See spot change: Lesion identification and management in primary care ERIN HENNESSEY DNP, APRN, FNP-C Learning objectives Discuss malignant skin lesions commonly seen in primary care. Identify common treatments and surgical procedures utilized for management. Review criteria for referral to appropriate specialty. Commonly seen malignant skin lesions in primary care. 1) Basal cell carcinoma 2) Squamous cell carcinoma 3) Melanoma 1
Skin Cancer Screening Recommendations from Various Organizations ORGANIZATION American Academy of Dermatology; Skin Cancer Foundation; and American Cancer Society RECOMMENDATION Annual complete skin examination for all patients Annual complete skin examination for all patients Age 20 to 39 years: complete skin examination every three years Age 40 years and older: annual complete skin examination U.S. Preventive Services Task Force and American Academy of There is insufficient evidence to recommend for or against Family Physicians Policy Recommendation for Periodic Health routine complete skin examination. Examination* Physicians should be alert to potentially malignant lesions when examining patients for other reasons, especially when they have risk factors for melanoma, and should consider referring patients with marker lesions (i.e., atypical nevi) to a skin cancer specialist. Non Melanoma and Melanoma Skin Cancer History and Physical With evaluating lesions that may be non healing or present for an extended period of time, it is helpful to obtain the following: - Ethnicity and skin color (fair, olive, African American) - Lifetime sun exposure (frequent vs. intermittent) - History of sunburn as a child or adult - Tanning bed use - Smoking or chewing tobacco use - Occupational exposure - Immunosuppression or organ transplantation (renal transplant patients have a 253 fold increase in the risk for squamous cell carcinoma) - History of radiation treatment for cancer or previous PUVA or UVA treatment for psoriasis Basal Cell Carcinoma Basal cell carcinoma is the most common invasive malignant cutaneous neoplasm. It is traditionally diagnosed by clinical identification and shave or scoop biopsy. The most common presenting complaint is a bleeding or scabbing sore that heals and recurs. Although it will not metastasize, if left untreated it will advance by direct extension and destroy normal tissue causing significant damage. 2
Basal Cell carcinoma Basal cell carcinoma Inferior lateral canthus Nodular Basal Call Carcinoma Left cheek / side burn area BCC Note the rolled borders BCC Location, Epidemiology and Pathogenesis 85% appear on the head and neck, 25 30% occur on the nose which is the most common site for basal cell carcinoma. 20% of tumors occur on sites that are typically sun protected such as the genitals and breasts. The average lifetime risk for Caucasians to develop BCC is 30% Individuals with fair skin, blonde or red hair, light eye color, poor tanning ability and sun damaged skin are at the highest risk. Male to female ratio is 2:1 with the exception being women under the age of 40. The closer one lives to the equator, the greater their risk is for developing BCC. UVB plays a greater role in BCC development than UVA Arise from basal keratinocytes of the epidermis and adnexal structures (e.g., hair follicles and eccrine sweat ducts) 3
- these folks took tanning to a whole new level Actinic Keratosis Clinically, these can be felt most times before they are seen. They begin as slightly rough textured skin and gradually an adherent yellow scale forms as the skin inferior becomes more erythematous. They can be biopsied, but most diagnoses are made based on clinical acumen. Often these progress to thickened or hypertrophic lesions and often times to squamous cell carcinoma. The extent of the disease may vary from a single lesion to diffuse lesions that most often present on the the forehead, balding scalp, temples and sideburn areas. Induration, erythema, pain, inflammation, ulceration and oozing are suggestive of progression to malignancy. Histologically is squamous cell carcinoma in situ confined to the epidermis. It is very difficult to say where a lesion stops being an actinic keratosis and begins to be SCC in situ because they are biologically the same. They are on a continuum of disease Actinic Keratosis 4
Management single lesions of Actinic Keratosis Cryotherapy liquid nitrogen is applied to the area causing separation of the dermis and epidermis. Benefits highly specific and in light skinned people is usually non scarring. Drawbacks in darker skinned folks, may cause hyperpigmentation. CO2 laser resurfacing, dermabrasion and chemical peels. Benefits fast and may also soften lines and aesthetically improve the appearance of skin. Drawbacks not covered by insurance and has a lower cure rate than topical therapies. Electrodessication and Curettage Surgical excision Management of multiple or diffuse actinic keratoses Field Directed therapy total sun avoidance is recommended. 5-fluorouracil topically applied chemotherapy agent Benefits good insurance coverage, can be done at home, does not harm healthy skin, can be used over a larger surface area. Drawbacks intense inflammation, erythema and crusting, at possible risk for secondary infection, poor compliance. Imiquimod topical immune response modifier cream. Applied 3x per week for 16 weeks or 3x per week for 4 weeks, 4 weeks of drug holiday, then a second 3x per week for 4 weeks. Can be reduced to 2x per week if there local skin reaction. Benefits reduction of 86.6% of Aks with 3.75% formulation. Drawbacks tricky prescription pattern for the patient to follow and possible issues with compliance. Picato (ingenol mebutate) plant based (Euphorbia puplus) from Australia once daily for 2-3 days. Creates the same inflammatory response as other topical chemotherapy agents with clearance in 2 weeks. Benefits compliance (2-3 days!) Drawbacks side effects and no long term studies available yet. Management of multiple or diffuse actinic keratoses (con t) PDT photo dynamic therapy topical chemotherapy provides much better histologic response Diclofenac (Solaraze) BID for 60 90 days great placebo control studies in transplant patients out of Germany: a complete clearance of AK lesions was achieved in 41% (9/22) compared to 0% (0/6) in the vehicle group. At 24 months 55% of the patients had recurrent AKs but there were 0 SCC within the group. 5
Squamous Cell Carcinoma 20% of all non melanoma skin cancers in the US are SCC (80% are BCC). They arise from the epithelium and common in the middle aged and elderly populations. Lifetime risk of 18 20% and rising. Risk factors include exposure to sunlight during childhood, sunburns, ionizing radiation, light skin, hazel, blue or green eyes, blond or red hair, outdoor occupations, freckling, living in the south, previous psoriasis therapy (oral psoralen and UVA radiation), and exposure to arsenic via medication or drinking water. UVB plays a major role in SCC. UVB damages DNA by inducing the formation of pyrimidine dimers and induces mutation of p53 tumor suppressor genes. These mutations are found in SCC lesions. Cell mediated immunity and immune function may be modulated by UVB as well. HPV virus 6 and 11 are found in genital tumors and HPV 16 in periungual tumors. Diagnosis is made by shave or scoop biopsy. Location, Epidemiology and Pathogenesis Most commonly found in sun exposed areas scalp, backs of the hands and the pinna BCC is rarely found on these sites. They may appear as flat, scaly lesions that indurate. Central crusting and ulceration is common. They can develop a thick, warty appearance on top. It is very common to see SCC of the mouth or lip in smokers or those who use chewing tobacco. Two major groups (based on malignant potential) A) Those arising in areas of radiation or thermal injury, chronic draining sinuses, and in chronic ulcers are typically aggressive and have a high frequency of metastasis. B) Those originating from actinically damaged skin are less aggressive and less likely to metastasize. Patients who have undergone solid organ transplantation or who are immunosuppressed need to be monitored closely for SCC. They can be very aggressive in these patients. Squamous Cell carcinoma invasive Squamous cell carcinoma Squamous cell carcinoma In situ Squamous cell carcinoma Of the lower right lip 6
Management of Basal cell and Squamous Cell carcinoma Mohs procedure micrographic surgery excellent in areas where conservation of tissue is salient (e.g., inner or outer canthus of the eye, nasal ala, vermillion border of the lip, fingers and ears. Benefits excellent cure rate (up to 99%) Drawbacks - time consuming and expensive. There is a risk that the Moh s surgeon will be unable to close the wound that day and the patient will have to find a plastic surgeon to close. PDT is FDA-approved for the treatment of superficial or nodular BCC.. A lightsensitizing agent, topical 5-aminolevulinic acid (5-ALA), is applied to the lesion in the physician s office. Subsequently, the medicated area is activated by a strong blue light; theoretically, this will selectively destroy BCCs while causing minimal damage to surrounding normal tissue Benefits - cure rates ranging from 70 to 90 percentdraw backs -. Some redness, pain, and swelling can result. Patients must strictly avoid sunlight for at least 48 hours, or UV exposure may further activate the medication, causing severe sunburn. Very time consuming. Electrodesiccation and curettage - The technique may not be as useful for aggressive BCCs, those in high-risk sites, or sites that would be left with cosmetically undesirable results. Typically, a round, whitish scar is left at the surgery site. Treatment of BCC and SCC (cont d) Surgical excision - gold standard treatment in our office. If the lesion is on the face, chest, shoulders, neck or lower extremities, referral to plastic surgery is warranted due to the possible need for skin grafting in these areas as well as an optimum aesthetic outcome for patients. Benefits - histologic margin control and rapid healing, and minimal pain Excellent cure rate with frozen section ( approx 99% in our office). Drawbacks requires a surgical procedure with anesthesia. BCC only: Erivedge (vismodegib) oral capsule used to treat adults with multiple BCCs, recurrent BCC or is not a candidate for surgery or radiation. Pregnancy category X. Females are required to use two forms of birth control for 7-8 months following treatment and Males may not donate semen or impregnate their partner for 3 months due to the birth defect risks associated. Benefit no surgical procedure needed. Drawbacks side effects and challenging to use in women of child bearing age. Malignant Melanoma Malignant melanoma is a cancerous neoplasm of pigment forming cells, melanocytes, and nevus cells. Clinically it s hallmarks are: irregularly shaped and pigmented patches, papules or plaques. Melanoma can arise from a preexisting lesion or de novo. There is no difference in the survival rate, but melanoma arising from a pre-existing lesion is more commonly found on the trunk, in younger individuals, and is more likely to be superficial spreading The earlier melanoma is diagnosed the better the changes of complete surgical eradication. Down and dirty - New research shows that having more than 11 nevi on one arm can indicate a increased risk for melanoma and patients can be appropriately advised to follow up with yearly skin exams 7
Melanoma Cutaneous melanoma types: Superficial spreading melanoma Nodular melanoma Acral lentiginous melanoma Lentigo maligna melanoma Epidemiology and Pathogenesis Melanoma is the fifth most common cancer in men and the sixth most common cancer in women. 1 in 50 Americans will develop melanoma in their lifetime For historical perspective, in 1935, the risk was 1 in 1500. The majority of melanoma in the US is diagnosed in the 15 50 year old age group. Patient with acute, episodic exposures to sunlight have a greater chance of developing melanoma than those with continuous exposure in either adulthood, adolescence or via occupational exposure. ABCDEs of identifying characteristics. A asymmetry B Border irregularity C Color variegation D Diameter > 6mm or approximately the size of a pencil eraser E Evolution or change Lesions can be red, white, blue, have notched borders or a papule or nodule within it. Ugly duckling rule 10% of melanoma do not follow the traditional rules. When a patient presents with any pigmented lesion that appear different from other nevi, it should be biopsied. 8
Malignant Melanoma Melanoma of the Lip Superficial spreading melanoma 70% of ALL cutaneous melanoma Location: Most commonly found on the trunks of men and the extremities of women (questionable correlation with intermittent sun exposure) Asymmetrical presentation with variation in color and border irregularities are common Papular or nodular component to the lesion may suggest a deeper invasion Can arise from preexisting moles 9
Nodular melanoma Nodular melanoma comprises 9-20% or invasive melanoma Occurs most often in the fifth or sixth decade and more often in men than women 2:1 It does not conform to the usual pattern is it occasionally flesh colored and resembles a flesh colored nevi or basal cell carcinoma. It is most frequently misdiagnosed as a blood blister, hemangioma, nevus, seborrheic keratosis or dermatofibroma. They have rapid growth patterns and tend to ulcerate. Lentigo Maligna Melanoma 4 15% of melanomas Located on the head, neck, arms and sun damaged skin Slow growing: 5 20 years Most commonly presents in the sixth or seventh decade Clinically appears as a brown to black or blue to black nodule Acral lentiginous melanoma 2 7% found in Caucasians 30 75% of melanomas in African American, Asian and Hispanic Located on the palms or soles as well as within the proximal nail fold 10
Management of melanoma A punch biopsy is performed and lesions are micro staged by a pathologist. If there is extension to the border, a wider excision is indicated. Breslow thickness, ulceration status, mitotic rate, peripheral and deep margin status, anatomic level of invasion and tumor infiltrating lymphocytes are all factored into the staging process. Surgical margins for invasive melanoma should be at least 1 2 cm clinically measured around the primary tumor. The decision to perform sentinel node biopsy is based on clinical staging. Pathologic stage 0 IA do not routinely need node biopsy. In the pipeline Sunscreen Scientists out of Yale have developed a method for encapsulating padimate O creating a bio adhesive nano particle that adheres to the stratum corneum and does not absorb into the skin. It is water resistant, but comes off with towel friction. Field treatment for actinic keratosis - Low-dose 5-FU/SA is an effective and well-tolerated treatment option licensed for the lesion-directed treatment of mild-to-moderate hyperkeratotic AK lesions and currently under investigation for field-directed treatment. Europe has developed guidelines for the treatment of actinic keratosis recently and I expect the US to adopt similar guidelines in the next couple years. Clinical snapshot If you suspect a non melanoma skin cancer on evaluation, shave or scoop biopsy is appropriate. For a suspected melanoma or pigmented nevus biopsy, punch is recommended to obtain Breslow thickness which better predicts prognosis. Encourage all patients to utilize chemical free sunscreen. Benefits of wearing chemical containing sunscreen outweigh the risk of damage from UVA and UVB rays in the absence of a better option. SPF 30 50 is recommended. Any SPF below 12 will prevent burn, but provide no protection against UVA / UVB radiation. Follow up for patients who have AKs or have had BCC or SCC treated should be evaluated once yearly with a full body skin exam. Patient s with a history of melanoma should be evaluated with a full body skin exam every 3 months for the first year then every 6 months or yearly there after. Patient s who have greater than 11 nevi on one arm on physical exam should be advised to obtain once yearly skin checks. 11
References Bradford PT, Goldstein AM, McMaster ML, Tucker MA. Acral lentiginous melanoma: incidence and survival patterns in the United States, 1986-2005.Arch Dermatol. 2009 Apr;145(4):427-434. doi: 10.1001/archdermatol.2008.609. Claas Ulrich, Antje Johannsen, Joachim Röwert-Huber, Martina Ulrich, Wolfram Sterry, Eggert Stockfleth Skin Cancer Centre Charité, Department of Dermatology, Charité Universitätsmedizin, Charité-Platz 1, 10117 Berlin, Germany Deng, Y., Ediriwickrema, A., Yang, F., Lewis, J., Girardi, M., & Saltzman, W. M. (2015). A Sunblock Based On Bioadhesive Nanoparticles. Nature Materials,14(12), 1278 1285. http://doi.org/10.1038/nmat4422 Habif, T. P. (2004). Clinical dermatology: A color guide to diagnosis and therapy. Edinburgh: Mosby. Lin, W. M., Luo, S., Muzikansky, A., Lobo, A. C., Tanabe, K. K., Sober, A. J., &... Duncan, L. M. (2015). Outcome of patients with de novo versus nevus-associated melanoma. Journal Of The American Academy Of Dermatology, 72(1), 54-58. doi:10.1016/j.jaad.2014.09.028 Marks, J. G., Miller, J. J., Lookingbill, D. P., & Lookingbill, D. P. (2006). Lookingbill and Marks' principles of dermatology. Philadelphia, PA: Saunders Elsevier. Ribero, S., Zugna, D., Osella-Abate, S., Glass, D., Nathan, P., Spector, T. and Bataille, V. (2016), Prediction of high naevus count in a healthy U.K. population to estimate melanoma risk. Br J Dermatol, 174: 312 318. doi:10.1111/bjd.14216 Werner RN, Jacobs A, Rosumeck S, Erdmann R, Sporbeck B, Nast A. Methods and Results Report - Evidence and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum. J Eur Acad Dermatol Venereol. 2015;29(11):e1-66. http://cms.sagepub.com/content/early/2016/07/19/1203475416659259 12