Diagnosis of Lentigo Maligna Melanomafsdpa.org/wp-content/uploads/2016/04/Management-of-LMM...•...
Transcript of Diagnosis of Lentigo Maligna Melanomafsdpa.org/wp-content/uploads/2016/04/Management-of-LMM...•...
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Diagnosis of
Lentigo Maligna Melanoma
Steven Q. Wang, M.D.
Memorial Sloan-Kettering Cancer Center
Basking Ridge, NJ
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Conflict of Interest: None
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Topics
• Epidemiology and Natural History
• Clinical and Histologic Presentations
• Diagnostic Challenges and Modalities
• Treatment Options
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Epidemiology
• Sun exposed sites
• Elderly patients
• Incidence• 1.3/100,000 in Australia1
• 0.8/100,000 in US2
• Most common subtype
of melanoma on face
• Long term cumulative
UVR
1. Holman CD, Int J Cancer 1980
2. Newell GR, Cancer Res. 1988
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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
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Histological Presentation
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Diagnostic Challenges
Differential Diagnoses include:
• Pigmented actinic keratosis
• Solar lentigo
• Seborrheic keratosis
• Pigmented BCCs
• LPLKs
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Diagnostic Modalities
• Careful clinical exam, include palpation
• Woods light
• Multiple mapping biopsies
• Control biopsy of sun damaged skin
• Dermoscopy
• Confocal reflectance microscopy
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Diagnostic Modalities
• Careful clinical exam, include
palpation
• Woods light
• Multiple mapping biopsies
• Control biopsy of sun damaged skin
• Dermoscopy
• Confocal reflectance microscopy
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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, epidermal-
dermal junction, and
papillary dermis not visible
to the naked eye.
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Light
Clinical Exam
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Addition of alcohol oil
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Application of dermoscopy
Glass
plate
light
oil
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Networks
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Networks
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Networks
Globules
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Networks
Globules
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Networks
Globules Vessels
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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
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Schiffner R. et al JAAD 2000
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Asymmetric pigmented follicular openings
EAR
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Asymmetric pigmented follicular openings
EAR
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Asymmetric pigmented follicular openings
EAR
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Slate gray dots and globules
progressing to short streaks
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Slate gray dots and globules
progressing to short streaks
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Slate gray dots and globules
progressing to short streaks
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Slate gray dots and globules
progressing to short streaks
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Streaks progressing to dark rhomboidal structures
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Streaks progressing to dark rhomboidal structures
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Streaks progressing to dark rhomboidal structures
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Homogeneous areas with hair follicles respected
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Homogeneous areas with obliterated hair follicles
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Polymorphous
vessels
Focal dark
structureless areas
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Differentiating
LM vs. AK vs. LPLK
Clue: Quality and distribution of the
“granular particles”
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Lentigo Maligna
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Pigmented Actinic Keratosis
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Lichen planus-like keratosis
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LMAK LPLK
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Pigmented Actinic Keratosis
-Very broad pseudonetwork
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Pigmented AK
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Challenging Cases
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Superior Cheek : LM Inferior Cheek: AK
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The Role of
Confocal Laser Microscope
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Confocal Laser Microscope
Subsurface Imaging
Technology:
• live in vivo imaging
• high resolution
• 0.5-1.0 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
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Confocal Microscope
Laser
830nm
Objective
30X
Specimen
Mirror
PMT• 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
pinhole
Confocal
pinhole400x450µm
Mirror
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SINGLE IMAGE, 30X, 1000 x 1000 pixels
0.5 mm
0.5 mm
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Imaging Modes
• Mosaic view
• Stack view
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Imaging Mode: MosaicField of view: 0.4 x 0.4 cm
8x8 images stitched together
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4mm,
4X
4mm
0.5 mm
0.5 mm
30X
MOSAIC, 4X
The light source moves horizontally over a 2D grid
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Imaging Mode: stackField of view: 0.5 x 0.5mm
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0.5 mm
0.5 mm
STACK, 30X
5 μm
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RCM imaging of
normal intact skin
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Stratum corneum
0.5 mm
0.9 NA, 30X
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Stratum granulosum
0.5 mm
0.9 NA, 30X
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Stratum spinosum
0.5 mm
0.9 NA, 30X
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Stratum basalis
0.5 mm
0.9 NA, 30X
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Dermal Papillae
0.5 mm
0.9 NA, 30X
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Dermis
0.5 mm
0.9 NA, 30X
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Lentigo Maligna
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Normal Epidermis
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11/10/2006
1
3 2
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Lentigo Maligna
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Normal Epidermis
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Therapeutic Options
• Surgery is the treatment of choice
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Therapeutic Options
Bub et al Arch Derm 2004
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Therapeutic Options
Bub et al Arch Derm 2004
Standard Excision-5mm margin for LM
-1992 NIH consensus panel
-Inadequate surgical margin
-High local recurrence rate of 15-20%
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Therapeutic Options
Bub et al Arch Derm 2004
Mohs Surgery
-Experience dependent.
-Require immunostains (e.g.,
MART-1).
-Enface section
-Difficult to differentiate true
LM vs. “background” sun-
induced melancyte atypia.
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LM: Frozen vs Permanent Sections
Paraffin-embedded sectionFrozen section
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Therapeutic Options
Bub et al Arch Derm 2004
Staged Excision
-Inconvenience
-close collaboration
with the pathologist
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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
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Tumor Center and Distinct Margin Areas
Are Submitted Separately
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12:00
3:00
6:00
9:00
Debulked
Center
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Distance between Tumor and
Margin
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Therapeutic Options
• Surgery is the treatment of choice
• Superficial treatments
– LN2
• 10-50% recurrence rate1-2
– 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
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Candidates For Alternative Treatment
• Patient refuses surgery
• Poor surgical candidate
• Poor health and multiple medical problem
• Advanced age
• Lesion too large
• difficult anatomic location
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Schon et al Br. J Derm 2007
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Buttieker et al Arch Derm 2008
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11/10/2008
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3/18/2009
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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.
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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
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What if there is a way to map out the
surgical border before Mohs surgery?
Future Direction
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