohypertrophy syndrome
Port wine stain + varices + hypertrophy of bone
94.
95. Hemangioma
Vascular malformation
Description
Abnormal endothelial
cell proliferation
Abnormal blood vessel
development
Elements
Includes no. of capillaries Mix of artery, vein,
capillaries (AV shunt)
Growth
Rapid congenital, ceases
puberty
Grows throughout
Boundaries
Circumscribed; rarely
affects bone
Poorly circumscribed
Thrill & bruit
absent
present
Involution
Spontaneous
Does not involute
Resection
Easy
Difficult, surgical
haemorrhage
Recurrence
Uncommon
Common
96. Blue rubber bleb nevus syndrome
• Bean’s syndrome
• Multiple small & large cavernous
hemangioma
• Skin & GI tract + mouth
• Childhood/young adulthood
• Life threatening-blood loss-> anemia & Fe
deficiency
97.
98. VARICES
Pathologic dilatation of veins or venules
Ventral tongue – most common site
―caviar tongue‖
Blue,
red, purple elevations that course over the
ventrolateral surface on the tongue with extension
anteriorly
Painless and not subject to rupture and haemorrhage
Varix
resembles hemangioma both clinically and
histologically but differs only in age of onset and
etiology
100. ANGIOSARCOMA
Malignant
the body
vascular neoplasm can arise any where in
Oral cavity extremely rare
If superficial -
red / blue / purple
If deep – nodular tumour
Can arise from blood or lymph vessels
Prognosis is poor
Treated by radical excision
101. KAPOSI’S SARCOMA
Tumor of putative vascular origin
Most commonly on hard palate and facial gingiva
Oral tumours – red , blue , purple
Skin tumours – localize in dorsal aspect of feet
and
great toe
2 forms- elderly men (oral mucosa & skin of lower
extremities), children in equatorial africa (lymph
nodes)– aggressive & lethal
In HIV seropositive patients, the oral lesions are flat red
macules of variable size & irregular configuration and
later increases in size to become
nodular growth
HHV-8
102. KAPOSI SARCOMA + HIV
• Oral lesions - posterior hard palate
• Begin as flat red macules of variable size
and irregular configuration
• Numerous isolated and coalescing plaques
• Eventually- increase in size -> nodular
growths- entire palate, protruding below
the plane of occlusion
• Facial gingiva
103. DDx- pyogenic granuloma, giant cell granuloma
Bacillary angiomatosis-bartonella henselae-rare
in oral mucosa
Early stage-no Rx; later-electrocautery/excision
Intralesional 1% vinblastine sulfate- less post
injection pain- multiple biweekly injections
Proliferating spindle cells with mild
pleomorphism + plump endothelial cells
extravasation of erythrocytes + hemosidrin
granules
104. HEREDITARY HEMORRHAGIC TELANGIECTASIA
Rendu-Osler-Weber syndrome
Multiple round or oval purple papules measuring less
than 0.5cm in diameter
Genetically transmitted disease
Over a hundred such purple papules on vermillion or
mucosal surface of lips, tongue & buccal mucosa
105. • Same lesion in nasal mucosa-epistaxis
• differential diagnosis-petechial
hemorrhages (platelet disorder)macular, red/blue, not genetic
• CREST syndrome
TREATMENT :
• Selective embolization
• electrocautery
(series of procedures)
using local anesthesia
107. ECCHYMOSIS
Traumatic
ecchymosis – most commonly on the lips
and face
Immediately after the trauma, erythrocytes extravasates
into the submucosa
Clinically appear bright red macule or swelling if a
hematoma forms
The lesion then assume a brown discoloration within
few days after haemoglobin is degraded to hemosiderin
TREATMENT :
Observation for 2 weeks
109. DDx for petechiae and ecchymosis
• Solitary- H/O trauma, change color from
bluish-brown to green to yellow and then
finally diassapear within 4-5 days.
• Do not blanch on pressure (as compared
to telangiectasias)
• Multiple:
–
–
–
–
–
Trauma from fellatio
Trauma from severe coughing
Trauma from severe vomiting
Prodromal sign of infectious mononucleosis
Prodromal sign of hemostatic disease
110. HAEMOCHROMATOSIS
Disorder
in which excess iron is deposited into the body and
results in eventual sclerosis and dysfunction of the tissues/organs
involved
Iron is then stored as HEMOSIDERIN AND FERRITIN
Cause of pigmentation is haemochromatosis i.e. an increase in
melanin production and not the deposition of hemosiderin in the
skin
This is due to increase in ACTH
Oral mucosal lesions - Brown to Grey, diffuse macules
Usually seen on palate and gingiva
HISTOPATHOLOGICALLY (lower labial gland Bx)- Basilar
melanosis
DIAGNOSIS – Biopsy – stained with PRUSSIAN BLUE
– Iron levels elevated in serum
Also called as BRONZE DIABETES
111. JAUNDICE
OCCUR DUE TO LIVER DISORDERS
CAUSES
BILE
IMPROPER METABOLISM OF
PIGMENTS
ASSOCIATED
WITH
DEPOSITION OF BILE PIGMENTS IN SKIN
AND ORAL MUCOUS MEMBRANE
112. CAROTENE
CAROTENEMIA
Chronic excessive level of carotene pigments in the
tissues
Long and continued consumption of large amounts of
food like carrots, egg yolk
Disturbance in metabolism of these food to produce
Vitamin A may also increase carotene level
Orange yellow pigmentation of mucosa
No treatment is required other that dietary
modifications
114. EXOGENOUS PIGMENTATION
GREY / BLACK / GREEN
IMPREGNATION OF FOREIGN SUBSTANCES
ACCIDENTAL
IMPREGNATION
IATROGENIC
IMPREGNATION
INCREASED EXOGENOUS PIGMENTATION
115. ACCIDENTAL IMPREGNATION
In road accident small bits of stone, gravel and send
get impregnated in the oral tissues, they, if removed
completely cause discoloration
Charcoal containing dentrifrices also produce black,
permanent discoloration due to constant use
117. AMALGAM TATTOO
Small pieces of amalgam can break off, impregnate into
gingival and oral tissues during fabrication and removal of
restoration or extrication of teeth
The lesions are macular and blushing gray of even black and
Usually seen in gingival and basement membrane and palate
Found in the vicinity of teeth with large amalgam rest or
crowned teeth
D/D- nevus , early melanoma
119. GRAPHITE TATTOO
Occurs
on the palate one to treatment implantation
of lead pencil
Lesions are macular, focal gray or black
Microscopically resembles amalgam.
120. INCREASED EXOGENOUS POISONING
Heavy
metal poisoning – Arsenic, bismuth, lead &
mercury
Heavy
metal and its excess leading to oral
manifestations is seen as most commonly in the
occupational hazards
121. INCREASED EXOGENOUS POISONING
Ingested pigments tend to extravasate from vessels in
foci of increased capillary permeability such as inflamed
tissues.
Free
marginal
gingiva-gingival
cuff,
resembling
eyeliner-gray-black app
Behavioral
changes,
intestinal pain.
neurologic
disorders,
and
122. MERCURALISM
PINK DISEASE/
SWIFT DISEASE/
ACRODYNIA
Potential occupational hazards for dentists and dental team mostly
arising from improper use of amalgam alloy
MECHANISM OF ACTION
Short chain alkyl and methyl mercury penetrate the erythrocyte
membrane and bind to hemoglobin
ORAL MANIFESTATIONS
Flow of ropy viscid saliva
Hot mouth, burning sensation, metallic taste
Diffuse greyish pigmentation in the form of a line/band along the
alveolar mucosa
Color: diffuse grayish pigmentation of alveolar mucosa, gums are
deeper hue than normal, teeth may exfoliate due to marked
periostitis.
123.
SYSTEMIC FINDINDS
Diarrhoea, headache, insomnia, depression, Renal symptoms,
Tremors
TREATMENT
Systemic- Bed rest, Diet control
Oral – Atropine & Belladona to lessen the salivary flow
Administration of BAL (British anti-lewisite)& dimercaprol
124. LEAD POISONING
(PLUMBISM)
Caused by lead from exhausts, paints glazed cooking vessels,
ointments, batteries.
Irrespective of the absorption pathways (Elementary tract or
lungs), lead is taken up by circulating erythrocytes and bound
to reactive sulfhydryl group of proteins and transmitted to soft
tissues
In red cells inhibit enzymes associated with haemoglobin
synthesis
-
Metallic taste, excessive salivation and dysphasia are oral
symptoms
A lead line (grey black) is present along gingival margin
125. BISMUTH POISONING
Medicinal use of bismuth in treatment of syphilis
A blue black bismuth line along gingival margin without
symptoms
Metallic taste with burning sensation
Tongue is frequently sore and enlarged
Maintain oral hygiene
126. ARSENIC POISONING
Industrial exposure, accidental or intentional poisoning
Oral lesions are externally painful and are deep red in color
Chronic gastritis and collitis are frequently the only symptoms
with occasional keratosis
Arsine gas combines with globin chain of haemoglobin in
RBCs to produce severe anemia, haemoglobinuria and
hematuria with in 3-4 hours of ingestion.
127. ARGYRIA
Permanent discoloration of skin and mucous membrane resulting
from local or systemic absorption of silver components
Bluish grey pigmentation is seen
Skin is slate grey, violet
or cyanotic
131. SELF INFLICTED WOUNDS WITH
COLORED PENCILS
The prognostic evaluation of the tattooing is based on
the chemical composition, solubility and quantity of
the coloring material
The acid base color materials usually present in
colored pencils (e.g. methyl blue, methyl violet &
others) are water soluble and used in food
manufacture (e.g. ink stamps for meat).
They tend, because of their water solubility, to expand
rapidly but also resorb and disappear rapidly.
132. RITUAL, DELIBERATE TATTOOING
Today, as in the past, decorative tattooing with
paint, soot,& metallic pigments is in fashion with
youths of certain population groups.
On the oral mucosa these findings are rare
In young Africans groups, there are also certain
ritual tattoos of the gingiva.They are considered
as Beauty marks.
For this purpose, soot obtained from burned wool
soaked in oil into oral mucosa using needles
bundles. The soot particles introduced in this
manner create a lasting darkening of the gingiva
which fades only after many years
134. HAIRY TONGUE
Involves dorsum,especially middle and posterior one third of
the tongue
Papillae are elongated which becomes pigmented
1) Colonization of chromogenic bacteria that imparts a variety
of colors ranging from green,brown,black
2) Various foods – Coffee, Tea
TREATMENT :
Patient is advised to brush the tongue and keep it clean.
135. NEVI OF OTA
Originally described by OTA and TANINO in 1939
Hematoma of dermal melanocytes
Clinically blue or grey speckled coalesced macules
or patches on the face
May be congenital or acquired
Occurs within the distribution of ophthalmic or
maxillary branches of trigeminal nerve
Usually unilateral but sometimes bilateral
May involve ocular or oral mucosal surfaces
136.
Most frequently in Asian population
with estimated prevalence of 0.2 – 0.6% in Japanese
Sex : Male : female 1 : 4.8
Age :
- First peak of onset occurs in infancy with as many as
50% of nevus of ota cases at birth or shortly after
- Second peak of onset during adolescent
- Cases have been reported in older patients also
•
HISTOPATHOLOGY
Increased dermal melanocytes with surrounding fibrosis and
melanophages
138. VITILIGO
• Vitiligo is a relatively common, acquired,
autoimmune disease that is associated with
hypomelanosis due to destruction of
melanocytes.
• Pathogenesis is multifactorial –genetic and
environmental.
• There maybe a single nucleotide
polymorphism in a vitiligo-susceptibility gene
that is also associated with susceptibility to
other autoimmune diseases, including
diabetes type 1, systemic lupus
erythematous, and rheumatoid arthritis.
139. • Variable clinical presentation.
• Focal areas of depigmentation or entire segment
on one side of the body maybe involved.
Occasionally, vitiligo universalis.
• Vitiligenous lesions often present as wellcircumscribed, round, oval or elongated, pale or
white-colored macules that may coalesce into
larger areas of diffuse depigmentation.
• Any age, before 3rd decade usually.
• No sex predilection.
• May also arise in patients undergoing
immunotherapy for malignant melanoma.
140. • Rarely affects the intraoral mucosal
tissues.
• However, hypomelanosis of the inner and
outer surfaces of the lips and perioral skin
maybe seen in upto 20% of patients.
141.
142. • A case of perioral leukoderma simulating
vitiligo developed in a 25-year-old woman. A
patch test to cinnamic aldehyde (present in a
toothpaste which the patient was using) was
positive; depigmentation was observed at the
patch test site three months after initial
application.
Mathias CG, Maibach HI, Conant MA. Perioral leukoderma simulating vitiligo from use
of a toothpaste containing cinnamic aldehyde. Arch Dermatol. 1980 Oct;116(10):11723.
143. • Microscopically, there is complete l/o
melanocytes and melanin pigmentation in
basal cell layer.
• Fontana Masson stain will confirm a/o
melanin.
NORMAL
VITILIGO
144. MANAGEMENT
• Topical corticosteroids
• Topical/systemic photochemotherapies
(PUVA)
• Medicinal depigmentation- cutaneous
bleaching for unified skin color.
• Labial vitiligo is more resistant to Rx.
• Surgical- autologous epithelial grafts,
punch grafting, micropigmentation.
146. Differential Diagnosis of Oral Pigmented Lesion
1. Full medical and dental history, the history should include the
onset and duration of the lesion, the presence of associated skin
hyperpigmentation the presence of systemic signs and
symptoms ( e.g malaise, fatigue, weight loss) and smoking
habits.
2. Extra oral and intra oral examinations. Pigmented lesions on the
face, perioral skin and lip should be noted. The number,
distribution, size, shape and colour of intraoral pigmented
lesions should be assessed.
3. Investigations such as diascopy test, radiography, biopsy and
laboratory investigations such as blood test can be used to
confirm a clinical impression and reach a definitive diagnosis.
147. RACIAL/PHYSIOLOGIC
PIGMENTATION
NO ATTRIBUTABLE
FACTORS OR PATHOLOGY
NON-PHYSIOLOGIC
PIGMENTATION
HISTORY
MEDICAL HISTORY
HISTORY OF SMOKING,
TOBACCO USE, PAAN
CHEWING, SMOKER’S
MELANOSIS
H/O OF FILLINGS
(AMALGAM TATTOO)
Pai A, Prasad S, Patil BA, Dyasanoor S, Hegde S. Oral pigmentation: Case report and
review of malignant melanoma with flow charts for diagnosis and treatment. General
Dentistry. 2012; 410-416.
148. MEDICAL HISTORY
If negative, consider
Positive for
Inflammatory conditions (LP)
Bleeding history
Vascular lesions
Endocrine disorders
History of intestinal polyposis
Other syndromes (LaungierHunziker, McCune-Albright,
PTEN hamartoma tumor)
HIV
Metal ingestion/toxicity
History of drug ingestion
Follow-up
Benign
pigmentations
Melanotic nevi
Melanoacanthoma
Melanotic macules
Malignant
melanoma
Diagnosis justified on history
If yes, treat
accordingly
If benign,
treat if necessary
If no, biopsy
If malignant,
treat immediately
Pai A, Prasad S, Patil BA, Dyasanoor S, Hegde S. Oral pigmentation: Case report and
review of malignant melanoma with flow charts for diagnosis and treatment. General
Dentistry. 2012; 410-416.
149. Laboratory Studies
• In Peutz-Jeghers syndrome, a complete blood cell
count should be obtained because the polyps
may be a source of blood loss.
• For amalgam tattoos, a periapical radiograph
reveals the presence of the amalgam.
• The only study effective for diagnosing oral
malignant melanoma is tissue biopsy. A biopsy
should be performed on any otherwise
unexplained lesions.
• To avoid iatrogenic pigmentations, eliminate the
causes (eg, smoking, sun exposure).
150. Imaging Studies
• Peutz-Jeghers syndrome: An enteroclysis study
and dedicated small bowel follow-through
radiography are used to determine the presence
and the location of small intestinal polyps.
• Amalgam tattoos: These lesions can be seen on
radiographs, which quickly verify the histologic
findings.
• Iatrogenic pigmented lesions do not require any
laboratory tests except photographs for
documentation.
151. Nevi and melanoma
• Imaging studies are not required for oral nevi, with the exception of
clinical photographs for documentation. However, contrastenhanced CT scanning is required to determine the extent of the
melanoma and whether local, regional, or lymph node metastasis is
present.
• Studies such as bone scanning with a gadolinium-based agent or
chest radiography can be beneficial in assessing metastasis of
melanoma.
• MRI may be used to diagnose melanoma in soft tissue. Atypical
intensity is correlated with the amount of intracytoplasmic melanin.
On T1-weighted images, such melanomas are hypointense. On T2weighted images, such melanomas are hyperintense and show
increased melanin production. To the authors' knowledge, oral
melanomas have not been assessed in this manner.
• Positron emission tomography has poor results in distinguishing
melanoma from nevi. However, combined positron emission
tomography and CT scanning may have diagnostic value. Surgical
lymph node harvesting depends on the identification of positive
nodes after clinical or imaging examination.
153. Procedures
• Peutz-Jeghers syndrome An esophagogastroduodenoscopy and a
colonoscopy may be performed.
• Hemorrhagic or large polyps (>5 mm) should be removed by
endoscopic polypectomy to confirm the diagnosis and to help
control symptoms.
• Laparotomy and resection should be performed for repeated or
persistent small intestinal intussusception or obstruction or for
persistent intestinal bleeding.
• MelanomaA pigmented lesion in the oral cavity always suggests oral
malignant melanoma. Any pigmented lesion of the oral cavity for
which no direct cause can be found requires biopsy.
• Sentinel node biopsy or lymphoscintigraphy, which is beneficial in
the staging of cutaneous melanoma, has little value in staging or
treating oral melanoma. Complex drainage patterns may result in
the bypass of some first-order nodes and in the occurrence of
metastasis in contralateral nodes.
154. Histologic Findings
• The characteristic pathologic finding of the pigmentation
seen in the Peutz-Jeghers syndrome is basilar
hyperpigmentation.
• Although any of the features of cutaneous malignancy can
be found, most oral melanomas have characteristics of the
acral lentiginous (mucosal lentiginous) and, occasionally,
superficial spreading types. The malignant cells often nest
or cluster in groups in an organoid fashion; however, single
cells can predominate. The melanoma cells may have large
nuclei, often with prominent nucleoli, and they have
nuclear pseudoinclusions due to irregularity of the nuclear
membrane. The abundant cytoplasm may be uniformly
eosinophilic or optically clear. Occasionally, the cells
become spindled or neurotize in areas.
155. • Melanomas have a number of histopathologic mimics, including
poorly differentiated carcinomas and anaplastic large cell
lymphomas. Differentiation requires the use of
immunohistochemical techniques to highlight intermediate
filaments or antigens specific for a particular cell line. Leukocyte
common antigen and Ki-1 are used to identify the lymphocytic
lesions. Cytokeratin markers, often cocktails of high- and lowmolecular – weight cytokeratins, can be used to help in the
identification of epithelial malignancies.
• S-100 protein and homatropine methylbromide (HMB-45) antigen
positivity are characteristic of, although not specific for, melanoma.
S-100 protein is frequently used to highlight the spindled, more
neural-appearing melanocytes, whereas HMB-45 is used to identify
the round cells. Melanomas, unlike epithelial lesions, are identified
using vimentin, a marker of mesenchymal cells.
• Recently, microphthalmic transcription factor, tyrosinase, and
melano-A immunostains have been used to highlight melanocytes.
The inclusion of these stains in a panel of stains for melanoma may
be beneficial.
156. • Various types of lasers have been
used, including superpulsed CO2, Qswitched Nd-YAG, and Q-switched
alexandrite lasers.
157. • Although laser and cryotherapy have been
used to successfully treat such
cases, experimental forms of phototherapy
have also been employed, including
intense pulsed light and fractional
photothermolysis.
158. • First-line therapy remains the application of
topical medicaments that is bleaching
creams.
• Although single agents such as azelaic acid
or hydroquinone have been used, more
commonly dual- or triple-combination therapy
is recommended.
• A combination of 4% hydroquinone- 0.05%
retinoic acid- 0.01% fluocinolone acetonide
has proven to be effective in greater than
90% of patients.
159. FOLLOW-UP
• Peutz-Jeghers syndrome: Close follow-up care is needed for the GI aspects
of the disease. Genetic counseling should be offered to families trying to
have children. Further outpatient care for patients with Peutz-Jeghers
syndrome includes the following: Annual physical examination that
includes evaluation of the breasts, the abdomen, the pelvis, and the testes
• Annual complete blood cell count
• Repeated removal of hemorrhagic or large polyps (>5 mm) by endoscopic
polypectomy
• Surveillance for cancer, possibly including the following:
–
–
–
–
–
Small intestine with small bowel radiography every 2 years
Esophagogastroduodenoscopy and colonoscopy every 2 years
Ultrasonography of the pancreas yearly
Ultrasonography of the pelvis (women) and testes (men) yearly
Mammography (women) at ages 25, 30, 35, and 38 years; every 2 years until
age 50 years; then annually
– Papanicolaou (Pap) test every 3 years
160. • Amalgam tattoos: No follow-up care is
necessary for amalgam tattoos once the
diagnosis is determined.
161. • Melanoma Patients with melanoma must
receive close follow-up care involving
oncologists, surgical
oncologists, radiologists, and dermatologists.
• In many instances, psychological assistance
and intervention is also necessary.
162. COMPLICATIONS
Peutz-Jeghers syndrome
• In young patients, small intestinal obstruction and
intussusception are the main complications.
• Cancer is the main consequence as patients with PeutzJeghers syndrome age (93% cumulative risk by age 64
y). The major sites are the small intestine, the
stomach, the pancreas, the colon, the esophagus, the
ovaries, the lungs, the uterus, and the breasts.
• In addition, other reproductive site cancers have been
associated with Peutz-Jeghers syndrome, including
adenoma malignum of the cervix, Sertoli cell
tumors, and sex cord tumors with annular tubules.
163. • Amalgam tattoos: No major complications are
reported.
• Melanoma complications stem from the loss
of anatomic structures as a result of the
surgical procedure.
• Interferon use is associated with
malaise, flulike symptoms, fever, and myalgia.
164. PROGNOSIS
• Peutz-Jeghers syndrome: Approximately 48%
of patients with Peutz-Jeghers syndrome
develop and die from cancer by age 57 years.
• Amalgam tattoos: The prognosis for patients
with amalgam tattoos is excellent because the
condition is not associated with any sequelae.
• Melanoma: 5-year survival rate is within a
broad range of 4.5-48%
165. PATIENT EDUCATION
• Patients with Peutz-Jeghers syndrome should
be educated on the potential symptoms of
intestinal obstruction and instructed on the
need for cancer surveillance.
• Reassurance is all that is necessary for
patients with amalgam tattoos.
• Patients with melanoma should learn how to
perform an effective oral examination.
166. REFERENCES
•
•
•
•
•
•
•
•
•
•
Burket’s Oral Medicine 11th Ed
Differential Diagnosis of Oral and Maxillofacial lesions 5th Ed Wood Goaz
Oral pthology 4th Ed Regezi Sciubba Jordan
Textbook of Oral Medicine 2nd Ed Anil Govindrao Ghom
Fundamentals of Oral Medicine and Radiology, Bailoor Nagesh
Adel Kauzman, Marisa Pavone, Nick Blanas. Pigmented Lesions of the Oral
Cavity: Review, Differential Diagnosis, and Case Presentations. Journal of
the Canadian Dental Association. November 2004, Vol. 70, No. 10
Pai A, Prasad S, Patil BA, Dyasanoor S, Hegde S. Orla pigmentation: Case
report and review of malignant melanoma with flow charts for diagnosis
and treatment. General Dentistry. 2012; 410-416.
Gondivkar SM, Indurkar A, Degwekar S, Bhowate R. Primary oral malignant
melanoma- A case report and review of literature. Quitessence
International. 2009; 40(1): 41-46.
Mathias CG, Maibach HI, Conant MA. Perioral leukoderma simulating
vitiligo from use of a toothpaste containing cinnamic aldehyde. Arch
Dermatol. 1980 Oct;116(10):1172-3.
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