Epidermal Nevi,
Neoplasms, and Cysts
Part II
David M. Bracciano, D.O.
Non-Melanoma Skin Cancers
Epidemiology

Basal cell carcinoma (BCC) and cutaneous
squamous cell carcinoma (SCC) are the
most common human cancers.
 Annual cost in U.S. is 2.6 billion
 2001 over one million NMSC’s
 Tumors increase with decreasing lattitude
NMSC’s Epidemiology

Majority of of NMSc deaths are due to
SCC’s arising on the ear
 SCC is the most common skin cancer in
darkly pigmented patients and is the major
cause of skin cancer related deaths (not
melanoma)
Actinic Keratoses
Epidemiology
 4th
most common reason for a visit to a
dermatologist
 U.S. 3 million annual visits (4 million if you
count Dr. Cleaver’s office)
 AK’s are precursors of SCC
 Lifetime risk of SCC in an individual with
Aks has been estimated to be 6-10%
NMSC’s History

SCC was first described in the liturature in 1775
by Sir Percivall Pott
 During the industrial revolution links to chimney
soot, arsenic, coal tar, shale oil, and creosote were
identified
 Late 1800’s Paul Unna made the connection to
ultraviolet light in sun-exposed sailors
 Nevoid basal cell syndrome identified in 4000
year old Egyptian mummies
Basal Cell Carcinoma
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Basal Cell
Epithelioma
Basalioma
Rodent ulcer
Jacobi’s ulcer
Rodent carcinoma
BCC: What are they?
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PEARLY PAPULES
OR NODULES
ROLLED BORDER
TELANGIECTASES
CENTRAL ULCER
CRUSTING
BLEED EASILY
BCC: Where are they?

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HEAD, NECK 85%
NOSE, 30%
FOREHEAD
EARS
CHEEKS
UPPER TRUNK
BCC: When?
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OFTEN – 1/3 OF
ALL CA IN USA.
Chronic UVB, X-ray
Immunosuppression
Renal Transplant
Genetics
Over 1million
NMSC/year
BCC: Who?

ELDERLY &
MIDDLE AGED
 Ages 40-79
 ANGLO-SAXON
Blue Eyes, Fair Skin
 X-Ray Exposure, ie
Physicians, Dentists,
Technicians, Workers
BCC: How?

Arise from immature pluripotential cells.
 Mutations in the HEDGEHOG pathway
(genes which controls cell growth)
 PATCHED (tumor suppressor) inactivated.
 HEDGEHOG and SMOOTHENED (cell
growth inhibitors) activated.
 P53 and RAS mutations also play a role.
BCC: peripheral palisading of
nuclei and stromal rx
Superficial BCC: discrete
nests of small basaloid cells
BCC look-alikes:
Sebaceous Hyperplasia
BCC look-alikes: KA
BCC Look alikes: SCC
BCC: Variants

SUPERFICIAL BCC
 MORPHEAFORM BCC
 PIGMENTED BCC
 CYSTIC BCC
 BASAL CELL NEVUS SYNDROME
(GORLIN’S SYNDROME)
SUPERFICIAL BCC

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PSORIASIFORM
TRUNK
LIMBS
FLAT GROWTHS
YOUNGER
PATIENTS
MORPHEAFORM BCC

RESEMBLES
LOCALIZED
SCLERODERMA
 ALMOST ALWAYS
ON THE CHEEKS
OR FOREHEAD
 MOH’S SURGERY
 AGGRESSIVE
PIGMENTED BCC
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DARK SKINNED
PATIENTS
LATIN
AMERICANS
JAPANESE
ARSENIC
INGESTION
6% OF ALL BCC
BCC – CYSTIC/SOLID

DOME SHAPED
 BLUE GRAY
 CYSTIC NODULES
 4-8% OF ALL BCCS
Fibroepithelioma of Pinkus

Premalignant fibroepithelial tumor
 Elevated, skin-colored sessile lesions on the
lower trunk
 Histology: interlacing basocellular sheets
that extend downward from surface to form
an epithelial meshwork enclosing a
hyperplastic mesodermal stroma

Fibroepithelioma of Pinkus: A composite
scan power view showing anastomosing
bands of epithelium separated by large
amounts of stroma. The stroma accounts for
over 50% of the total volume of the tumor.

Another composite scan power view. This is
from a section taken parallel to the one
above. The strands of epithelium are
generally more delicate than those seen
above.
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Peripheral palisading of nuclei is associated with a cleft
between the epithelium and the delicately fibrillar,
slightly basophilic stroma.
This clefting resembles that seen in basal cell
carcinomas.
Amyloid (AMY) is seen below an area wherein parallel,
coarse collagen fibers (VC) are oriented perpendicular
to the interface of the epithelium and stroma.
BCC TREATMENT
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EXCISION
FULGURATION AND CURETTAGE
IONIZING RADIATION
CRYOSURGERY
TOPICAL 5-FU
LASER
MOHS’ MICROGRAPHIC 99% CURE
Imiquimod for Superficial BCC
BCC Treatment

Pigmented BCCs should have deep or
excisional biopsies to r/o melanoma
 Consider MOHs surgery for recurrent
lesions, Morpheaform BCC’s, or anatomic
high risk areas
Solitary Basal Cell Carcinoma in
Young Persons

Solitary Basal Cell Carcinoma in Young
Persons
 These lesions usually located in the region
of embryonal clefts in the face
 Deeply invasive
 Deep surgical excision is much safer than
curettage for their removal
NEVOID BCC SYNDROME
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JAW CYSTS
PALMAR PITS
SKELETAL
DEFECTS
FRONTAL
BOSSING
CALCIFICATION
OF FALX CEREBRI
MOHS SURGERY
Jaw Cysts

70% of patients.
 Both Mandible and Maxilla
 Mandibular involvement twice as often
 Jaw pain, unable to close mouth, tenderness
 First decade onset, maybe the first
presentation
Pits of hands and feet

87% of patients
 Second Decade of life
Skeletal Defects

Spinal Bifida
 Deformed ribs
 Scoliosis and Kyphosis
 Shorten metacarpal and metatarsal bones
 Dimple on the fourth metacarpophlangeal
joint (Albright’s sign)
CNS disorders

Calcification of:
– falx cerebri,
– falx cerebelli, and
– dura or basal ganglia
Intraepidermal Epithelioma

Tan-brown, keratotic scaly, flat, someimes
verrucous lesions. Clinically resembles
Seborrheic keratosis.
 Simple excision or EDC
 Also Known as:
– Borst Jadassohn epithilioma
– Intraepidermal epithelioma of Jadassohn
Intradermal Nests of
Basaloid Cells
Squamous cell carcinoma

Squamous cell carcinoma (SCC) is a malignant
neoplasm of keratinocytes with many features one
of which is the production of keratin.
 SCC can be categorized histologically into in situ
(intraepidermal) or invasive (penetrating the
dermal-epidermal junction).
 Some examples of in situ SCC include Bowen's
disease and erythroplasia of Queyrat.
Squamous cell carcinoma

Squamous cell carcinoma is the second
most common skin cancer after basal cell
carcinoma.
 It typically occurs on sun-exposed areas of
the body and is more common in lightskinned men greater than 55 years.
 The incidence of SCC increases closer to
the equator.
Predisposing factors for SCC

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family history of skin cancer
precursor lip lesions from smoking
actinic keratosis
old burn scars
Immunosuppression
ultraviolet radiation
radiation therapy
chemical carcinogens such as soot and arsenic
Squamous cell carcinoma

Lesions on the lower lip (13.7%), or in a scar
(37.9%), have up to a 40% probability of
metastasizing.
 Desmoplastic SCC are 6 times more likely for
metastasis
 Lesions on sun-damaged skin have a 2% tendency
to metastasize.
 Metastasis is primarily by way of the lymphatics,
generally first to regional lymph nodes.
SCCs

33% of SCCs arising in blacks are
associated with non-healing ulcers
 May also arise in chronic lesions of discoid
lupus, lichen planus, lichen sclerosis.
 SCC of anus increased in AIDS patients
Verrucous Carcinoma

A distinct variety of SCC
 Slow-growing, low grade, deeply invasive,
rarely metastasize
 May become more aggressive or
metastasize after treatment with radiation
therapy, therefore rad tx is contraindicated
Verrucous Carcinoma
Synonyms
Oral mucosa: “oral florid papillomatosis”
 Anogenital region: “giant condyloma of
Buschke and Lowenstein”
 Plantar surface of the foot: “carcinoma
cuniculatum or epitheloma cuniculatum.”
Most common form, resembles a large
plantar wart.

Treatment

Treatment choice is dependent on lesion
type, size, location, depth of penetration and
the patient's age and general health.
 Treatment modalities include excisional
surgery, curettage and electrodessication,
cryosurgery, radiation therapy, Mohs
surgery, and laser surgery.
SCC with cutaneous horn
Here is a cutaneous horn,
overlying a tumor which
on biopsy proved to be a
squamous cell carcinoma.
The presence of cutaneous
horn is grounds for a
biopsy of the underlying
lesion.
Encrusted squamous cell
carcinoma
Another firm tumor on
the abdomen, this time
with both scale and
crust. Biopsy of this
tumor revealed
squamous cell
carcinoma.
Chronic sun exposure and
squamous cell carcinoma
This gentleman was in his
60s when he presented to
the clinic because of the
frequent development of
skin cancers. You can see
his scarred skin from the
multiple previous
procedures. On the
superior aspect of the left
breast is a crusted lesion
which to palpation is firm.
Biopsy confirms SCC.
Squamous cell carcinoma
of the lip
Sun damage on the
lower lip can result in
actinic cheilitis and
even squamous cell
carcinoma as shown
here.
Squamous cell carcinoma of the
scalp
In his 30s when he presented to
the clinic, this engineer had
spent some years in Saudi
Arabia and had neglected a
growth on the top of his head at
the site of a burn. At the time of
presentation the tumor had
been present for about 2 years.
Biopsy revealed SCC and a
workup revealed distant
metastases. Shortly after
presentation, he died from this
tumor.
Squamous cell carcinoma of the
scalp
Crusted and
eroded tumor of
the scalp in this
elderly man was
histologically
SCC.
Actinic keratosis
These are scaly papules
which occur on exposed
skin of older, fairerskinned, persons resulting
from chronic
overexposure to ultraviolet
light from the sun. A small
percentage of these lesions
do develop into invasive
squamous cell carcinoma.
Actinic keratosis
Here on the top outer edge
of the ear is a palpably
rough area, an actinic
keratosis in one of the
more common
presentation sites for men.
(In women, the ear is often
protected from excess
sunlight by the hair).
Marjolin’s Ulcer

SCC arise in chronic ulcers, sinuses, and
scars of various etiologies
 Burns are most common cause
Acantholytic SCC

Fast growing tumor
 Oral cavity and conjunctiva may also be
involved
 Acantholysis with adenoid preliferation
 Surgical excision is preferred treatment.
Verrucous Carcinoma

Slow-growing lesion and very invasive
 May invade the bony structures around the
tumor
 Bulbous rete ridges that are topped by an
undulating keratinized mass.
 Excision or Mohs’
Verrucous
carcinoma can
occur on the
foot, in the
groin, or in the
mouth. It is a
low grade tumor
that seldom
metastasizes.
Note the
destruction of
normal
structures in
this verrucous
carcinoma of the
toe.
Verrucous
carcinoma of the
groin. Note the
destruction of
the penis.
Verrucous carcinoma is
very low grade and has
almost no atypia on
histologic examination.
Diagnosis is made by the
extent of invasion. It is
important to get a large,
deep biopsy when one
suspects this type of tumor.
Bowen’s Disease

SCC in situ
 Stains for mucin is negative for Bowen’s
but positive for Paget’s
 No dyskeratosis in Paget’s
 Wind blown pattern in histology
 Tinea circinata must be considered as well
as Paget’s
Erythroplasia of Queyrat
Bowen’s located on glans penis
 Treat with 5-FU is effective because of the
absence of follicles
 Resemble Zoon’s Balanitis

Balanitis Plasmacellularis
(ZOON)
Zoon’s Balanitis is a condition found on the
glans penis and/or inner surface of the
prepuce of the uncircumcised, middle-aged
to older male.
 presents most often as a solitary, glistening,
red or cayenne pepper-colored, persistent
plaque on the glans penis or inner surface of
the prepuce of the uncircumcised male

Balanitis Plasmacellularis

Histologically, the epidermis appears
thinned, often showing an absence of the
upper layers
 The upper dermis demonstrates a lichenoid
infiltrate with copious plasma cells
Balanitis Plasmacellularis

Treatments start with topical therapies.
 Mild topical steroids are the initial
treatment of choice, however, recurrence
upon their discontinuation is the rule.
 Circumcision is curative in nearly all cases.
Close follow-up is recommended.
Pseudoepitheliomatous Keratotic
and Macaceous Balanitis

Rare condition
 Ulceration, cracking, and fissuring on
surface of glans
 Phimosis will develop in adult life
 Many believe it to be a form of verrucous
carcinoma
 Require Mohs or 5-FU
Paget’s Disease of the Nipple

Unilateral sharply defined eczema caused
by epidermal metastases from underlying
ductal adenocarcinoma of the breast
 Presence of paget cells
 CEA and apocrine epithelial antigen usually
positive
 Bilateral lesions suggests neurodermatitis,
contact, or nummular.
Involvement of the
epidermis by malignant
adenocarcinoma cells. The
cells are large with
abundant clear cytoplasm
and large anaplastic nuclei
with prominent nucleoli.
Extramammary Paget’s

presents clinically as an erythematous
plaque, often several centimeters in
dimension, and such lesions are sometimes
pruritic.
 Delay in diagnosis is common as many of
these cases are erroneously treated for
dermatitis or superficial fungus infection
prior to the establishment of the real
diagnosis.
Low power view from one part of the biopsy.
Medium power view of above. The cells are large and have a
rather bland appearance in this area. Some are found singly in
a pagetoid distribution, and others are in clusters. The
intervening keratinocytes are free of atypia.
High power view of above. This solitary focus of
lumen production was found after examining
numerous sections.
Composite high power .
These cells are cytologically
malignant. Some have
vacuolated cytoplasm.
Trabecular Carcinoma
(Merkel Cell Carcinoma)

Rapid growing nodule
 Head and neck (44%) leg (28%) arm (16%)
and buttock (9%)
 Region nodal metastases is 53%
 Distant metastases is 75%
Trabecular Carcinoma
(Merkel Cell Carcinoma)

Local recurrence 26% to 44%
 5 Year survival rate 30% to 64%
 Prognosis is worse than Melanoma
 Mohs excision, some recommended 3 cm
margin
Merkel cell carcinoma with
formation of lobular structures in
dermis and prominent
lymphocytic infiltration
Nevus Sebaceus
(Organoid Nevus)

AKA Nevus Sebaceus of Jadassohn
 Present at birth, usually near vertex of scalp
 BCC may develop from the lesion 5-10% of
the time
 Deletion of Patched gene has been
identified and may be responsible for
development of BCC
Nevus Sebaceus
(Organoid Nevus)

May be associated with development of
intracranial masses, seizure, MR, skeletal
abnormalities, ocular lesions, hamartomas
of the kidney
 Excision recommended if possible.
 Patient with BCC on scalp during the
inspection.
There are no large, anagen phase hair follicles in most of the field,
and there are no fibrous tracks of the type that follow a telogen
phase follicle. This is characteristic of nevus sebaceus of
Jadassohn. The variety and degree of proliferation of follicular
components varies from lesion to lesion.
Sebaceous Neoplasms

Spectrum of sebaceous neoplasms
 Sebaceous Hyperplasia  Sebaceous
Adenoma  Sebaceoma  Sebaceous
Epithelioma  Sebaceous Carcinoma
Sebaceous Hyperplasia

AKA senile sebaceous hyperplasia and
senile sebaceous adenoma
 Proliferation of mature sebaceous glands
 Germinative layer 1 cell thick
 Lobules may be grouped around a central
dilated duct
Sebaceous Adenoma

Sebaceous adenoma presents as a yellow
circumscribed nodule located either on face or scalp.
 Histologically sebaceous adenoma is a
multilobulated tumour sharply demarcated from the
surrounding tissue.
 Two types of cells are present in the lobules.
 The large mature sebaceous cells (sebocytes) are
present at the centre.
Smaller,undifferentiated basaloid cells in the
periphery
Sebaceous Adenoma

Proliferation of sebaceous glands
 Germinative layer comprise to to 50% of
lobules
 Retains lobular architecture
 The cellular lobules contain ductal
structures with holocrine secretion.
Sometimes lobules contain cystic spaces in
the center due to disintegration of mature
sebaceous cells.

Very low power (direct scan of glass slide)
view. The tumor communicates with the
surface in multiple points, and holocrine
secretion is prominent along the surface.
Low power view. Note the holocrine secretion along the
surface.

High power view. Most of the tumor cells have welldifferentiated sebaceous cytology.
Sebaceous Epithelioma
Sebaceoma

Circumscribed, symmetric lobules
 Larger lobules extending into deeper dermis
 >50% germinative cells
 Same morphologic characteristic as basal
cell carcinoma
 Histologically, consists of neat oval nests of
irregularly shaped basaloid cells.
Tumor lobules
have invaded
into the reticular
dermis in the
lower right
corner of this
picture.
Low power view of one of the nests of tumor in the lower right
hand corner of the picture above. There is focal retraction from
the surrounding stroma, and there is sebaceous differentiation
within the central part of this tumor nest.
Sebaceous Gland Carcinoma

Rare carcinoma arise on the eyelids from
meibomian or Zeis glands. Upper eyelid 75% of
the time
 Fatal metastasic disease occur 20-30% of eyelid
cases
 May be seen in Muir-Torre syndrome
 Histologically, shows lobules containing
sebaceous cells with numerous mitotic figures.
Nuclei are lighter than those of the sebaceous
epithelioma.
Sebaceous Gland Carcinoma

Large, asymmetric, infiltrative
 Generally lacks well defined lobules
 May have pagetoid spread
 Necrosis
 Mature sebocytes maybe few or rare
 Pleomorphic, mitotically active basaloid
cells
Muir-Torre Syndrome

The criteria for diagnosis include
presence of sebaceous neoplasm (adenoma,
sebaceoma or carcinoma), presence of
internal malignancy (eg. colorectal
carcinoma) .
 Keratoacanthoma
has been frequently noted in this syndrome.
Muir-Torre Syndrome

Patients with multiple sebaceous neoplasms
of the skin should be examined for other
visceral malignancies,
(eg.
colonic,hematological,urothelial,kidney,
endometrial etc) .
THE END
Thanks to Rick Lin, D.O., M.P.H,
M.B.A., D.D.S., J.D., Ph.D., for
his work on this lecture!