Melanoma

ByDr Abeer Elsayed Aly

Lecturer of medical oncologySECI

19/03/2013

Melanoma Incidence and Mortality

• Incidence (US)–59,580 new cases

• 33,580 new male cases • 26,000 new female cases• 12 per 100,000 population

• Mortality (US)–7,770 total

• 4,910 males• 2,860 females

American Cancer Society, Cancer Facts and Figures. 2005.

Melanoma: risk factors

• Constitutional predisposition– Fair skin/hair color/ freckling– Burn vs tan– >20 benign nevi (moles) or >3 atypical nevi– Family history of dysplastic nevi– Increasing age– Immunosuppression– Xeroderma pigmentosum– H/O solar keratosis, squamous cell carcinoma

Melanoma: risk factors

• Risk behaviors– >3 sunburns– Episodic excessive

sunlight exposure– Long term

continuous sunlight exposure

– UV exposure at tanning salons

Melanoma

The challenge (historically):– Early detection– Rapid growth/high

proliferation rate – Chemotherapy resistant– Radiation resistant– Short anticipated

survival

Types of Melanoma

• Acral lentiginous• Mucosal melanoma• Superfical spreading melanoma• Lentigo maligna melanoma• Nodular melanoma

Superficial spreading

• most common head and neck, 50%• 4th to 5th decade• clinical mixture of brown/tan, pink/white

irregular borders, biphasic growth• irregular nests in epidermis • underlying lymphoid infiltrate• enlarged nests and single cells in all epidermal

layers

Lentigo maligna

• 20% of head and neck• longest radial growth phase >15 yrs• elderly sun exposed areas• clinical dark, irregular ink spot• contiguous lintiginous proliferation, dyshesive,

variable shape, atrophic epidermis, infundibular basal cell layer of hair follicles

Lentigo maligna

Nodular melanoma

• 30% of head and neck• 5th decade• aggressive monophasic growth• sun-exposed and nonexposed areas• well circumscribed blue/black or nodular with

involution in irregular plaque• downward tumorigenic growth, expand

papillary dermis into reticular dermis

Nodular melanoma

Mucosal melanoma

• 8% head and neck• histologic staging little use• local control predicts survival• neck dissection for clinical N+• XRT for histo N+• adjuvant interferon alpha 2-b

Biopsy techniques

• Excisional biopsy 1-3 mm marginsavoid wider margins (accurate lymphatic mapping)

• Full thickness incisional/punch biopsy for large lesionslesions of the palms, soles, digits, face, ears

• Deep shave biopsiesWhen suspicion for melanoma is low

NCCN Guidelines 2005

Staging system

Clark staging

• Based upon histologic level of invasion• Level I – Epidermis only (in situ)

• Level II – Invades the papillary dermis, but not to the papillary-reticular interface

• Level III – Invades to the papillary-reticular interface, but not into the reticular dermis

• Level IV – Into the reticular dermis

• Level V – Into subcutaneous tissue

Breslow staging

• Based upon absolute depth of invasion• Stage I – < 0.75 mm• Stage II – 0.76 – 1.5 mm• Stage III – 1.51 – 4.0 mm• Stage IV - > 4.0 mm

Work up• Labs

– LDH• Radiology

– CXR– Possible CT for metastasis– Possible CT abdomen, MRI brain– Possible Lymphoscintigraphy

• Excision– 2 cm margins

• Adjunctive Therapy– Possible elective neck dissection– Possible sentinel lymph node biopsy– Possible elective radiation

Prognostic indicators

• Thickness (Breslow depth)• Nodal status• Ulceration• Mitosis• Satellite lesions• In transit lesions

Prognostic indicators

• Thickness (Breslow depth)• Nodal status• Ulceration• Mitosis• Satellite lesions• In transit lesions

Prognostic indicators

• Thickness (Breslow depth)• Nodal status• Ulceration• Mitosis• Satellite lesions• In transit lesions

Prognostic Indicators: Nodal status

• OS for patients with 1 positive sentinel node is 60% at 5 years

• OS for patients with a single palpable node is 40% at 5 years

• Gershenwald et al, 2001

Prognostic indicators

• Thickness (Breslow depth)• Nodal status• Ulceration• Mitosis• Satellite lesions• In transit lesions

Mitotic Index

• N = 3661 from the Sydney Melanoma Database• Correlated

– clinical information (survival)– primary tumor thickness (Breslow depth)– ulcerative state (infiltrative, attenuative, and traumatic)– tumor mitotic rate (TMR) (at the invading front, deep border)

• Conclusion: TMR is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma

Azzola et al, Cancer 2003

Prognostic indicators

• Thickness (Breslow depth)• Nodal status• Ulceration• Mitosis• Satellite lesions• In transit lesions

Risk of In-Transit Metastasis

• In- transit metastasis– Cutaneous / subcutaneous tissue– Between the primary tumor – and the draining lymph node basin

• 5 yr survival rates: 12% - 37%• Risk factors:

– Thicker primary– Lower extremity– Regional LN metastasis

Other prognostic factors:

• LDH– Elevated levels correlate with:

Early recurrenceShorter survival (Newcki et al, 2008)

• Serum S100 level– Early studies suggest:

Shorter survivalEarly distant relapsePoorer response to treatment (Smith et al, 2008)

• Microvessel Density

Other prognostic factors:

• LDH– Elevated levels correlate with:

Early recurrenceShorter survival (Newcki et al, 2008)

• Serum S100 level– Early studies suggest:

Shorter survivalEarly distant relapsePoorer response to treatment (Smith et al, 2008)

• Microvessel Density

Other prognostic factors:

•LDH– Elevated levels correlate with:

Early recurrenceShorter survival (Newcki et al, 2008)

• Serum S100 level– Early studies suggest:

Shorter survivalEarly distant relapsePoorer response to treatment (Smith et al, 2008)

• Microvessel Density

Adjuvant treatment

Metastatic Melanoma

Dendritic cell

T cell

MHC

B7

TCR

CD28

Antigen

CTLA4

Blocking Antibodies to CTLA4

Leach DR, et al. Science 1996;271:1734-1736.

Vaccine

Phase I GVAX: Melanoma

Vax DTH

Met Vasculopathy

Pre Met

CD4 CD8

Adaptive Immune Therapy

BRAF Inhibitor