Congenital melanocytic nevi when to worry & when to treat

Congenital melanocytic nevi when to worry & when to treat

1. Congenital Melanocytic Nevi:
When to Worry &
When to Treat
Julie V. Schaffer, MD
Associate Professor of Dermatology and Pediatrics
Director of Pediatric Dermatology
NYU School of Medicine

2. Congenital Melanocytic Nevi:
When NOTto Worry &
When NOTto Treat
Julie V. Schaffer, MD
Associate Professor of Dermatology and Pediatrics
Director of Pediatric Dermatology
NYU School of Medicine

3. Overview
•evolving definitions and concepts
•natural history
•risks
–neurocutaneous melanocytosis
–melanoma
•management strategies

4. Goal: Neither You nor Your Patients
Order These Products
McAllister et al Ped Derm 2009

5. Congenital Melanocytic Nevi:
Traditional Concepts
•
classic definition: present at birth
•1-6% of neonates in large series
–clinicaldiagnosis in older studies
–dermatoscopicdiagnosis more recently
–may be more evident in newborns with
darker skin

6. 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

10. 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

11. Congenital Melanocytic Nevi:
Histologic Features
•
nevomelanocytes extend
deeper into dermis and
subcutis
•single- file arrangement
between collagen bundles
•track along appendages &
neurovascular structures

12. Congenital Melanocytic Nevi:
Evolving Concepts
•‘tardive CMN’, ‘early onsetnevi’, ‘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

13. Natural History of
Congenital Melanocytic Nevi
•darker or lighter color
•increase in overall thickness
•changes in topography

14. Development of a Verrucous Surface

15. Papules, Nodules and ‘Pebbling”

18. 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

19. ‘Hybrid’: SLN + Classic CMN

20. Evolution: SLN → Classic CMN
6 months
12 months
24 months

21. 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 2006
Happle. Clin Exp Derm 2009

23. 4 years 10 years 14 years
Haenssle et al. Clin Exp Derm 2009

24. 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 1999
Gonzalez et al JAAD 2003

25. 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
–notstructural changes (gains/losses of chromosomal
fragments) that characterize >95% of melanomas
Bastian et al Am J Pathol 2002
Murphy et al JAAD 2008
Phadke et al Am J Surg Path 2011
*Can use paraffin-embedded tissue

26. Neurotized Nevi
A
B
C
Type of
Nevus Cell
Morphology of
Nevus Cell

27. Neurotized
Nevus Neurofibroma
S-100 + +
Leu-7 - +*
GFAP - +*
Myelin basic protein - +*
Factor XIIIa - +
GFAP = glial fibrillary acidic protein *Stains minority of cells

28. Halo Phenomenon

29. Regression of Halo CMN

30. Halo Nevus with Dermatitis
Rolland et al. Ped Derm 2009; Patrizi et al Br J Derm 2005

31. Tauscher et al. Arch Ped Adol Med 2007
vsPure ‘Meyerson Phenomenon’:
No Regression of the Nevus

32. 1 month 1 year
2 years 3 years
Bonifazi et al. Eur J Ped Dermatol 2001

33. ‘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 2008
Vilarrasa et al JAAD 2008

34. Strauss & Newton Bishop JAAD 2008
4 months
26 months
birth
21 months
birth
26 months

35. 2 years 4 years

36. 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

37. Desmoplastic Hairless
Hypopigmented CMN
•woody induration
•progressive loss
of pigmentation
•alopecia
•intense pruritus
Ruiz-Maldonado et al. Br J Dermatol 2003
Martin et al. JAAD 2007
1 month 5 months 2 years

38. Birth 2 years
Hernandez-Martin et al. Clin Exp Derm 2007

39. Gass et al. Ped Derm 206
Birth 5 years
S100

40. Spontaneous ‘Scarification’

42. Risks of Congenital Melanocytic Nevi
Small-&medium-sized
Large- or giant-sized
Skin disease
Systemic disease

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

44. 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 2008
Hale et al. Br J Derm 2005
Marghoob AA et al. Arch Derm 2004

45. Multiple Satellites
associated with >75%
of large CMN
in the absence of a
‘mother ship’

47. 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 2001
Hale EK et al. Br J Dermatol 2005
Lovett et al. JAAD 2009

48. Age 5 mos Age 18 mos Age 9 y

49. 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)

50. 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

52. 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

53. 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

54. 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

55. Caveatwith regard to
Statistics on Melanoma Risk in CMN
•selection biasin studies can lead to
overestimatesof melanoma incidence
–retrospective case collections
–tertiary referral centers
–small studies
Krengel et al Br J Dermatol 2006

56. 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 2009
Swerdlow et al. JAAD 1995
Sahin et al. JAAD 2008

57. Melanomas in
Small and Medium-Sized CMN
•risk virtually all after
puberty
•tend to arise at the
dermo- epidermal
junction

58. Psychosocial/cosmetic concerns
Anxiety level
Ease of monitoring
Natural history
Factors that affect healing/scarring
Type of anesthesia required

59. THERE IS NOTONE ‘RIGHT’
ANSWER FOR EVERYONE

60. 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
Removebeforebody image
begins to
solidify at ~age 4 y
Remove if/when
bothersome to the patient
EncourageNOTto
remove or to wait X

61. There is No ‘Mole Eraser’
McAllister et al Ped Derm 2009

62. 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

63. 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

64. Anxiety of Child & Family
•High level of anxiety
regarding the lesion
•High level of anxiety regarding the procedure
SOONER
LATER IF AT ALL

65. Factors that Affect Healing/Scarring
•Scalp, lower legs, forearms,
palms/soles
–
Increased tissue flexibility and less scar
spread in 1
st
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

66. Type of Anesthesia Required
•General anesthesia required even if
done in an adolescent or adult
•Local anesthesia
–Girls: average 9-10years
–Boys: average 10-11 years
–VARIES CONSIDERABLY!
SOONER
LATER

68. Margulis, Alder, Bower Plast Reconst Surg 2009

70. 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

71. Small and Medium:
risk ~all after puberty
Large:
~half of risk in 1
st
5 y
~5-10%

72. 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 2005
Bett BJ. J Am Acad Dermatol 2005

73. 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

74. 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

75. Large/Giant CMN –Internet Registry-Based
Data on Risk of Melanoma
Nevus
Network*
(Bett, 2005)
Nevus
Outreach*
(Ka, 2005)
524 truncal/garment
336 head/extremity
379
5.2 y
**
15 (2.9%)
1 (0.3%)
(2 extracutaneous)
0
* no physician confirmation
** median age = 4 y
N follow- upmelanomasstudy

76. 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

77. 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

82. 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. CO
2, erbium:YAG)
•other lasers (e.g. Nd- YAG, ruby, alexandrite)

84. 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-switched
ruby laser
Kishi et al. Br J Derm. 2007

85. 36 mos latertreated at ages:
2 wks with CO
2
5 wks with Nd-YAG
Dave et al. Br J Plast Surg 2004
27-y-old woman –melanoma
10 y s/p argon laser therapy
Woodrow et al. Br J Derm 2003