malignant cutaneous neoplams sbhpp

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

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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

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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

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Crusted, ulcerated, bleeds easily

Nodular Basal Cell Cancer

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Slowly developed, bleeding, papule that has been there

Superficial Basal Cell Cancer

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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.

QUIZ

©kathleenhaycraft@yahoo.com

©kathleenhaycraft

◦ ©kathleenhaycraft

©kathleenhaycraft

©kathleenhaycraft

©kathleenhaycraft

©kathleenhaycraft

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

Contact me:

kathleenhaycraft@yahoo.com 5737952808 7 San Remo, Hannibal, MO