Skin Cancer

September 17th 2008Cormac Joyce

Basal Cell Carcinoma

BCC

Most common cutaneous malignancy Almost NEVER metastasizes• Often leads to local destruction Usually arise from epidermis or outer

root sheath of hair follicle

Epidemiology

Most common in fair skin• Fitzpatrick types : I and II Males > Females Rarely found before age 40

Fitzpatrick Skin Types

Type 1• Pale skin• Blond, red hair• Never tans

Fitzpatrick Skin Types

Type 2• Fair skin, blue eyes• Burns easily• Tans poorly

. .

Fitzpatrick Skin Types

Type 3• Darker white skin• Tans after burning first

Fitzpatrick Skin Types

Type 4• Light brown skin• Burns minimally• Tans easily

Fitzpatrick Skin Types

Type 5• Brown skin• Tans easily• Rarely burns

Fitzpatrick Skin Types

Type 6• Black skin• Never burns

Aetiology

Sunlight: mainly UVB Artificial UVB: Tanning salons Ionizing radiation• For acne treatment Immunosuppression• Renal transplants etc

Aetiology

Xeroderma Pigmentosa• Autosomal recessive: inability to repair UV

damaged DNA,increased risk of all skin Ca.• Other features: corneal deposits, blindness Gorlin syndrome• Autosomal Dominant• Odontogenic keratocysts, palmoplantar

pitting, intracranial calcs, rib anomalies

Aetiology

Bazex Syndrome• Features:

-follicular atrophoderma : “ice pick hands”

-local anhydrosis

-multiple BCCs Hx of previous non-melanoma skin Ca

Types of BCC

Nodular-Ulcerative Cystic Pigmented Sclerosing Superficial

Types of BCC

Nodular-ulcerative• Most common type• Raised, round pearly lesion• As it enlarges : telangiectasia and

central ulceration• Mainly on face

Nodular BCC

Types of BCC

Cystic• Uncommon variant of nodular• Polypoid appearance• Typically blue-grey cyst

Types of BCC

Pigmented• Brown - black macules in some areas• Difficult to distinguish from MM

Types of BCC

Sclerosing• White-yellow, waxy sclerotic plaque• Increased collagen deposit from

fibroblasts- thus resembling a scar• Margins are difficult to see

Types of BCC

Superficial• Erythematous patch or plaque• Multicentric

-normal skin interspersed with malignant patches

Investigations

Biopsy• Punch• Shave• Incisional• Excisional• Deep-wedge

Investigations

Imaging• Not required as very little risk of

metastasis < 0.01%

Treatment

Medical• 5-FU cream (Efudex)

-T bd x 2/52

-cure in 93% in some trials

-surgery is preferred

Treatment

Surgery• Excision

-direct closure

-local flap

-FTSG ie PAWG (Wolf)• Mohs Micrographically controlled

surgery

Mohs Surgery

Tumour excised and 1mm of surrounding tissue is examined under microscope

Additional pieces of tumour are removed in the persisting area

Highest cure rate: 99% Time consuming, LA top ups required

Recurrence

Risk factors:• BCC in NL fold• Recurrent tumours• Large tumours >2cm• Deeply infiltrating tumours• Young females

Squamous Cell Carcinoma

Squamous Cell Carcinoma

2nd most common skin Ca Malignant tumour of epidermal

keratinocytes Can Metastasize Strongly related to sun exposure 70% occur on head and neck

Epidemiology

Age > 50 Fitzpatrick I and II Males Closer to equator

Aetiology

Sunlight: UVB Sunbeds Ionizing Radiation Arsenic Xeroderma

Pigmentosa Transplants:

greatest in heart

HPV: 5,6,8,11,16 Chronic Ulcers:

Marjolins Burns Necrobiotic

Lipoidica Hidradenitis Actinic Keratosis

SCC

Bowens Disease

Intra-epidermal form of SCC SCC in situ: BM not invaded Well demarcated erythematous plaque• Irregular border• Surface crusting or scaling Rx: Photodynamic therapy, Cryotherapy

or topical 5-FU.

Bowens Disease

SCC Types

Typical: most common Periungual Perioral Marjolins Anogenital Verrucous

Typical SCC

A raised, firm, pink-to-flesh–coloured keratotic papule or plaque arising on sun-exposed skin

70% occur on head and neck Surface changes may include: Scaling Ulceration Crusting

SCC Pathophysiology

malignant tumour of epidermal keratinocytes

De novo or from actinic keratoses Capable of: Local infiltration Spread to regional nodes Distant mets

Investigations

Biopsy Incisional Excisional Punch Must reach level of mid dermis to see if

invasion has occurred

Investigations

If a patient has lymphadenopathy:• Imaging studies: CT• LN biopsy or FNA• May require lympadenectomy of the

draining basin

Staging: AJCC

Use TNM guidelines Most SCC are not metastatic at time of

presentation

Staging: AJCC

Classification of primary tumour:• T0: no evidence of primary• Tis: Ca in situ• T1: <2cm in greatest diameter• T2: 2-5cm in greatest diameter• T3: >5cm in greatest diameter• T4: deep invasion; bone,cartilage, muscle

Medical Care

Topical therapy• For premalignant and in-situ lesions• Efudex (5 FU)Topical immune response modifier enhances cell-mediated immune

responses via the induction of proinflammatory cytokines

e.g. imidazoquinoline (Imiquimod)

Medical Care

Radiotherapy• Indications:

-patients refusing/not fit for surgery

-metastatic disease

Medical Care

Radiotherapy problems:• Expensive and time consuming• Irritation at site: erythema, erosions• Pain: requiring narcotic analgesia• Poor long term cosmesis: cutaneous atrophy,

dyspigmentation, telangiectasia• Increased risk of further cutaneous

malignancy

Surgery

Cryotherapy• Liquid nitrogen• For selective SCCs: AKs or Cis• Complications:

-transient pain

-oedema

-blistering

Surgery

Electrodessication and Curettage• Indications; AK and Cis• Tumour margins are delineated with a

curette and scraped out: tumour is far more friable than normal tissue

• Main disadvantage is loss of margin• Cure rates of 96-99% have been quoted

Surgery

Excision with conventional margins• 4mm margin for low risk lesions:

<2cm, well differentiated, without fat invasion

• 6mm margin for higher risk lesions:

>2cm, fat invasion, high risk areas- central face, ears, genitalia

Surgery

Mohs Micrographic Surgery • Excellent option if tissue preservation is

required• Almost 100% of histologic margin is

examined (compared to 1% in conventional excision)

Surgery

Mohs Micrographic Surgery• Best cure rates for SCC (94-99%)• Local recurrences are fewer

Chemotherapy

Useful for metastatic disease Capecitabine (Xeloda) and IFN α

Prognosis

Variable:• Tumor- and patient-related risk

factors associated with higher rates of recurrence and metastasis are as follows:

Prognosis

Tumor-related factors in high-risk SCC:

• Location: lips, ears, scar• Tumour size > 2cm• Poorly diff tumour• Recurrent tumour• Perineural involvement

Prognosis

Patient-related factors in high-risk SCC

• Organ transplant recipient• Haematological malignancy ie CLL• Chronic immunosuppression• HIV infection

Prognosis: Overall

The 3-year disease-specific survival rate is 85%

Almost 100% if none of previous risk factors

70% if 1 risk factor present

The Future?

NSAIDS:• May protect against SCC development• COX 2 often overexpressed in SCC• Studies are ongoing

Malignant Melanoma

MM

A malignancy of pigment producing melanocytes

Predominantly skin Also: eyes, ears, GI tract, and oral and

genital mucous membranes

MM

Accounts for 4% of skin cancers Responsible for 74% of all skin cancer

deaths

Frequency

6th most common cancer in U.S. 1 in 60 lifetime risk of developing

melanoma in Caucasians Highest incidence in Australia and NZ Incidence increasing worldwide.

Epidemiology

Primarily disease of whites• Whites: African-Americans = 20:1• MR far higher in darker skin types Incidence greatest in females Mortality highest in males Median age at Dx = 53

Aetiology/Risk factors

Changing mole Atypical naevus Large numbers of

common naevi >100 Naevus >20cm Previous melanoma Sun exposure 1st degree relative

BCC/SCC Male >50 XP Fitzpatrick I and II Immunosuppression

Pathophysiology

Tumour progression: 5 stages

1. Benign melanocytic naevus

2. Dysplastic naevus: cytolological atypia

3. Primary MM: radial growth phase

4. Primary MM: vertical growth phase

5. Metastatic MM

Classification

1. Superficial Spreading Melanoma

2. Nodular Melanoma

3. Lentigo Maligna Melanoma

4. Acral Lentiginous Melanoma

5. Amelanocytic Melanoma

6. Rare sub-types

Superficial Spreading Melanoma

Most common, accounts for 70% Usually > 6mm in diameter Occurs most commonly:• On trunk in men• On legs in women

Superficial Spreading Melanoma

Irregular, asymmetric borders are characteristic

Histologically, characterized by “buckshot scatter “(pagetoid) of atypical melanocytes within the epidermis

Superficial Spreading Melanoma

Nodular Melanoma

Second most common : 25% Legs and trunk are most common sites Raised dark brown-black papule or

nodule Usually lacks the ABCDE warning signs Lacks radial growth phase

Nodular Melanoma

Nodular Melanoma

Lentigo Maligna Melanoma

Accounts for 4-10% Most common on head, neck and arms Precursor lesion = lentigo maligna• Usually present for 10-15yrs• Dark brown macule or patch Dermal invasion characterized by raised

blue-black lesions within precursor

Lentigo Maligna Melanoma

In Australia: on the face..• More common in men on RHS• More common in women on LHS

Lentigo Maligna Melanoma

Acral Lentiginous Melanoma

Accounts for 2-4% Accounts for 55% in dark skinned

individuals Usually occurs in glabrous skin or beneath

the nail plate (subungual variant) Pigment spread to the proximal or lateral

nail folds is termed the “Hutchinson sign”

Acral Lentiginous Melanoma

Characteristic features:• Irregular pigmentation• Large size > 3cm• Plantar location

Acral Lentiginous Melanoma

Amelanotic Melanoma

Non pigmented Pink or flesh coloured – often mimicking

BCC or SCC

Rare Sub-Types

Desmoplastic Melanoma Mucosal Melanoma Malignant Blue Naevus Melanoma of Soft Parts (clear cell

sarcoma)

Assessment

History Exam• Inspection alone can diagnose 65%• Nodes: axillary, cervical and groin

Assessment

MacKies 7 point checklist Major (2 points each)• Change in size• Irregular pigmentation• Irregular outline• Diameter > 6mm

Assessment

MacKies 7 point checklist Minor (1 point each)• Inflammation• Oozing• Itch or altered sensation

Assessment

MacKies 7 point checklist Needs further evaluation in presence of

one major or if score = 3

Assessment

American ABCDE• A: asymmetry• B: border is irregular• C: colour variation• D: diameter >6mm• E: examine other lesions

ABCDE

Biopsy

Incisional Excisional Punch

NB not shave

Biopsy

Information gained from biopsy:• Tumour depth• Anatomical level• Ulceration• Presence of mitoses• LVI• Host response (tumour infiltrating

lymphocytes)

Biopsy

Information gained from biopsy: ctd• Regression• Immunohistochemical staining for

lineage: (S-100) or for proliferation markers (Ki67)

Biopsy

Excisional biopsy• 1-3mm of normal skin should be

removed with the lesion as more than this could disrupt lymphatic drainage and compromise subsequent LN mapping

Clarkes Level

Classifies level of invasion Level 1: only epidermis involved Level 2: invades part of papillary dermis Level 3: invasion fills papillary dermis Level 4: invades reticular dermis Level 5: invades subcutaneous tissue

Breslows Thickness

Most important histological determinant of prognosis

Measured vertically in mm• From top of granular layer (base of

superficial ulceration)• To deepest point of tumour invasion

Breslows Thickness

5yr survival

1. </= 0.75mm 90%

2. 0.76mm – 1.5mm 80%

3. 1.5mm – 4mm 65%

4. >/= 4mm 35%

Breslows Thickness

Gives better indication of prognosis• As depth (Clarkes) of papillary and

reticular dermis vary throughout the body

Staging

AJCC• Incorporates TNM with Clarkes and

Breslow

Spread

Locally, in LN basins or distally:• Remote skin• Remote nodes• Viscera• Skeleton• CNS

Surgery

Excision margins;• 0.5 cm for melanoma in situ• 1cm with Breslow thickness <2mm• 2cm with Breslow thickness >/= 2mm

Surgery

Melanomas near vital structures may require a reduced margin

Aggressive histological features may necessitate a wider margin

Mohs surgery may have certain "niche" indications- MM of face, neck or hands

Sentinel Node Mapping

Growing in popularity Isosulfan blue dye and

lymphoscintigraphy Is it as useful as mapping in breast Ca?

Sentinel Node Mapping

Advantages• If node –ve, no need for nodal

clearance• More thorough pathological assessment

of nodes• Psychological relief to patient if node

negative

Sentinel Node Mapping

Disadvantages• Poor mapping in head and neck

tumours• Tumour may skip SN

Sentinel Node Mapping

Indications: controversial• Patients in whom the estimated risk of

LN metastasis is at least 10%• Clinically node –ve patients with

tumours >/= 1mm Not indicated in tumours <0.75mm 0.76-0.9mm: nebulous area

Elective LN Dissection

Lymphadenectomy when nodes are clinically negative

Rationale is that MM spreads to nodal basin first – so clearing the LNs reduces risk of spread

Controversial: studies have conflicting results

Nodal Dissection

Patients with palpable, clinically +ve nodes should undergo complete nodal dissection

Adjuvant Therapy

Interferon α 2b• For high risk resected MM: >4mm depth Regional nodal metastases• Diminishes occurrence of mets• Prolongs disease free survival

Chemotherapy

For unresectable regional mets or distant mets

Dacarbazine is the most active chemotherapeutic agent

Biological Therapy

Interleukin 2• Useful for metastatic melanoma• In one study, 7% had complete

response with patients remaining disease free for up to 8yrs

Biological Therapy

Monoclonal antibody therapy• Experimental but very promising Vaccines • Undergoing trials currently

Perfusion Chemo

Isolated Limb Perfusion (ILP)• Tourniquet applied• Artery and vein cannulated• Agent infused and removed from

circulation• Most effective method of Rx for local

recurrence or in-transit metastases• Agents used: TNFα, melphalan

Radiotherapy

For palliation Specific indications:• Brain metastases• Pain with bony mets• Superficial subcutaneous mets

Prevention

Public education• Australia: “slip, slop, slap” campaign Adequate clothing Avoid UV rays Systemic carotenoids : retinol• Useful in preventing malignant

transformation

Thank You

Will be on Blackboard tomorrow!!