2. 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 Science University of Waterloo, CANADA

3. Commercial Interests None

4. Lid Lesion!!!!!  What is the most common clinical diagnosis provided with surgical specimens removed from the skin around the eye?

5. Skin The largest organ of the body  Epidermis  Dermis  Hypodermis –Hypodermis of the lids contains no adipose tissue. Sebaceous gland attached to follicles of lashes are the Glands of Zeis Lashes have no arrector pili muscle

6. Skin Epidermis Rete peg DermisPapillaryReticular

7. Histology of Epidermis LAYERS OF EPIDERMIS  Stratum germinativum –Basal layer - mitotic division only in this layer  Stratum spinosum –Prickle cell layer  Stratum granulosum –Granular layer  Stratum corneum –Keratin layer Papillary Dermis Rete peg Reticular Dermis

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

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

10. 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.

11. Primary Dermatological Descriptors  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

12. 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

13. Macules and Patches A hyperemic or red scaly macule representing actinic keratosis A hyperemic patch in contact dermatitis

14. Papules and Plaques  A papular rash on the forehead  Rashes start flat and then become raised. In these cases, terms can be combined, such as maculo-papular A Xanthelasma Plaque With papules and plaques you get a sense that the lesion is raised above the skin but not anchored deeply into it.

15. Nodules and Tumors  A nodule with keratin-filled central umbilication (belly-button)  In practice we usually do not use the accurate term tumor because of the implications it carries. We often call all such lesions either small or large nodular masses. With nodules and tumors you get a sense that these are anchored deeply into the skin

16. Vesicles and Bullae Small vesicles in poison ivyBullae in bullous pemphigoid These are also called “blisters” Remember that all such lesions, regardless of size, when on the cornea are called Bullae

17. Petechiae and Purpura Conjunctival petechiae in endocarditis Areas of purpura do not blanch

18. Secondary Dermatological Descriptors  Sessile: A lesion fixed to the skin on a broad base  Pedunculated: A lesion on a stalk  Papillomatous: A lesion exhibiting a surface resembling a cauliflower or artichoke  Scales: Shedding, dead epidermal cells, dry or greasy  Umbilicated: The lesion exhibits a central crater like an umbilicus or belly button  Crusts: Dried masses of skin exudates  Ulcer: Irregularly sized and shaped excavations extending into the dermis  Lichenification: Scales preserving natural skin creases

19. 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 L arge pedunculated papillomatous mass hanging from a stalk attached to the superior fornix

20. 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

21. Papillomatous Masses: Squamous papilloma Pedunculated papillomatous masses, often multiples. Most are viral induced, caused by human papilloma virus. (HPV)

22. Sessile Papillomatous Mass Verruca vulgaris (viral-induced wart)  Scaly nodule with Artichoke-like papillomatosis. Sometimes in clusters. At lid margin, can give rise to follicular conjunctivitis, like mollsucum.

23. Lichenification

24.  Macules and Patches

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

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

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

28. Actinic Keratosis

29. Actinic keratosis - can also appear as a scaly papule. Again note blotchy appearance of surrounding skin.

30.  Papules and Plaques

31. Syringoma - multiple, yellow papules representing benign growths of eccrine sweat glands. No treatment except for cosmesis.

32. Xanthelasma plaques  Hyper beta lipidemias

33.  Sessile Papillomatous Masses

34. Seborrheic Keratosis Rarely before age 30. Usually >50  Varies from scaly, non-inflamed macule, plaque to sessile, papular papillomatous lesion that varies in degree of pigmentation

35. Leser-Trelat Sign  The sudden appearance of numerous seborrheic keratoses in a short period can herald the existence of underlying malignancy, most often an adenocarcinoma of the GI system.

36. Seborrheic Keratosis - when this dark they can be confused with melanoma Often described as a “button stuck on the face” Often multiples, some still macules and others papules

37. An Aside: How to Evaluate Darkly Pigmented Lesions A Asymmetry – more asymmetry is worse B Borders – more irregular borders are worse C Color – more variegation of color is worse D Diameter – bigger than a pencil eraser or the tip of a Goldmann tonometer tip E Evolution (has it changed?)

38. Sessile papillomatous mass  A Papilloma

39. Factors in Assessment of Lid Lesions Alteration of lash-line Factors in Assessment of Lid Lesions - Alteration 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.

40. Sessile Papillomatous Mass Molluscum contagiosum  Appearance at lids in this form not classical.  Viral-induced lesion  At the lid margin it will produce a chronic follicular conjunctivitis

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

42. Molluscum 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 within 2 to 3 months in the immunocompetent individual.  Spread by physical contact with an infected individual or material (eg, clothing, towel).

43. Molluscum contagiosum  In immunocompromised patients, improvement of lesions was seen in individual cases with the use of ritonavir, cidofovir (intravenous and topical), AZT, intralesional interferon alpha, and topical injections of streptococcal antigen OK-432.  Prevalance in HIV 5-18%

44. Molluscum contagiosum Molluscum Bodies

45. Molluscum Contagiosum in HIV/AIDS  10% of HIV-infected individuals may develop hundreds of lesions.  Some become "giant" (greater than 1 cm), and display a predilection 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 effective.  Cyrotherapy and pricking lesion with toothpick dipped in phenol may provide transient relief, but recurrences common.  Cidofovir, an anti-cytomegalovirus agent, is under investigation for treatment of molluscum contagiosum. 7 y/o HIV+ boy with a CD4 count of 150 cells/microliter

46.  Nodules and Tumors

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

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

49. Squamous 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 (UVR) or human papilloma virus (HPV) infection.  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.

50. Squamous Cell Carcinoma- Etiology Ultraviolet Radiation –Sunlight, phototherapy with oral PUVA, ionizing radiation, or a history of methotrexate (tx. for psoriasis).  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.

51. Squamous Cell Carcinoma Noteasymmetry and lack of roundeddomeappearance

52. Squamous Cell Carcinoma Note asymmetry and lack of dome shape 360 degrees.

53. Rounded, symmetric dome with central nidus of keratin vs non-domed irregular 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.

54. Basal Cell Carcinoma Nodulo-ulcerative type

55. 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

56. Basal Cell Carcinoma  Age of onset: >40 years of age.  Sex: Males > females.  Incidence: In US, 500-1,000 per 100,000; >400,00 new cases each year.  Race: Higher in Caucasians, rare in brown and black skinned people.  Predisposing factors: White-skin with poor tanning capacity, albinos, exposure to x-rays for facial acne, arsenic ingestion, heavy sun exposure before age 14.

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

58. Nodular Basal Cell CA

59. Nodulo-ulcerative Basal Cell CA Notetelangiectatic vessels near centralulceration.

60. Differential Diagnosis: Nodulo-ulcerative Basal Cell CA vs Squamous cell carcinoma Squamous cell - Central crater dry, filled with brown-yellow, scaly, greasy keratin Basal Cell - Central crater ulcerated and moist, often with hemorrhage and translucent border

61. Cystic Basal Cell Carcinoma  Cystic: Become tense and translucent, and show cystic spaces on histology

62. Cystic Basal Cell Carcinoma Cystic Cavity

63. Morpheaform (sclerosing) Basal Cell Carcinoma Cystic Cavity

64. Morpheaform (sclerosing) Basal Cell Carcinoma Management is difficult

65. Defining the Surgical margin

66. Sebaceous Gland Carcinoma masquerades may include seemingly recurrent chalazion

67. Sebaceous Gland Carcinoma  Masquerade presentations may include an unusual, unresponsive unilateral blepharitis with red thickened lid margins and madarosis.

68. Pagetoid Spread of Sebaceous Gland Carcinoma  Pagetoid spread can significantly complicate the surgical management of this disease.

69. Review of Macules and Patches  Red, scaly in an older individual with light but mottled or blotchy skin - Actinic keratosis / early squamous cell CA.  Brown, scaly in an older individual- Sebborheic keratosis or melanoma. Melanomas rarely multiple, sebborheic commonly multiple. Also follow ABCDs.

70. Papules and Plaques  Multiple, small yellow papules - syringoma  Multiple pink/tan papules with central umbilication - molluscum  Multiple very scaly papules on fair, blotchy skin - actinic keratosis (actinic may also be macule)  Yellow plaques - xanthelasma  Brown to black plaque - seborrheic keratosis especially if multiples. If solitary use ABCDs.  Smooth plaque looking like scar- morpheaform BCC

71. 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