A Logical Approach to Differential Diagnosis of Peri-orbital Skin Lesions

Thomas F. Freddo, O.D., Ph.D., F.A.A.O.Professor and Former Diretor

School of Optometry and Vision ScienceUniversity of Waterloo, CANADA

Commercial Interests

None

Lid Lesion!!!!!Lid Lesion!!!!!

What is the most common What is the most common clinical diagnosis provided with clinical diagnosis provided with surgical specimens removed surgical specimens removed from the skin around the eye?from the skin around the eye?

SkinSkinThe largest organ of The largest organ of the bodythe body

EpidermisEpidermis

DermisDermis

HypodermisHypodermis– Hypodermis

of the lids contains no adipose tissue.

Sebaceous gland attached to follicles oflashes are theGlands of Zeis

Lashes have no arrector pili muscle

SkinSkin

EpidermisEpidermis

Rete pegRete peg

DermisDermisPapillaryPapillaryReticularReticular

HistologyHistology of Epidermis of Epidermis

LAYERS OF LAYERS OF EPIDERMISEPIDERMIS

Stratum germinativumStratum germinativum– Basal layer - mitotic Basal layer - mitotic

division only in this layerdivision only in this layer Stratum spinosumStratum spinosum

– Prickle cell layerPrickle cell layer Stratum granulosumStratum granulosum

– Granular layerGranular layer Stratum corneumStratum corneum

– Keratin layerKeratin layer

PapillaryDermis

Rete peg

Reticular Dermis

Melanocytes (M) reside near the Melanocytes (M) reside near the basal surface of the epithelium.basal surface of the epithelium.

Langerhans Cells (L) are responsible for Langerhans Cells (L) are responsible for antigen recognition and processing, a antigen recognition and processing, a required step for immune responses.required step for immune responses.

The Road to Dermatological Diagnosis In order to diagnose, you must first be able

to accurately describe the lesion you are examining.

To properly describe a skin lesion you must first learn the basic terminology used by dermatologists and other medical professionals.

Primary Dermatological Primary Dermatological DescriptorsDescriptors Macule: Macule: Circumscribed, flat discoloration , <1cmCircumscribed, flat discoloration , <1cm

Patch: Patch: Circumscribed, flat discoloration , >1cmCircumscribed, flat discoloration , >1cm Papule Papule Circumscribed, elevated superficial solid lesions, < 1cmCircumscribed, elevated superficial solid lesions, < 1cm

Plaque Plaque Circumscribed, elevated superficial solid lesions, > 1cmCircumscribed, elevated superficial solid lesions, > 1cm Nodule Nodule Solid lesions with depth, above, level with or below surface, < Solid lesions with depth, above, level with or below surface, <

1cm1cm

Tumor Tumor Solid lesions with depth, above, level with or below surface, < Solid lesions with depth, above, level with or below surface, < 1cm1cm

Vesicle Vesicle Circumscribed elevations containing serous fluid, < 1cmCircumscribed elevations containing serous fluid, < 1cm

Bulla Bulla Circumscribed elevations containing serous fluid, > 1cmCircumscribed elevations containing serous fluid, > 1cm

Petechia Petechia Circumscribed deposits of blood or blood products, < 1cmCircumscribed deposits of blood or blood products, < 1cm

Purpura Purpura Circumscribed deposits of blood or blood products, < 1cmCircumscribed deposits of blood or blood products, < 1cm

Discoloration Note that the term

discoloration used in these descriptions means either darker or lighter than the surrounding skin and they can be ANY colour.

Above: An “ash leaf macule” in Tuberous Sclerosis

Below: A “café au lait macule” in Neurofibromatosis

Macules Macules and and PatchesPatches

A hyperemic or red scaly macule representing actinic keratosis

A hyperemic patch in contact dermatitis

Papules and PlaquesPapules and Plaques

A papular rash on the foreheadA papular rash on the forehead

Rashes start flat and then become raised. In these cases, terms can be combined, such as maculo-papularRashes start flat and then become raised. In these cases, terms can be combined, such as maculo-papular

A Xanthelasma Plaque

With papules and plaques With papules and plaques you get a sense that the you get a sense that the lesion is raised above the lesion is raised above the skin but not anchored skin but not anchored deeply into it.deeply into it.

Nodules and TumorsNodules and Tumors A nodule with A nodule with

keratin-filled keratin-filled central central umbilication umbilication (belly-button)(belly-button)

In practice we In practice we usually do not usually do not use the accurate use the accurate term tumor term tumor because of the because of the implications it implications it carries. We carries. We often call all often call all such lesions such lesions either small or either small or large nodular large nodular masses.masses.

With nodules and tumors you get a sense that these are anchored deeply into the skin

Vesicles and BullaeSmall vesicles in poison ivy Bullae in bullous pemphigoid

These are also called “blisters”Remember that all such lesions, regardless of size, when on the cornea are called Bullae

Petechiae and Purpura

Conjunctival petechiae in endocarditis

Areas of purpura do not blanch

Secondary Dermatological Secondary Dermatological DescriptorsDescriptors Sessile: Sessile: A lesion fixed to the skin on a broad baseA lesion fixed to the skin on a broad base Pedunculated:Pedunculated: A lesion on a stalk A lesion on a stalk Papillomatous: Papillomatous: A lesion exhibiting a surface resembling a A lesion exhibiting a surface resembling a

cauliflower or artichokecauliflower or artichoke Scales:Scales: Shedding, dead epidermal cells, dry or greasy Shedding, dead epidermal cells, dry or greasy Umbilicated: Umbilicated: The lesion exhibits a central crater like an The lesion exhibits a central crater like an

umbilicus or belly buttonumbilicus or belly button Crusts:Crusts: Dried masses of skin exudates Dried masses of skin exudates Ulcer:Ulcer: Irregularly sized and shaped excavations extending Irregularly sized and shaped excavations extending

into the dermisinto the dermis Lichenification:Lichenification: Scales preserving natural skin creases Scales preserving natural skin creases

Sessile vs Pedunculated

Sessile means it is fixed on a broad base.

Pedunculated means its on a stalk like grapes on stem

Conjunctival papillomas, one sessile and the other pedunculated

Large pedunculated papillomatous mass hanging from a stalk attached to the superior fornix

Papillomatous – This is a description, not a diagnosis All lesions that resemble a

cauliflower or an artichoke are papillomatous. Some are sessile and others are pedunculated. A papilloma is but one of the lesions in the differential diagnosis of papillomatous masses

So ALL papillomas are papillomatous but not all papillomatous masses are

papillomas A sessile papillomatous mass

Papillomatous Masses:Papillomatous Masses: Squamous papillomaSquamous papilloma

Pedunculated Pedunculated papillomatous papillomatous masses, often masses, often multiples. Most multiples. Most are viral are viral induced, caused induced, caused by human by human papilloma papilloma virus.virus.

(HPV)(HPV)

Sessile Papillomatous MassSessile Papillomatous MassVerruca vulgaris Verruca vulgaris (viral-induced wart)(viral-induced wart)

ScalyScalynodule withnodule withAArtichoke-likertichoke-likepapillomatosis.papillomatosis.

Sometimes inSometimes inclusters.clusters.At lid margin, At lid margin,

can give rise can give rise to follicular to follicular conjunctivitisconjunctivitis, like , like mollsucum.mollsucum.

LichenificationLichenification

Macules and Patches

Actinic Keratosis Actinic Keratosis - red, scaly macule or - red, scaly macule or

patch. PRE- MALIGNANT. May give rise to Squamous cell CA. If so, patch. PRE- MALIGNANT. May give rise to Squamous cell CA. If so, these are generally non-invasive EXCEPT when they occur on the lip!these are generally non-invasive EXCEPT when they occur on the lip!

On the nose, in the right location, this lesion could On the nose, in the right location, this lesion could be disregarded as being merely irritation from be disregarded as being merely irritation from framesframes

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

Actinic KeratosisActinic Keratosis

Actinic keratosis - Actinic keratosis - can also appear can also appear

as a scaly papule. Again note blotchy appearance of as a scaly papule. Again note blotchy appearance of surrounding skin.surrounding skin.

Papules and Plaques

Syringoma - Syringoma - multiple, yellow papules multiple, yellow papules

representing benign growths of eccrine sweat representing benign growths of eccrine sweat glands. No treatment except for cosmesis. glands. No treatment except for cosmesis.

Xanthelasma plaquesXanthelasma plaques Hyper beta Hyper beta

lipidemiaslipidemias

Sessile Papillomatous Masses

Seborrheic Seborrheic KeratosisKeratosisRarely before age 30. Usually Rarely before age 30. Usually >50>50

Varies from scaly, Varies from scaly, non-inflamed non-inflamed macule, plaque to macule, plaque to sessile, papular sessile, papular papillomatous papillomatous lesion that varies lesion that varies in degree of in degree of pigmentationpigmentation

Leser-Trelat SignLeser-Trelat Sign The sudden appearance The sudden appearance

of numerous seborrheic of numerous seborrheic keratoses in a short keratoses in a short period can herald the period can herald the existence of underlying existence of underlying malignancy, most often malignancy, most often an adenocarcinoma of an adenocarcinoma of the GI system.the GI system.

Seborrheic Keratosis Seborrheic Keratosis - when this - when this

dark they can be confused with melanomadark they can be confused with melanoma

Often described as a “button stuck on the face”

Often multiples, some still macules and others papules

An Aside: How to Evaluate Darkly Pigmented Lesions

AAAsymmetry – more asymmetry is Asymmetry – more asymmetry is worseworseBBBorders – more irregular borders Borders – more irregular borders are worseare worseCCColor – more variegation of color is Color – more variegation of color is worseworseDDDiameter – bigger than a pencil Diameter – bigger than a pencil eraser or the tip of a Goldmann eraser or the tip of a Goldmann tonometer tiptonometer tipEEEvolution (has it changed?)Evolution (has it changed?)

Sessile papillomatous massSessile papillomatous mass A Papilloma

Factors in Assessment Factors in Assessment of Lid Lesionsof Lid Lesions -Alteration of lash-lineAlteration of lash-line

Many lesions at the lid margin will make lashes point in different directions but they do not disturb the continuity of the lash line. If they disturb the continuity of the lash line, however, they are more worrisome and likely merit referral.

Sessile Papillomatous Mass Sessile Papillomatous Mass Molluscum contagiosumMolluscum contagiosum

Appearance at lids Appearance at lids in this form not in this form not classical. classical.

Viral-induced Viral-induced lesionlesion

At the lid margin it At the lid margin it will produce a will produce a chronic follicular chronic follicular conjunctivitisconjunctivitis

Molluscum Molluscum contagiosumcontagiosum

The more classic The more classic presentation is multiple presentation is multiple shallow papules with a shallow papules with a central umbilication. Severe central umbilication. Severe outbreaks especially common outbreaks especially common as a complications of AIDSas a complications of AIDS

Molluscum Molluscum contagiosumcontagiosum

Classical presentation is of clusters of Classical presentation is of clusters of smooth papules with small central smooth papules with small central umbilication.umbilication.

A skin disorder caused by a DNA A skin disorder caused by a DNA virus of the poxvirus group.virus of the poxvirus group.

Generally resolves without therapy Generally resolves without therapy within 2 to 3 months in the within 2 to 3 months in the immunocompetent individual.immunocompetent individual.

Spread by physical contact with an Spread by physical contact with an infected individual or material (eg, infected individual or material (eg, clothing, towel).clothing, towel).

Molluscum Molluscum contagiosumcontagiosum

In immunocompromised patients, In immunocompromised patients, improvement of lesions was seen improvement of lesions was seen in individual cases with the use of in individual cases with the use of ritonavir, cidofovir (intravenous ritonavir, cidofovir (intravenous and topical), AZT, intralesional and topical), AZT, intralesional interferon alpha, and topical interferon alpha, and topical injections of streptococcal antigen injections of streptococcal antigen OK-432.OK-432.

Prevalance in HIV 5-18%Prevalance in HIV 5-18%

Molluscum contagiosumMolluscum contagiosum

MolluscumBodies

Molluscum Contagiosum in Molluscum Contagiosum in HIV/AIDSHIV/AIDS

10% of HIV-infected individuals 10% of HIV-infected individuals may develop hundreds of lesions.may develop hundreds of lesions.

Some become "giant" (greater Some become "giant" (greater than 1 cm), and display a than 1 cm), and display a predilection for the eyelids.predilection for the eyelids.

The lesions are often pruritic and The lesions are often pruritic and may become superinfected.may become superinfected.

Ocular lesions can be sight-Ocular lesions can be sight-threatening. Treatment is threatening. Treatment is unsatisfactory.unsatisfactory.

Antiretroviral therapy, particularly Antiretroviral therapy, particularly in the early stages, is sometimes in the early stages, is sometimes effective. effective.

Cyrotherapy and pricking lesion Cyrotherapy and pricking lesion with toothpick dipped in phenol with toothpick dipped in phenol may provide transient relief, but may provide transient relief, but recurrences common.recurrences common.

Cidofovir, an anti-Cidofovir, an anti-cytomegalovirus agent, is under cytomegalovirus agent, is under investigation for treatment of investigation for treatment of molluscum contagiosum.molluscum contagiosum.

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

Nodules and Tumors

Keratoacanthoma - Keratoacanthoma - rounded dome-rounded dome-shape nodule with keratin filled central shape nodule with keratin filled central umbilication.umbilication.

Keratoacanthoma - Keratoacanthoma - rounded, usually rounded, usually symmetric, dome shaped nodule with symmetric, dome shaped nodule with keratin- filled umbilicationkeratin- filled umbilication

Squamous Cell CarcinomaSquamous Cell Carcinoma The second most frequent skin carcinoma. The second most frequent skin carcinoma.  Usually arise in an area of damaged skin. Usually arise in an area of damaged skin.  Most often caused by ultraviolet radiation Most often caused by ultraviolet radiation

(UVR) or human papilloma virus (HPV) (UVR) or human papilloma virus (HPV) infection.  infection. 

On the face it presents most often as solitary On the face it presents most often as solitary or multiple nodules, which may be or multiple nodules, which may be hyperkeratotic or scaling.hyperkeratotic or scaling.

More likely to metastasize than basal cell More likely to metastasize than basal cell carcinoma.carcinoma.

Squamous Cell Carcinoma-Squamous Cell Carcinoma-EtiologyEtiologyUltraviolet RadiationUltraviolet Radiation

– Sunlight, phototherapy with oral PUVA, ionizing Sunlight, phototherapy with oral PUVA, ionizing radiation, or a history of methotrexate (tx. for radiation, or a history of methotrexate (tx. for psoriasis).psoriasis).

Age of onset:Age of onset: In the US, >55 years of age; In In the US, >55 years of age; In Australia and New Zealand, in the 20-30s among Australia and New Zealand, in the 20-30s among whites due to fair skin and hole in the ozone layer.whites due to fair skin and hole in the ozone layer.

Sex: Sex: Male>female; commonly on legs of females.Male>female; commonly on legs of females. Incidence: Incidence: In continental US, 12 per 100,000 white In continental US, 12 per 100,000 white

males.males. Race: Race: White skin with poor tanning capacity.White skin with poor tanning capacity.

Squamous Cell CarcinomaSquamous Cell CarcinomaNoteNote

asymmetryasymmetry

and lack ofand lack of

roundedrounded

domedome

appearanceappearance

Squamous Cell CarcinomaSquamous Cell CarcinomaNote asymmetry and lack of dome shape Note asymmetry and lack of dome shape 360 degrees.360 degrees.

Rounded, symmetric dome with central Rounded, symmetric dome with central nidus of keratin vs non-domed irregular nidus of keratin vs non-domed irregular border with larger central crater of keratinborder with larger central crater of keratin

Squamous cellSquamous cellCarcinomaCarcinoma

KeratoacanthomaKeratoacanthoma

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

Basal Cell CarcinomaBasal Cell Carcinoma

Nodulo-ulcerative type

Basal Cell CarcinomaBasal Cell Carcinoma Commonest form of skin cancerCommonest form of skin cancer Typically seen on sun-exposed areas Typically seen on sun-exposed areas

such as the face and neck.such as the face and neck. Originate from the basal keratinocyteOriginate from the basal keratinocyte Histologically reminiscent of skin Histologically reminiscent of skin

adnexal structures such as hair follicles.adnexal structures such as hair follicles. Locally invasive, but rarely metastasizeLocally invasive, but rarely metastasize

Basal Cell CarcinomaBasal Cell Carcinoma Age of onset:Age of onset: >40 years of age. >40 years of age. Sex: Sex: Males > females.Males > females. Incidence:Incidence: In US, 500-1,000 per 100,000; In US, 500-1,000 per 100,000;

>400,00 new cases each year.>400,00 new cases each year. Race:Race: Higher in Caucasians, rare in brown Higher in Caucasians, rare in brown

and black skinned people.and black skinned people. Predisposing factors: Predisposing factors:  White-skin with poor White-skin with poor

tanning capacity, albinos, exposure to x-rays tanning capacity, albinos, exposure to x-rays for facial acne, arsenic ingestion, heavy sun for facial acne, arsenic ingestion, heavy sun exposure before age 14.exposure before age 14.

Basal Cell Carcinoma - TypesBasal Cell Carcinoma - Types

1) Nodular (and nodulo-ulcerative): 1) Nodular (and nodulo-ulcerative): Most Most common.  Begins as a small, skin-colored common.  Begins as a small, skin-colored papule which shows fine telangiectasia and a papule which shows fine telangiectasia and a glistening pearly edge.  Frequently, there is glistening pearly edge.  Frequently, there is central necrosis that leaves a small ulcer with central necrosis that leaves a small ulcer with an adherent crust.  They are usually less than an adherent crust.  They are usually less than 1 cm in diameter (I.e. NODULES), but grow 1 cm in diameter (I.e. NODULES), but grow larger if present for several years.larger if present for several years.

NodularNodularBasal Cell Basal Cell CACA

Nodulo-ulcerative Basal Cell CANodulo-ulcerative Basal Cell CA

NoteNote

telangiectatictelangiectatic

vessels nearvessels near

centralcentral

ulceration.ulceration.

Differential Diagnosis:Differential Diagnosis: Nodulo-ulcerative Basal Cell CA vs Squamous cell Nodulo-ulcerative Basal Cell CA vs Squamous cell carcinomacarcinoma

Squamous cell - Central Squamous cell - Central crater dry, filled with crater dry, filled with brown-yellow, scaly, brown-yellow, scaly, greasy keratingreasy keratin

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

Cystic Basal Cell CarcinomaCystic Basal Cell Carcinoma Cystic: Cystic:

Become Become tense and tense and translucent, translucent, and show and show cystic spaces cystic spaces on histologyon histology

Cystic Basal Cell CarcinomaCystic Basal Cell Carcinoma

Cystic CavityCystic Cavity

Morpheaform (sclerosing) Basal Morpheaform (sclerosing) Basal Cell CarcinomaCell Carcinoma

Cystic CavityCystic Cavity

Morpheaform (sclerosing) Basal Morpheaform (sclerosing) Basal Cell CarcinomaCell Carcinoma

Management is difficult

Defining the Surgical margin

Sebaceous Gland CarcinomaSebaceous Gland Carcinomamasquerades may include seemingly recurrent chalazionmasquerades may include seemingly recurrent chalazion

Sebaceous Sebaceous Gland Gland CarcinomaCarcinoma

Masquerade Masquerade presentations may presentations may include an unusual, include an unusual,

unresponsive unresponsive unilateral blepharitis unilateral blepharitis with red thickened lid with red thickened lid

margins and margins and madarosis.madarosis.

Pagetoid Spread of Sebaceous Pagetoid Spread of Sebaceous Gland CarcinomaGland Carcinoma

Pagetoid Pagetoid spread can spread can significantly significantly complicate complicate the surgical the surgical management management of this of this disease.disease.

Review of Review of Macules and PatchesMacules and Patches RedRed, scaly in an older individual with light but , scaly in an older individual with light but

mottled or blotchy skin - Actinic keratosis / early mottled or blotchy skin - Actinic keratosis / early squamous cell CA.squamous cell CA.

BrownBrown, scaly in an older individual-, scaly in an older individual-Sebborheic keratosis or melanoma. Melanomas Sebborheic keratosis or melanoma. Melanomas rarely multiple, sebborheic commonly multiple. rarely multiple, sebborheic commonly multiple. Also follow ABCDs.Also follow ABCDs.

Papules and PlaquesPapules and Plaques

Multiple, small yellow papules - syringomaMultiple, small yellow papules - syringoma Multiple pink/tan papules with central umbilication - Multiple pink/tan papules with central umbilication -

molluscummolluscum Multiple very scaly papules on fair, blotchy skin - Multiple very scaly papules on fair, blotchy skin -

actinic keratosis (actinic may also be macule)actinic keratosis (actinic may also be macule) Yellow plaques - xanthelasmaYellow plaques - xanthelasma Brown to black plaque - seborrheic keratosis Brown to black plaque - seborrheic keratosis

especially if multiples. If solitary use ABCDs.especially if multiples. If solitary use ABCDs. Smooth plaque looking like scar- morpheaform BCCSmooth plaque looking like scar- morpheaform BCC

Nodules and TumorsNodules and Tumors Papillomatous, scalyPapillomatous, scaly

– Seborrheic keratosis - usually pigmented, always sessileSeborrheic keratosis - usually pigmented, always sessile– Solitary molluscum contagiosum at the lid margin - sessileSolitary molluscum contagiosum at the lid margin - sessile– Verrucous - sessile or cutaneous hornVerrucous - sessile or cutaneous horn– Squamous or viral papilloma - sessile or pedunculatedSquamous or viral papilloma - sessile or pedunculated

Non-papillomatous:Non-papillomatous:– With central crater of keratin - keratoacanthoma or squamous cell With central crater of keratin - keratoacanthoma or squamous cell

carcinoma - based upon symmetry and time of existencecarcinoma - based upon symmetry and time of existence– With central ulceration/translucent border - basal cell carcinomaWith central ulceration/translucent border - basal cell carcinoma– With no central ulceration - seborrheic keratosis or basal cellWith no central ulceration - seborrheic keratosis or basal cell– With no central ulcertaion at lid margin, disrupting lash line - With no central ulcertaion at lid margin, disrupting lash line -

sebaceous gland carcinomasebaceous gland carcinoma