Epidermal Nevi, Neoplasms, and Cysts Part II

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Epidermal Nevi, Neoplasms, and Cysts Part II

• David M. Bracciano, D.O.

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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 NMSCs
• Tumors increase with decreasing lattitude

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NMSCs Epidemiology

• Majority of of NMSc deaths are due to SCCs
  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)

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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. Cleavers office)
• AKs are precursors of SCC
• Lifetime risk of SCC in an individual with Aks
  has been estimated to be 6-10

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NMSCs 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 1800s Paul Unna made the connection to
  ultraviolet light in sun-exposed sailors
• Nevoid basal cell syndrome identified in 4000
  year old Egyptian mummies

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Basal Cell Carcinoma

• Basal Cell Epithelioma
• Basalioma
• Rodent ulcer
• Jacobis ulcer
• Rodent carcinoma

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BCC What are they?

• PEARLY PAPULES OR NODULES
• ROLLED BORDER
• TELANGIECTASES
• CENTRAL ULCER
• CRUSTING
• BLEED EASILY

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BCC Where are they?

• HEAD, NECK 85
• NOSE, 30
• FOREHEAD
• EARS
• CHEEKS
• UPPER TRUNK

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BCC When?

• OFTEN 1/3 OF ALL CA IN USA.
• Chronic UVB, X-ray
• Immunosuppression
• Renal Transplant
• Genetics
• Over 1million NMSC/year

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BCC Who?

• ELDERLY MIDDLE AGED
• Ages 40-79
• ANGLO-SAXON Blue Eyes, Fair Skin
• X-Ray Exposure, ie Physicians, Dentists,
  Technicians, Workers

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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.

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BCC peripheral palisading of nuclei and stromal
rx
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Superficial BCC discrete nests of small
basaloid cells
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BCC look-alikes Sebaceous Hyperplasia
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BCC look-alikes KA
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BCC Look alikes SCC
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BCC Variants

• SUPERFICIAL BCC
• MORPHEAFORM BCC
• PIGMENTED BCC
• CYSTIC BCC
• BASAL CELL NEVUS SYNDROME(GORLINS SYNDROME)

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SUPERFICIAL BCC

• PSORIASIFORM
• TRUNK
• LIMBS
• FLAT GROWTHS
• YOUNGER PATIENTS

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MORPHEAFORM BCC

• RESEMBLES LOCALIZED SCLERODERMA
• ALMOST ALWAYS ON THE CHEEKS OR FOREHEAD
• MOHS SURGERY
• AGGRESSIVE

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PIGMENTED BCC

• DARK SKINNED PATIENTS
• LATIN AMERICANS
• JAPANESE
• ARSENIC INGESTION
• 6 OF ALL BCC

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BCC CYSTIC/SOLID

• DOME SHAPED
• BLUE GRAY
• CYSTIC NODULES
• 4-8 OF ALL BCCS

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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

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• 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.

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• 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. 

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BCC TREATMENT

• EXCISION
• FULGURATION AND CURETTAGE
• IONIZING RADIATION
• CRYOSURGERY
• TOPICAL 5-FU
• LASER
• MOHS MICROGRAPHIC 99 CURE
• Imiquimod for Superficial BCC

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BCC Treatment

• Pigmented BCCs should have deep or excisional
  biopsies to r/o melanoma
• Consider MOHs surgery for recurrent lesions,
  Morpheaform BCCs, or anatomic high risk areas

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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

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NEVOID BCC SYNDROME

• JAW CYSTS
• PALMAR PITS
• SKELETAL DEFECTS
• FRONTAL BOSSING
• CALCIFICATION OF FALX CEREBRI
• MOHS SURGERY

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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

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Pits of hands and feet

• 87 of patients
• Second Decade of life

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Skeletal Defects

• Spinal Bifida
• Deformed ribs
• Scoliosis and Kyphosis
• Shorten metacarpal and metatarsal bones
• Dimple on the fourth metacarpophlangeal joint
  (Albrights sign)

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CNS disorders

• Calcification of
• falx cerebri,
• falx cerebelli, and
• dura or basal ganglia

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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

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Intradermal Nests of Basaloid Cells
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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.

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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 light-skinned men
  greater than 55 years.
• The incidence of SCC increases closer to the
  equator.

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Predisposing factors for SCC

• 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

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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.

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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

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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

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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Squamous cell carcinoma of the scalp

• Crusted and eroded tumor of the scalp in this
  elderly man was histologically SCC.

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Actinic keratosis

• These are scaly papules which occur on exposed
  skin of older, fairer-skinned, persons resulting
  from chronic overexposure to ultraviolet light
  from the sun. A small percentage of these lesions
  do develop into invasive squamous cell carcinoma.
  

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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).

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Marjolins Ulcer

• SCC arise in chronic ulcers, sinuses, and scars
  of various etiologies
• Burns are most common cause

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Acantholytic SCC

• Fast growing tumor
• Oral cavity and conjunctiva may also be involved
• Acantholysis with adenoid preliferation
• Surgical excision is preferred treatment.

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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

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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.
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Verrucous carcinoma of the groin. Note the
destruction of the penis.
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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.
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Bowens Disease

• SCC in situ
• Stains for mucin is negative for Bowens but
  positive for Pagets
• No dyskeratosis in Pagets
• Wind blown pattern in histology
• Tinea circinata must be considered as well as
  Pagets

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Erythroplasia of Queyrat

• Bowens located on glans penis
• Treat with 5-FU is effective because of the
  absence of follicles
• Resemble Zoons Balanitis

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Balanitis Plasmacellularis (ZOON)

• Zoons 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

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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

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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.

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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

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Pagets 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.

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Involvement of the epidermis by malignant
adenocarcinoma cells. The cells are large with
abundant clear cytoplasm and large anaplastic
nuclei with prominent nucleoli.
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Extramammary Pagets

• 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.

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Low power view from one part of the biopsy.
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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.
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High power view of above. This solitary focus of
lumen production was found after examining
numerous sections. 
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Composite high power . These cells are
cytologically malignant. Some have vacuolated
cytoplasm.
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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

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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

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Merkel cell carcinoma with formation of lobular
structures in dermis and prominent lymphocytic
infiltration
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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

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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.

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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.
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Sebaceous Neoplasms

• Spectrum of sebaceous neoplasms
• Sebaceous Hyperplasia ? Sebaceous Adenoma ?
  Sebaceoma ? Sebaceous Epithelioma ? Sebaceous
  Carcinoma

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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

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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

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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.

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• 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.

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Low power view. Note the holocrine secretion
along the surface.
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• High power view. Most of the tumor cells have
  well-differentiated sebaceous cytology.

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Sebaceous EpitheliomaSebaceoma

• Circumscribed, symmetric lobules
• Larger lobules extending into deeper dermis
• gt50 germinative cells
• Same morphologic characteristic as basal cell
  carcinoma
• Histologically, consists of neat oval nests of
  irregularly shaped basaloid cells.

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Tumor lobules have invaded into the reticular
dermis in the lower right corner of this picture.
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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.
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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.

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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

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Muir-Torre Syndrome

• The criteria for diagnosis include presence  of
  sebaceous neoplasm (adenoma, sebaceoma or
  carcinoma), presence of internal malignancy (eg.
  colorectal carcinoma) .
• Keratoacanthomahas been frequently noted in this
  syndrome.

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Muir-Torre Syndrome

• Patients with multiple sebaceous  neoplasms of
  the skin should be examined for   other visceral
  malignancies,(eg. colonic,hematological,urothelia
  l,kidney,endometrial etc) .

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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!

• THE END