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MALIGNANT CUTANEOUS NEOPLAMS
SBHPPKathleen Haycraft, DNP, FNP/PNP-BC, DCNP, FAANP
Objectives
Identify actinic keratosis (vs keratoses) and squamous cell cancer
Determine treatment plans for actinic keratosis and squamous cell cancer including pharmacology, surgery, radiation, light treatments of the above
Identify basal cell cancer
Determine treatment plans for basal cell cancer including pharmacology, surgery and radiation
Identify dysplastic nevi and malignant melanoma
Determine treatment plans for dysplastic nevi and melanoma.
Conflicts of Interest:
Celgene
Lilly
Pfizer
Abvie
Valeant
Novartis
Sanofi/Aventis/Regeneron
Maui Dermatology Faculty
None will influence the discussion today.
Actinic Keratosis
◦ AK
©kathleenhaycraft
Etiology/Pathophysiology
More likely
Over 40, more common in men.
Have a history of frequent or intense sun exposure or sunburn.
Have pale skin, red or blond hair, and blue or light-colored eyes.
Progressively lower incidence in 1-5, almost nonexistent in 6.
Personal history of an actinic keratosis or skin cancer.
Have a weak immune system as a result of chemotherapy, chronic leukemia, AIDS or organ transplant medications.
If not treated they have at least a 20% chance of conversion to SCC.
Etiology/Pathophysiology
A skin biopsy is indicated to confirm the diagnosis and to rule out invasive squamous cell carcinoma for suspicious or more advanced lesions (hyperkeratosis, increased erythema, or induration or nodularity) or if they are recurrent that did not respond to therapy.
UV-induced mutations in key genes, including TP53 and deletion of the gene coding for p16 tumor suppressor protein.
Appearance
Small red, brown, flesh colored, pink, or white scaly patches that do not go away.
Distribution pattern on face, ears, scalp, hands, but may occur anywhere.
May be numerous and coalesce.
If they itch, are tender, or bleed they need to be biopsied.
Types of Actinic
Keratoses
◦ AK
◦ Pigmented AK
Treatment
Cryotherapy.
Photodynamic Therapy after treatment with ALA or MLAthat activates the light in the AK to destroy the lesion.
Electrodessication and curettage.
Shave biopsy to treat and assess that it has not converted.
Treatment
Laser resurfacing.
Topical agents such as 5-FU (Efudex, Carac both may increase nodular BCC), Imiquimod (Aldara, Zyclara), Picato (ingenol mebutate), and diclofenac (Solaraze, Voltaren) gel. Nearly all topical agents cause tremendous inflammation
AK is a field disease and needs to be treated as such:
Cryo
PDT
Laser treatments
Chemical peels
Discuss Prevention
UVA, UVB, UVC waves.
Ultraviolet rays are electromagnetic radiation with a wave length less than that of visible light.
UVA penetrate deeply into the dermis and subcutaneous tissue (may easily penetrate glass).
UVB penetrate into the epidermis and upper dermis.
UVC usually bounce off the ozone layer.
UVA waves are associated with autoimmune disease.
More on UV
UVA, UVB, and UVC can all damage collagen and accelerate aging
UVA and UVB destroy Vitamin A in the skin further damaging collagen and accelerating photo-aging.
UVA was not recognized to be as harmful but it creates many oxygen free radicals which cause further DNA damage
UVA is immunosuppressive. Because UVA is not measured by most SPF testing there is no good measurement for UVA protection. According to the Skin Cancer Foundation Even if it’s not hot outside, 50 to 80 percent of UV rays still burn right through the clouds.
More on UV
UVA waves give a quicker tan but a non-protective tan.
UVB waves take about two days to begin to create a tan but the tan is protective.
However, the production of melanin by UVB is called melanogenesis and direct DNA damage occurs.
Melanogenesis increases the risk of cutaneous carcinoma.
Balanced discussion
Being outdoors reduces your risk of depression, obesity, hypertension, MI, stroke, and solid organ cancer
Vitamin D replacement does not reduce these risks
Wearing sun protection does not reduce vitamin D levels
What is the message? Be outdoors with sun protection.
Prevention
Broad rimmed UV hat.
Broad rimmed sunglasses.
Avoid mid day sun.
Wear sunscreen DAILY (minerals better and chemicals may be associated with alopecia.
Think of the bucket theory with sunscreen.
Long sleeve white UV shirt
Clinical Pearl
If it is severely itchy or tender biopsy it.
Remember that actinic keratosis is a field disease
and needs to be treated as such.
Nothing like MOHS on a patient with BCC or SCC that has been recurrently
treated by cryo you may be there for 6 or more stages.
Recent study shows if severe hypertension post PDT,
likely to have BCC.
Squamous cell cancer SCC
©kathleenhaycraft
Etiology/Pathophysiology
Second most common.
Rarely fatal except in transplant and immune compromised patients where mortality can exceed 20%.
Linked to alcohol, HPV, and tobacco as well as UV.
Unlike BCC, SCC more linked to chronic rather than intense intermittent UV exposure.
PUVA is a risk factor.
Appearance
An ulcer or plaque with scaling,
ulceration, and/or crusting.
Frequently on sun exposed skin.
May present as a cutaneous horn
(height greater than width).
Peri-neural involvement is associated with pain, numbness,
change in vision, or muscle twitching.
Types of Squamous Cell Cancer
SQUAMOUS CELL CARCINOMA IN SITU
SQUAMOUS CELL CARCINOMA
KERATOACANTHOMA IS RAPIDLY GROWING
Treatment
Surgical excision. MOHSEDCT on low risk lesions, low risk sites, and low risk patients.
Radiation.
If patients have invasive SCC, on high risk areas, in high risk patients consider imaging for metastasis first.
SCC has a higher mortality rate than melanoma in individuals over 80
Consider high risk location site….need to be referred for treatment sooner
Systemic treatment
Libtayo (cemipulab)for locally advanced of metastatic squamous cell cancer
AE include: immune mediated disease pneumonitis, colitis, hepatitis, encephalitis, thyroid, pituitary, DM, SJS, TENS, connective tissue disease, myocarditis, pancreatitis, aplastic anemia, severe infusion reactions, teratogenic
Pearls
If the height of a cutaneous horn exceeds the width is is more apt
to be benign.
If more than 50 % of the base of a lesion is
erythematous it is more likely to be a SCC.
Immune compromised patients are at high risk for metastasis and may need imaging prior to
treatment.
Basal Cell Cancer
© Kathleen Haycraft
Crusted, ulcerated, bleeds easily
Nodular Basal Cell Cancer
© Kathleen Haycraft
Slowly developed, bleeding, papule that has been there
Superficial Basal Cell Cancer
© Kathleen Haycraft
Pink patch of skin that has been there
Etiology/Pathophysiology
Most common skin cancer.
Represent 90% of cutaneous carcinoma.
Almost never metastasize but can cause significant local destruction.
Risk factors include: low Fitzpatrick score, sun exposure, weakening of the immune system by disease or medication.
3 in 10 Caucasians will develop a BCC in their lifetime.
Appearance
Appears as a small, dome shaped
bump covered with telangectasias.
It may appear pearl like or
shiny/translucent.
They are usually somewhat firm to
the touch.
Appear as a “pimple that comes and
goes or comes and stays or a patch that comes and goes or comes and stays”.
Types of BCC
Superficial BCC
Nodular BCC
Pigmented BCC
Cystic BCC
Infiltrative BCC• Morpheaform• Micronodular BCC
Types of BCC ◦ Nevoid Basal Cell Carcinoma Syndrome also known as Gorlin syndrome.
Treatment
Shave Biopsy to determine diagnosis but all biopsies that involve skin cancer require excision or other treatment beyond the biopsy even if margins are negative.
EDCT
Topical
Excision
Treatment
◦ MOHS
◦ Topical Imiquimod, Picato (ingenol mebutate) under aluminum disc
◦ Radiation therapy
◦ PDT with photosensitizer (ALA, MAL)
Systemic therapy for BCC
Hedgehog PathwayInhibition For locally advanced, recurrent or cannot be treated with
other therapy…on again off again treatment due to AE
Muscle spasms Severe alopecia Fatigue Nausea/Diarrhea
Anorexia and weight loss and abnormal taste
(ageusia)
Musculoskeletal pain
Severe teratogenic
Worsening kidney function, elevated blood
sugar, liver enzyme
elevation, anemias
Odomzo (sonidegib), Erivedge (vismodegib), Daurismo (glasdegib)
Pearls
If a BCC occurs at a site where you
have had recurrent
cryo…always MOHS.
The pimple or patch that comes
and goes.
DYSPLASTIC NEVI AND MELANOMA
Dysplasia, mild, moderate, severe, Clark’s etc.
© Kathleen Haycraft
Asymmetric
Irregular Border
Dark Black
6mm
It is getting bigger
What do you do with this?
© Kathleen Haycraft
Etiology/Pathophysiology
Atypical nevi (Dysplastic nevi). Atypical to the eye and dysplastic to the microscope.
1Some atypical nevi become melanoma but the majority do not.
2Roughly half of melanomas arise in these dysplastic nevi whereas the other half arise de novo.
3Melanomas can occur on sun or non-sun exposed sites.
4
Etiology/Pathophysiology
Cytological atypia is of more significance than architectural atypia.
Individuals with dysplastic nevus syndrome have an associated CDKN2A gene defect.
If 50 or more, 10 times increased risk of melanoma.
Presentation
ABCDE are helpful with these nevi.
Ugly duckling…the pretty duckling…what doesn’t belong with
the rest.
Gestalt…if the patient worries consider
biopsy
Treatment
Individuals with multiple dysplastic nevi should be monitored in a dermatology setting annually.
Some dermatologists excise all, some monitor, our system is:
Mild….Monitor
Moderate….Most monitor
Severe…Excise with 9 mm margin
Melanoma
© Kathleen Haycraft
New lesion, dark and asymmetric
Melanoma
© Kathleen Haycraft
When you see it with a derm-llite it is so easy
Lentigo Maligna
© Kathleen Haycraft
Chronically UV exposed skin
Changing small structures
Peppering
Etiology/Pathophysiology
Melanoma is a malignancy arising from the melanocyte.
Less common than basal or squamous but results in 75% of the deaths from cutaneous carcinoma.
Caused by damage to the DNA by UV rays.
Genetic links with BRAF, MEK, CDND2A and many more.
Genetic risk is higher with associated BRCA mutations.
Eumelanin is more protective than pheomelanin
Appearance
◦ May appear as ◦ Asymmetric◦ Irregular border◦ Black, gray, blue, red, white or multiple
colored lesion◦ White veil◦ Greater than 6 mm diameter◦ Evolving
◦ Nodular elevated, firm, and growing.
Types of Melanoma
Superficial spreading melanoma
Nodular melanoma
Lentigo maligna melanoma
Acral lentiginous melanoma
Mucousal melanoma…ANYwhere
Intraocular melanoma (Uveal)
Desmoplastic melanoma (connective tissue disease)
Treatment
Biopsy properly.
Treatment indicated by:
• Breslow depth (Clark value with thin areas)• Ulceration• Mitotic Index• Castle Genetic assessment• Many personal factors
Surgery, SLNB, chemotherapy, checkpoint inhibition, radiation, interferon, and vaccine.
Lentigo maligna is a field disease.
Melanoma pharmacology treatments
Ipilumab (Yervoy) targets CTLA-4 pathway Side effects…may lead to serious colitis that can cause death
Hepatitis
Serious TENS skin rashes
Neuralgia
Endocrine…thyroid, pituitary and adrenal
Graft vs host as often use with bone marrow stem cell prior to treatment
Infusion reactions
Nivolumab (Opdivo) targets PD-1/PD-L1 pathwayInfusion reactions
Endocrine..thyroid, pituitary and adrenal
Renal and hepatic impairment
Increased amylase and lipase
Pneumonitis
Serious colitis
Encephalitis
Serious Tens skin rashes
Muscle and chest pain
More Melanoma Treatments
◦ Pembrolizumab (Keytruda) Targets the PD-1/PDL1 pathway◦ Anemia and lymphocyte reduction◦ Hypothyroid◦ Cellulitis◦ Abnormal liver function including autoimmune
hepatitis◦ Pneumonitis◦ Arrythmias◦ Bullous pemphigoid◦ Guillain-Barre◦ Hypoxia◦ Renal impairment◦ Pneumonia◦ SJS and TENS◦ Vasculitis
Melanoma treatments continued
Aldesleukin (Proleukin) given IV targets IL2/IL2R
Capillary leak syndrome third
space with hypotension and organ
hypoperfusion
Arrythmias Angina and MI Respiratory failure GI bleeding Renal
insufficiency
Cognitive impairment and
coma
Infection and sepsis risk
Combination of nivolumab and ipilumab
Melanoma treatment continued
Interferon (Intron A ) alfa-sb target the IFNAR1/2 pathway for some subsets of melanoma
• Flu like symptoms• May aggravate preexisting cardiac symptoms• Depression and suicidal behavior• Supression of bone marrow• Loss of vision through a variety of mechanisms• Hypo or hyperthyroid• GI including hepatoxicity• Respiratory failure• Autoimmune diseases and rhabdomyolysis• Peripheral neuropathy• Used with Ribavirin tetragenic
Peginterferon alfa 2b (sylatron/PEG-Intron) targets the above pathways as well
• Similar to above
Melanoma treatment
T-VEC (Imlygic) modified herpes virus infects tumor cells for some subsets of melanoma
Injected into local cutaneous, sub-q and nodal lesions
Precaution in handling
• Herpetic infection• Local reaction• Also, may chemotherapeutic drugs are used for
melanoma mets
Pearls◦ Many of the systemic therapies that are
immune based can cause psoriasis, psoriatic arthritis and vitiligo. Do not treat these symptoms they are a positive sign of treatment.
©kathleenhaycraft
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Questions
On the topic
Off the topic
Favorite Sites
◦ Websites for patients and providers:
◦http://www.mayoclinic.com/health/DiseasesIndex/DiseasesIndex
◦ http://emedicine.medscape.com/dermatology
◦ http://www.nlm.nih.gov/
◦ http://www.dermnetnz.org/sitemap.html
◦ Wolf, K., & Johnson, R. A. (2013). Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology (7th Ed. ed.). Columbus OH: McGraw Hill.
References Bolognia, Schafer and Cerroni (2017). Dermatology: 4th ed, Elsevier
Habif (2015). Clinical Dermatology, 6th ed, Elsevier
