Cutaneous/ Malignant Basal Cell Squamous Cell

Melanoma Carcinoma Carcinoma

Age 52 y/o
Most common cancer
in young adults US 25-
29 y/o
2nd most common in
adolescents and young
adults 15-29 y/o
M:F incidence M<F <40 y/o
M>F >40 y/o
M:F mortality I in men
Risk Factors Sun exposure:
intermittent exposure
measured by: sunburn
history: blistering and
peeling

latitude gradient: higher

near equator

most common site:

men: trunk esp upper back
women: lower legs>trunk
older: chronically exposed
areas

psoralen, PUVA, UVB,

tanning booths (<35 y/o
most harmful)

Skin phenotype:
Light, blond/red hair,
blue/green eyes, prominent
freckling, tendency to
sunburn Fitzpatrick
phenotype I-II

Melanocytic nevi: >100

typical-appearing nevi
Children: >50 typical-
appearing nevi
Any atypical nevi

Most melanomas arise de

novo
 Large congenital nevi at the
posterior axis or in
conjunction w/ multiple
satellite lesions: risk for
neurocutaneous melanosis
w/ increased risk of
developing melanoma in
CNS

Family History

Personal History
Subsequent melanomas are
thinner than first

Hx of actinic keratosis or
nonmelanoma skin cancer

Genetics
Mutations in ch 9p21 tumor
suppressor gene CDKN2A:
p16 (inhibits CDK4 and 6->
inhibits progession through
G1 cell cycle phase) and
p14ARF (inhibits hdm2->
acc. Destruction of p53
tumor-suppressor gene

Mutation in B-RAF:
intermittent sun exposure
Progression 5 Stages:
1. Benign
malignant nevi
2. Atypical nevi
3. Primary
malignant
melanoma,
radial growth
-
intraepidermal
proliferation of
melanocytes,
small invasion
of papillary
dermis
-w/ e-cadherin
 |
V
Critical step

4. Primary
malignant
melanoma,
vertical growth
-aggregative
-formation of
expansile
nests or
nodules of
cells
-no e-cadherin
-w/ n-cadherin
-intravasation
of malignant
cells
5. Metastatic
malignant
melanoma

1st pathway:
-(esp. superficial
spreading melanoma
(SSM)
-Develop in assoc. w/
melanocytic nevi
Initiated by: UV,
perhaps early age

2nd pathway:
-(esp. lentigo maligna
melanoma (LMM)
Cumulative sun
exposure ->
cumulative insult to
DNA of melanocytes
Subtypes SSM
-most common (70%)
-intermittently sun-
exposed ares: lower
extremity (F), upper
back (M)
Classical appearance:
Irregular borders,
irregular pigmentation,
focal area darkening of
pre-existing nevus
-shades of brown, dar-
brown to black, blue-
grey, pink, red, gray-
white (regression)
-most commonly assoc
w/ pre-existing nevi
-hp: uniformly atypical
-Diff:
Atypical nevus,
seborrheic keratosis
Common nevus
BCC

Nodular Melanoma
-2nd most common
-most common site:
trunk
-rapid evolution
-no radial growth
phase
-begin de novo
-uniformly dark blue-
black, bluish-red
raised, amelanotic
-little intraepidermal
growth, atypical mass
of dermal melanocytes
-diff dx:
pigmented:
-common nevus
Blue nevus
Pigmented spitz nevus
Pigmented BCC

Amelanotic:
-BCC
-hemangioma
-pyogenic granuloma
-merkel cell carcinoma

Lentigo maligna (LM)

and Lentigo Maligna
melanoma (LMM)
-in situ, prolonged
radial growth phase,
may progress to
invasive LMM in time
-7th-8th decade,
uncommon ,40 y/o
-most common
location: chronically
sun-exposed face,
cheeks, nose
neck, scalp, ears in
men
-cumulative sun
exposure
-flat, slowly enlarging,
brown, freckle-like
macule, irregular
shape, differing shades
of brown and tan, in
background of
photodamage
-high recurrence rates
-least common
association w/ nevi
-highest rate of assoc.
with desmoplastic
melanoma (DM)
-hp: atypical
melanocytes singly and
in nest in basal layer,
comfluent w/o
pagetoid spread, cells
may extend down hair
follicles and
appendages, thin and
atrophic epidermis,
loss of rete ridges,
variavle cytologic
atypia, highly
pleomorphic cells
-diff dx:
-solar lentigo
-pigmented actinic
keratosis
Flat seborrheic
keratosis
Superficial pigment
BCC

Acral lentiginous
melanoma (ALM)
-most common form in
darker people
-median onset 65 y/o
-most common site:
sole, palm, subungual,
periungual skin
(Hutchinson sign)
-most commonly
brown-black
-not assoc w/ sun
exposure
-subungual melanoma
most common on
great toe or thumb,
melanonychia striata –
irregularly pigmented
longitudinal nail streak
Hp: irregular
acanthosis,
melanocytes uniformly
malignant and
dendritic
-diff dx:
plantar wart,
hematoma,
palmoplantar nevus,
longitudinal
melanocyhia,
onychomycosis,
pyogenic granuloma

other variants:
DM
-6th or 7th decade on
sun-exposed head and
nek
-firm, sclerotic,
indurated, ½ are
amelanotic, ½ assoc w/
LM
-high local recurrence
rate
-hp: w/ strands of
elongated, spindle-
shaped cells infiltrating
deeply

Mucosal melanoma
-w/ radial growth

Nevoid melanoma
-resemble benign nevi
-marked
hyperchromasia of the
nuclei of tumor cells,
mitoses, expansile
 growth of dermal cells
w/ effacement of
adventitia
Tan papule or nodule,
>1cm

Spitzoid melanoma
-resembles spitz nevus
-large >1cm,
asymmetric, irregular,
thick invasive 2mm,
numerous mitoses,
atypical
Rapid growth,
satellitosis

Atypical spitz tumor:

-not dx of spitzoid
melanoma nor benign
spitz nevi, w/
overlapping features

others Pregnancy
2nd most common
cancer in women of
child-bearing age
Does not increase risk
of melanoma
SLNB w/o blue dye

Pediatric
Risk factors: increasing
age, UV, Caucasian
Diagnosis Asymmetirc
Border (irregular,
notched, scalloped,
ragged, poorly
defined)
varying Color
Diameter (>6mm, app.
Pencil eraser)
Evolution

Most common early

sign: change in color
and increase in size (or
new lesion), + itching

More advanced
primary lesion:
ulceration, bleeding,
tenderness

Ugly duckling sign

-pigmented lesion diff
from other pigmented
lesions on the
individual

Suspect in >40-50y/o
w/ new pigmented
lesion

PE: hotography to
document appearance

Dermoscopy
(epiluminescence
microscopy,
dermatosopy, incident
light microscopy,
surface microscopy)

Contact dermoscopy:
Examine through film
of liquid (immersion
oil), nonpolarized light

Noncontact
dermoscopy:
No contact medium,
polarized light

Histopathology
-gold standard
-cytologic atypia:
Cellular enlargement,
nuclear enlargement,
nuclear pleomorphism,
hyperchromasia of
nuclei, nucleolar
variability, w/ mitoses
esp deep in dermis
-major archi features:
asymmetry, poor
cirumscription (cells at
edge are small, single,
scattered), large (>5-
6mm)
-lack of maturation of
nests w/ descent into
the dermis
-diagnostic: pagetoid
spread of large solitary
epidermal
melanocytes
-also seen in spitz
nevi, spindle cell nevi,
vulvar nevi, and acral
nevi

Immunohistochemistr
y
-in poorly diff w/ little
or no pigment, spindle
cell tumors, pagetoid
spread
S100 protein
HMB-45-high
specificity (+)
melanoma (-)DM

DM (+) S100 (+)

vimentin

Melan-A and MART-1

In melanocytic diff in
skin and retina

Melan-A (+) benign

and malignant
melanocytic lesions, (-)
DM
-more sensitive than
HMB45
-more specific than
S100

Microphthalmia-
associated
transcription factor
(Mtif) also in
amelanotic melanoma,
marker in nucleus, (+)
most melanoma (-) but
variable DM

*other markers:
cytoplasm

Stage 0 and 1A: no

addl workup
Stage 1B and II: opt.
CXR
Stage III: opt. CXR and
LDH
Stage IV: CXR and/or
chest CT + LDH
III and IV: CT, MRI, or
PET recommended
Prognosis and -Staging forms the
clinical course basis for prognosis and
tx

-Thickness
Nodal metastasis
Metastasis (distant)

Thickness
-single most important
prognostic factor for
survival and clinical
mgmt of stage I and II
-Breslow
-measure from
granular layer of epi to
extent of depth
-clark, inaccurate, not
used routinely

Ulceration
-high risk for
advancement, low
survival rate
-frequently in thick
lesions
-evidence of host
response at site
including fibrin and
nuclear debris, if none,
due to trauma or
surgery

Mitotic rate
-increase, decrease
survival
-2nd predictor of
survival mitotic rate of
1/mm2
-clark level IV or V only
to define T1b for w/c
cannot determine rate
for nonulcerated T1
-no. of mitoses/mm2 =
no. of mitoses in 4-5
HPF starting in field w/
most mitoses

Angiolymphatic
invasion
-in dermis

Microscopic satellites
-stage III

SLNB
-predictor of
melanoma outcome

Age
Increasing, worsening
>60M highest
mortality rate

Gender
F better survival than
M

Anatomic site
Not strong prognostic
factor

Regional (nodes)
-most powerful
prognostic factor for
survival
-no. is most significant
-2nd most impt: tumor
burden:
micrometastatic
 (SLNB) or
macrometastatic
(palpable)
-(-) node, SLN is most
significant prognostic
factor

Distant metastasis
-worst prognosis
-AJCC staging
visceral metastasis
poorer prognosis than
nonvisceral
-increased LDH poor
prognosis, despite site
of metastasis
Clinical course Stage I and II
-5-10 yr survival
-recurrence manifest
1st 5 yrs

Stage III
-most impt: no. of LN

Stage IV
-most common
visceral sites: lungs,
liver brain, git
-median survival: 6-8
mos.

Metastatic melanoma
of unknown primary
-LN (60%) and
metastatic melanoma,
no known primary
lesion
-similar survival rates
w/ staged known
primary origin
 -look for primary site:
wood’s lamp to id
subclinical
hypopigmented
(regressed primary)

Primary dermal
melanoma
-primary lesion
confined to dermis or
SC
-look for primary site:
wood’s lamp to id
subclinical
hypopigmented
(regressed primary)
Tx Staging
Biopsy
-Excisional biopsy w/
narrow margins
*avoid wider margin:
permits accurate SLNB
if indicated
-incisional full-
thickness to adipose
skin biopsy: large
and/or located on
palm/sole, digit, face,
ear
-incisional: most
elevated darkest area

-macrometastases: do
FNAB. If inconclusive
or not feasible, do
excisional biopsy

-micrometastasis:
SLNB
-detect occult
micrometastasis
-high sensi and speci
-technetium-99-
labeled radiocolloid
soln w/ vital blue dye
-same time w/ WLE of
primary
-SLN-> serial
sectioning: H&E and
immunochemistry
(S100, HMB-45,
Melan-A) if H&E is
inconclusive
-also for relatively
healthy px w/ primary
localized >/_1mm
-imprt and predictor of
(+) SLN: Breslow depth
-also done for thinner
lesions if w/
elceration, young age,
mitotic rate >/_1mm,
shave biopsy w/ pos
deep margin,
angiolymphatic
invasion

Tx
Std tx is WLE –
prevents local
recurrence
<1mm = 0.5-1cm
1-2mm = 1-2cm
>2mm = 2 cm (w/
pathologic
confirmation of clear
peripheral margins for
all)

Complete amputation
of digit: subungual
invasive melanoma

LM
-confirm (-) margins
-0.5cm LM
-1cm LMM <1mm thick

Formalin fixed
permanent section
histology- gold std for
eval of margin
assessment