Melanoma and Merkel Cell tumours

1
Melanoma and Merkel Cell tumours

• Trefor Nodwell MDCM
• Resident Plastic Surgery
• Dalhousie University

2
Outline

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

3
Outline

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

4
Outline

• Merkel Cell Tumours
• Definition
• Epidemiology
• Presentation
• Prognosis
• Risk Factors
• Histology
• Management

5
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.

6
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

7
Introduction

• Canadian Cancer Society estimates
• 2001 - 3,800 new cases
• Nova Scotia 22/100 000 males, 17/100 000 females
• 1985 1135
• 2000 174

8
Risk Factors

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

9
Risk Factors

• Sun Exposure

10
Introduction
11
Phototypes
12
Risk Factors

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

13
Introduction

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

14
Differential

• Dysplastic Nevi (BK Moles, Clarks Nevus)
• Poor terminology
• Potential precursors to MM
• Solitary Risk doubles
• gt10 Risk 12-fold

15
Differential

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

16
Clinical Presentation

• American Cancer Society ABCDs of melanoma
• Asymmetric
• Border irregularity
• Colour variability
• Diameter gt 6mm.

17
Clinical Presentation

• Be suspicious of lesions that change in
• size
• colour
• elevation
• Pruritis
• Bleeding
• Ulceration

18
Clinical Presentation

• Region
• Women lower limbs
• Men Trunk
• 20-50 arise from preexisting nevi

19
Approach to suspicious lesions

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

20
Approach to suspicious lesions

• Excisional biopsy
• lt2cm dia.
• Representative Incisional biopsy
• Larger lesions
• thickest portion
• most typical part
• transition zone

21
Growth Patterns

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

22
Growth Patterns

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

23
Growth Patterns

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

24
Growth Patterns

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

25
Growth Patterns

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

26
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 thepapillary-reticular dermal interface
• level III
• invasion fills and expands the papillary dermis,
  but does notpenetrate the reticular dermis
• Breslow
• mm thickness at thickest portion
• top of granular cell layer to base of malignant
  cell
• Other (mitoses, atypia, nests, neural invasion,
  inflammatory cells)

27
Staging

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

28
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

29
Staging

• AJCC TNM Classification
• pTx unable to assess
• pT0 no primary
• pT1 lt0.75mm, Clarks II
• pT2 0.75-1.5 mm,III
• pT3 1.5-4 mm, IV
• pT4gt4mm, /- satellites, V

30
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 metastasisN2c Both (N2a and
  N2b)

31
Staging

• Distant metastasis (M)
• MX Distant metastasis cannot be assessedM0 No
  distant metastasisM1 Distant metastasis
• M1a Metastasis in skin or subcutaneous tissue or
  lymph node(s) beyond the regional lymph
  nodesM1b Visceral metastasis

32
Staging

• AJCC Groupings
• Stage 0
• pTis, N0, M0
• Stage I
• pT1, N0, M0pT2, N0, M0
• Stage II
• pT3, N0, M0

33
Staging

• Stage III
• pT4, N0, M0Any pT, N1, M0Any pT, N2, M0
• Stage IV
• Any pT, Any N, M1

34
Metastatic Workup

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

35
Prognostic Factors

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

36
Prognostic Factors
37
Prognostic Factors

• Nodal Involvement
• Ulceration
• Mitotic Number

38
Management

• Early diagnosis
• Prompt excision, within 21 days.
• Margins
• In situ 0.5cm (1992 NIH Consensus)
• MM lt1mm thick 1cm is safe
• MM 1.5-4.0 mm thick, 2cm
• MMgt4mm 2-3cm.

39
Lymphadenectomy

• Therapeutic
• for palpable disease- always indicated
• lt2cm 5 year survival 46
• Elective LND
• controversial, conflicting studies

40
Sentinel Node Biopsy

• Indications
• truncal melanoma lt0.76mm
• all melanomas 0.76-1.0
• male patients with thin, Clarks III ulcerated
  lesions
• Intermediate thickness MM

41
Sentinel Node Biopsy

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

42
Recurrence

• Stage I and II - 2.5-3.2 rate
• 80 within 3 years
• Remainder over 15-20 years.
• Local recurrence
• In-transit mets

43
Recurrence

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

44
Metastases

• Stage I and II - 34 months
• Stage III lt12months
• Median survival 6months
• Five year survival 6

45
Metastases

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

46
Adjuvant therapies

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

47
Adjuvant therapies

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

48
Prevention!!
49
Merkel Cell Carcinoma
50
History

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

51
Epidemiology

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

52
Clinical Presentation

• Nonspecific
• Sun exposed skin
• Caucasian
• DDx
• SCC, BCC, Keratoacanthoma, MM

53
Clinical Presentation

• Head and Neck 40
• Upper extremity 19
• MaleFemale 32
• Age at diagnosis
• Mean 66 years
• 2/3 are over 60.

54
Prognosis

• Early Disease 90 5 year survival

55
Risk Factors

• Prolonged Sun Exposure
• Agegt60
• PUVA
• Arsenic (Fowlers)
• Immunosuppression

56
Histology

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

57
Histology

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

58
Histology

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

59
Management

• Excision
• margins
• 0.5 cm - 100 recurrence
• 2.5cm - 49 recurrence
• Mohs micrographic surgery
• 50 recurrence

60
Management

• Lymph nodes
• ELND only independent variable for improved
  relapse free survival.
• Sentinel node
• Radiation therapy
• improves disease free survival

61
Management

• Radiation as adjuvant therapy

62
Management

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

63
Summary

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

64
Summary

• Excise
• Nodes
• Radiation
• chemotherapy

65
THE END