There is a wide spectrum of
pigmented lesions which present an oral mucosa or skin in the head and neck
area. In the oral cavity some of the
pigmented lesions are physiologic, but most are considered pathologic. The clinical features of benign and malignant
lesions of oral mucosa are, in most instances, virtually
indistinguishable. This makes it
impossible for the clinician to arrive at a definitive diagnosis without biopsy
and histopathologic examination of such lesions.
Some of the pigmented lesions of
oral mucosa and facial skin include:
1.
Normal physiologic pigmentation
2.
Ephelis
3.
Lentigo
4.
Melanotic macule
5.
Melanoacanthoma
6.
Nevi
7.
Melanoma
8.
Pigmentation secondary to pregnancy
9.
Pigmentation secondary to some other pathologic condition
Melanocytic
Lesions
1.
Normal physiologic intra-oral pigmentation
- observed in all racial groups, but
to varying degrees
- characterized by symmetry
- virtually always asymptomatic
- most common sites involved are
gingiva and buccal mucosa
- melanin pigment incontinence
(spillage from epithelium into underlying
connective tissue)
2.
Ephelis
- Freckle
-
Usually limited to sun exposed facial skin, but may involve lip mucosa.
-
Normal number of melanocytes in relation to keratinocytes.
-
Melanocytes have increased number of melanosomes in their cytoplasm
hence more melanin is produced.
-
Physiologic response to protect epithelium from uv radiation in
sunlight
-
Normal thickness of epithelium, no increase in keratinocyte population
3.
Lentigo
- 3 variants: simple, solar, and
maligna
- Simple lentigo features
a) no predilection for
sun exposed skin
b) flat surface and
uniform brown color
c) relative increased
number of melanocytes as epithelial layer is
thicker (elongated rete ridges)
- solar lentigo features
a) sun exposed skin
b) middle age or elderly
population
c) multiple lesions of
uniform brown color
- lentigo maligna features
a) histopathologically
atypical melanocytes limited to epithelium
b) melanoma in situ or
precancerous melanosis
c) lacks invasion
warranting diagnosis of lentigo maligna melanoma
4.
Melanotic macule
- flat (macular) surface
- well circumscribed border
- focal concentration of normal
melanocytes in basal layer of epithelium
5.
Melanoacanthoma
- facial skin and oral mucosal
lesions significantly different
- facial skin lesion
a) elderly
b) caucasians
c) slow growth
- oral mucosa lesion
a) young adults
b) blacks
c) rapid growth to large
size (4 cm in 4 weeks)
d) oral lesion can
frequently be associated with irritation or trauma
e) increased number of
both normal appearing melanocytes and
keratinocytes, with melanocytes migrating
through all layers of
epithelium which is also a feature of
melanomas
f) potential for misdiagnosis
and radical overtreatment
g) resolves following
biopsy or removal of irritation
6. Nevi
- congenital and acquired variants
- may be flat, slightly elevated
papillary, pedunculated (on stalk) or nodular
(dome shaped)
- usually well circumscribed
- pigmented or amelanotic
(non-pigmented)
- congenital nevus
a) incidence 1% live
births
b) usually larger than
acquired nevi (>1.5 cm diameter)
c) considered giant
nevus if >20 cm
d) often has shape of
garment
e) can exhibit hair growth
as well as pigmentation
f) malignant
transformation 1%, if giant nevus 6-12%
g) excise if possible
- intradermal nevus
a) most common oral
variant (55%)
b) can have any surface
morphology
c) nests and sheets of
nevus cells within supporting connective tissue
(dermis) without epithelial melanocyte
proliferation
d) neural nevus is a
type of intradermal nevus in which nevus cells
assume a spindle shape and this lesion can
be misdiagnosed by
pathologists as a
neurofibroma
- junctional nevus
a) usually presents as a
flat (macular) lesion which relates to lack of
connective tissue involvement
b) nodule formation
observed in intradermal or compound nevi or when
flat surface melanoma in situ invades
connective tissue
c) melanocytes in basal
layer of epithelium aggregate into clusters or
nests called theques
- compound nevus
a) combination of
intradermal and junctional nevus features, that is
nevus cells observed as islands in dermis
and forming intra-epithelial
theques
b) some believe
junctional activity decreases as lesion matures
- blue nevus
a) second most common
oral variant (35%)
b) characteristic
blue-black color
c) common form <1 cm
in diameter, cellular form >1 cm
d) melanocytes usually
appear as pigmented spindle cells in deeper
connective tissue having failed to migrate
to epithelium from neural
crest during embryogenesis
e) extremely rare
malignant blue nevus reported
- mongolian spot
a) bluish discoloration
clinically resembling bruise at base of spinal cord
b) more common in black
and asian population
c) presents at or near
birth, resolves by early childhood in blacks, may
persist into adulthood in asians
d) results from delayed
disappearance of dermal melanocytes
- nevus of Ota
a) speckled blue-black
pigmentation following distribution of trigeminal
nerve branches 1 and 2
b) may have synchronous
skin and intra-oral lesions
- nevus of Ito
a) associated with nevus
of Ota
b) follows distribution
of supraclavicular, scapular and deltoid nerves
- epithelioid and spindle cell
(Spitz) nevus
a) first reported in
1948 by Spitz as benign juvenile melanoma
b) pink skin nodule
c) clinically resembles
pyogenic granuloma
d) most common in
children but 25% are reported in patients over age 30
e) epithelioid and
spindle shaped cells, clefting at the junction of
epithelium and supporting connective tissue
and fibrosis
- halo nevus
a) clinically pigment
nevus of any variant surrounded by a zone of
depigmented epithelium
b) correlates with a
prominent lymphocyte response surround nevus on
histopathologic examination
- dysplastic nevus
a) first reported as
lesion of BK mole syndrome describing familial
tendency of patients with multiple
pigmented lesions to develop
melanoma
b) subsequently patients
with single isolated lesions with this histo-
pathologic presentation failed to develop
melanoma
c) large size (>5 cm
diameter), ill defined border
d) irregular
pigmentation, multinodular
e) clinically similar to
superficial spreading melanoma
f) compound nevus with
elongation of epithelial rete ridges
g) some consider a
borderline or premalignant lesion
7.
Melanoma
- background information
a) incidence (US):
14/100,000 males and 10/10,000 females
b) 1995 ACS statistics:
34,100 new cases
c) 1995 ACS
statistics: 7,200 deaths
d) predominantly
caucasians (13:1)
e) incidence predicted
to increase due to sun exposure and loss of
protective effect afforded by ozone layer
UVB (290-320 mm) being most carcinogenic
f) increased risk with
fair complexion, tendency to sunburn rather
than tan, history of blistering sunburn in
childhood
g) family history of
melanoma increases risk eightfold
h) as incidence
increases, so does improved prognosis
i) in oral cavity,
metastatic melanoma significantly most likely than
primary disease
- signs and symptoms
a) change in color or
size of a pigmented lesion
b) satellite areas of
pigmentation
c) bleeding or
ulceration of lesion
d) inflammation
surrounding lesion
e) pain and/or itching
of lesion
- classification of primary skin
melanoma
a) lentigo maligna
melanoma
* acral
lentiginous melanoma
b) superficial spreading
melanoma
c) nodular melanoma
- growth phases
a) horizontal
(peripheral expansion) and vertical (downward invasion)
b) extent and duration
of horizontal growth phase differs for each
variant of melanoma
c) prognosis after
invasion similar for all variants
- lentigo maligna melanoma
a) terminology
* lentigo
maligna: melanoma in situ
* lentigo
maligna melanoma: invasive melanoma
b) large size (4-6 cm
average diameter)
c) flat surface
d) long horizontal
growth phase averaging 10-15 years
e) earliest expected
vertical growth phase is 2-4 after onset
- acral lentiginous melanoma
a) observed on oral or
genital mucosa and the extremities
b) essentially an
aggressive form of lentigo maligna melanoma
c) prominent dendritic
processes similar to melanoacanthoma
d) vertical growth phase
lacks clinical warning sign of nodularity
from a previously flat lesion
e) exhibits multifocal
invasion and widespread dissemination
- superficial spreading melanoma
a) most common skin
variant (70%)
b) predominant sites
*males:
head, neck and trunk
*females:
back of legs
c) typically smaller
size than lentigo maligna melanoma with average
diameter of 2 cm
d) slightly elevated
e) shorter duration for
horizontal growth phase before invasion
downwards, averaging 1 year from onset
- nodular melanoma
a) rapid increase in
size
b) very short horizontal
growth phase before invasion, measured in
weeks
c) worst prognosis
- primary oral melanoma
a) uncommon, 1% of all
primary melanoma, oral cavity melanoma much
more likely to represent metastasis
b) most common sites:
maxillary alveolar ridge and palate (80%)
c) male predominance
(2:1)
d) middle age (average
55 years)
e) prognosis grave, 5
year survival < 10%
- classification of oral melanoma
a) acral lentiginous
(most common)
b) superficial spreading
c) nodular
- biopsy considerations
a) melanocytic lesions
are clinically indistinguishable making all, at
least potentially malignant melanoma;
therefore, all require biopsy
and histopathologic examination to
establish a definitive diagnosis
b) total excision as a first
procedure is preferred
c) suggest referral to
surgeon who will perform definitive surgery
rather than perform incisional biopsy with
referral following
histopathologic interpretation
d) cervical lymph nodes
following incisional biopsy may be clinically
enlarged and suggest metastasis, mandating
surgical exploration of
the neck
e) if lesion is too
large to excise for biopsy, sample from darkest or
most nodular area
- treatment considerations
a) surgical
* wide to
radical tumor excision
*
therapeutic regional lymph node dissection for obvious
metastasis, elective dissection in search of
occult metastasis
* tumor
invasion < 0.75 mm predictably non metastatic
* tumor
invasion > 1.50 mm worrisome for occult metastasis
* tumor
invasion > 3.59 mm generally too late to prevent
metastasis
* 40%
primary oral melanoma have metastasized when patient
initially presents
* distant
metastasis associated more with uncontrolled disease
at primary site (i.e.: inadequate initial
surgery) than regional
nodal metastasis
* average
interval to relapse following surgery 8.5 months
b) radiation therapy
* high dose
fractions 2400cGy over 21days had 53% partial and
30%
complete remission in one study
* fast
neutrons vis a vis orthovoltage
*
hyperthermia enhancement
*
radiosensitizers: boron (absorbs fast neutrons) combined with
chlorpromazine (affinity for melanoma cells)
c) adjunctive
chemotherapy
* DTIC
* cisplatin
* nitrosurea
* tamoxifen
d) immunotherapy
* bacillus
calmette-guerin (BCG) stimulation of immune system
effective in early disease but has little
positive effect (7%) once
melanoma has metastasized
e)
biologic response modifiers
* high dose
interleuken II stimulates tumor infiltrating
lymphocytes (TIL) to attack melanoma cells
* monoclonal
tumor antibody vaccine
- prognostic factors
a) histopathologic
factors and clinical stage (extent) both considered
important in determining patient outcome
b) tumor thickness
(volume) and depth of invasion are most important
histopathologic factors in determining
patient outcome
c) Clark method measures
tumor invasion utilizing anatomic layers
d) Breslow method
measures tumor invasion in mm utilizing calibrated
microscope
e) mitotic index of
>2 per 10 microscopic high power fields reduces 5
year survival 20%, all other factors being
equal
f) ulceration due to
ischemia (tumor growth outrunning its blood supply)
associated with reduced survival
g) increased patient age
reduces prognosis
h) females have slightly
better survival rate (7%) than men, all other
factors being equal
- survival estimates based on depth
of invasion
a) Clark method of
determining depth of invasion
Clark 1 melanoma in situ (no
invasion)
Clark 2 tumor in papillary
dermis
Clark 3 tumor to junction of
papillary and reticular dermis
Clark 4 tumor in reticular
dermis
Clark 5 tumor in subcutaneous
tissues
Level 5 Year 10 Year
1
100% 96%
2 92% 96%
3 65% 90%
4 54% 67%
5 48% 26%
b) Breslow method of determining depth of
invasion
Breslow 1 0.00 - 0.75 mm invasion
Breslow 2 0.76 - 1.69 mm invasion
Breslow 3 1.70 - 3.50 mm invasion
Breslow 4 3.60 mm or greater invasion
Level 5 Year 10 Year
1 99% 98%
2 94% 89%
3 81% 67%
4 49% 43%
- survival estimates based on
staging
a) TNM method
stage 1 lesions without metastasis
stage 2 lesions with metastasis to only 1
regional
lymph
node
stage 3 disseminated metastasis
TNM 5 Year 10 Year
stage 1
89% 81%
no recurrence 88%
local recurrence 42%
stage 2
61% 47%
1 node 45%
2 nodes 28%
3 nodes 9%
stage 3
2% 0%
- metastatic melanoma to the oral
cavity based on 800 cases NIH study
a) 3% of skin melanoma
metastasize to oral cavity
b) primary is usually in
the head or neck area
c) male predilection
(3:2)
d) average age 40 years
e) average interval
between primary and metastatic lesion is 4.2 years
f) most common
metastatic sites: tongue, cheek, parotid gland, alveolus
g) metastatic melanoma
to parotid gland lymph nodes commonly from
primary in scalp
h) metastatic melanoma
may be non-pigmented
i) symptoms may include
tooth mobility, non-healing extraction sites
and tumor expressing from
extraction socket
8.
Pigmentation secondary to pregnancy
- probable association with
increased ACTH during pregnancy
- ACTH mimics chemical structure of
HSH (melanin stimulating hormone)
- chloasma: (pregnancy mask)
irregular, flat areas of pigmentation on facial
skin of women during 2nd and 3rd trimesters
- melasma: circumoral pigmentation
at vermilion border may also been
observed in women taking birth control pills
9.
Pigmentation secondary to Acanthosis Nigricans
- thickened skin and oral mucosa
- seen in childhood as a benign
process
- cutaneous marker for internal
malignancy in adults, chiefly gastrointestinal
carcinoma
- oral lesion may exhibit papillary
surface and/or pigmentation
10. Pigmentation secondary to Peutz-Jegher
syndrome
- syndrome characterized by
circumoral pigmentation and multiple intestinal
polyps
- polyps can involute (intusseption)
and obstruct causing surgical emergency
- malignant transformation very low
in comparison to polyposis of Gardner’s
syndrome
11. Pigmentation secondary to neurofibromatosis
- multiple neurofibroma of skin and
oral mucosa
- multiple areas of skin
pigmentation known as café au lait spots (coffee with
cream color)
- low potential (2%) for malignant
transformation of benign neurofibroma
into neurogenic sarcoma
- Von Recklinghausen’s disease of
skin
12. Pigmentation secondary to chronic
adrenocortical insufficiency
- primary form of condition due to
autoimmune destruction of adrenal cortex
- pituitary gland continues to
secrete ACTH as biofeedback mechanism to
terminate process cannot be performed by affected adrenal cortex
- ACTH stereochemically similar to
MSH (melanin stimulating hormone)
- excess ACTH causes bronzing of
skin and oral pigmentation
- Addison’s disease
13. Pigmentation secondary to malignant tumors
- oat cell carcinoma of the lung
produce ectopic ACTH which may elicit oral
pigmentation
- generalized melanosis of skin observed
in patients with disseminated
metastatic melanoma
14. Pigmentation secondary to vitamin deficiency
- pellegra (niacin deficiency) can
produce a skin rash and hyperpigmentation
of exposed facial skin
- oral lesion is an enlarged beefy red
tongue
15. Pigmentation secondary to therapeutic drugs
- oral contraceptives
- chloroquinine used as
anti-malarial and control of lupus erythematosus
- tetracycline administered over
long duration can alter oral microflora and
enhance conditions for development of brown or black hairy tongue
- thorazine used in the treatment of
psychosis
- minocine antibiotic causes blue
gray discoloration of bone
- quinibrine used as anti-helminthic
causes yellow discoloration of skin and
oral mucous clinically similar to jaundice
- over the counter preparations such
as laxatives taken in excess can cause
pigment deposition in mucosa
16. Pigmentation secondary to Albright’s syndrome
- polystotic (multiple site) fibrous
dysplasia
- café au lait colored skin and oral
mucosal pigmentation
- in females, precocious puberty
17. Neonatal pigmentation secondary to tumor
- neuroectodermal tumor of infancy
a) most common site is
anterior maxilla
b) melanin pigmentation
deposition in mucosa
c) radiographic
presentation is well circumscribed radiolucency
surrounding developing tooth
d) vanillymandelic acid
(VMA) from metabolism of excess
catecholamines (epinephrine and
norepinephrine) found in urine
18. Pigmentation secondary to systemic
intoxication (poisoning) by heavy metals
- lead poisoning
a) lead sulfate
deposition in gingival sulcus (Burton’s line)
b) excessive salivation
(ptyalism)
c) peripheral neuropathy
and learning defects associated
d) treat with chelating
agents
- mercury
- bismuth
- arsenic
- gold
19. Pigmentation secondary to foreign body
implantation
- amalgam tattoo
a) most common sites are
gingiva and buccal mucosa
b) radiographic
discovery may allow clinical correlation precluding
necessity for biopsy and histopathologic
examination
c) focal argyrosis
- graphite
a) most common sites are
palate, floor of mouth and lip
b) history of accidental
puncture by pencil may be recounted
20. Pathologic conditions which mimic melanocytic
lesions
- hematoma
a) secondary to trauma
b) recurrent lesions
suggest abuse
- hemangioma
a) most common
mesenchymal tumor in childhood
b) dioscopy test
positive
c) treat by a variety of
modalities
- varix
a) vascular anomaly
often with thrombus
b) essentially a
varicose vein
- Kaposi sarcoma
a) usually red to purple
in color but may exhibit a brown hue
b) malignant blood
vessel tumor
c) incidence of oral
lesion in AIDS 50%
d) predisposing factors
???
e) treat with intralesion
vinca alkyloids or interferon
- thrombocytopenia
a) blood platelets <
100,000/ cc
b) marrow suppression
due to infection, leukemic infiltrate, aplastic
anemia
- seborrheic keratosis
a) middle aged to
elderly
b) head, neck, trunk
c) sharply demarcated
plaques with rough surface
d) in African Americans,
dermatosis papulosa nigra 35% incidence
21. Depigmented Lesions
- vitiligo
a) autoimmune
destruction of melanocytes
b) autoantibody to
melanocytes formed inkeratinocytes
c) scalp lesions common
- albinism
a) melanocytes are
inactive but not destroyed
22. Yellow and Orange Lesions
- Fordyce granules
a) multiple small
elevated asymptomatic papules
b) ectopic sebaceous
glands
c) buccal mucosa most
common location
d) increase at puberty
- parulis
a) dento-alveolar
abscess with purulent drainage
b) may be painful until
drainage occurs
c) strep, staph,
actinomyces
- lymphoepithelial inclusion cyst
a) lymph appears yellow
clinically
b) embryologically
entrapped epithelium in lymphoid aggregates
c) superficial floor of
mouth location common
d) conservative excision
- lipoma
a) common to skin,
uncommon to mucosa
b) tongue, buccal
mucosa, labial mucosa most common sites
- lymphonodular pharyngitis
a) multiple aggregates
in Waldheyer’s ring area
b) coxsackle A10 virus
c) 5 day incubation
followed by sore throat, fever, headache
d) 2 week course
e) supportive therapy
- jaundice
a) secondary to organ
dysfunction or drug therapy
* viral hepatitis
* sickle
cell or hemolytic anemia
* congestive
heart failure
* renal
failure
*
hepatocellular carcinoma or metastatic tumor to liver
* quinacrine
therapy
b) liver metabolism of
hemoglobin breakdown to bilirubin
* liver
capacity to metabolize bilirubin 2.0 mg/dl
*
unconjugated bilirubin brought to liver bound to albumin
* liver
conjugates to water soluble form for excretion in bile
c) excess rbc breakdown
overwhelms hepatic capacity in hemolytic
anemia
d) hepatitis and
cirrhosis prevent conjugation to water soluble state
e) obstruction by tumor
or gallstones prevents excretion of bile once
conjugated
- Tangier’s disease
a) hereditary high
density lipoprotein deficiency
b) Tangier’s island inhabitants
- consanguinity allows autosomal
recessive trait to be expressed
c) gingival enlargement
and deposition of cholesterol in tonsillar
tissue producing orange discoloration
d) loss of protective
effect from high density lipoprotein results in
higher than expected incidence of
atherosclerosis and arteriosclerosis
