Actinic keratoses: Erythematous scaly lesions on sun-damaged skin & considered “precancerous” lesions that have the potential to progress into invasive SCC. Bowen’s disease: SCC in situ It has the potential to progress to invasive SCC. Leukoplakia: Leukoplakia refers to a white patch or plaque on the oral mucosa that cannot be wiped off and cannot be characterized clinically or pathologically as any other disease.

1. PREMALIGNANT
SKIN LESIONS
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3. PREMALIGNANT SKIN CONDITIONS
I. PRE-MALIGNANT LESIONS:
1. Actinic keratoses  SCC
2. Bowen’s disease  SCC
3. Leukoplakia  SCC
4. Sebaceous nevus  BCC
5. Dysplastic nevi  Melanoma
6. Lentigo maligna  LMM
II. VERY HIGH RISK:
1. Xeroderma Pigmentosum  melanoma, BCC, SCC
2. Immunosuppression (e.g. organ transplant)

5. ACTINIC KERATOSES (AKs)

8. ACTINIC KERATOSES (AKs/SOLAR
KERATOSES)
Erythematous scaly lesions on sun-damaged
skin.
AKs are considered “precancerous” lesions
that have the potential to progress into
invasive SCC.
The risk of squamous cell carcinoma
occurring in a patient with more than ten
actinic keratoses is about 10 to 15%.
The atypical keratinocytes are confined to
the lower portion of the epidermis.

9. ACTINIC KERATOSES (AKs/SOLAR
KERATOSES)
They are especially common in middle-
aged to older fair-skinned persons or
those who have worked outdoors for
long periods without skin protection.

11. Multiple AKs on the face of an elderly woman with fair complexion, blue
eyes, and moderate to severe photodamage; the AKs vary in size from a
few millimeters to more than 1 cm. On the left forehead, the red nodule
with slight scale-crust represents a well-differentiated SCC.

12. Multiple hypertrophic AKs
on the bald scalp with
hypopigmentation at sites
of previous treatment.
Pink-colored atrophic AK
with minimal scale on the
forehead.

14. Multiple, large hypertrophic AKs on the shin of an elderly woman;
note the thick scale.

16. Inflamed AK tend to have white circles on a pink background. The circles
have 4 white dots in them called rosettes

17. Lesions are said to have a strawberry-like appearance. The arrow
denotes one of the many 'pips'. These findings will only be evident in
lesions with little scale, or where the scale has been lifted off

18. C/P OF AKs
The patient may complain of uncomfortable
and disfigurement.
Multiple circumscribed flat or thickened, scaly
or warty lesion may be skin colored or
erythematous.
The associated scale is usually white to yellow
in color and feels rough.
Diagnosis usually made by visual inspection
and palpation; because of the rough texture,
it is sometimes easier to detect lesions via
touch.

20. C/P OF AKs
Occur primarily in sites that have received the
greatest amount of cumulative sun exposure
(e.g. scalp in bald individuals, face most often
affecting the cheeks, temples and forehead,
nose, ears also neck, dorsal forearms and
hands, shins).

21. C/P OF AKs
AK may develop into a cutaneous horn.

22. C/P OF AKs
AKs have the potential to persist,
spontaneously regress, or progress to
SCC, but clinically it is difficult to predict
which course a given AK will take.

23. C/P OF AKs
Clinical clues to progression to invasive SCC and need for
biopsy:
1. Tenderness
2. Volume (particularly thickness)
3. Ulceration
4. Bleeding
5. Inflammation
6. Failure to respond to appropriate therapy

24. CLINICAL VARIANTS OF AKs
1. Hypertrophic
(HAK) 2. Pigmented 3. Lichenoid 4. Atrophic 5. Actinic cheilitis

25. A hyperkeratotic actinic keratosis
This patient had a number of AK. One of the lesions was hyperkeratotic
(red arrow) - it is important to remove the scale if there is any uncertainty
about the diagnosis

29. Actinic cheilitis: Dry, whitish–gray, scaly plaques with possible erythema,
erosion, or ulceration
Due to chronic sun exposure; also may be associated with smoking and
chronic irritation

30. ACTINIC CHEILITIS (SOLAR CHEILITIS)
Pre-malignant changes on the lip due to
chronic sun exposure and tends to be
more severe in smokers.
Invasive squamous cell carcinoma should
be suspected if a persistent ulcer or
nodule develops.

31. ACTINIC CHEILITIS (SOLAR CHEILITIS)
Actinic cheilitis most commonly results in the following
features:
1. Dry lips
2. Thinned skin of the lips
3. Scaly patches
Less common features of actinic cheilitis include:
1. Swelling of the lip
2. Redness and soreness
3. Ulceration and crusting
4. Loss of demarcation between the vermilion border of the lip and its adjacent skin
5. Prominent folds and lip lines
6. White thickened patches (leukokeratosis)
7. Discolored skin with pale or yellow areas

32. DDx OF AKs
1. SCC in situ
2. Invasive SCC in case of thicker lesions (e.g. HAK)
3. BCC
4. lichen planus-like keratosis (LPLK)
5. Irritated seborrheic keratosis (SK)
6. Verruca vulgaris
7. Amelanotic melanoma
8. Actinic porokeratosis

40. HISTOPATHOLOGY OF AKs
Hyperkeratosis.
Focal parakeratosis overlying atypical keratinocytes (mainly
basal) that show  mitosis.
Dyskeratosis may be seen.
Loss of granular layer.
Sparing adnexae and acrosyringium.
The dermis: perivascular/lichenoid lymphocytic infiltrate; solar
elastosis.

41. HYPERKERATOTIC AK with alternating pink and blue colors in the
cornified layer; the pink-colored parakeratotic columns within the
stratum corneum are located above the atypical keratinocytes in the
spinous layer, while the blue-colored columns of orthohyperkeratosis are
above the acrosyringia . Atypical epidermal keratinocytes also display a
pinkish color that contrasts with the color of the basophilic, normal
keratinocytes of the acrosyringia

42. Hypertrophic actinic keratosis

43. PIGMENTED ACTINIC KERATOSIS with increased melanin pigmentation
within the basal layer. Note the solar elastosis in the dermis

44. ACTINIC CHEILITIS: Alternating orthokeratosis and parakeratosis;
disordered maturation of epidermal cells with increased mitosis and
atypia; prominent solar elastosis; moderate infiltrate (including plasma
cells below ulcerations)

45. Rx OF AKs
I. LOCALIZED/
LESION-
TARGETED
TREATMENTS
II. TOPICAL
FIELD
TREATMENTS
III. PROCEDURAL
FIELD
TREATMENTS

46. Rx OF AKs
Lesion-targeted treatments are best for an isolated or limited
number of lesions while field treatments are best for more
numerous or larger lesions.
It is not practical to remove all Aks in those with very
extensive sun damage; in such cases it is important to get rid
of thickened or tender lesions as these are the ones at
greatest risk of progressing to skin cancer.

47. COMMON TREATMENT OPTIONS FOR ACTINIC
KERATOSES
LOCALIZED/LESION-TARGETED TREATMENTS
Lesion-Targeted Treatment Helpful Hints
1. Liquid nitrogen
cryosurgery
• Blistering & shedding of the sun damaged skin
• 99% cure rate
• No cutting or anesthesia necessary
• 10- to 14-day healing period
• Risk of hypopigmentation
2. Curettage &
electro-
desiccation
• Preferred with thicker keratoses
• Requires local anesthesia
• Crust forms which heals over few weeks
• Risk of hypopigmentation and scarring (less so
if curettage alone)
3. Excision (Shave excision or excisional biopsy) • Requires local anesthesia
• Usually the surgical wound is sutured
• Risk of scarring

49. TOPICAL FIELD TREATMENTS
Topical Agent Dosing Helpful Hints
1. 5-Fluorouracil • 0.5% cream apply at bedtime × 4 weeks
• 1.0% or 5.0% cream apply twice /d for 2–4 wk.
• 2.0% and 5.0% solutions apply twice a day for
2–4 weeks
• When treating extensor extremities,
pretreatment with a topical retinoid for 1–2
weeks may be required
• When there are many lesions on the face
• Warn of photosensitivity, which can be severe
• Optimal results occur if treatment continues until
there is significant inflammation or superficial
erosions
• Healing usually occurs within 2 weeks of stopping
treatment
2. Imiquimod • 2.5% or 3.75% cream – apply at bedtime for 2
weeks; take a 2-week break, and then repeat
2-week application cycle
• 5% cream – apply twice a week for 16
consecutive weeks
• Recommended treatment area is 25 cm2
• It is an immune response modifier
• It causes an inflammatory reaction
• May cause systemic flu-like symptoms
• Not recommended if patient has an underlying
autoimmune condition
• May cause hypopigmentation at the treated site
3. Diclofenac • 3% gel – apply twice a day for 90 days
• A maximum amount of 8 g daily should not be
exceeded
• It is well tolerated
• Do not use if patient is allergic to non-steroidal
anti-inflammatory drugs (NSAIDs)
• It has less severe cutaneous reaction but poor
compliance (longer application period)
4. Ingenol mebutate • 0.015% gel – apply at bedtime for 3
consecutive nights (face and scalp)
• 0.05% gel – apply at bedtime for 2 consecutive
nights (trunk and extremities)
• About half of all lesions resolve after two to
three days of treatment
• Was approved by the FDA in 2012
• Rapid onset of action; typically within 24 hours of
application, patient will experience erythema and
burning
• Healing occurs within 10–14 days
• Supposedly does not cause hypopigmentation

50. Actinic keratoses with
field change on the right
forehead
Same patient after 4
weeks of Efudix cream
Same patient 8 weeks
after treatment had
finished. The skin has
responded very well and
healed nicely

51. Actinic keratoses treated with 5-FU

52. Actinic keratoses treated with imiquimod

54. PROCEDURAL FIELD TREATMENTS
Procedure Helpful Hints
1. Photodynamic therapy (PDT)
(e.g. 5-ALA + blue
light)
• Involves applying a photosensitizer to the
affected area prior to exposing it to a source of
visible light (including daylight).
• Can be painful
• Requires 48 hours of no outdoor exposure
post-treatment
• Relatively quick recovery over 1–2 weeks
2. Chemical peels (e.g. trichloracetic acid) • May require local anesthesia
• May cause significant irritation and temporary
discoloration
• Healing typically over 7 days
3. Ablative laser techniques
(e.g. ablative fractional lasers,
erbium:YAG laser)
• Requires local anesthesia
• Depending on the technique, recovery period
varies
• Hypopigmentation a potential complication

56. PREVENTION OF AK
Prevention is possible with broad-spectrum sunscreens and
sun avoidance measures.

57. Rx OF ACTINIC CHEILITIS
IN ADDITION TO THE ABOVE
MENTIONED MEASURES:
Smoking should be stopped.
Men can consider growing a
moustache.
Using a lip balm contains sunscreen
is recommended.
Vermilionectomy (surgical removal of
the lip).

59. BOWEN’S DISEASE
(SCC IN SITU/INTRAEPIDERMAL SCC)

60. BOWEN’S DISEASE
Keratinocyte atypia is seen throughout
the entire epidermis (full-thickness).
It has the potential to progress to
invasive SCC, with an estimated risk of
~3–5% if untreated.
Bowen’s disease may arise de novo or
from a pre-existing AK.

61. ETIOLOGY OF BOWEN’S DISEASE
1. SUN EXPOSURE: most often found on sun exposed sites of fair
skinned individuals. This is because UVR damages the DNA  a
mutant clone of the gene p53  of uncontrolled growth of the
keratinocytes. UVR also suppresses the immune response preventing
recovery from this damage.
2. ARSENIC INGESTION: this may result in multiple areas of
intraepidermal SCC on the trunk and limbs years after exposure.
3. IONIZING RADIATION: intraepidermal SCC was common on the hands
of radiologists early in the 20th century.
4. HUMAN PAPILLOMAVIRUS INFECTION (oncogenic strains HPV-16 or -
18): rarely causes intraepidermal SCC. However, HPV infecting genital
sites is the cause of vulval and penile intraepithelial neoplasia or
mucosal SCC in situ.

63. Scaly red plaque on the chest with skip areas.

64. Bright-red, well-demarcated plaque on the proximal nail fold with
associated horizontal nail ridging; the possibility of HPV infection
needs to be considered

65. Extensive involvement of the finger, which is often misdiagnosed
clinically as psoriasis or chronic eczema and therefore treated for
years with corticosteroid creams (as was this patient).

68. C/P OF BOWEN’S DISEASE
The most common presentation of SCC in
situ is an erythematous scaly patch or
slightly elevated plaque.
The development of a induration, ulceration
or bleeding may indicate progression into
invasive SCC.

69. C/P OF BOWEN’S DISEASE
It usually presents as an asymptomatic,
well-defined erythematous patch or thin
plaque with scales and irregular border
that expands centrifugally.

70. C/P OF BOWEN’S DISEASE
Although it may arise on any area of skin,
the lesions are most often diagnosed on
sun exposed sites such as the head (ears,
face) and neck, followed by the
extremities and trunk.

71. C/P OF BOWEN’S DISEASE
Less common sites (non-sunexposed sites):
Related to HPV infection:
1. Beard area.
2. Periungual and subungual may results in a red
streak (erythronychia) that later may destroy
the nail plate.
3. Anogenital (now referred to as intraepithelial
neoplasia/IEN).
Related to arsenic exposure.

74. C/P OF BOWEN’S DISEASE
MAJOR CLINICAL VARIANTS:
Pigmented variant
Penile intraepithelial neoplasia (PIN).

78. Squamous cell carcinoma, in situ, of the penis, also known as penile
intraepithelial neoplasia (PIN). Formerly called SCC in situ, erythroplasia
of Queyrat type. Large eroded erythematous plaque with
welldemarcated borders. The lesion began on the shaft of the penis.

79. PENILE INTRAEPITHELIAL NEOPLASIA (PIN)
Synonyms:
Bowen’s disease of the penis
Erythroplasia of Queyrat
SCC-in-situ of the penis
10-30% progress to invasive SCC.
Usually affecting uncircumcised males over 50
years of age.
The diagnosis is often delayed as it may
resemble other forms of chronic balanitis. Skin
biopsy should be performed to confirm the
diagnosis, and to rule out invasive SCC, which
requires more aggressive treatment.

80. ETIOLOGY OF PIN
1. CHRONIC INFECTION WITH HUMAN PAPILLOMA VIRUS (HPV): HPV-16
is the most common type identified. Partners of patients with PIN
should be screened for other forms of intraepithelial neoplasia caused
by HPV in the genital area.
Many national immunization programs now include a vaccine against
the causative HPV-16 and 18. Vaccination of boys and young men
should be included, to  the risk of developing PIN in the future.
2. CHRONIC SKIN DISEASE: especially lichen sclerosus & lichen planus.
3. SMOKING
4. IMMUNE SUPPRESSION: by medications or disease.
5. CHRONIC IRRITATION: by urine, friction or injury to the penile area.

81. C/P OF PIN
Circumscribed, asymptomatic, bright red, shiny
plaque on the glans of penis or inner aspect of the
foreskin.
It may have a smooth, velvety, moist, scaly,
eroded or warty surface.
The following signs and symptoms may occur:
Redness and inflammation
Itching
Pain
Crusting or scaling
Ulcers
Bleeding
In the late stages, discharge from penis, phimosis or dysuria

83. DDx OF BOWEN’S DISEASE
1. AK
2. Invasive SCC
3. Superficial BCC
4. LPLK
5. Irritated SK
6. Amelanotic melanoma
7. Occasionally may be misdiagnosed as an isolated lesion of
psoriasis or nummular eczema, but a clue is its lack of
response to appropriate therapy

89. HISTOPATHOLOGY OF BOWEN’S DISEASE
Atypical keratinocytes involving full thickness of epidermis that shows
acanthosis.
Loss of granular layer.
Hyperkeratosis and diffuse confluent parakeratosis.
“Wind-blown epidermis” (loss of orderly maturation).
“Flip sign” (superficial epidermis appears like deeper epidermis instead of
normal superficial epidermis with larger, mature, eosinophilic cells).
Atypical keratinocytes more commonly extend down the adnexa than in an
AK.
Perivascular infiltrate.
Pigmented variant, in which there is abundant melanin in the epidermis.
The “pagetoid” variant (the presence of desmosomal spines can be helpful
in Dx).
PIN shows the same histopathology.

90. Rx OF BOWEN’S DISEASE
Surgical:
1. Shave excision with curettage
2. Curettage and electrodesiccation (especially for smaller lesions)
3. Liquid nitrogen cryotherapy
4. Photodynamic therapy
5. Surgical excision
6. Laser ablation
7. Mohs micrographic surgery (e.g. head and neck, acrogenital) especially in severe or recurrent
cases
Medical:
1. Imiquimod cream
2. Topical 5% fluorouracil (twice daily for a longer period, e.g. 8 weeks) may be used when a
surgical approach would prove difficult to perform because of location or extent.
Superficial radiotherapy

92. LEUKOPLAKIA

93. LEUKOPLAKIA
Leukoplakia refers to a white patch or plaque
on the oral mucosa that cannot be wiped off
and cannot be characterized clinically or
pathologically as any other disease.
Typically occurs in middle-aged and older
adults (men > women).
It is the most common premalignant
condition of the oral mucosa as longstanding
lesions may transform to SCC in ~5% of
cases.

94. ERYTHROPLAKIA
Similarly, ERYTHROPLAKIA is defined
as a red intraoral patch or slightly
elevated, velvety plaque that cannot
be diagnosed as a particular disease.

95. LEUKOPLAKIA
LEUKOPLAKIA IS ASSOCIATED WITH:
1. Smoking (six times more common in smokers than non-smokers).
2. Alcohol intake.
3. Chronic persistent irritants such as jagged teeth, ill-fitting dentures.

96. Intra-oral photograph showing white patch, with crack mud appearance
on the left buccal mucosa, suggestive of homogenous leukoplakia

99. Erythroplakia

100. Erythroleukoplakia

102. Leukoplakia. Sharply demarcated, white plaque involving the ventral
surface of the tongue and floor of the mouth.

106. Erythroleukoplakia ("speckled leukoplakia"), left commissure. Biopsy
showed mild epithelial dysplasia and candida infection. Antifungal
medication may turn this type of lesion into a homogenous
leukoplakia (i.e. the red areas would disappear)

107. Nodular leukoplakia

108. Nodular leukoplakia in right commissure. Biopsy showed severe
dysplasia

109. Exophytic leukoplakia on the buccal mucosa

110. Leukoplakia of the soft palate

111. The lower mandibular gingiva exhibits multifocal corrugated
leukoplakia affecting the marginal and attached gingiva between
teeth #21 and #26. Multiple biopsies revealed a histologic
diagnosis ranging from verrucous hyperplasia to mild epithelial
dysplasia.

112. Proliferative Verrucous Leukoplakia (tends to occur in women
without traditional risk factors, is characterized by multifocal red
and white patches that eventually develop a verrucous surface;
difficult to treat and associated with high risk of transformation to
SCC).

113. Verrucous proliferative leukoplakia of the oral cavity. The lesions have
focally progressed to invasive squamous cell carcinoma; HPV DNA was
not detectable by PCR.

115. C/P OF LEUKOPLAKIA
THE SITES AFFECTED:
1. Buccal mucosa
2. Alveolar mucosa
3. Inner aspect of lower lip
4. Floor of mouth
5. Lateral or ventral tongue
6. Soft palate

116. CLINICAL TYPES OF LEUKOPLAKIA

117. C/P OF LEUKOPLAKIA
HOMOGENEOUS NON-HOMOGENEOUS
• Refers to homogeneous uniform
colour AND texture
• Refers to irregularity of either the
colour OR the texture
• Uniform white colour
• Predominantly white or white-red
speckled (erythroleukoplakia)
• Uniform flat, thin appearance
• The surface may become leathery –
smooth, wrinkled, corrugated or
with shallow cracks.
• Irregular texture which can be flat,
nodular, exophytic, verrucous
(including proliferative verrucous)
• This form is usually asymptomatic.
• This form may be associated with
mild discomfort or localized pain.

118. C/P OF LEUKOPLAKIA
The following signs suggesting malignant
transformation;
Ulceration
Induration
Bleeding
Outgrowth
The presence of dysplasia, carcinoma in-
situ and invasive carcinoma cannot
always be predicted clinically.

119. Dx OF LEUKOPLAKIA
Oral leukoplakia is a clinical diagnosis of
exclusion.
Toluidine blue supravital staining: Areas of
significant dysplasia or carcinoma have a
strong affinity for the dye & contain
intracellular wider canals that may facilitate
penetration of the dye whereas the normal
mucosa does not. This response permits
detection of small and early lesions and also
permits their surface delineation.
Biopsy: to rule out malignancy.

121. SEVERITY OF DYSPLASIA

122. Histopathological photomicrograph showing area of increased epithelial
thickness together with hyperkeratosis, suggestive of mild dysplasia

123. Histopathological photomicrograph showing squamous
hyperparakeratosis blunt and elongated epithelial ridges and
cytonuclear atypia confined to the lower epithelial half, suggestive of
moderate dysplasia.

124. Histopathological photomicrograph showing epithelial alterations
involving nearly the entire epithelial thickness, suggestive of severe
dysplasia

125. The Phases of Leukoplakia and Dysplasia

126. HISTOPATHOLOGY OF LEUKOPLAKIA
Biopsies should be taken from either a symptomatic area, or
if asymptomatic then from red or indurated areas.
The histopathology of oral leukoplakia is not diagnostic.

127. HISTOPATHOLOGY OF LEUKOPLAKIA
Hyperkeratosis is seen most frequently.
Epithelial changes range from atrophy to acanthosis.
Dysplasia may be mild, moderate, severe, carcinoma in situ
or invasive carcinoma.
Erythroplakia generally shows more advanced dysplastic
features, with 90% of lesions demonstrating severe epithelial
dysplasia, carcinoma in situ or invasive carcinoma at the time
of biopsy.

128. HISTOPATHOLOGY OF LEUKOPLAKIA
FACTORS INFLUENCES RISK OF TRANSFORMATION TO SCC;
1. The degree of histologic epithelial dysplasia.
2. Nonhomogeneous leukoplakia particularly erythroplakia.
3. Lesions located on the floor of the mouth or lateral/ventral
tongue also have higher malignant potential.

129. Rx OF LEUKOPLAKIA
AVOIDANCE OF
AGGRAVATING
FACTORS
MEDICAL Rx SURGICAL Rx

130. Rx OF LEUKOPLAKIA
I. AVOIDANCE OF AGGRAVATING FACTORS:
1. Quit smoking
2. Stopping alcohol consumption
3. Avoid irritation/ trauma
After elimination of possible causative factors
for 2–6 weeks, persistent lesions should be
biopsied.

131. Rx OF LEUKOPLAKIA
II. MEDICAL Rx:
1. Topical imiquimod.
2. Systemic retinoids (acitretin or isotretinoin).

132. Rx OF LEUKOPLAKIA
III. SURGICAL Rx:
For leukoplakia with moderate to severe
dysplasia or in high-risk sites and for
erythroplakia often require complete removal
and continued monitoring (lifelong follow-up)
and should avoid carcinogenic habits.
Options include:
1. Surgical excision
2. CO2 laser ablation
3. Electrofulguration
4. Cryosurgery
5. Photodynamic therapy

134. REFERENCES
Dermatology essentials.
Google images.
http://dermoscopymadesimple.blogspot.com
http://www.dermnetnz.org
http://www.pcds.org.uk
Recognition & Treatment of Pre-Malignant & Malignant skin lesions
by Bruce Philp St. Andrews Centre Broomfield Hospital
(Presentation)
www.facebook.com/groups/dermatologycourseonline/