Fundamentals of Photobiology & Skin Cancer

Skin cancer Epi:

Skin cancer Epi:

• 1 in 5 Americans will develop skin cancer by the age of 70.

• Skin cancer= MC in US and worldwide.

• 5 or more sunburns, especially early in life = 2x  risk for melanoma.

• Melanoma, if detected early =  99% 5-year survival rate

• Melanoma + cervical lymph node metastases = 5% 5-year survival rate 

• Almost all skin cancers are caused by radiation from the sun or other sources such as tanning beds.

• BCC = MC skin Cancer

• SCC = 2nd MC

• Prevention = Regular Broad Spectrum Sunscreen (UVA & UVB) SPF 30 or higher; reduces risk by 40%

• Organ transplant patients are approximately 100 times more likely than the general public to develop skin cancer

Draw out the EMS

1. What are UV Rays?

2. Imp?

3. UVA vs B

• What are UV rays?

  • Sunlight emits a wide range of radiation energy: 

    • 1.Visible 

    • 2.Ultraviolet (UV) 

    • 3.Infrared light.

  • UV = invisible + most damaging. 

• Importance of UV

  • UVA/B = main factors responsible for DNA damage -> Skin Cancers

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UVA vs B:

• A:

  • Absorbed  deep into dermis

  • Causes TANNING, PHOTOAGING (pre-mature wrinkles).

  • SKIN CANCER

  • Penetrates through glass

• B:

  • Absorbed primarily within the epidermis

  • Major cause of SUNBURNS  and delayed tanning, 

  • Key role in development of SKIN CANCER

  • Do not penetrate glass but reflect off reflective surfaces such as water, sand, snow, ice.

• NOTE C:

  • Most dangerous but do not reach the earth’s surface due to the protective Ozone layer

UVA CAUSING EXTREME PHOTOAGING

Describe the multimodel pathogenesis of Skin Cancer

SKIN CANCER : Multi-Step Patho

• UV mediated DNA damage

  • Direct damage: Thymine-dimer formation

  • Indirect damage: (ROS) formation

• Genetic mutation formation

  • Inactivation of tumor suppressor genes 

    • (p53, PTCH, CDKN2A) 

  • Activation of oncogenes 

    • (Ras, BRAF)

  • Evasion of apoptosis 

    • (p53, Bcl-2)

  • Limitless replicative potential 

    • (Telomerase)

1. MOA for how UV damage leads to cancer?

What is the UV Index?

Factors Affecting UV Index:

Factors Affecting UV Index:

• ALTITUDE

  • Higher = more UV

• TIME OF DAY

  • Sun rays are strongest from 10 am to 4 pm.

• SEASON

  • Spring and summer experience higher levels of UV radiation than winter months.

• PROXIMITY TO THE EOIJATOR

  • Equator = higher UV Index.

• REFLECTIVE SURFACES

  • Water , sand, and snow

What type of UV activate Vit. D and how?

Describe the Fitzpatrick skin typing test

• What is it?

• Types:

Fitzpatrick skin typing test

• What is it?

  • numerical classification (Types I-VI) for human skin shades 

    • relates to sunburns and skin tanning.

• Types:

  • Type I :  always burns, never tans 

  • Type II : always burns, minimal tan 

  • Type III : burns minimally, tans moderately and gradually

  • Type IV : burns minimally, always tans well 

  • Type V :rarely burns, tans easily

  • Type VI :never burns, tans deeply

What are the different types of Skin Cancer

Types of Skin Cancer

• Non-melanoma (NMSC)

  1. Pre-cancer: Actinic Keratosis (AK) 

  2. Squamous Cell Carcinoma (SCC)

  3. Basal Cell Carcinoma (BCC)

• Melanoma 

  1. Dysplastic nevi: precursor for melanoma

  2. MELANOMA

Actinic Keratosis

Describe Actinic keratosis

• Clinical characteristics:

• Classic presentation

• Classic history:

• Likely causes: 

• Risk factors: (3)

• Precursor to

• Tx (4)

• Epi

Actinic keratosis = Solar keratosis= Pre-cancer

• Clinical characteristics:

  • Skin-colored to reddish brown or yellowish ill-defined 

  • Macule or papule w/ dry adherent scale. 

• Classic presentation

  • Fair skinned (Fitzpatrick I-III) + sand-paper feel + red/brown macule 

    • scalp, forehead, cheek or forearm. 

• Classic history:

  • Pt has history of reoccurring red spot that they keep scratching off 

• Likely causes: 

  • UV damage induced DNA mutations and subsequent cell dysplasia. 

• Risk factors: 

  • Fitzpatrick I-III

  • Prior sunburns esp as a child, 

  • Unprotected  repeated UV exposure

• Precursor to

  • SCC

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Treatments:

• Cryotherapy: Liquid Nitrogen (LNO2)

• PDT (Levulan + Blue Light)

• Excision with biopsy if hypertrophic

• Various topical therapies

  • 5 Flourouracil (5-FU)

  • Imiquimod

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Epi:

• majority of those diagnosed are white males over 40.

Histology of different skin cancers

Dermatopathology of an AK:

• KERATINOCYTES OF THE BASAL LAYER ARE ABNORMAL: EPIDERMIS EXHIBITS HYPERKERATOSIS AND PARAKERATOSIS

Dermatopathology of SCC

Describe SCC:

• What is it?

• Arises w/in:

• Locations:

• Importance:

• SCC Types (3)

Squamous cell skin cancer (SCC)

• What is it?

  • Common form of keratinocytic skin cancer

• Arises w/in:

  • solar/actinic keratosis

  • SCC in situ

• Locations:

  • MC = head, neck or hands of older patients

• Importance:

  •  Account for 1/3 of deaths from skin cancer among persons 65 - 84 y/o

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SCC types

• In-situ

  • Bowen’s disease

  • Erythroplasia of Queyrat

• Invasive SCC

• Keratoacanthoma

Bowen’s disease: Squamous Cell Carcinoma in-situ

Describe Bowen’s disease

• Helpful descriptors: (3)

• Risk Factors: (5)

• Classic distribution:

• Typical management: (5) 

Squamous cell In-situ = Bowen’s disease

• Helpful descriptors: 

  • Red crusty or scaly patch, 

  • Erythematous, 

  • Ulcerated plaque + irregular borders

• Risk Factors:

  • sun-damage, 

  • age, 

  • immunosuppression, 

  • HPV 16, 

  • arsenic exposure

• Classic distribution:

  • sun exposed regions, 

    • head, neck, forearms, hands, legs

• Typical management: 

  • Surgical removal, 

  • cryotherapy, 

  • topical chemotherapy, 

  • 5- FU, 

  • imiquimod

Squamous cell carcinoma in-situ

SCC in-situ

SCC in-situ:

• In-situ SCC; uncircumcised men, may progress to invasive SCCErythroplasia of Queyrat

Invasive Squamous cell carcinoma

• Erythematous nodule, indurated lesion, Sun exposed skin, Men> women

  Slow growth

Keratoacanthoma:

Squamous Cell Carcinoma: Cutaneous Horn: Well differentiated squamous cell carcinoma

1. Dx/ Treatment of SCC

2. Prognosis

Dx/ Treatment of SCC

• Biopsy = needed for Dx

• Tx = complete surgical excision 

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Prognosis:

• SCC = locally invasive and destructive

• Prognosis = good for properly removed SCCs

  • Pt @ increased for other skin cancers

• Metastases in 1-3 % of cases

  • To lymph nodes (50-73% survival)

  • Distant sites (lungs) incurable

BCC

Describe BCC

• What is it?

• Epi:

• Course:

• Risk Factors:

• Types (4)

Basal Cell Carcinoma (BCC)

• What is it?

  • Neoplasm of basal keratinocytes : 

• Epi:

  • Incidence: men>women

  • 2.8 million/year in the US in 2010

  • Can occur at any age, but is more common after age 40.

• Course:

  • Locally invasive, but rarely metastasizes.

• Risk Factors:

  • intermittent UV exposure, ionizing radiation, indoor tanning, chemicals, arsenic, psoralen plus UVA, coal tar, Fitzpatrick I, organ transplantation and some genetic syndromes: xeroderma pigmentosa, oculocutaneous albinism, Muir-Torre syndrome, basal cell nevus syndrome (Gorlin syndrome)

• Types

  • Nodular

  • Superficial

  • Infiltrative (Morpheaform)

  • Pigmented BCC

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NOTE: * 7% of all BCCs are pigmented: any BCC subtypes can be pigmented, but the nodular subtypes comprises the majority of pigmented. Pigmented BCC most commonly occur on head & neck.

Nodular BCC

Describe the Characteristics of Nodular BCC (5)

Nodular BCC

• Epi:

  • Most common subtype >50%

• Characteristics:

  • Chronic lesion

  • Easy bleeding

  • Pearly border

  • Surface telangiectasias

  • Face, cheeks, nose, melolabial fold, forehead and eyelids most common.

Superficial BCC

Characteristics of Superficial BCC (4)

Superficial BCC Characteristics:

• Erythematous scaly plaque

• Slow growth

• Asymptomatic

• Trunk, extremities, face

Pigmented BCC

Characteristics of Pig. BCC

Pigmented BCC

Characteristics

• 7% of all BCC are pigmented

  • Any BCC can be pigmented

  • MC = nodular

• Typical black discoloration

  • (Melanin deposits)

• Most common area is head and neck

Infiltrative (Morpheaform) BCC

Describe Infiltrative (Morpheaform) BCC

• Characteristics: (6)

• MOA:

• Tx:

Infiltrative (Morpheaform) BCC

• Characteristics:

  • Uncommon variant 10% of all BCC

    •  Aggressive with local tissue invasion

  • ILL defined margins, 

  • Slightly depressed, 

  • Flat, 

  • Fibrotic 

  • Firm.

  • Marked subclinical extension

• MOA:

  • Tumor cells -> proliferation of fibroblasts w/in dermis + increased collagen deposition  (sclerosis) 

    • white, yellow or waxy scar.

• Tx:

  • Mohs micrographic surgery is the treatment of choice

BCC; Rodent Ulcers

Dermatopathology of BCC

Basal Cell Carcinoma Tx options

Basal Cell Carcinoma Tx options

• Excisional biopsy (traditional vs Mohs)

  • - 95% cure rate

• Electrodessication and curettage (ED&C)

• Radiation therapy

• Imiquimod (topical 

  • -50-75% cure rate

NOTE:

• Even with low chance of metastasis, patients must still be followed after treatment.

How to do MOHS micrographic surgery

List the Risk factors for the development of non-melanoma skin cancer (NMSC)

Risk factors for the development of  non-melanoma skin cancer (NMSC)

• Fair Skin (Fitzpatrick types I-III)

• Family history 

• Genetic syndromes: 

• Chronic sun exposure (UV rays)

• Radiation therapy

• Arsenic ingestion, topical tars and oils

• Organ transplant patients

• Viral infection (some strains of HPV)

• Medications (voriconazole, B-RAF inhibitors, PUVA therapy)

• Environmental pollutants

Dysplastic Nevus

Describe Dysplastic or Clark nevus

• What are they?

• Characteristics? (3)

• Clinical Procedure: (3)

Dysplastic or Clark nevus

• What are they?

  • precursors for melanoma

• Characteristics?

  • Larger + irregular shape

  • Uneven color/edges

  • Can be hereditary 

• Clinical Procedure:

  • Important to note changes in moles 

    • common during pregnancy or with oral contraception. 

  • Always check ABCDE changes

  • Always biopsy if suspicious for melanoma

Malignant Melanoma (MM)

Describe Melanoma 

• What is it

• Epi:

• Pathogenesis:

• Melanoma therapies

• Risk factors 

• Clinical types of Malignant Melanoma (5)

Melanoma 

• What is it

  • aggressive skin cancer resulting from malignant transformation of melanocytes

• Epi:

  • < 2% global cancer diagnoses

  • Responsible for 80% of skin cancer deaths

  • MC cancer in ages 25-29

• Pathogenesis:

  • BRAF = most frequent mutated oncogenes

    •  V600E -> constitutive act. Of BRAF/MEK/ERK (MAPK) signaling pathway. 

• Melanoma therapies

  • Mutated BRAF = useful target for molecular therapy

    • BRAF kinase inhibitors (vemurafenib)

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Risk factors 

• Fair, blonde or red hair and blue eyes 

• Intermittent sun exposure (Hx sunburns, tanning beds use)

• Freckles and melanocytic nevi

• Family history

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Clinical types of Malignant Melanoma

• Superficial spreading melanoma

• Acral lentiginous melanoma

• Lentigo maligna melanoma

• Nodular melanoma

• Amelanotic melanoma

Melanoma Histo Characteristics (5)

Melanoma Histo Characteristics

• Consumption of epidermis, 

• Pagetoid spread of melanocytes, 

• Nests of melanocytes with variable size and shape 

  • (which may be confluent and lack maturation), 

• Melanocytes w/in lymphovascular spaces,

• Deep and atypical mitoses and increased apoptosis.

Histopathology of Melanoma

Acral lentiginous melanoma

Superficial spreading melanoma

Acral lentiginous melanoma- very aggressive

Lentigo maligna melanoma

Nodular melanoma

Melanoma

Differentiate between:

• Melanoma in Situ

• Invasive Melanoma

• Metastatic Melanoma

Describe Breslow & Clark Level Staging System

• Dif:

• Clark Levels:

Breslow & Clark Level Staging System

• Dif:

  • Breslow = thickness of melanoma

  • Clark  = staging system that describes the layer that has been breached

• Clark Levels:

  • Level 1: 

    • Melanoma confined to epidermis

  • Level 2: 

    • Melanoma has invaded the papillary dermis (the outermost layer of the dermis)

  • Level 3: 

    • Melanoma has invaded throughout the papillary dermis and is touching on the next, deeper layer of the dermis.

  • Level 4: 

    • Melanoma has reticular dermis.

  • Level 5: 

    • Melanoma has invaded the fat under dermis.

Describe Melanoma Prognosis:

Describe Course of Melanoma

Melanoma Prognosis:

• VERTICAL INVASION = worst prognosis

  • If penetrated basement membrane, dermis and entered subcutaneous fat, 5 year survival is = 49%

• S-100 protein can help determine prognosis

  • Elevated correlates with worse prognosis.

• Detection of melanoma at early stages is crucial.

• Also correlated w/ Breslow:

  • Good prognosis Breslow < 1mm

  • Intermediate prognosis: Breslow 1-4 mm

  • Bad prognosis: Breslow > 4 mm

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Course of Melanoma:

• Initially, spread horizontally -> vertical growth 

• Can spread hematogenously or via lymphatics. 

• MC metastasize: brain, lung, liver and bone