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

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

Overview

• evolving definitions and concepts

• natural history

• risks– neurocutaneous melanocytosis– melanoma

• management strategies

Goal: Neither You nor Your Patients Order These Products

McAllister et al Ped Derm 2009

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

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

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

Congenital Melanocytic Nevi: Histologic Features

• nevomelanocytes extend deeper into dermis and subcutis

• single-file arrangement between collagen bundles

• track along appendages & neurovascular structures

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

Natural History of Congenital Melanocytic Nevi

• darker or lighter color

• increase in overall thickness

• changes in topography

Development of a Verrucous Surface

Papules, Nodules and ‘Pebbling”

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

‘Hybrid’: SLN + Classic CMN

Evolution: SLN → Classic CMN

6 months

12 months

24 months

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

http://162.129.70.33/images/agminate_spitz_nevus_1_041006.jpg�

4 years 10 years 14 years

Haenssle et al. Clin Exp Derm 2009

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

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

Neurotized Nevi

A

B

C

Type ofNevus Cell

Morphology ofNevus Cell

NeurotizedNevus Neurofibroma

S-100 + +

Leu-7 - +*

GFAP - +*

Myelin basic protein - +*

Factor XIIIa - +

GFAP = glial fibrillary acidic protein *Stains minority of cells

Halo Phenomenon

Regression of Halo CMN

Halo Nevus with Dermatitis

Rolland et al. Ped Derm 2009; Patrizi et al Br J Derm 2005

Tauscher et al. Arch Ped Adol Med 2007

vs Pure ‘Meyerson Phenomenon’: No Regression of the Nevus

1 month 1 year

2 years 3 yearsBonifazi et al. Eur J Ped Dermatol 2001

‘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

Strauss & Newton Bishop JAAD 2008

4 months

26 months

birth

21 months

birth

26 months

2 years 4 years

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

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

Birth 2 years

Hernandez-Martin et al. Clin Exp Derm 2007

Gass et al. Ped Derm 206

Birth 5 years

S100

Spontaneous ‘Scarification’

Risks of Congenital Melanocytic Nevi

Small- & medium-sized

Large- or giant-sized

Skin disease

Systemic disease

Neurocutaneous Melanocytosis

• proliferation of melanocytes within the leptomeninges (in addition to the skin)– melanocytomas– melanomas

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

Multiple Satellites

associated with >75% of large CMN

in the absence of a ‘mother ship’

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

Age 5 mos Age 18 mos Age 9 y

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)

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

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

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

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

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

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

Melanomas in Small and Medium-Sized CMN

• risk virtually all afterpuberty

• tend to arise at the dermo-epidermal junction

Psychosocial/cosmetic concerns

Anxiety level

Ease of monitoring

Natural history

Factors that affect healing/scarring

Type of anesthesia required

THERE IS NOT ONE ‘RIGHT’ ANSWER FOR EVERYONE

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

There is No ‘Mole Eraser’

McAllister et al Ped Derm 2009

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

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

Anxiety of Child & Family

• High level of anxiety regarding the lesion

• High level of anxiety regarding the procedure

SOONER

LATER IF AT ALL

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

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

Margulis, Alder, Bower Plast Reconst Surg 2009

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

Small and Medium:risk ~all after puberty

Large:~half of risk in 1st 5 y

~5-10%

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

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

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

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

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

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

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)

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

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