Melanoma and Merkel Cell tumours Trefor Nodwell MDCM Resident Plastic Surgery Dalhousie University

Outline

 Introduction The Melanocyte and melanoma  Epidemiology  Risk Factors  Clinical Presentation  Approach to suspicious lesions  Growth Patterns

Outline

 Workup  Staging/Prognostic Factors  Surgical Options  Adjuvant Therapy

Outline

 Merkel Cell Tumours  Definition  Epidemiology  Presentation  Prognosis  Risk Factors  Histology  Management

Introduction

 Embryology  ectodermal derivatives:  epidermis, pilo-sebaceous and apocrine units eccrine sweat glands, nail units  Neuroectoderm:  melanocytes, nerves, sensory receptors  Mesoderm:  macrophages, mast cells, Langerhans cells, Merkel cells, fibroblasts, blood and lymph vessels, fat cells.

Introduction

 Epidemiology  2% of all cancers  2nd to lung Cancer in Women  Incidence Doubling every decade  1925 1.1/100 000, 1975 6.2/100 000  40 000 new cases per year in the US

Introduction

 Canadian Cancer Society estimates:  2001 - 3,800 new cases  Nova Scotia 22/100 000 males, 17/100 000 females  1985 1:135  2000 1:74

Risk Factors

 Phenotype  Light skin  Numerous nevi (+/- dysplastic)  Burn easily  Blue-green, grey eyes  blond/red hair  Freckling  Family History

Risk Factors

 Sun Exposure

Introduction No. Skin Phototype Skin Colour

I II III IV

Never tans/always burns Sometimes tans/usually burns Usually tans/ sometimes burns Always tans/rarely burns Pale/ Alabaster Very light Brown: sometimes freckles Light tan, brown or olive Brown, dark brown, black.

Tanning history

Red sunburn, painful swelling, skin peels Pinkish or red, light brown tan can gradually develop Rarely burns, moderately rapid tanning response Rarely burns, very rapid tanning response

Phototypes

Risk Factors

 Genetic Predisposition  Xeroderma Pigmentosum  Familial Atypical Multimole Melanoma  Sun Exposure  Chemical induction (Petroleum Products)  Trauma (Soles of feet)  hormonal (pregnancy)

Introduction

 Genetics  Tumour Suppressor Gene p16 on Ch 9p21  Growth factors  Epidermal, Nerve, Insulin-like, fibroblast, platelet derived, transforming growth factor beta

Differential

 Dysplastic Nevi (BK Moles, Clark’s Nevus)  Poor terminology  Potential precursors to MM  Solitary: Risk doubles  >10 Risk 12-fold

Differential

 Congenital Nevi  Present at birth  No Clear histological definition  Nevomelanocytes  Large =20cm  Spitz Nevus (aka Juvenile Melanoma)

Clinical Presentation

 American Cancer Society ABCD’s of melanoma  Asymmetric  Border irregularity  Colour variability  Diameter > 6mm.

Clinical Presentation

 Be suspicious of lesions that change in  size*  colour*  elevation  Pruritis  Bleeding  Ulceration

Clinical Presentation

 Region  Women lower limbs  Men Trunk  20-50% arise from preexisting nevi

Approach to suspicious lesions

 Clinical Diagnosis  Management  Markers for patients at risk for Melanoma  Excise- changing lesions, atypical lesions  Routine self and physician exam

Approach to suspicious lesions

 Excisional biopsy  <2cm dia.

 Representative Incisional biopsy  Larger lesions  thickest portion  most typical part  transition zone

Growth Patterns

 Superficial Spreading  Nodular  Lentigo Maligna  Acral Lentiginous (acro lentiginous)  BANS

Growth Patterns

 Superficial spreading  70-80% of MM  Slow growing  Variable colour  Lower metastatic potential

Growth Patterns

 Nodular  aggressive, develop rapidly  Usually arise denovo  Vertical growth  Typical appearance  easily detected

Growth Patterns

 Lentigo Maligna Melanoma  Pigmented lesions in sun damaged skin (Face)  large irregular borders  Notched

Growth Patterns

 Acral Lentiginous  Palms, soles, nail bed  All ALMs occur on extremities  Large, slow growing]  50-60 yo  Big toe and thumb

Staging

 Clark  level I: • lesions involving only the epidermis (in situ melanoma); not an invasive lesion  level II: • invasion of the papillary dermis, but does not reach the papillary-reticular dermal interface  level III: • invasion fills and expands the papillary dermis, but does not penetrate the reticular dermis

Staging

 level IV: • invasion into the reticular dermis but not into the subcutaneous tissue  level V: invasion through the reticular dermis into the subcutaneous tissue

Staging

 Breslow  thickness: 0.75 mm or less  thickness: 0.76 mm to 1.50 mm  thickness: 1.51 mm to 4.0 mm  thickness: 4.0 mm or greater

Staging

 AJCC TNM Classification  pTx unable to assess  pT0 no primary  pT1 <0.75mm, Clarks II  pT2 0.75-1.5 mm,III  pT3 1.5-4 mm, IV  pT4>4mm, +/- satellites, V

Staging

 Regional lymph nodes (N)  NX: cannot be assessed  N0: No node metastasis  N1: Metastasis 3 cm or less  N2: Metastasis more than 3 cm and/or in transit metastasis  N2a: Metastasis more than 3 cm in greatest dimension  N2b: In-transit metastasis N2c: Both (N2a and N2b)

Staging

 Distant metastasis (M)  MX: Distant metastasis cannot be assessed M0: No distant metastasis M1: Distant metastasis  M1a: Metastasis in skin or subcutaneous tissue or lymph node(s) beyond the regional lymph nodes M1b: Visceral metastasis

Staging



AJCC Groupings



Stage 0

 pTis, N0, M0 

Stage I

 pT1, N0, M0 pT2, N0, M0 

Stage II

 pT3, N0, M0

Staging



Stage III

 pT4, N0, M0 Any pT, N1, M0 Any pT, N2, M0 

Stage IV

 Any pT, Any N, M1

Metastatic Workup

 Physical Exam  Adjuvant tests  Liver tests  Chest X-ray  limited CT scanning

Prognostic Factors

 Clinical  Female sex better  Older, worse  Extremities better than trunk or scalp  Histologic  vertical thickness

Prognostic Factors

Thickness in mm <0.75 0.76-1.49 1.50-2.49 2.5-3.99 >4 Five year survival (%) 96 87 75 66 47

Prognostic Factors

 Nodal Involvement  Ulceration  Mitotic Number

Management

 Early diagnosis  Prompt excision, within 21 days.

 Margins  In situ 0.5cm (1992 NIH Consensus)  MM <1mm thick 1cm is safe  MM 1.5-4.0 mm thick, 2cm  MM>4mm 2-3cm.

Lymphadenectomy

 Therapeutic  for palpable disease- always indicated  <2cm 5 year survival 46%  Elective LND:  controversial, conflicting studies

Sentinel Node Biopsy

 Indications  truncal melanoma <0.76mm

 all melanomas 0.76-1.0

 male patients with thin, Clarks III ulcerated lesions  Intermediate thickness MM

Sentinel Node Biopsy

 Preoperative technitium  Vital blue dye  Gamma probe intra-op  Histological exam of the entire node  May obviate the need for ELND

Recurrence

 Stage I and II - 2.5-3.2% rate  80% within 3 years  Remainder over 15-20 years.

 Local recurrence  In-transit mets

Recurrence

 Treatment  excision- for single lesions only  regional limb perfusion  intra-arterial or systemic chemotherapy  Radiation - reserved for poor surgical candidates

Metastases

 Stage I and II - 34 months  Stage III <12months  Median survival 6months  Five year survival 6%

Metastases

 Sites  Lymph nodes, Skin and subcutaneous 59%  Lungs- 36%  Liver 20%  Brain  20%  Bone 17%  GI 7%

Adjuvant therapies

 To compliment surgical excision  Immunotherapy  Interferon alpha 2b  Vaccines  BCG  Chemotherapy  Dacarbazine based  10-20% response rate

Adjuvant therapies

 Intra-arterial Perfusion  30 year experience  Melphalan directly into the vasculature  Hyperthermic Perfusion  38-40degrees  DTIC or Melphalan

Prevention!!

Merkel Cell Carcinoma

History

 Touch Cell (Tastzellen) 1875  Uncertain histogenisis  Trabecular Carcinoma of the Skin 1972

Epidemiology

 400 cases/year in the US  100 times more rare than Melanoma  26% fatality

Clinical Presentation

 Nonspecific  Sun exposed skin  Caucasian  DDx:  SCC, BCC, Keratoacanthoma, MM

Clinical Presentation

 Head and Neck 40%  Upper extremity 19%  Male:Female 3:2  Age at diagnosis  Mean 66 years  2/3 are over 60.

Prognosis

 Early Disease: 90% 5 year survival

Risk Factors

 Prolonged Sun Exposure  Age>60  PUVA  Arsenic (Fowlers)  Immunosuppression

Histology

 Full thickness dermis  subcutaneous fat and muscle  epidermal ulceration  Associated actinic elastosis

Histology

 Subtypes  Intermediate  Small Cell  Trabecular narrow ribbons 1-2 cells thick  Diffuse sheets or nests  Scant cytoplasm  round/oval nuclei

Histology

 Differential  metastatic small cell lung ca  lymphoma  metastatic carcinoid  amelanotic small cell melanoma  Immuno-reagents

Management

 Excision  margins:  0.5 cm - 100% recurrence  2.5cm - 49% recurrence  Mohs’ micrographic surgery  50% recurrence

Management

 Lymph nodes  ELND only independent variable for improved relapse free survival.

 Sentinel node  Radiation therapy  improves disease free survival

Management

 Radiation as adjuvant therapy

Management

 Chemotherapy  No role as adjuvant therapy  Metastatic disease  Follow up  q 3mo for one year  62% disease specific survival if recurrences treated aggressively

Summary

 Highest grade variant of skin cancer  100 times more rare than melanoma  nonspecific appearance  immuno-histochemistry  Treatment

Summary

 Excise  Nodes  Radiation  chemotherapy

THE END