Pediatric Skin Lesions with Predisposition to Cancer Mark A. Bechtel, M.D.

Document technical information

Format pdf
Size 2.1 MB
First found Jun 9, 2017

Document content analysis

Language
Italian , English
Type
not defined
Concepts
no text concepts found

Persons

Organizations

Places

Transcript

Pediatric Skin Lesions
with Predisposition to
Cancer
Mark A. Bechtel, M.D.
Director of Dermatology
The Ohio State University College of Medicine
Pediatric Primary Malignant Skin Tumors
„
„
„
Melanoma
‰ Congenital nevi
‰ Xeroderma pigmentosa
‰ Nevus spilus
‰ Develop de novo
‰ Radiotherapy
Squamous Cell Carcinoma
‰ Xeroderma pigmentosa
‰ Renal, bone marrow, other solid organ transplants
‰ Immunosuppressive therapy
‰ Immunodeficiency disorders
‰ Nevus sebaceous
B
Basal
lC
Cellll C
Carcinoma
i
‰ Gorlins syndrome
‰ Renal, bone marrow, other solid organ transplants
‰ Nevus sebaceous
Skin cancers following
gp
pediatric organ
g
transplant. S Euvrard et.al. Dermatol
g 2004;; 30: 616-621
Surg
„
„
„
Skin cancer is the most frequent malignancy
following pediatric renal transplantation and the
second most common after p
pediatric nonrenal
transplantation.
Squamous cell and basal cell carcinoma, and
rarely Kaposi’s sarcoma
Usually develop in early adulthood
Pediatric Melanoma
„
„
„
„
„
„
2% of melanomas occur in patients younger than 20 years of
age.
0.3% of melanomas occur in patients younger than 14 years
of age.
Risk factors for melanoma in children parallel those in adults
adults.
Predisposing factors
‰ Large congenital nevi
‰ Xeroderma pigmentosa
Melanomas proportionately more common children
‰ Small cell melanomas
‰ Melanomas
M l
with
ith ffeatures
t
off S
Spitz
it nevii with
ith atypical
t i l
features
Childhood melanomas histiologically resemble adult
melanomas
Pitfalls in Diagnosis & Management of
P di t i M
Pediatric
Melanomas
l
„
„
„
Low index of suspicion
Atypical presentation
‰ Amelanotic
‰ Verrucous
‰ Pyogenic granuloma-like
Delay in biopsy
Melanoma in children and teenagers: an analysis of
patients from the National Cancer Data Base.
Lange JR et.al. J Clin Oncol 2007; 25: 1363-1368.
„
Evaluated 3158 patients ages 1-19 with malignant
melanoma
Age
1-4
5-9
10-14
15-19
% of study subjects
3.8%
5 7%
5.7%
17.3%
73 2%
73.2%
Lange – Pediatric Melanoma
„
„
„
Overall survival of patients aged 1-9 was
significantly worse than those aged 10-24.
Male patients aged 10-24 had worse outcome
than females in this age group.
In patients 1
1-19,
19 survival was not correlated with
primary tumor thickness
Congenital Melanocytic Nevi
„
„
„
„
Nevomelanocytic proliferations that are present at
birth
Congenital nevus “tardive” – develops during the
first 2 years of life and is clinically and
histologically indistinguishable from congenital
melanocytic nevi
Congenital nevi are present in 1% of newborns
newborns.
Large congenital nevi (> 20 cm) occur in 1:20,000
newborns.
Congenital Nevi Classification
„
„
„
„
< 1.5 cm – small congenital nevus
1.5 cm to 20 cm – medium congenital nevus
> 20 cm – large congenital nevus
In the newborn or infant – a CMN of 6 cm on the
b d or 9 cm on th
body
the h
head
d will
ill attain
tt i a size
i off 20 cm
in adulthood
Kopf
p AW. J Am Acad Dermatol 1979;; 1: 123-130.
Large
g Congenital
g
Nevi – Melanoma Risk
„
„
„
„
„
The lif
Th
lifetime
ti
risk
i k off d
developing
l i melanoma
l
h
has
been estimated at 5-20%.
Melanoma often develops during childhood
childhood.
Melanoma usually arises deep within the dermis
where it is not easily detectable on clinical
examination until it reaches an advanced stage.
More than half of melanomas develop during the
first 10 years of life
life.
The highest rate of malignancy occurs during the
y
first 5 years.
Small and Medium Congenital Nevi
– Melanoma Risk
„
„
„
The lifetime risk of developing melanoma is not
well established.
Melanoma often develops in adulthood
Melanoma usuallyy arises in the epidermal-dermal
p
junction and can be detected at an earlier stage by
clinical examination
A study of large congenital melanomcytic
nevii and
d associated
i t d malignant
li
t melanomas.
l
DeDavid M et. al. J Am Acad Dermatol. 36:
409 416 1997
409-416,
1997.
„
„
Reviewed 289 patients with large congenital nevi
in NYU registry and the world literature.
34 patients (12%) developed primary cutaneous
melanoma
Results of DeDavid Study
„
„
„
„
„
„
All the melanomas had congenital nevi in an axial
location (32 – torso, 2 – posterior scalp).
Satellite nevi were reported
p
in 91% of p
patients with
primary cutaneous melanoma.
No melanomas developed on an extremity or
within
ithi a satellite
t llit
50% of melanomas were diagnosed before 5
years (median – 4.6).
62% of patients died from melanoma.
Median age
g of death was 7.1 yyears.
Clinical appearance of the ulcerated nodule within the scalp giant congenital nevus of patient 1
Leech, S. N. et al. Arch Dermatol 2004;140:83-88.
Copyright restrictions may apply.
5 yyear cumulative risk of developing
p g
melanoma in large congenital nevi
„
„
Marghoob
Egan
g
4.5%
5.7%
Marghoob et al, Arch Dermatol. 1996; 132: 170-175.
Egan et al, J Am Acad Dermatol. 1998; 39: 923-932.
Risk of melanoma in medium-sized
congenital melanocytic nevi. Sahin S, et al.
J Am Acad Dermatol. 1998; 39: 428-433.
„
„
Followed a cohort of 230 p
patients with CMN ((1.519.9 cm) for an average of 6.7 years (median 5.8
years).
No melanomas observed.
The risk of melanoma in patients with
congenital nevi: a cohort study. Swerdlow AJ,
et al. J Am Acad Dermatol. 1995; 32: 595-599.
„
„
„
Followed CMN involving less than 4% body
surface (< 20 cm) in 232 patients.
Observation period median of 25 years
No melanomas developed
Large
g CMN May
y Be Biologically
g
y Different
From Small and Medium CMN
„
„
Large CMN
‰ NRAS mutations (70%)
‰ BRAF mutations (15%)
Small and medium CMN
‰ NRAS mutations (14-56%)
‰ BRAF mutations (70-94%)
Dessars B
B, et al
al. J Invest Dermatol
Dermatol. 2009; 129: 139-147
139-147.
Management
g
of Large
g Congenital
g
Nevi
„
„
Treatment should be individualized
Considerations for management
‰ Risk of melanoma
‰ Risks and functional impact of surgery
‰ Disfigurement of surgery
‰ Cosmetic concerns of lesion
‰ Ease of observation for changes in CMN
Tromberg et al. Dermatol Ther 2005:;18 (2) : 144
Treatment options
treatment
benefits
risks
Full thickness
excision
i i
1.
2.
1.
Reduces melanoma risk
Cosmesis
2.
3.
Partial-thickness
excision
1.
2.
Reduces melanoma risk
Less potential for scarring than full thickness
excision
1.
2.
3.
4.
curettage
1.
2.
Potential reduction of melanoma risk if done
early
May produce good cosmetic result
1.
2.
3.
3
4.
5.
dermabrasion
laser
Chemical peel
1.
2
2.
3.
Reduces melanoma risk
May produce good cosmetic result
Reduced pigmentation may allow for easier
detection of developing melanoma
1.
1.
1.
2.
3.
Unknown to what extent it may or may not
reduce melanoma risk
Low potential for scarring
p
recovery
y time
Improved
1.
2.
May reduce melanoma risk
cosmesis
1.
2.
2.
3.
2.
Excision of large CMN may leave cosmetically
disfiguring scar
Often requires serial excisions, tissue
expanders, skin grafts
Requires general anesthesia
Melanoma may develop from residual
melanocytes
Excision of large CMN may leave cosmetically
di fi i scar
disfiguring
Requires general anesthesia
Difficult to detect subcutaneous melanoma
Melanoma may develop from residual
melanocytes
Requires general anesthesia
Must be performed within the first few weeks of
life
Repigmentaiton of scarred skin
Scarring may make it difficult to detect
development of MM
Case reports of melanoma development after
dermabrasion
Post-dermabraded skin is thin, fragile, tender,
reduced hair density
Melanoma may develop from residual
melanocytes
Repigmentation
Unknown mutagenic
g
p
potential
Melanoma may develop from residual
melanocytes
Most effective in superficial CMN that are lightly
pigmented
Neurocutaneous Melanosis
„
„
„
Excessive proliferation of melanocytes within the
CNS, including the leptomeninges as well as brain
parenchyma
h
A congenital error in morphogenesis of embryonal
neuroectoderm
Risk factors include posterior axial location of a
LCMN and the presence of multiple satellite nevi
nevi.
Neurocutaneous melanosis (cont.)
„
„
„
CMN typically involve the lumbosacral region,
posterior thorax, and especially the head and
neck.
neck
Patients with more than 20 satellite nevi have a
5 1 fold increased risk of neurocutaneous
5.1
melanosis.
34% of patients have multiple CMN rather than a
single large CMN.
Neurocutaneous Melanosis Symptoms
„
„
„
„
„
„
Increased intracranial pressure
Seizures
Hydrocephalus
Cranial nerve palsy
Hemiparesis
Developmental delays
y
Symptomatic Neurocutaneous Melanosis
„
„
„
„
Most children present within the first 5 years of life
Prognosis is poor with incidence of death of 79%
with 50% dying before 5 years of age.
Primary CNS melanoma occurs in over 50% with
median age
g of death of 3 yyears
Treatment is only palliative.
DeDavid M et al. J Am Acad Dermatol. 1996; 35: 529-538.
MRI Findings in Neurocutaneous Melanosis
„
„
Diagnosis established by MRI
Characteristic hyper intense regions in T1 –
weighted images in the cerebellar hemispheres
hemispheres,
pons, and/or amygdala
Spitz Tumors
„
„
„
„
„
„
Usually acquired
acquired, but may be congenital
Majority develop in children, adolescents, and
young adults,
adults but may occur at any age
Most often present as solitary asymptomatic,
red/pink, hairless, dome-shaped,
dome shaped, smooth nodule
Some lesions are skin colored, tan, brown, or
black
Lesions are usually < 1 cm in diameter
Predilection for face and extremities
Spitz
p Tumors - Histology
gy
„
„
„
„
„
„
„
Large spindle – shaped and/or epithelioid
melanocytes
Overall monomorphous population of cells
Occasional striking pleomorphism in a minority of
cells
Symmetry
Sharp
p lateral demarcation
Zonation in depth (maturation)
Absent or rare mitoses in deep
pp
parts
Spitz
p Tumor with Atypical
yp
Features
„
„
„
„
May be difficult distinguishing from conventional
Spitz tumors and melanoma
Diameter ≥ 10 mm in diameter
Ulceration may be present
S
Sometimes
ti
iinvolvement
l
t off subcutaneous
b t
fat
f t
Spitz Tumors with Atypical FeaturesHi t l
Histology
„
„
„
„
„
„
Poor circumscription
Pagetoid melanocytosis over a large front
Lack of zonation and maturation
Asymmetry
Significant mitotic rate, > 2-6/mm2
Deep
p marginal
g
mitoses
Assessment of Spitz Tumors for Risk of Metastasis
Parameter
Score
Age (years)
0-10
11-17
0
1
Diameter (mm)
0-10
> 10
0
1
Involvement of subcutaneous fat
absent
present
0
2
Ulceration
absent
present
0
2
Mitotic activity (mm2)
0-5
6-8
>9
0
2
5
scoring
Low risk – 0-2
Hi h risk
High
i k – 5-11
5 11
Management of Spitz Tumors
„
„
„
„
„
„
„
Examination of entire lesion
Extensive histopathological and clinical evaluation
Placement into risk category
Complete excision of non atypical and low-risk Spitz
tumors
Excision of high risk and biologically indeterminate
lesions with approximately 1 cm margins
Sentinel lymph node biopsy may be considered for
selected lesions > 1 mm in thickness
Long
g term follow up
p
The atypical Spitz tumor of uncertain
biological potential
potential. Ludgate et al
al.
Cancer 2009; 115 (3): 631-641.
„
„
„
„
„
Evaluated 67 patients with AST (median age 23.7
years)
57 had SLNB with 27 (47%) being positive
Mean age SLNB positive was 17
17.9
9 years
Mean age SLNB negative was 28.7 years
All positive SLNB were alive and well with median
follow up of 43.8 months
Nevus Sebaceous
„
„
„
„
„
„
Organoid hamartoma of appendageal structures usually
evident at birth
Seen in 0.3% of newborns
Typical appearance is a pink-yellow
pink yellow or yellow-orange
yellow orange plaque
with a velvety surface located on the scalp or face
Circumscribed alopecia is common.
Develops neoplastic growth – most are benign appendageal
tumors, such as syringocystadenoma papilliferum,
tricholemmoma, trichoblastoma.
Malignant tumors occur, including basal cell, squamous cell,
apocrine, and sebaceous carcinoma. (Locally invasive, rarely
metastasize).
)
Management of Nevus Sebaceous
„
„
„
Prophylactic excision is controversial.
Monitor for surface ulceration or development of a
nodule
Surgery should be individualized and may be
performed in infancy or postponed until later in
childhood or adolescence.
Nevus Spilus
„
„
„
„
„
Present at birth with a speckled appearance
Histology – lentigo with junctional nevi
Light brown patch
patch, which may contain or
acquire dark brown macules
T k and
Trunk
d proximal
i l extremities
t
iti mostt common
location
2% d
develop
l melanoma
l
Xeroderma Pigmentosum
„
„
„
„
„
Autosomal recessive
One per million newborns in Western
countries
1 per 40,000 - 100,000 newborns in Japan
M k d iincrease iin iincidence
Marked
id
off cutaneous
t
malignancies at an early age
photosensitivity
h t
iti it
Xeroderma Pigmentosum – Genetic Factors
„
„
„
„
„
Seven genetically different complementation groups (A
to G)
Defective global genomic nucleotide excision repair of
ultraviolet radiation-induced DNA damage
g ((such as
pyrimidine dimers)
Impairment in removal of DNA damage from any place in
the genome
XP-variant due to mutations that encodes DNA
polymerase-n,
p
y
, which results in insertion of erroneous
residues during replication
Cells are hypersensitive to killing by ultraviolet light
Xeroderma Pigmentosum - Clinical Features
„
„
„
„
„
„
„
„
Skin normal at birth, but sunburns easily
Freckling and dryness on light-exposed surfaces are earliest
manifestations, presenting by age 2.
Actinic keratoses are frequent
First cutaneous malignancies develop as early as 3-4 years of
age with median onset of 8 years.
Malignancies include basal and squamous cell carcinomas
and
d malignant
li
t melanoma
l
Patients up to age 20 have a 1000 times greater incidence of
melanoma and non-melanoma skin cancers
Approximately 20-30% of patients develop neurologic
abnormalities.
Ocular abnormalities occur in 40%
Xeroderma Pigmentosum
- Skin Malignancies
„
„
„
„
Basal cell carcinoma is common in large
numbers, often pigmented.
Squamous cell cancer is common and may
involve the anterior tongue.
Melanomas may be multiple and lead to early
death from widespread metastases.
Di
Disease
often
ft fatal
f t l before
b f
the
th age off 10 and
d twot
thirds die before 20 years of age
Xeroderma Pigmentosum Treatment
„
„
„
„
„
Protect from sunlight by every means
possible.
Early and adequate excision of all cutaneous
malignancies
Topical 5-FU
Oral retinoids
Mi bi l enzyme T
Microbial
T-4
4 endonuclease
d
l
applied
li d
regularly as a topical liposome lotion
Nevoid Basal Cell Carcinoma Syndrome
(Gorlins Syndrome)
„
„
Autosomal dominant with 50% representing
new mutations
Caused by mutations in the tumor suppressor
gene PTCH
NBCCS – Clinical Features
„
„
„
„
„
„
„
Numerous basal cell cancers
Odontogenic keratocytes of the jaws
Palmer and p
plantar p
pits
Calcified dural folds
Bifid ribs
Macrocephaly
medulloblastomas
Management of NBCCS
„
„
„
„
„
„
Radiation therapy is best avoided
Excision
Photodynamic therapy
Imiquimod
Sun avoidance
Anti hedge hog therapy is experimental

Similar documents

×

Report this document