2014-01-14

A Logical Approach to Differential Diagnosis of ♦What is the most common Peri-orbital Skin Lesions clinical diagnosis provided with surgical specimens removed Thomas F. Freddo, O.D., Ph.D., F.A.A.O. from the skin around the eye? Professor and Former Director School of Optometry University of Waterloo Lid Lesion!!!!!

Skin The largest organ of the body Skin

♦ Epidermis

♦ Dermis Epidermis

Sebaceous Rete peg gland attached ♦ Hypodermis to follicles of – Hypodermis lashes are the Glands of Zeis of the lids contains no Lashes have Dermis no arrector pili adipose Papillary muscle tissue. Reticular

Histology Melanocytes (M) reside near the of Epidermis basal surface of the epithelium. LAYERS OF EPIDERMIS ♦ Stratum germinativum – Basal layer - mitotic division only in this layer ♦ Stratum spinosum – Prickle cell layer ♦ Stratum granulosum Papillary – Granular layer Dermis ♦ Stratum corneum – Keratin layer Rete peg

Reticular Dermis

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Langerhans Cells (L) are responsible for Primary Dermatological antigen recognition and processing, a Descriptors required step for immune responses. ♦ Macule: Circumscribed, flat discoloration , <1cm ♦ Patch: Circumscribed, flat discoloration , >1cm ♦ Papule Circumscribed, elevated superficial solid lesions, < 1cm ♦ Plaque Circumscribed, elevated superficial solid lesions, > 1cm ♦ Nodule Solid lesions with depth, above, level with or below surface, < 1cm ♦ Tumor Solid lesions with depth, above, level with or below surface, < 1cm ♦ Vesicle Circumscribed elevations containing serous fluid, < 1cm ♦ Bulla Circumscribed elevations containing serous fluid, > 1cm ♦ Petechia Circumscribed deposits of blood or blood products, < 1cm ♦ Purpura Circumscribed deposits of blood or blood products, < 1cm

Macules and Patches Papules and Plaques

♦ A papular rash on the forehead

A hyperemic or red scaly macule/patch

Nodules and Tumors Secondary Dermatological Descriptors ♦ A nodule with keratin- Sessile: A lesion fixed to the skin on a broad base filled central ♦ umbilication ♦ Pedunculated: A lesion on a stalk ♦ Papillomatous: A lesion exhibiting a surface resembling a cauliflower ♦ Scales: Shedding, dead epidermal cells, dry or greasy ♦ Crusts: Dried masses of skin exudates ♦ Excoriations: Abrasions of the skin, usually superficial and traumatic ♦ Fissures: Linear breaks in the skin ♦ Ulcer: Irregularly sized and shaped excavations extending into the dermis ♦ : Replacement formations of connective tissue ♦ : Hypertrophic ♦ Lichenification: Area of thickened, scaly skin, retaining skin creases

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Lichenification Papillomatosis (sessile)

What’s wrong with this epithelium? Lipid-laden histiocytes What’s wrong with this dermis?

Factors in Assessment Xanthelasma plaques of Lid Lesions - Alteration of lash-line ♦ Hyper beta lipidemias

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Actinic Keratosis - red, scaly macule or On the nose, in the right location, this lesion could patch. PRE- MALIGNANT. May give rise to Squamous cell CA. If so, be disregarded as being merely irritation from frames these are generally non-invasive EXCEPT when they occur on the lip!

Note the very fair color and generally mottled appearance of the skin. These are the individuals Actinic Keratosis most susceptible.

Actinic keratosis - the scaly appearance is actually parakeratosis Actinic keratosis - can also appear indicating rapid turnover of the epithelium. The basal half of the as a scaly papule. Again note blotchy appearance of epithelium looks worrisome, with lateral budding of the rete pegs, but the apical half looks OK. Squamous cell CA-Grade 1/2. surrounding skin.

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Syringoma - multiple, yellow papules Keratoacanthoma - rounded dome- representing benign growths of eccrine sweat shape nodule with keratin filled central glands. No treatment except for cosmesis. umbilication.

Keratoacanthoma - rounded, usually symmetric, dome shaped nodule with Squamous Cell Carcinoma keratin- filled umbilication ♦ The second most frequent skin carcinoma. ♦ Usually arise in an area of damaged skin. ♦ Most often caused by ultraviolet radiation (UVR) or human papilloma virus (HPV) infection. ♦ On the face it presents most often as solitary or multiple nodules, which may be hyperkeratotic or scaling. ♦ More likely to metastasize than basal cell carcinoma.

Squamous Cell Carcinoma- Squamous Cell Carcinoma Etiology Note Ultraviolet Radiation asymmetry – Sunlight, phototherapy with oral PUVA, ionizing and lack of rounded radiation, or a history of methotrexate (tx. for dome psoriasis). appearance ♦ Age of onset: In the US, >55 years of age; In Australia and New Zealand, in the 20-30s among whites due to fair skin and hole in the ozone layer. ♦ Sex: Male>female; commonly on legs of females. ♦ Incidence: In continental US, 12 per 100,000 white males. ♦ Race: White skin with poor tanning capacity.

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Squamous Cell Carcinoma Rounded, symmetric dome with central Note asymmetry and lack of dome shape nidus of keratin vs non-domed irregular 360 degrees. border with larger central crater of keratin Squamous cell Carcinoma

Keratoacanthoma

The other major clue to this differential is how long the lesion has been present.

Basal Cell Carcinoma Basal Cell Carcinoma

♦ Commonest form of skin cancer ♦ Typically seen on sun-exposed areas such as the face and neck. ♦ Originate from the basal keratinocyte ♦ Histologically reminiscent of skin adnexal structures such as hair follicles. ♦ Locally invasive, but rarely metastasize

Nodulo-ulcerative type

Basal Cell Carcinoma Basal Cell Carcinoma - Types

♦ Age of onset: >40 years of age. ♦ Sex: Males > females. ♦ 1) Nodular (and nodulo-ulcerative): Most ♦ Incidence: In US, 500-1,000 per 100,000; common. Begins as a small, skin-colored >400,00 new cases each year. papule which shows fine telangiectasia and a ♦ Race: Higher in Caucasians, rare in brown glistening pearly edge. Frequently, there is and black skinned people. central necrosis that leaves a small ulcer with ♦ Predisposing factors: White-skin with poor an adherent crust. They are usually less than tanning capacity, albinos, exposure to x-rays 1 cm in diameter (I.e. NODULES), but grow for facial , arsenic ingestion, heavy sun larger if present for several years. exposure before age 14.

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Nodular Nodulo-ulcerative Basal Cell CA

Basal Cell Note CA telangiectatic vessels near central ulceration.

Differential Diagnosis: Nodulo-ulcerative Basal Cell CA vs Squamous cell Cystic Basal Cell Carcinoma carcinoma Squamous cell - Central ♦ Cystic: crater dry, filled with Become brown-yellow, scaly, tense and greasy keratin translucent, and show cystic spaces on histology

Basal Cell - Central crater ulcerated and moist, often with hemorrhage and translucent border

Morpheaform (sclerosing) Basal Cystic Basal Cell Carcinoma Cell Carcinoma

Cystic Cavity Cystic Cavity

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Morpheaform (sclerosing) Basal Molluscum contagiosum Cell Carcinoma ♦ Transition areas Management is predisposed to difficult development of viral-induced lesions.

♦ Appearance at lids in this form not classical. ♦ At the lid margin it will produce a chronic follicular conjunctivitis

Molluscum Molluscum contagiosum contagiosum

Classical presentation is of clusters of smooth papules with small central umbilication. ♦ A skin disorder caused by a DNA virus of the poxvirus group. ♦ Generally resolves without therapy Molluscum within 2 to 3 months in the immunocompetent individual. Bodies ♦ Spread by physical contact with an infected individual or material (eg, clothing, towel).

Molluscum Molluscum contagiosum contagiosum

In immunocompromised ♦ In immunocompromised patients, patients, such as those improvement of lesions was seen in individual cases with the use of with AIDS, the lesions ritonavir, cidofovir (intravenous are usually far more and topical), AZT, intralesional interferon alpha, and topical numerous. injections of streptococcal antigen OK-432. ♦ Prevalance in HIV 5-18%

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Molluscum Contagiosum in Seborrheic HIV/AIDS

10% of HIV-infected individuals Keratosis ♦ may develop hundreds of lesions. Rarely before age 30. Usually ♦ Some become "giant" (greater than 1 cm), and display a predilection >50 for the eyelids. ♦ The lesions are often pruritic and may become superinfected. ♦ Ocular lesions can be sight- threatening. Treatment is unsatisfactory. ♦ Antiretroviral therapy, particularly in the early stages, is sometimes ♦ Varies from scaly, effective. non-inflamed ♦ Cyrotherapy and pricking lesion with toothpick dipped in phenol macule, plaque to may provide transient relief, but recurrences common. sessile, papular ♦ Cidofovir, an anti-cytomegalovirus agent, is under investigation for papillomatous treatment of molluscum contagiosum. lesion that varies in degree of

7 y/o HIV+ boy with a CD4 count of 150 cells/microliter pigmentation

Seborrheic Keratosis - when this Leser-Trelat Sign dark they can be confused with melanoma ♦ The sudden appearance of numerous seborrheic keratoses in a short period can herald the existence of underlying A malignancy, most often Assymetry an adenocarcinoma of B the GI system. Borders irregular C Color variegation D Diameter

Sebaceous Gland Carcinoma Sebaceous masquerades may include seemingly recurrent chalazion Gland Carcinoma

♦ Masquerade presentations may include an unusual, unresponsive unilateral blepharitis with red thickened lid margins and madarosis.

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Pagetoid Spread of Sebaceous Papillomatous Masses: Gland Carcinoma Verruca vulgaris

♦ Pagetoid ♦ Scaly spread can nodule with significantly “Spikey” papillomatosis complicate Sometimes in the surgical Clusters. At lid margin, management can give rise of this to follicular conjunctivitis, disease. like mollsucum.

Papillomatous Masses: Papillomatous Masses: Squamous papilloma

Pedunculated Sessile papillomatous Papillomatous nodule/tumor masses, often Usually multiples. Most pigmented, are viral with greasy induced, caused scale by human papilloma virus. (HPV)

Review of Papules and Plaques Macules and Patches ♦ Red, scaly in an older individual with light but ♦ Multiple, small yellow papules - syringoma mottled or blotchy skin - Actinic keratosis / early ♦ Multiple pink/tan papules with central squamous cell CA. umbilication - molluscum ♦ Multiple very scaly papules on fair, blotchy skin - ♦ Brown, scaly in an older individual- actinic keratosis (actinic may also be macule) Sebborheic keratosis or melanoma. Melanomas ♦ Yellow plaques - xanthelasma rarely multiple, sebborheic commonly multiple. ♦ Brown to black plaque - seborrheic keratosis Also follow ABCDs. especially if multiples. If solitary use ABCDs. ♦ Smooth plaque looking like scar- morpheaform BCC

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Nodules and Tumors

♦ Papillomatous, scaly – Seborrheic keratosis - usually pigmented, always sessile – Solitary molluscum contagiosum at the lid margin - sessile – Verrucous - sessile or cutaneous horn – Squamous or viral papilloma - sessile or pedunculated ♦ Non-papillomatous: – With central crater of keratin - keratoacanthoma or squamous cell carcinoma - based upon symmetry and time of existence – With central ulceration/translucent border - basal cell carcinoma – With no central ulceration - seborrheic keratosis or basal cell – With no central ulcertaion at lid margin, disrupting lash line - sebaceous gland carcinoma

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