Diagnosis of Lentigo Maligna Melanoma. Steven Q. Wang, M.D. Memorial Sloan-Kettering Cancer Center Basking Ridge, NJ

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1 Diagnosis of Lentigo Maligna Melanoma Steven Q. Wang, M.D. Memorial Sloan-Kettering Cancer Center Basking Ridge, NJ

2 Conflict of Interest: None

3 Topics Epidemiology and Natural History Clinical and Histologic Presentations Diagnostic Challenges and Modalities Treatment Options

4 Epidemiology Sun exposed sites Elderly patients Incidence 1.3/100,000 in Australia 1 0.8/100,000 in US 2 Most common subtype of melanoma on face Long term cumulative UVR 1. Holman CD, Int J Cancer Newell GR, Cancer Res. 1988

5 Natural History The majority of lesions are slowly growing intraepidermal melanocytic proliferations When invasion is detected, it is usually minimal (Clark level II) A small subset of LMs progresses rapidly to invasive melanoma A small subset is associated with desmoplastic melanoma

6 Histological Presentation

7 Diagnostic Challenges Differential Diagnoses include: Pigmented actinic keratosis Solar lentigo Seborrheic keratosis Pigmented BCCs LPLKs

8 Diagnostic Modalities Careful clinical exam, include palpation Woods light Multiple mapping biopsies Control biopsy of sun damaged skin Dermoscopy Confocal reflectance microscopy

9 Diagnostic Modalities Careful clinical exam, include palpation Woods light Multiple mapping biopsies Control biopsy of sun damaged skin Dermoscopy Confocal reflectance microscopy

10 Dermoscopy Powerful tool to aid the diagnosis of benign vs. malignant pigmented skin lesions. A hand-held microscope that provides detailed visualization of the structures contained within the epidermis, epidermaldermal junction, and papillary dermis not visible to the naked eye.

11 Clinical Exam Light

12 Addition of alcohol oil

13 Application of dermoscopy light oil Glass plate

14

15 Networks

16 Networks

17 Globules Networks

18 Globules Networks

19 Networks Globules Vessels

20 Lentigo Maligna Melanoma Asymmetric pigmented follicular openings Formation of rhomboidal structures Slat-gray dots and globules Obliteration of hair follicles Change over time Polymorphous vessels

21 Schiffner R. et al JAAD 2000

22 EAR Asymmetric pigmented follicular openings

23 EAR Asymmetric pigmented follicular openings

24 EAR Asymmetric pigmented follicular openings

25 Slate gray dots and globules progressing to short streaks

26 Slate gray dots and globules progressing to short streaks

27 Slate gray dots and globules progressing to short streaks

28 Slate gray dots and globules progressing to short streaks

29 Streaks progressing to dark rhomboidal structures

30 Streaks progressing to dark rhomboidal structures

31 Streaks progressing to dark rhomboidal structures

32 Homogeneous areas with hair follicles respected

33 Homogeneous areas with obliterated hair follicles

34 Polymorphous vessels Focal dark structureless areas

35 Differentiating LM vs. AK vs. LPLK Clue: Quality and distribution of the granular particles

36

37 Lentigo Maligna

38 Pigmented Actinic Keratosis

39

40 Lichen planus-like keratosis

41 AK LM LPLK

42 Pigmented Actinic Keratosis -Very broad pseudonetwork

43

44 Pigmented AK

45 Challenging Cases

46

47

48 Superior Cheek : LM Inferior Cheek: AK

49 The Role of Confocal Laser Microscope

50 Subsurface Imaging Confocal Laser Microscope Technology: live in vivo imaging high resolution m (lateral) 3-5 m (axial) visualization of nuclear, cellular architecture max depth 350 m of the skin Field of view: 0.4 x 0.4 cm

51 Confocal Microscope Laser 830nm Confocal pinhole 400x450µm Objective 30X Specimen PMT Mirror light from outside focal plane optically rejected only in-focus information collected (resolution 5 µm) can be focussed below specimen surface to isolate sub-surface images (max depth 400 µm = papillary dermis) Incremental movement of the focal depth produces 3D image sets

52

53

54

55 SINGLE IMAGE, 30X, 1000 x 1000 pixels 0.5 mm 0.5 mm

56 Imaging Modes Mosaic view Stack view

57 Imaging Mode: Mosaic Field of view: 0.4 x 0.4 cm 8x8 images stitched together

58 MOSAIC, 4X 4mm 0.5 mm 4mm, 4X 0.5 mm 30X The light source moves horizontally over a 2D grid

59

60 Imaging Mode: stack Field of view: 0.5 x 0.5mm

61 STACK, 30X 0.5 mm 0.5 mm 5 μm

62

63

64

65

66

67 RCM imaging of normal intact skin

68 Stratum corneum 0.9 NA, 30X 0.5 mm

69 Stratum granulosum 0.9 NA, 30X 0.5 mm

70 Stratum spinosum 0.9 NA, 30X 0.5 mm

71 Stratum basalis 0.9 NA, 30X 0.5 mm

72 Dermal Papillae 0.9 NA, 30X 0.5 mm

73 Dermis 0.9 NA, 30X 0.5 mm

74

75

76 Lentigo Maligna

77 Normal Epidermis

78 /10/2006

79 Lentigo Maligna

80 Normal Epidermis

81 Thank You

82 Therapeutic Options Surgery is the treatment of choice

83 Therapeutic Options Bub et al Arch Derm 2004

84 Therapeutic Options Standard Excision -5mm margin for LM NIH consensus panel -Inadequate surgical margin -High local recurrence rate of 15-20% Bub et al Arch Derm 2004

85

86 Therapeutic Options Mohs Surgery -Experience dependent. -Require immunostains (e.g., MART-1). -Enface section -Difficult to differentiate true LM vs. background suninduced melancyte atypia. Bub et al Arch Derm 2004

87 LM: Frozen vs Permanent Sections Frozen section Paraffin-embedded section

88

89

90

91

92 Therapeutic Options Staged Excision -Inconvenience -close collaboration with the pathologist Bub et al Arch Derm 2004

93 MSKCC SERIAL EXCISION TECHNIQUE Woods light marking Initial 5, 7, 10 mm margin Central pigmented lesion excised Margins excised 12-3, 3-6, 6-9, 9-12 Await pathology 24 hours Re-excise as needed

94 Tumor Center and Distinct Margin Areas Are Submitted Separately

95 12:00 Debulked Center 9:00 3:00 6:00

96 Distance between Tumor and Margin

97

98 Therapeutic Options Surgery is the treatment of choice Superficial treatments LN % recurrence rate 1-2 Radiotherapy Farshad et al 2002: retrospective review of 150 patients, 2yr follow up, a 7% recurrence rate Aldara Laser, 5FU, ED&C Collins P Clin Exp Dermatol 1991 Zacarian SA Arch Derm 1982

99 Candidates For Alternative Treatment Patient refuses surgery Poor surgical candidate Poor health and multiple medical problem Advanced age Lesion too large difficult anatomic location

100

101 Schon et al Br. J Derm 2007

102 Buttieker et al Arch Derm 2008

103 11/10/2008

104 3/18/2009

105 Conclusions Clinical diagnosis of LMM is difficult. Dermoscopy and confocal laser microscopy are valuable diagnostic tools. Surgery is the treatment of choice Alternative treatments include Aldara and radiation.

106 Acknowledgement Allan Halpern, MD Kishwer Nehal, MD Milind Rajadhyaksha, PhD Alon Scope, MD Jocelyn Lieb, MD Ashfaq Marghoob, MD Jason Chen, MD Career Development Award

107 Future Direction What if there is a way to map out the surgical border before Mohs surgery?

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