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

 4 th 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

 Basal Cell Epithelioma  Basalioma   Rodent ulcer Jacobi’s ulcer  Rodent carcinoma

BCC: What are they?

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PEARLY PAPULES OR NODULES

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ROLLED BORDER

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TELANGIECTASES

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CENTRAL ULCER

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CRUSTING

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BLEED EASILY

BCC: Where are they?

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HEAD, NECK 85%

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NOSE, 30%

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FOREHEAD

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EARS

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CHEEKS

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UPPER TRUNK

BCC: When?

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OFTEN – 1/3 OF ALL CA IN USA.

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Chronic UVB, X-ray

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Immunosuppression

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Renal Transplant

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Genetics

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Over 1million NMSC/year

BCC: Who?

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ELDERLY & MIDDLE AGED

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Ages 40-79

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ANGLO-SAXON Blue Eyes, Fair Skin

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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

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TRUNK

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LIMBS

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FLAT GROWTHS

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YOUNGER PATIENTS

MORPHEAFORM BCC

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RESEMBLES LOCALIZED SCLERODERMA

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ALMOST ALWAYS ON THE CHEEKS OR FOREHEAD MOH’S SURGERY

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AGGRESSIVE

PIGMENTED BCC

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DARK SKINNED PATIENTS

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LATIN AMERICANS

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JAPANESE

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ARSENIC INGESTION

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6% OF ALL BCC

BCC – CYSTIC/SOLID

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DOME SHAPED

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BLUE GRAY

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CYSTIC NODULES

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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.

 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

 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

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PALMAR PITS

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SKELETAL DEFECTS

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FRONTAL BOSSING

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CALCIFICATION OF FALX CEREBRI

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

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

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, 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.

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  Adenoma  Sebaceoma  Sebaceous 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 well differentiated 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!