Nodular Malignant Melanoma · Valeria, et al.: Nodular Malignant Melanoma 2 Asclepius MedicAl cAse RepoRts • Vol 2 • issue 1 • 2019 disease.[6,7] The most common clinical variant

Asclepius MedicAl cAse RepoRts • Vol 2 • issue 1 • 2019 1

INTRODUCTION

Malignant melanoma is one of the most aggressive neoplasms of the skin. It originates from the melanocytes, which are cells embryologically

derived from the neural crest to end up in the epidermal basal layer forming the melanic-epidermal unit where melanocytes and keratinocytes have a proportionality of 1/36.2. It is characterized by producing pigmentation as well as being susceptible to metastasis.[1,2]

It frequently occurs in four clinical varieties according to Clark et al. and McGovern: (1) Surface extension melanoma, (2) lentigo malignant melanoma, (3) nodular melanoma, and (4) lentiginous acral melanoma. There are some other less common clinical varieties such as mucosal and paramucosal melanoma. It is a multifactorial disease

where the predisposing factor is intense exposure to ultraviolet (UV) rays and Caucasian race.[3,4]

The factors that increase the possibility of suffering a malignant melanoma are family history of melanoma (regardless of type or location), personal history of some type of cancer, large congenital nevi, high number of acquired nevi or atypical pigmented lesions, and genetic predisposition for mutations in CDKN2A and CDK4.[5]

In the world the incidence of skin cancer has been increasing, every year 2–3 million cases of non-melanoma skin cancer and 132,000 cases of melanoma. One in three patients diagnosed with cancer has skin cancer.[3,4]

Cutaneous melanoma represents 4% of malignant tumors of the skin, and its survival depends on the extent of the

CASE REPORT

Nodular Malignant MelanomaJiménez-Báez María Valeria1, Cachón-Santana Cindy Margarita2, Rodríguez-Cruz Andrea Elizabeth2, Milla-González Ludivina3, Luis Sandoval Jurado1, Maria Margarita Chavez Hernandez1, Enrique Leobardo Ureña Bogarín1

1Department of Medical Services, Mexican Social Security Institute, Delegation in Quintana Roo, Clinical Research Group of IMSS in Quintana Roo (GRICIQ), Mexico, 2Health Sciences Division, University of Quintana Roo, Mexico General Hospital Clinical Cycles No. 17, Mexican Institute of Social Security, Cancun, Quintana Roo, México, 3Department of Internal Medicine, Mexican Social Security Institute (IMSS), Medical Dermatologist of IMSS Cancún, Mexico

ABSTRACT

Malignant melanoma is one of the most aggressive neoplasms of the skin. It originates from the melanocytes, which are cells derived embryologically from the neural crest and migrate to the epidermal basal layer. It is characterized by producing pigmentation as well as being susceptible to metastasis. We report the case of a 36-year-old female patient with advanced clinical stage and distant commitment. The biopsy confirmed the presence of Grade III invasive nodular cutaneous melanoma in the left subscapular region with lymph node metastasis with reactive hyperplasia. An exploratory research is carried out with the bibliographic review in scientific journals with evidence level II–IV. In portals PubMed, Redalyc, BVS, and UpToDate. 81241 met criteria 2248 of which 629 were chosen for having access to the full text and of these 496 are more current (as of 2008), and in the end, 27 articles were selected that met all the inclusion criteria to this article. Due to the increase in the incidence of this disease in recent years and its poor prognosis in short to medium term, it is important to know and follow-up on patients with known risk factors for this disease such as the presence of previous nevi, with emphasis on measures of prevention.

Key words: Metastasis, nodular malignant melanoma, skin

Address for correspondence: Jiménez-Báez María Valeria, Jefatura de Servicios Prestaciones Médicos Av. Politécnico Nacional S/N SMZ 509, CP. 77533 Cancún, Quintana Roo, Mexico. E-mail: [email protected]

© 2019 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.

Valeria, et al.: Nodular Malignant Melanoma

2 Asclepius MedicAl cAse RepoRts • Vol 2 • issue 1 • 2019

disease.[6,7] The most common clinical variant of malignant melanoma in the world is a superficial extension (60–70% of cases) followed by nodular melanoma (15–30%) and acral lentiginous melanoma (5–10%).[5,6]

In Latin America, the International Agency for Research on Cancer estimates a frequency of presentation of 2 per 100,000 inhabitants. In Mexico, melanoma ranks tenth in all neoplasms and third in skin cancer with 14.1%.[8]

It is one of the most common neoplasms in the young adult, with predominance in the female sex during the three decades of life.[6]

The presentation in men is in the trunk and women, it is in the lower extremities.[3]

Its incidence has increased in recent years around the world, having a higher peak in tropical countries because they are exposed to the sun since childhood, the lack of habit by not using sunscreen, and the greater diagnosis by the dermatoscope that allows detecting early lesions.[9]

Melanoma ranks third with 7.9% in Mexico and is the cause of 75% of deaths from skin cancer.[10] In Mexico, the true incidence of malignant melanoma is unknown;[11] however, in 2012 the Dermatological Center of Yucatan found 177 patients with skin cancer, where melanoma had a prevalence of 1.7% [12] The purpose of this work is to report a case of malignant nodular malignant melanoma, with an apparent spontaneous regression, whose personal ignorance of the patient for attention to the presence of spots or moles and the doctor of opportunity for the appropriate derivation, led to an injury invasive.

CASE REPORT

This is a 33-year-old female patient, originally from Holpelchen, Campeche and residing in Cancún, Quintana Roo, referred to primary health-care medical unit with a diagnosis of Nevo Melanocitico, who goes to the dermatology service for presenting dermatosis located in the left infrascapular region, constituted by neoformation formed by two exophytic lesions with 4 cm, hyperchromic macula with an exophytic center and heterochromia of three variations color, hypochromic with pink tint, dark brown and bluish black, with perilesional achromic halo and palpation with induration, mobile and painful and not adhered to deep planes [Figure 1]. He began his condition 5 years ago with a small nevus, which has been adding occasional bleeding and pain for 3 years, with progressive growth to the present date. He mentions faster growth after his last pregnancy.

An excisional biopsy of the lesion was performed in the dermatology department where an asymmetric proliferation of atypical epithelioid and spindle-shaped melanocytes was observed, individually and confluently arranged in

discohesive nests and mantles that invade the nerve fibers, and the muscle tissue present in the cut. The melanocytes are large, pleomorphic with pale cytoplasm, eosinophilic with melanic pigment in their interior. The nuclei are of irregular, hyperchromatic, and pleomorphic contours, some of them show individual cell necrosis.

Given the histopathology result, a secondary intervention was performed 14 days after the first one for the widening of margins and left axillary dissection. The histopathological report of the piece showed 3 mitoses/mm2. In the papillary dermis and superficial reticular lymphocyte inflammatory infiltrate that surrounds and infiltrates the neoformation, there is a fall of pigment with melanophages and cytoid bodies. Residual axillary conglomerate with melanoma metastasis, nine ganglia with reactive hyperplasia.

The final histopathological report details a Grade III invasive nodular cutaneous melanoma of at least 12 mm thickness on the Breslow, Clark level V scale of the skin of the left subscapular region.

It is sent to the oncology service 2 days after the second intervention where a computerized axial tomography (CT) is indicated that reported asymmetric breasts in size, cystic lesion of the right ovary 21 mm × 17 mm suggestive of metastasis. As prophylaxis against a possible invasion of the central nervous system, it was indicated to initiate radiotherapy and pegylated interferon and ipilimumab as adjuvant therapy.

DISCUSSION

Nodular malignant melanoma is a tumor that affects people of any age, especially young adults.[13] The main risk factor is exposure

Figure 1: Neoformation consisting of two exophytic lesions on a hyperchromic macula with an exophytic center and heterochromia of the color of three variations, hypochromic with pink tint, dark brown, and bluish black, with acromic halo perilesion



to sunlight, which produces variations in DNA and its suppression of cellular apoptosis bound to skin phototype I and II.[14] It appears mainly in the trunk and extremities, presenting initially and exclusively vertical growth phase, conditioning aggressive behavior, and worse prognosis.[14] This type of melanoma has an orientation to lymphatic and hematic dissemination, and up to 4% of cases it is discovered by metastasis.[15]

In this case, the location of the tumor was found in a protected photo area in the subscapular region, characteristic of this variant of melanoma and skin phototype III, as well as metastases to lymph nodes.

In most patients, the disease is detected when localized and can be cured by excreting the primary tumor in situ; however, many patients are diagnosed in the metastatic phase. The 10-year survival rate with metastasis is <10%.[8] The delay in the diagnosis of malignant melanoma is common in the

pediatric population and can be attributed to the atypical presentation, although on other occasions it is due to the reluctance to consider the condition.[9] It is fundamental, therefore, to apply the ABCDE criteria with the help of dermatoscopy and biopsy in highly suggestive cases.[9,10]

As for the clinic, it depends fundamentally on its growth pattern; the majority is initially presented with a phase of radial growth (intraepidermal) and later a vertical growth consisting of a growth toward the dermis leading to the vicinity of vascular and lymphatic structures causing or increasing the chances of metastasis, a situation that occurred in our case where the radial phase was minimal, and the vertical phase was the one that prevailed leading to a darker prognosis. In a study conducted by Calderón et al. in 2017, they found nRAS mutations in 28%, as well as their mean evolution time was 7.79 years.[16-18] In the case of our patient, she had a diagnostic delay of 4.5 years.

Chart 1: Studies related to the results of nodular malignant melanoma



(Con

td...

)

Tabl

e 1:

Sum

mar

y Ta

ble

of in

clud

ed s

tudi

esN

o.R

efer

ence

Met

hods

Res

ults

Con

clus

ions

1M

elan

oma

cutá

neo[1

]R

evie

wR

evie

wC

utan

eous

mel

anom

a is

the

mos

t m

alig

nant

tum

or o

f the

ski

n an

d ha

s a

grea

t cap

acity

to m

etas

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Eve

n w

hen

som

e ris

k fa

ctor

s ar

e kn

own,

dia

gnos

is a

nd e

arly

tr

eatm

ent a

re th

e on

ly s

trat

egie

s th

at h

ave

been

sho

wn

to im

prov

e th

e pr

ogno

sis

of th

ose

who

suf

fer

from

it, a

nd it

s m

anag

emen

t is

a ch

alle

nge

2E

stud

io e

pide

mio

lógi

co d

e m

elan

oma

mal

igno

en

el A

mer

ican

Brit

ish

Cow

dray

M

edic

al C

ente

r[2]

Ret

rosp

ectiv

e, d

escr

iptiv

e,

and

linea

r st

udy

123

hist

opat

holo

gica

l rep

orts

wer

e in

clud

ed, c

orre

spon

ding

to 6

3 m

ale

patie

nts

and

60 fe

mal

e pa

tient

s. T

he

age

rang

ed b

etw

een

19 a

nd 9

7 ye

ars.

73

cas

es w

ere

prim

ary,

of t

hem

61,

of

skin

and

12,

ext

racu

tane

ous,

50

wer

e m

etas

tase

s: 3

0 in

lym

ph n

odes

and

20

extr

anod

al. T

he p

redo

min

ant C

lark

leve

l w

as II

I, an

d B

resl

ow II

. 57

case

s w

ere

HM

B45

and

50

posi

tive

to S

100

The

freq

uenc

y of

this

neo

plas

m

attr

acts

atte

ntio

n in

com

paris

on w

ith

othe

r gr

oups

, as

wel

l as

the

num

ber

of e

xtra

cuta

neou

s m

alig

nant

m

elan

omas

and

the

num

ber

of e

xtra

noda

l met

asta

ses.

We

cons

ider

an

impo

rtan

t con

trib

utio

n to

an

epid

emio

logi

cal s

tudy

that

sh

ould

be

carr

ied

out a

t the

nat

iona

l le

vel

3E

pide

mio

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a de

l cán

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iel e

n pa

cien

tes

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Clín

ica

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erm

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logí

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l Cen

tro

Der

mat

ológ

ico

Dr.

Lad

isla

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la P

ascu

a. E

stud

io

retr

ospe

ctiv

o de

los

últim

os o

cho

años

[3]

Des

crip

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and

retr

ospe

ctiv

e st

udy

case

s an

d co

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e re

view

ed 2

185

reco

rds

with

474

3 hi

stop

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logi

cally

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sion

s.

The

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w

as b

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a

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f 74%

(w

ith p

redo

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ance

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the

clin

ical

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or a

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uper

ficia

l va

riety

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pect

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ollo

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alig

nant

mel

anom

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ith 3

% (

nodu

lar

varie

ty a

nd le

ntig

inou

s ac

ral).

We

also

fo

und:

Sar

com

as, c

utan

eous

lym

phom

as

and

derm

atof

ibro

ma

spro

tube

rans

. B

asal

cel

l and

epi

derm

oid

carc

inom

as

pred

omin

ated

in th

e se

vent

h de

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of

life

(26

and

24%

, res

pect

ivel

y), m

alig

nant

m

elan

oma

was

obs

erve

d in

the

sixt

h de

cade

(20

%)

and

the

rest

of t

he

neop

lasm

s in

the

fifth

dec

ade.

The

mos

t co

mm

on v

arie

ties

in th

e hi

stop

atho

logi

cal

findi

ngs

wer

e: S

olid

bas

al c

ell c

arci

nom

a,

The

res

ults

of t

his

stud

y co

inci

de w

ith th

at r

epor

ted

in

the

inte

rnat

iona

l bib

liogr

aphy

, ex

cept

for

the

high

er fr

eque

ncy

of

neop

lasm

s in

wom

en. W

e ag

ree

with

the

info

rmat

ion

that

is r

epor

ted

in o

ur c

ount

ry



Tabl

e 1:

(Con

tinue

d)

(Con

td...

)

wel

l-diff

eren

tiate

d sq

uam

ous

cell

carc

inom

a, m

alig

nant

lent

igo

mel

anom

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Kap

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sar

com

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d cu

tane

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B-c

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ymph

oma.

Neo

plas

ms,

incl

udin

g m

ucou

s m

embr

anes

, wer

e fo

und

in a

ll bo

dy s

egm

ents

. Mos

t of t

he le

sion

s w

ere

foun

d in

the

phot

o-ex

pose

d ar

eas

4P

reva

lenc

ia d

el c

ánce

r de

piel

en

tres

ciud

ades

de

Méx

ico[5

]R

etro

spec

tive,

des

crip

tive

and

linea

r st

udy

Fre

quen

cy w

as s

tudi

ed b

y ge

nder

, age

, top

ogra

phy,

af

fect

ed o

rgan

, Cla

rk a

nd

Bre

slow

leve

ls, s

tudi

es w

ith

imm

unoh

isto

chem

istr

y an

d m

etas

tase

s

We

exam

ined

443

sub

ject

s in

whi

ch

eigh

t cas

es o

f ski

n ca

ncer

wer

e do

cum

ente

d, s

even

in w

omen

and

one

in

men

, of w

hich

six

cor

resp

ond

to b

asal

ce

ll ca

rcin

oma

and

two

to m

alig

nant

m

elan

oma,

thre

e of

thes

e in

pat

ient

s w

ith

phot

otyp

e II,

two

with

pho

toty

pe II

I and

th

ree

with

pho

toty

pe IV

. 75%

of p

atie

nts

diag

nose

d w

ith s

kin

canc

er h

ad n

o hi

stor

y of

pre

mal

igna

nt le

sion

s, h

owev

er,

anal

yzin

g th

e su

spic

ious

lesi

ons

foun

d a

sign

ifica

nt r

elat

ions

hip

betw

een

the

pres

ence

of c

ance

r an

d th

ese

lesi

ons,

w

ith a

n in

crea

sed

risk

of 3

.4 ti

mes

The

sam

ple

size

was

sm

all,

with

he

tero

gene

ous

popu

latio

n gr

oups

, so

the

resu

lts a

re n

ot c

ompa

rabl

e to

wha

t hap

pens

in o

ther

sta

tes

of

the

coun

try

5E

pide

mio

logí

a de

l cán

cer

de p

iel e

n el

Cen

tro

Der

mat

ológ

ico

de Y

ucat

án

dura

nte

2012

[6]

Ret

rosp

ectiv

e, d

escr

iptiv

e an

d ob

serv

atio

nal s

tudy

.A

ll pa

tient

s di

agno

sed

with

sk

in c

ance

r co

nfirm

ed w

ith

the

hist

opat

holo

gica

l stu

dy.

The

ana

lysi

s of

the

data

was

ca

rrie

d ou

t with

des

crip

tive

stat

istic

s, c

alcu

latio

n of

pr

opor

tions

and

mea

sure

s of

ce

ntra

l ten

denc

y

We

foun

d 17

7 pa

tient

s w

ith s

kin

canc

er.

The

pre

vale

nce

was

1.7

%, 3

9% m

en

and

61%

wom

en. T

he a

vera

ge a

ge w

as

63.7

yea

rs. 5

3.6%

wer

e en

gage

d in

ho

usew

ork.

93.

8% c

ame

from

Yuc

atan

. T

he m

ost f

requ

ent t

umor

was

bas

al c

ell

(77%

), fo

llow

ed b

y sp

inoc

ellu

lar

(21%

) an

d m

elan

oma

(2%

). T

he m

ost a

ffect

ed

regi

on w

as th

e fa

ce (

74.2

%).

The

re w

ere

28 p

atie

nts

with

mul

tiple

ski

n ca

ncer

. The

av

erag

e tim

e of

evo

lutio

n w

as 3

1 m

onth

s

Ski

n ca

ncer

was

one

of t

he m

ain

reas

ons

for

cons

ulta

tion

at th

e C

entr

o D

erm

atol

ógic

o de

Yuc

atán

in

201

2. It

was

mor

e fr

eque

nt in

Y

ucat

ecan

wom

en in

the

seve

nth

deca

de o

f life

. Ped

iatr

ic c

ases

and

m

ultip

le s

kin

canc

er w

ere

desc

ribed

*Mor

e st

udie

s ar

e re

quire

d to

kno

w

the

real

effe

ct o

f the

dis

ease

6M

elan

oma

cutá

neo:

12

años

de

expe

rienc

ia[7

]R

etro

spec

tive,

obs

erva

tiona

l, de

scrip

tive

and

tran

sver

sal

stud

y. W

e re

view

ed th

e fil

es o

f pat

ient

s of

the

Der

mat

olog

y an

d D

erm

ato-

onco

logy

Dep

artm

ent o

f the

G

ener

al H

ospi

tal o

f Mex

ico

with

a r

egis

tere

d di

agno

sis

of

hist

opat

holo

gica

lly p

rove

n

We

incl

uded

195

cas

es o

f cut

aneo

us

mel

anom

a co

nfirm

ed w

ith th

e hi

stop

atho

logi

cal r

epor

t, of

thes

e 19

ca

ses

with

inco

mpl

ete

file

wer

e ex

clud

ed.

176

case

s w

ere

obta

ined

, of w

hich

57

(32%

) w

ere

men

. Len

tigin

ou s

acra

l m

elan

oma

affe

cted

105

cas

es (

60%

),

follo

wed

by

nodu

lar

mel

anom

a w

ith 3

6 ca

ses

(20%

), le

ntig

o m

alig

nant

The

freq

uenc

y of

mel

anom

a sh

owed

var

iabl

e in

crea

se in

eac

h re

gist

ered

yea

r. A

hig

her

prop

ortio

n of

affe

cted

wom

en w

as fo

und,

the

aver

age

age

of th

e po

pula

tion

was

62

.62

year

s. T

he m

ost f

requ

ent

subt

ype

was

lent

igin

ous

acra

l m

elan

oma,

follo

wed

by

nodu

lar

mel

anom

a. S

ubun

gual

mel

anom

a



Tabl

e 1:

(Con

tinue

d)

(Con

td...

)

cuta

neou

s m

elan

oma,

at

tend

ed fr

om J

anua

ry 1

, 20

03, t

o D

ecem

ber

31, 2

014.

T

he s

tatis

tical

ana

lysi

s w

as

carr

ied

out d

escr

iptiv

ely

thro

ugh

the

prog

ram

SP

SS

v

20.0

mel

anom

a in

23

case

s (1

3%)

and

supe

rfic

ial e

xten

sion

mel

anom

a in

12

case

s (7

%).

Sub

grou

p an

alys

is w

as

perf

orm

ed fo

r ea

ch s

ubty

pe o

f mel

anom

a

affe

cted

28.

5% o

f pat

ient

s. M

ost

of th

e ca

ses

wer

e de

tect

ed in

ad

vanc

ed s

tage

s

7F

rom

mel

anoc

ytes

to m

elan

omas

[8]

Rev

iew

Rev

iew

Hav

e a

visi

on o

f gen

etic

s of

m

elan

omas

from

thei

r ce

lls o

f orig

in

thro

ugh

diffe

rent

type

s of

pre

curs

or

lesi

ons

will

allo

w u

s to

ach

ieve

an

impr

oved

dia

gnos

is, e

arly

re

cogn

ition

of l

esio

ns th

at h

ave

a hi

gher

ris

k of

pro

gres

sion

and

to

be a

ble

to in

terv

ene

in e

arly

sta

ges

of c

ance

r. T

he g

old

stan

dard

to

eval

uate

the

mal

igna

nt p

oten

tial

of m

elan

ocyt

ic n

eopl

asm

s is

the

hist

opat

holo

gy (

biop

sy).

Bio

mar

kers

ar

e ex

pect

ed to

hel

p us

def

ine

the

prog

ress

ion

of th

e le

sion

s in

divi

dual

ly a

nd a

re e

xpec

ted

to

play

an

incr

easi

ngly

impo

rtan

t ro

le in

hel

ping

the

diag

nost

ic

clas

sific

atio

n.T

he in

fluen

ce o

f UV

rad

iatio

n on

th

e de

velo

pmen

t and

evo

lutio

n of

m

elan

omas

in C

auca

sian

s re

quire

s th

at p

ublic

hea

lth c

ampa

igns

be

diss

emin

ated

to a

void

exc

essi

ve

expo

sure

to th

e su

n

8M

elan

oma.

Fun

dam

ento

s de

l di

agnó

stic

o y

la te

rapé

utic

a[9]

Rev

iew

Rev

iew

Its e

tiolo

gy is

mul

tifac

toria

l, an

d it

has

been

rep

orte

d th

at th

e pr

eval

ence

has

incr

ease

d fo

r ap

prox

imat

ely

two

deca

des.

In

Mex

ico

it ra

nks

seve

nth

in

freq

uenc

y am

ong

all n

eopl

asm

s,

80%

of c

ases

are

in lo

cally

ad

vanc

ed s

tage

s

9C

ompo

rtam

ient

o de

l cán

cer

de p

iel e

n G

üine

s y

San

Jos

é de

las

Laja

s[10]

Rev

iew

Rev

iew

The

mai

n ge

nes

reco

gniz

ed in

m

elan

oma

are

CD

KN

2A a

nd C

DK

4,

invo

lved

in th

e co

ntro

l of t

he c

ell



Tabl

e 1:

(Con

tinue

d)

(Con

td...

)

cycl

e. In

20%

–50%

of f

amili

al c

ases

of

mel

anom

a m

utat

ions

are

foun

d in

CD

KN

2A. T

he p

olym

orph

ism

s in

the

MC

1R r

ecep

tor,

key

in th

e fo

rmat

ion

of m

elan

in in

res

pons

e to

U

V r

adia

tion,

are

als

o as

soci

ated

w

ith a

n in

crea

sed

risk

of m

elan

oma

10V

alor

ació

n in

icia

l, di

agnó

stic

o,

esta

dific

ació

n, tr

atam

ient

o y

segu

imie

nto

de lo

s pa

cien

tes

con

mel

anom

a m

alig

no p

rimar

io d

e pi

el.

Doc

umen

to d

e co

nsen

so d

e la

“X

arxa

de

Cen

tres

de

Mel

anom

a de

Cat

alun

ya

i Bal

ears

”[11]

Con

sens

usdo

cum

ent

Con

sens

us d

ocum

ent.

Con

fron

tatio

n w

ith

rece

nt li

tera

ture

(in

clud

ing

natio

nal a

nd

inte

rnat

iona

l clin

ical

gui

delin

es),

as

wel

l as

dia

gnos

is, m

onito

ring

and

trea

tmen

t pr

otoc

ols

agre

ed o

n in

the

diffe

rent

ho

spita

l cen

ters

thro

ugho

ut C

atal

onia

an

d th

e B

alea

ric Is

land

s be

long

ing

to

the

Xar

xa d

e C

ente

rs d

e M

elan

oma

de

Cat

alun

ya i

Bal

ears

The

kno

wle

dge

and

diag

nosi

s of

mel

anom

a ar

e of

utm

ost

impo

rtan

ce s

ince

it is

wro

ngly

un

dere

stim

ated

with

res

pect

to

othe

r ty

pes

of c

ance

r.

11M

elan

oma:

Pat

ogén

esis

, clín

ica

e hi

stop

atol

ogía

[12]

Rev

iew

art

icle

Rev

iew

art

icle

The

mai

n ge

nes

reco

gniz

ed in

m

elan

oma

are

CD

KN

2A a

nd C

DK

4,

invo

lved

in th

e co

ntro

l of t

he c

ell

cycl

e. In

20%

–50%

of f

amili

al c

ases

of

mel

anom

a m

utat

ions

are

foun

d in

CD

KN

2A. T

he p

olym

orph

ism

s in

the

MC

1R r

ecep

tor,

key

in th

e fo

rmat

ion

of m

elan

in in

res

pons

e to

U

V r

adia

tion,

are

als

o as

soci

ated

w

ith a

n in

crea

sed

risk

of m

elan

oma

12M

elan

oma

mal

igno

cut

áneo

en

paci

ente

s de

la p

rovi

ncia

de

Las

Tun

as[1

3]

Des

crip

tive

stud

y of

tr

ansv

erse

cut

31 p

atie

nts

atte

nded

at t

he p

lace

and

tim

e pe

riod

refe

rred

to a

bove

Cut

aneo

us m

elan

oma

pred

omin

ated

in th

e m

ale

sex,

in

the

low

er e

xtre

miti

es a

nd a

late

di

agno

sis

was

man

ifest

ed in

the

patie

nts,

with

the

prev

alen

ce o

f C

lark

inva

sion

leve

l IV

and

the

nodu

lar

mel

anom

a as

the

mos

t fr

eque

nt h

isto

logi

cal t

ype

(AU

)

13H

alo

Nev

o y

Vití

ligo:

A p

ropó

sito

de

un

caso

Clin

ic C

ase

We

pres

ent t

he c

ase

of a

boy

with

ac

quire

d ne

vi le

sion

s in

the

back

who

de

velo

ped

strik

ing

achr

omic

are

oles

and

la

ter

achr

omic

spo

ts o

n th

e kn

ee

Mal

igna

nt M

elan

oma

is th

e m

ost

impo

rtant

diff

eren

tial d

iagn

osis

. For

th

is, t

he c

hara

cter

istic

of t

he h

alo

is

orie

nted

: Sym

met

ric a

nd re

gula

r in

the

nevu

s, ir

regu

lar a

nd a

sym

met

ric

in th

e m

elan

oma.

The

cha

ract

eris

tics

of th

e pi

gmen

ted

lesi

on a

lso

mat

ter,

whi

ch m

ust b

e ev

alua

ted

acco

rdin

g to

the

AB

CD

rule



Tabl

e 1:

(Con

tinue

d)

(Con

td...

)

14C

órdo

va B

, Alb

erto

C. M

elan

oma

nodu

lar

en b

orde

de

pie.

Rev

Cie

nc

Méd

201

4;18

:329

-36.

Ava

ilabl

e fr

om: h

ttp://

ww

w.s

ciel

o.sl

d.cu

/sci

elo.

php?

scrip

t=sc

i_ar

ttext

&pi

d=S

1561

-31

9420

1400

0200

016&

lng=

es. [

Last

ac

cess

ed o

n 20

17 O

ct 1

3]

Pre

sent

atio

n of

a c

ase

Eld

erly

pat

ient

with

an

asym

ptom

atic

le

sion

on

the

right

foot

, 4 y

ears

old

, w

ith r

apid

gro

wth

in th

e pa

st 3

mon

ths.

A

clin

ical

-his

topa

thol

ogic

al d

iagn

osis

w

as m

ade,

com

patib

le w

ith n

odul

ar

mel

anom

a. T

he tr

eatm

ent o

f cho

ice

is

surg

ical

rem

oval

Nod

ular

mel

anom

a is

a v

ery

aggr

essi

ve tu

mor

and

sur

viva

l de

pend

s on

an

early

dia

gnos

is,

enab

ling

the

heal

ing

>90%

of c

ases

15S

anto

s V

M, L

eal C

T, V

asco

ncel

los

MJ.

La

te d

iagn

osis

of n

odul

ar m

elan

oma

of

the

foot

in a

74-

year

-old

Bra

zilia

n m

an.

Rev

Med

Chi

l 201

1;13

9:14

81-3

.

Pre

sent

atio

n of

a c

ase

We

desc

ribe

the

late

dia

gnos

is o

f nod

ular

m

elan

oma

of th

e fo

ot in

a 7

4-ye

ar-o

ld

Afr

o-B

razi

lian

mal

e

Sur

gery

is th

e m

ost e

ffect

ive

trea

tmen

t for

MM

in th

e ea

rly

stag

es, a

nd ly

mph

aden

ecto

my

may

be

nece

ssar

y. T

reat

men

t of

late

-sta

ge m

elan

oma

incl

udes

ch

emot

hera

py, c

ryot

hera

py, d

rug

com

bina

tions

, rad

iatio

n th

erap

y,

tum

or in

ject

ions

, tum

or-in

hibi

ting

chem

ical

age

nts,

and

vac

cine

s.Th

e ro

le o

f ear

ly d

iagn

osis

sho

uld

be e

mph

asiz

ed b

ecau

se M

M is

su

scep

tible

to c

ure

if it

is tr

eate

d at

an

early

sta

ge. S

kin

lesi

ons

that

su

gges

t MM

sho

uld

be e

valu

ated

by

a de

rmat

olog

ist b

efor

e th

e bi

opsy

si

nce

timel

y di

agno

sis

and

prop

er

treat

men

t pre

vent

tum

or s

prea

d

16C

eped

a-V

aldé

s R

, Ski

nner

-Tay

lor

C,

Flo

res-

Gut

iérr

ez J

, Ala

nís

S. M

etás

tasi

s en

trán

sito

de

mel

anom

a m

alig

no

cutá

neo:

Rep

orte

de

caso

y r

evis

ión

de la

bib

liogr

afía

. Der

mat

olog

ía C

MQ

20

10;8

:62-

3. A

vaila

ble

from

: http

://w

ww

.med

igra

phic

.com

/pdf

s/co

smet

ica/

dcm

-201

0/dc

m10

1l.p

df. [

Last

acc

esse

d on

201

7 N

ov 0

8].

Pre

sent

atio

n of

a c

ase

A 6

4-ye

ar-o

ld H

ispa

nic

fem

ale

who

pr

esen

ted

met

asta

sis

afte

r th

e su

rgic

al

rem

oval

of m

alig

nant

mel

anom

a

The

evo

lutio

n of

a p

atie

nt

unde

rgoi

ng th

e re

mov

al o

f m

alig

nant

mel

anom

a sh

ould

be

care

fully

rev

iew

ed b

y th

eir

trea

ting

phys

icia

ns to

dia

gnos

e ea

rly th

e pr

obab

ility

of d

ista

nt m

etas

tasi

s

17M

ar V

, Rob

erts

H, W

olfe

R, E

nglis

h D

R, K

elly

JW

. Nod

ular

mel

anom

a: A

di

stin

ct c

linic

al e

ntity

and

the

larg

est

cont

ribut

or to

mel

anom

a de

aths

in

Vic

toria

, Aus

tral

ia. J

Am

Aca

d D

erm

atol

20

13;6

8:56

8-75

.

Ana

lysi

s of

4 C

ohor

ts: 1

989,

19

94, 1

999,

and

200

4.F

our

coho

rts

wer

e es

tabl

ishe

d to

per

form

th

e an

alys

is, t

he o

rigin

al

path

olog

ical

rep

orts

wer

e re

view

ed, a

nd th

e m

elan

oma

The

inci

denc

e of

thic

k tu

mor

s (4

mm

) in

crea

sed

by 3

.8%

(95

% c

onfid

ence

in

terv

al: 1

.4–6

.2)

and

2.5%

(95

%

conf

iden

ce in

terv

al o

f 0.5

–5.5

) pe

r ye

ar fo

r m

ale

and

fem

ale

patie

nts,

re

spec

tivel

y. T

he m

edia

n th

ickn

ess

of

the

nodu

lar

mel

anom

a at

dia

gnos

is w

as

2.6

mm

com

pare

d to

0.6

mm

for

The

inci

denc

e of

thic

k m

elan

omas

co

ntin

ues

to in

crea

se. N

odul

ar

mel

anom

a is

clin

ical

ly b

ette

r di

ffere

ntia

ted

and

the

pred

omin

ant

cont

ribut

or to

dea

ths

rela

ted

to

mel

anom

as. T

his

repr

esen

ts a

http://www.medigraphic.com/pdfs/cosmetica/dcm-2010/dcm101l.pdf





Tabl

e 1:

(Con

tinue

d)

(Con

td...

)

inci

denc

e ra

tes

stan

dard

ized

by

age

from

198

9 to

200

4 w

ere

com

pare

d w

ith a

nnua

l pe

rcen

tage

cha

nge

usin

g th

e P

oiss

on r

egre

ssio

n

supe

rfici

al e

xten

sion

mel

anom

a. O

ne-th

ird

of p

atie

nts

who

die

d of

mel

anom

a du

ring

the

follo

w-u

p pe

riod

had

thic

k tu

mor

s (4

m

m),

mos

t of w

hich

wer

e no

dula

r sub

type

(6

1%).

Nod

ular

mel

anom

a ac

coun

ted

for 1

4% o

f inv

asiv

e m

elan

omas

but

w

as re

spon

sibl

e fo

r 43%

of d

eath

s fro

m

mel

anom

a in

a to

tal o

f 57,

461

year

s/pe

rson

of f

ollo

w-u

p. In

com

paris

on

and

supe

rfici

al d

iffus

ion,

mel

anom

a co

ntrib

uted

with

56%

of i

nvas

ive

mel

anom

as b

ut o

nly

with

30%

of d

eath

s

chal

leng

e in

pub

lic h

ealth

to r

educ

e m

orta

lity

from

ski

n ca

ncer

18H

ugda

hl E

, Kal

vene

s M

B, P

unte

rvol

l H

E, L

adst

ein

RG

, Aks

len

LA.

BR

AF

-V60

0E e

xpre

ssio

n in

prim

ary

nodu

lar

mel

anom

a is

ass

ocia

ted

with

agg

ress

ive

tum

our

feat

ures

an

d re

duce

d su

rviv

al. B

r J

Can

cer

2016

;114

:801

-8.

Des

crip

tive,

obs

erva

tiona

l ar

ticle

. In

a se

ries

of 2

48

nodu

lar m

elan

oma

posi

tive

patie

nts,

the

tota

l exp

ress

ion

of B

RA

F an

d th

e pr

esen

ce o

f B

RA

F-V

600E

and

tota

l BR

AF

ex

pres

sion

wer

e ev

alua

ted

usin

g im

mun

ohis

toch

emis

try

usin

g tis

sue

sect

ions

ob

tain

ed b

y bi

opsy

. The

st

atus

of t

he m

utat

ion

was

ev

alua

ted

usin

g re

al-ti

me

PC

R in

cas

es w

ith s

uffic

ient

tu

mor

tiss

ue (n

=191

)

A p

ositi

ve e

xpre

ssio

n of

BR

AF

-V60

0E,

pres

ent i

n 86

(35

%)

of th

e ca

ses,

was

fo

und

in a

ser

ies

of 2

48 p

ositi

ve p

atie

nts

with

nod

ular

mel

anom

a, a

nd it

was

si

gnifi

cant

ly a

ssoc

iate

d w

ith a

n in

crea

se

of th

e tu

mor

al th

ickn

ess,

the

pres

ence

of

tum

or u

lcer

atio

n an

d re

duce

d su

rviv

al.

In a

dditi

on, t

he e

xpre

ssio

n B

RA

F-V

600E

w

as a

n in

depe

nden

t pro

gnos

tic fa

ctor

, w

here

as th

e B

RA

F m

utat

ion

stat

us

was

not

sig

nific

ant.

The

re w

as 8

8%

agre

emen

t bet

wee

n B

RA

F a

nd V

600E

in

the

expr

essi

on a

nd s

tatu

s of

the

mut

atio

n

The

exp

ress

ion

of B

RA

F-V

600E

is

a n

ovel

pro

gnos

tic m

arke

r in

pr

imar

y m

elan

oma

19G

utié

rrez

-Vid

rio R

M, C

orté

s-Lo

zano

M

. Con

front

ando

al m

elan

oma

en

el s

iglo

XX

I. M

ed C

utan

Iber

Lat

Am

20

07;3

5:3-

13. A

vaila

ble

from

: http

://w

ww

.med

igra

phic

.com

/pdf

s/cu

tane

a/m

c-20

07/m

c071

b.pd

f. [L

ast a

cces

sed

on 2

017

Oct

27]

.

Rev

iew

art

icle

Rev

iew

art

icle

Ear

ly d

iagn

osis

and

tim

ely

trea

tmen

t are

the

only

str

ateg

ies

to

impr

ove

the

prog

nosi

s of

pat

ient

s w

ith m

elan

oma

20C

amac

ho C

P, G

erso

n R

, Gón

gora

M

A, V

illal

obos

A, B

lanc

o Y

C, L

ópez

O

. Act

ualid

ades

par

a el

trat

amie

nto

del m

elan

oma

met

astá

sico

, est

ado

del a

rte.

Med

Ass

oc M

ed H

osp

AB

C

2017

;62:

196-

207.

Ava

ilabl

e fr

om:

http

://w

ww

.med

igra

phic

.com

/pdf

s/ab

c/bc

-201

7/bc

173g

.pdf

. [La

st a

cces

sed

on

2017

Oct

20]

.

Rev

iew

art

icle

Rev

iew

art

icle

The

incu

rsio

n of

imm

unot

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http://www.medigraphic.com/pdfs/cutanea/mc-2007/mc071b.pdf



http://www.medigraphic.com/pdfs/abc/bc-2017/bc173g.pdf

http://www.medigraphic.com/pdfs/abc/bc-2017/bc173g.pdf



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Tabl

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(Con

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d)The first 5 years of follow-up after removing melanoma are the most important since 90% of all metastases occur during this period.[11] Follow-up should be done at 3-month intervals in the first 3 years and subsequently every year.[12] The skin should be examined at depth, including the scalp and genital region, particularly in the regional distribution of primary palpation, and the lymph nodes, with attention to the regional lymph node chain, in addition to offering psychosocial support and W of the private sector in the states of Guadalajara and Monterrey. In the country, there are only two public-level teams of this type that are located in the Autonomous University of Mexico and the ABC Medical Center, so their access is complicated for their authorization together with their high cost.

The standard of treatment for melanoma metastasis is surgical intervention, and its goal is to provide relief of symptoms and increase survival time. Due to the great possibility of metastasis at the level of the central nervous system, prophylactic radiotherapy can be considered, as was done in the patient.[23]

In a meta-analysis of 3262 patients with malignant melanoma, it was found that single drug chemotherapy is well tolerated, but is associated with response rates of only 5–20%.[24] In addition, combination chemotherapy and biochemotherapy may raise response rates, but they do not prolong survival and cause greater toxicity.[25]

Immunotherapeutic approaches, such as high doses of interleukin 2, are associated with durable responses in a small percentage of patients.[26] In the case of the patient, chemotherapy was adjuvant with excisional surgery due to the advanced stage of the disease. The chemotherapeutic treatment used in the patient complies with the internationally recommended scheme consisting of pegylated interferon with ipilimumab.[26]

At present, some of the main pathways of melanoma progression are better understood, and it is likely that molecular techniques (specific genomic incorporation and intratumoral expression) play an essential role in making classification schemes that have more power in predicting response to therapy.[27]

It is vital to inform the general population of the risk of suffering from melanoma, especially from the premise of multiple nevi and prolonged exposure to the sun, so that, in an almost routine and obligatory way, it would be the use of appropriate clothing such as hats wide-brimmed, clothing that covers most of the body, the use of sunscreen filters (especially in childhood and adolescence) and self-assessment with application of the ABCDE method.

Melanomas and skin cancers are generally painless, but in this patient, the degree of depth of invasion, as well as the perineural compromise and ulceration, made it painful.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926755/pdf/f1000research-5-8869.pdf





melanoma de Catalunya i Balears”. Actas Dermatosifiliogr. 2010;101:129-42. Available fromttp://www.actasdermo.org/es/valoracion-inicial-diagnostico-estadificacion-tratamiento/articulo/S0001731010000591. [Last accessed on 2017 Oct 24].

12. Acosta AE, Fierro E, Velásquez VE, Rueda X. Melanoma: Patogénesis, clínica e histopatología. Rev Assoc Col Dermatol 2009;17:87-108. Available from: http://www.antoniorondonlugo.com/blog/wp-content/uploads/2009/08/revision-m-elanomas.pdf.

13. Palomo AM, Pérez MD, Pérez OR, Yabor VD, Fontaine AM. Melanoma maligno cutáneo en pacientes de la provincia de Las Tunas. Revista electrónica Dr. Zoilo E. Marinello Vidaurreta 2015;12:40. Available from: http://www.revzoilomarinello.sld.cu/index.php/zmv/article/view/483.

14. Aldama C, Arnaldo B, Victoria R, Graciela G, Liz D, Olga A, et al. Halo Nevo y Vitíligo: A propósito de un caso. Pediatrics 2007;34:31-3. Available fromttp://www.scielo.iics.una.py/scielo.php?script=sci_arttext&pid=S1683-98032007000100005&lng=en. [Last accessed on 2017 Oct 04].

15. Córdova B, Alberto C. Melanoma nodular en borde de pie. Rev Cienc Méd 2014;18:329-36. Available fromttp://www.scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1561-31942014000200016&lng=es. [Last accessed on 2017 Oct 13].

16. Santos VM, Leal CT, Vasconcellos MJ. Late diagnosis of nodular melanoma of the foot in a 74-year-old Brazilian man. Rev Med Chil 2011;139:1481-3.

17. Cepeda-Valdés R, Skinner-Taylor C, Flores-Gutiérrez J, Alanís S. Metástasis en tránsito de melanoma maligno cutáneo: Reporte de caso y revisión de la bibliografía. Dermatología CMQ 2010;8:62-3. Available fromttp://www.medigraphic.com/pdfs/cosmetica/dcm-2010/dcm101l.pdf. [Last accessed on 2017 Nov 08].

18. Mar V, Roberts H, Wolfe R, English DR, Kelly JW. Nodular melanoma: A distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia. J Am Acad Dermatol 2013;68:568-75.

19. Hugdahl E, Kalvenes MB, Puntervoll HE, Ladstein RG, Akslen LA. BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features and reduced survival. Br J Cancer 2016;114:801-8.

20. Gutiérrez-Vidrio RM, Cortés-Lozano M. Confrontando al melanoma en el siglo XXI. Med Cutan Iber Lat Am 2007;35:3-13. Available fromttp://www.medigraphic.com/pdfs/cutanea/mc-2007/mc071b.pdf. [Last accessed on 2017 Oct 27].

21. Camacho CP, Gerson R, Góngora MA, Villalobos A, Blanco YC, López O. Actualidades para el tratamiento del melanoma metastásico, estado del arte. Med Assoc Med Hosp ABC 2017;62:196-207. Available fromttp://www.medigraphic.com/pdfs/abc/bc-2017/bc173g.pdf. [Last accessed on 2017 Oct 20].

22. Serna-Macías J, Sánchez-Casas N, Morató-López A, Reyes-García M, Isusi-Alcazar J. Melanoma maligno cutáneo. El rol del PET-CT. GAMO. 2012;11(2):104-12. Disponible en: http://www.elsevier.es/es-revista-gaceta-mexicana-oncologia-305-articulo-melanoma-maligno-cutaneo-el-rol-X1665920112306599

23. Gallegos J, Nieweg O. Melanoma cutáneo (MC): Diagnóstico y tratamiento actuales. Gac Méd Méx 2014;150 Suppl 2:175-82. Available fromttp://www.medigraphic.com/pdfs/gaceta/

Health personnel and patients should be alert to injuries. In case of suspicion of metastatic melanoma, the diagnostic criteria should be applied and the diagnosis confirmed with biopsy and histopathological study, since early identification is decisive. Follow-up must be done to establish the diagnosis in a timely manner.

REFERENCES1. Fuente-García AD, Ocampo-Candiani J. Melanoma cutáneo.

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2. Frías AG, Ortiz HC, Lara HM. Estudio epidemiológico de melanoma maligno en el American British Cowdray medical center. Ann Med 2011;56:196-204. Available from http://www. medigraphic.com/pdfs/abc/bc-2011/bc114d.pdf.

3. Hernández-Zárate S, Medina-Bojórquez A, López-Tello Santillán A, Alcalá-Pérez D. Epidemiología del cáncer de piel en pacientes de la clínica de dermato-oncología del centro dermatológico Dr. Ladislao de la Pascua. Estudio retrospectivo de los últimos ocho años. Dermatología Rev Mex 2012;56:30-7. Available fromttp://www.medigraphic.com/pdfs/derrevmex/rmd-2012/rmd121e.pdf. [Last accessed on 2017 Sep 24].

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How to cite this article: Valeria JM, Margarita CC, Elizabeth RA, Ludivina M, Jurado LS, Hernandez MMC, Bogarín ELU. Nodular Malignant Melanoma. Asclepius Med Case Rep 2019;2(1):1-13.

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Nodular Malignant Melanoma · Valeria, et al.: Nodular Malignant Melanoma 2 Asclepius MedicAl cAse RepoRts • Vol 2 • issue 1 • 2019 disease.[6,7] The most common clinical variant