congenital melanocytic nevi when to worry & when to treat
TRANSCRIPT
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Congenital Melanocytic Nevi: When to Worry &
When to Treat
Julie V. Schaffer, MD
Associate Professor of Dermatology and PediatricsDirector of Pediatric Dermatology
NYU School of Medicine
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Congenital Melanocytic Nevi: When NOT to Worry &
When NOT to Treat
Julie V. Schaffer, MD
Associate Professor of Dermatology and PediatricsDirector of Pediatric Dermatology
NYU School of Medicine
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Overview
• evolving definitions and concepts
• natural history
• risks– neurocutaneous melanocytosis– melanoma
• management strategies
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Goal: Neither You nor Your Patients Order These Products
McAllister et al Ped Derm 2009
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Congenital Melanocytic Nevi: Traditional Concepts
• classic definition: present at birth
• 1-6% of neonates in large series– clinical diagnosis in older studies– dermatoscopic diagnosis more recently– may be more evident in newborns with
darker skin
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Congenital Melanocytic Nevi (CMN): Traditional Classification by Size
• small – <1.5 cm final size
• medium – 1.5-20 cm final size
• large– >20 cm final size– ≥9 cm on the head of an infant– ≥6 cm on the body of an infant
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Congenital Melanocytic Nevi (CMN): Growth in Proportion to Child
• estimated increase in size from infancy to adulthood– ~2-fold on head– ~3-fold on trunk &
extremities
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Congenital Melanocytic Nevi: Histologic Features
• nevomelanocytes extend deeper into dermis and subcutis
• single-file arrangement between collagen bundles
• track along appendages & neurovascular structures
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Congenital Melanocytic Nevi:Evolving Concepts
• ‘tardive CMN’, ‘early onset nevi’, ‘congenital nevus-like nevi’– become apparent during infancy or early childhood,
esp. before 2-3 years of age– clinical, dermatoscopic & histologic features identical
to ‘true’ CMN
• 1-4% of children & adults have a CNLN ≥1.5 cm (medium-sized)
• in a recent series, 17% of Italian schoolchildren (ages 12-17y; 592/3406) had a CMN/CNLN ≥0.6 cm
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Natural History of Congenital Melanocytic Nevi
• darker or lighter color
• increase in overall thickness
• changes in topography
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Development of a Verrucous Surface
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Papules, Nodules and ‘Pebbling”
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Speckled Lentiginous Nevus: Subtype of CMN
• prevalence of ~2-3%– background tan patch apparent
at birth or during infancy– progressive development of
spots
• patterns reflect origin during embryogenesis– block-like with sharp midline
demarcation– following lines of Blaschko
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‘Hybrid’: SLN + Classic CMN
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Evolution: SLN → Classic CMN
6 months
12 months
24 months
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Speckled Lentiginous Nevus: two variants
• exclusively macular speckles
• papular + macular speckles– ‘garden’ of nevi – any type– ‘SLN syndrome’ – weakness,
dysesthesia, hyperhidrosis
Vidaurri-de la Cruz & Happle. Dermatology 2006Happle. Clin Exp Derm 2009
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4 years 10 years 14 years
Haenssle et al. Clin Exp Derm 2009
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CMN in Infants: Transient Erosions
• skin breakdown due to skin fragility in neonatal period– evident at birth or during first
few days of life– favors thickest part of nevus
• heal spontaneously over days to weeks
Giam et al Pediatr Derm 1999Gonzalez et al JAAD 2003
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CMN in Infants: Proliferative Nodules
• can mimic melanoma, but benign course– rapid growth– atypical histologic features
• clues from comparative genomic hybridization*– no chromosomal aberrations or only numeric changes– most often loss of chromosome 7– not structural changes (gains/losses of chromosomal
fragments) that characterize >95% of melanomas
Bastian et al Am J Pathol 2002Murphy et al JAAD 2008Phadke et al Am J Surg Path 2011*Can use paraffin-embedded tissue
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Neurotized Nevi
A
B
C
Type ofNevus Cell
Morphology ofNevus Cell
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NeurotizedNevus Neurofibroma
S-100 + +
Leu-7 - +*
GFAP - +*
Myelin basic protein - +*
Factor XIIIa - +
GFAP = glial fibrillary acidic protein *Stains minority of cells
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Halo Phenomenon
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Regression of Halo CMN
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Halo Nevus with Dermatitis
Rolland et al. Ped Derm 2009; Patrizi et al Br J Derm 2005
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Tauscher et al. Arch Ped Adol Med 2007
vs Pure ‘Meyerson Phenomenon’: No Regression of the Nevus
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1 month 1 year
2 years 3 yearsBonifazi et al. Eur J Ped Dermatol 2001
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‘Disappearing’ CMN on the Scalp
• clinical fading over the first 1-4 years of life
• histologic evaluation performed in 2 of 7 children recently reported – nevomelanocytes remained in deep
dermis and adnexae– no inflammation or fibrosis
Strauss & Newton Bishop JAAD 2008Vilarrasa et al JAAD 2008
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Strauss & Newton Bishop JAAD 2008
4 months
26 months
birth
21 months
birth
26 months
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2 years 4 years
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8 mos 6 years
5 mos 4 years
3 years 11 years
‘Peas in a pod’(parallel furrow + crista dotted)
Decreased pigmentation
Minagawa et al. Arch Derm 2011
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Desmoplastic Hairless Hypopigmented CMN
• woody induration• progressive loss
of pigmentation• alopecia• intense pruritus
Ruiz-Maldonado et al. Br J Dermatol 2003Martin et al. JAAD 2007
1 month 5 months 2 years
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Birth 2 years
Hernandez-Martin et al. Clin Exp Derm 2007
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Gass et al. Ped Derm 206
Birth 5 years
S100
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Spontaneous ‘Scarification’
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Risks of Congenital Melanocytic Nevi
Small- & medium-sized
Large- or giant-sized
Skin disease
Systemic disease
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Neurocutaneous Melanocytosis
• proliferation of melanocytes within the leptomeninges (in addition to the skin)– melanocytomas– melanomas
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Risk Factors for Neurocutaneous Melanocytosis (NCM)
• multiple satellite nevi– 5-fold increased risk with >20 satellites
(2.5%→12.5%)– ~1/3 of NCM cases without ‘mother ship’
• final size of CMN >40 cm
• ?posterior axial location– inconsistent results– no associated risk in recent large study of
high-risk CMN patients with CNS imaging (n=120)
Kinsler et al. Br J Derm 2008Hale et al. Br J Derm 2005Marghoob AA et al. Arch Derm 2004
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Multiple Satellites
associated with >75% of large CMN
in the absence of a ‘mother ship’
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Neurocutaneous Melanocytosis• symptomatic NCM
– classically 3–4% of those with high-risk nevi– median onset ~2 y, median survival 6 months– hydrocephalus, seizures, vomiting– with localized mass, median onset ~9 y and more
likely focal sensorimotor deficits
• asymptomatic NCM – + MRI in 5–25% of those with high-risk nevi but no
neurologic symptoms– in 5-y follow-up study, 1 of 10 asymptomatic patients
with +MRI developed neurologic symptoms– ?higher proportion symptomatic, e.g. recent
Montreal series Foster RD et al. Plast Reconstr Surg 2001Hale EK et al. Br J Dermatol 2005Lovett et al. JAAD 2009
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Age 5 mos Age 18 mos Age 9 y
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Neurocutaneous Melanocytosis: MRI Findings
• best detected by MRI of brain and spine with and without gadolinium– progressive myelination after 6 months of age may
obscure melanin T1 signal
• MRI findings– areas of brain parenchyma (especially temporal
lobes/amygdala) with increased T1 signal – enhancement of diffusely thickened leptomeninges– obvious masses– other CNS/spinal malformations (e.g. Dandy Walker
complex/posterior fossa cysts, intraspinal lipomas)
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Neurocutaneous Melanocytosis: Recent Clinical Insights
• study of 120 children with high-risk CMN who underwent MRI of the CNS– mean age at MRI = 2.5 y– mean follow-up = 8 y
• 19% (23/120) had neurologic abnormalities– 11% clinical + MRI (most symptomatic by age 2 y)– 4% MRI only (asymptomatic)– 4% clinical only– included relatively mild clinical findings, e.g.
developmental delay, abnormal muscle tone– significantly more common in boys than girls
Kinsler et al Br J Derm 2008
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Risk of Cutaneous Melanoma in CMN –Correlated with Size
>60 cm 4 (2 cutaneous/axial, 2 extracutaneous)
20-60 cm
<20 cm
nevus size N*
204
94
28
multiple 13
melanomas
Kinsler et al Br J Derm 2009
0
0
1 (CNS)
*mean age at entry, 3 y; mean follow-up, 9 y
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Risk of Cutaneous Melanoma in CMN –Correlated with Size
>60 cm 4 (2 cutaneous/axial, 2 extracutaneous)
20-60 cm
<20 cm
nevus size N*
204
94
28
multiple 13
melanomas
Kinsler et al Br J Derm 2009
0
0
1 (CNS)
*mean age at entry, 3 y; mean follow-up, 9 y
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Risk of Cutaneous Melanoma in CMN –Correlated with Size
>60 cm 4 (2 cutaneous/axial, 2 extracutaneous)
20-60 cm
<20 cm
nevus size N*
204
94
28
multiple 13
melanomas
Kinsler et al Br J Derm 2009
0
0
1 (CNS)
*mean age at entry, 3 y; mean follow-up, 9 y
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Caveat with regard to Statistics on Melanoma Risk in CMN
• selection bias in studies can lead to overestimates of melanoma incidence– retrospective case collections– tertiary referral centers– small studies
Krengel et al Br J Dermatol 2006
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Melanoma Risk for Small and Medium-Sized CMN
• exact risk not known– estimated to be <1% over a lifetime
• 3 large cohort studies (total n = 680)– mean age at entry ~10 y– mean follow-up period 13.5 y– no melanomas observed
Kinsler et al. Br J Derm 2009Swerdlow et al. JAAD 1995Sahin et al. JAAD 2008
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Melanomas in Small and Medium-Sized CMN
• risk virtually all afterpuberty
• tend to arise at the dermo-epidermal junction
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Psychosocial/cosmetic concerns
Anxiety level
Ease of monitoring
Natural history
Factors that affect healing/scarring
Type of anesthesia required
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THERE IS NOT ONE ‘RIGHT’ ANSWER FOR EVERYONE
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Psychosocial/Cosmetic Ramifications
• Face >> other highly visible areas– Larger lesions– Conspicuous sites (eg tip of nose)– ‘Ugly’ lesions (eg thick, warty, hairy)
• Subjectively unappealing lesions, especially in visible sites
• Lesions that are clearly more cosmetically appealing than the resultant SCAR
SOONER
LATER IF AT ALL
Remove before body image begins to
solidify at ~age 4 y
Remove if/when bothersome to the patient
Encourage NOT to remove or to wait
X
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There is No ‘Mole Eraser’
McAllister et al Ped Derm 2009
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Natural History
• Clinically and/or histologically worrisome changes
• Functional issues (e.g. bulky/exophytic lesions)
SOONER
LATER IF AT ALL
• Signs of involution• Remember that risk of melanoma is low
and begins after puberty
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BUTTOCK FOREARM
BLACK OR MOTTLED HOMOGENEOUS TAN
THICK, IRREGULAR, MULTINODULAR THIN, UNIFORM
VERY DENSE MINIMAL
location
pigmentation
topography
hypertrichosis
Factors that Affect Ease of Monitoring
patient/family AWARE, MEDICALLY SOPHISTICATED
RELUCTANT
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Anxiety of Child & Family
• High level of anxiety regarding the lesion
• High level of anxiety regarding the procedure
SOONER
LATER IF AT ALL
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Factors that Affect Healing/Scarring
• Scalp, lower legs, forearms, palms/soles– Increased tissue flexibility and less scar
spread in 1st year of life
• Risk of functional impairment from scar (e.g. over joint/ circumferential, eyelid margin)
• Sports season currently or in the near future
SOONER
LATER IF AT ALL
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Type of Anesthesia Required
• General anesthesia required even if done in an adolescent or adult
• Local anesthesia– Girls: average 9-10 years– Boys: average 10-11 years– VARIES CONSIDERABLY!
SOONER
LATER
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Margulis, Alder, Bower Plast Reconst Surg 2009
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Small and Medium-Sized CMN: Longitudinal Evaluation
• baseline photography
• (self) skin examination by patient/parents– bring focal changes in color, border or
topography to dermatologist’s attention
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Small and Medium:risk ~all after puberty
Large:~half of risk in 1st 5 y
~5-10%
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Large/Giant CMN – Risk of Melanoma
• higher risk– posterior axial location– large number of satellite nevi– larger size of CMN (e.g. >50 cm)
• lower risk– restricted to an extremity or the head– satellite nevi themselves
Hale EK et al. Br J Dermatol 2005Bett BJ. J Am Acad Dermatol 2005
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Melanomas Associated with Large/Giant CMN
• cutaneous melanomas often arise sub-epidermally, making recognition difficult
• extracutaneous primary sites are relatively common– CNS– retroperitoneum
• occasionally, the primary site is not found
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Large/Giant CMN –Prospective Studies on Risk of Melanoma
Ruiz-Maldonado, 1992
Hale, 2005
Egan, 1998
80
46*
170**
8.6 y
7.3 y
5.3 y
2 (2.5%)(cutaneous/axial)
2 (4%)(cutaneous/axial)
4 (2.5%)(all extracutaneous)
* mean age = 8 years**mean age = 6 years
Nstudy follow-up melanomas
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Large/Giant CMN – Internet Registry-Based Data on Risk of Melanoma
Nevus Network*(Bett, 2005)
Nevus Outreach* (Ka, 2005)
524 truncal/garment336 head/extremity
379
5.2 y
**
15 (2.9%)1 (0.3%)
(2 extracutaneous)
0
* no physician confirmation** median age = 4 y
N follow-up melanomasstudy
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How Does Excision of Large CMN Affect the Risk of Cutaneous Melanoma?
• no clear-cut answer in the literature– trend toward lower incidence of melanoma in patients
whose nevi were excised– however, the largest nevi (which have a higher
melanoma risk) are more likely to be ‘inoperable’
• although early and ‘complete’ excision is often recommended, it is usually impossible to remove every nevus cell in the lesion – location– extensive size– involvement of deeper structures
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Other Considerations Regarding Excision of Large CMN
• cons– scar may restrict joint
mobility or impair function
– morbidities of procedures, e.g. discomfort, limitation of activity, risk of infection, anesthesia risk
• pros– functional benefits
(e.g. bulky lesions)– scar more
cosmetically acceptable than nevus
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Procedures for Cosmetic and Psychological Benefit (not to decrease melanoma risk)
• neonatal curettage – takes advantage of a cleavage plane between the
upper dermis (where ‘active’ nevus cells are concentrated) and mid dermis in first 2-3 weeks of life
• dermabrasion
• laser resurfacing (e.g. CO2, erbium:YAG)
• other lasers (e.g. Nd-YAG, ruby, alexandrite)
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Age 6 mos Age 7 mos, 1 mo after curettage
Age 7 mos, 2 wks after Q-switched ruby laser
Age 8 mos, 1 mo after Q-switchedruby laser
Kishi et al. Br J Derm. 2007
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36 mos latertreated at ages:2 wks with CO25 wks with Nd-YAG
Dave et al. Br J Plast Surg 2004
27-y-old woman – melanoma10 y s/p argon laser therapy
Woodrow et al. Br J Derm 2003
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