4 MEDICAL REVIEWS

Congenital Melanocytic Nevi and the Risk of Malignant

Melanoma: Establishing a Guideline for Primary-Care
Physicians
Jeremy Nikfarjam, MD1, and Earle Chambers, MPH, PhD2
1Department

of Surgery, Division of Plastic & Reconstructive Surgery, Montefiore Medical Center, Bronx, NY; 2Department of Family and Social
Medicine, Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY

Objective: The objective of this review is to determine what

size congenital melanocytic nevi (CMN) increases the risk of
malignant melanoma in affected patients.
Background: Congenital melanocytic nevi are benign proliferations of cutaneous melanocytes apparent at birth or in the
first postnatal weeks. The Kopf system classifies nevi based
on size: small, <1.5 cm in diameter; medium, 1.519.9 cm
in diameter, and large, 20 cm in diameter. Great variability
exists in quantifying the risk of malignant transformation from
congenital nevi of different sizes. Evidence-based standard
guidelines for clinical investigation need to be established.
Methods: Literature search included studies on medium,
large, and giant congenital nevi in association with melanoma.

formation from small CMN was determined to be 20.9 by history and 10.5 by histology in 238 patients in the case-control
study selected. No malignant transformation was found in a
prospective study of 230 individuals with medium-sized melanocytic nevi. Finally, a 5% risk of malignant transformation
was reported in a prospective study of patients with large congenital nevi.
Conclusion: All patients should receive total body skin and
mucosal surface exams. Patients with small CMN (<1.5 cm in
diameter) and medium CMN (1.5 cm19.9 cm in diameter)
should be closely observed over their lifetimes and given the
option of specialist referral. Finally, patients with large CMN
(20 cm in diameter) should be referred to specialists upon initial presentation. More original data and follow-up are needed
for maturation of evidence-based clinical recommendations.

Results: Three studies pertaining to small, medium, and large

congenital nevi are defined. The odds ratio of malignant trans-

INTRODUCTION
Congenital melanocytic nevi (CMN) are benign proliferations of cutaneous melanocytes clinically apparent
at birth or within the first postnatal weeks (Walton et
al., 1976). At least 2.5% of white infants are noted to
have some type of pigmented lesion at birth, but only
1% have biopsy-confirmed nevocellular nevi (Walton et
al., 1976). Prevalence of CMN ranges from 0.2% to 2.7%
in lesions less than 1.5 cm in greatest diameter (Pratt,
1953; Walton et al., 1976; Alper et al., 1979) to 0.005% in
lesions greater than 10 cm in greatest diameter (Castilla
et al., 1981).
Clinical appearance of congenital melanocytic nevi varies with respect to size, morphology, texture, age, and
location. Although considered controversial in the past,
the Kopf system is now the most widely accepted sizebased standard for the classification of CMN: small,
<1.5 cm in greatest diameter; medium, 1.519.9 cm in
greatest diameter; and large or giant, 20 cm in greatest diameter (Kopf et al., 1979). In addition to size, CMN
can be distinguished on the basis of having a round or
oval shape, with a regular, smooth, well-demarcated
border. The surface texture can be papular, rugose, pebbly, verrucous, or cerebriform, with combinations of
textures in a single lesion or in different lesions. During
the neonatal period, CMN may appear light in color,
hairless and flat, or raised. As the child grows, the same

lesion may become more uniform in color with darker

pigmentation, and acquire long, coarse, dark hairs. CMN
can appear anywhere on the body, with a slight predilection for giant CMN to appear on the posterior trunk
(Egan et al., 1998). Anatomical location also appears
to influence the progression in size of CMN with age.
According to Rhodes et al. (1996), the growth rate of
CMN is usually correlated with anatomic site after early
infancy, with lesions on the head increasing in size by
a factor of 1.5, and lesions on other anatomic areas
increasing in size by a factor of 3.
The embryological origin of melanocytes found in CMN
is the neural crest. As the progression from formation to
closure of the neural tube takes place, the cells of the
neural crest are delineated as a separate functional entity
from those of the neural tube. The neural crest cells ultimately give rise to the ectoderm, most notably melanocytes, the leptomeninges, and the peripheral nervous
system. Cramer (1998) proposed a theory of the melanocytic differentiation pathway, describing the migration,
plasticity, and differentiation of pluripotent stem cells of
the neural crest. The consequences of this theory account
for aberrations in the melanocyte differentiation pathway, namely the capability of melanoma to arise in a
nevus and leptomeninges as observed in neurocutaneous
melanocytosis. Furthermore, nevi may also contain pluripotent cells capable of differentiation and proliferation
throughout the lifetime of the nevi (Soyet et al., 2007).

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Congenital Melanocytic Nevi and the Risk of Malignant Melanoma: Establishing a Guideline for Primary-Care Physicians

The inception of CMN in utero has not been definitively evidenced by imaging modalities or in utero studies. Nevertheless, Hamming (1983) reported a case of a
kissing nevus in which a congenital melanocytic nevus
developed on adjacent parts of the upper and lower
eyelids and appeared as a single, contiguous lesion
when the eyelids were closed. Based on this observation,
CMN were estimated to develop between the 9th and
20th weeks of gestation.
Histological analysis can aid in differentiating CMN from
acquired nevi. Although there are no pathognomonic
features of CMN, histological analysis can be employed
when CMN are suspected in the absence of documentation of nevus presence at birth (Cribier et al., 1999).
In contrast to acquired nevi, nevomelanocytes of CMN
proliferate in the subjacent dermal tissue and can
spread to the deep dermis and even subcutis (Zaal et
al., 2004). These nevomelanocytes can extend between
collagen bundles of the reticular dermis, within and
around hair follicles, sebaceous glands, vessel walls, and
nerves (Mark et al., 1973; Rhodes et al., 1985; Barnhill
and Fleischli, 1995). The depth and the pattern of nevus
cell migration are directly related to the size of the CMN
in infants (Barnhill and Fleischli, 1995). Nevertheless,
nevus cell migration may continuously occur even after
birth. Walton et al. (1976) studied biopsies of small CMN
taken within 72 hours after birth, and concluded that
the spread of congenital nevi into deeper layers of the
dermis and subcutis occurs largely after birth. In addition, Mark et al. (1973) demonstrated that the epidermal-dermal junction aspect of a nevus may disappear
with time, rendering a dermal nevus without epidermal
involvement. On the other hand, malignant melanoma
arising within CMN usually originates at the epidermaldermal junction (Reed et al., 1965).
Thus, the determination of malignancy is of far greater
importance than the question of whether the nevus
is congenital or acquired (Zaal et al., 2004). Studies
attempting to quantify the percentage of primary melanoma originating from a CMN have shown inconsistent
results. In a study conducted by Schmid-Wendtner et al.
(2002), 9 of 6,931 (0.13%) patients under the age of 18
years developed cutaneous melanoma associated with
a congenital nevus. Previous to this analysis, Illig et al.
(1985) reported that at least 2.8% of melanoma cases
arose from congenital nevi, mostly those that were single and less than 10 cm. In a study assessing the risk of
melanoma from CMN in a lower-risk black population,
Shpall et al. (1994) calculated an actual risk in blacks up
to age 75 to be approximately 1 in 2,000 (0.05%). The
level of risk reported among these studies results varies from tenfold to a hundredfold and thus is of limited aid to clinicians in gauging the risk of malignancy in
patients with CMN.
Several studies assessing the lifetime risk of malignant
melanoma from CMN based on size have been under-

60 EJBM, Copyright 2012

taken in order to empower clinicians with practical and

simple measures for evaluating malignancy risk in their
patients. Among patients with giant CMN, a lifetime risk
of malignancy of 5% to 60% has been reported in the
literature (Kaplan, 1974; Kang et al., 1992; Sober and
Burstein, 1995). Marghoob et al. (1996) concluded a
lifetime increased risk of 3.3% for melanoma in large
CMN measuring 20 cm or more in largest diameter, or
CMN predicted to attain this size by adulthood. Quaba
and Wallace (1986) calculated an 8.52% lifetime risk for
melanoma in a retrospective analysis of 39 patients with
giant CMN.
Among patients with medium and small-sized CMN, the
risk of transformation to malignant melanoma seems to
be controversial. Scalzo et al. (1997) of the Massachusetts
General Hospital Pigmented Lesion Clinic reported that
in a 30-year period, no child (<20 years old) developed
melanoma in association with a congenital nevus less
than 5 cm in diameter. Similarly, Swerdlow et al. (1995)
reported that none of their 239 patients with CMN from
1 to 19 cm in diameter followed over a mean of 25 years
developed melanoma. However, in a study by Illig et al.
(1985), 52 patients with melanoma that arose in CMN
were observed to occur in patients age 18 or older. Based
on these results, the authors concluded that melanoma
can, in fact, arise from congenital nevi less than 10 cm
in diameter.
These disparate and sometimes conflicting study
results make it challenging for primary-care physicians
to develop the appropriate standard of treatment for
patients with CMN. Although these congenital lesions
may not be common in the population, primary-care
physicians may well be the first to detect such nevi, and
the ones ultimately to decide whether such skin lesions
warrant referral to a specialist. More importantly, the
role of the primary-care physician is critical in underserved areas, where the patient population has poor
access to healthcare, is largely uninsured, and may have
recently emigrated from another country with poor
healthcare. These underserved patients may present
with CMN for the first time well into adulthood, when
risk of melanoma from CMN has been reported. Such
delayed presentation may endanger the life of a patient
with a preventable disease. In addition, the African
American and Caribbean American population may be
protected from acquired melanoma due to dark skin
pigmentation, but CMN are equally present in these
populations, as is the risk of melanoma from CMN. Not
only may these factors contribute to physicians overlooking the importance of CMN in these populations,
but detection of CMN may be more difficult due to dark
skin pigmentation.
In order for primary-care physicians to provide the best
and most efficient treatment for patients with CMN,
evidence-based standard guidelines for clinical investigation need to be established. The objective of this

4 MEDICAL REVIEWS
Congenital Melanocytic Nevi and the Risk of Malignant Melanoma: Establishing a Guideline for Primary-Care Physicians

review is to answer the following question: What size

CMN increases the risk of malignant melanoma in the
affected patients?

METHODS
A literature search was performed using the biomedical bibliographical database Medline from 1966 to
December 2008. Initial searches used the keywords congenital nevus, congenital melanocytic nevus, and
congenital nevocellular nevus. We included studies
on medium, large, and giant congenital nevi in association with melanoma. We excluded all articles that were
not prospective analyses and/or case-control studies,
articles with five or fewer CMN patients, articles that
dealt only with aspects of treatment, articles that classified size by methods other than the Kopf model, and
data presented in letters to the editor and abstracts. The
remaining studies were individually placed into Google
Scholar, and were selected based on the number of
citations received. Manual cross-referencing was performed. Finally, one representative article was selected
with respect to CMN classification by size: small CMN,
medium CMN, and large CMN.

RESULTS
No prospective studies met our search criteria for small
CMN, so a case-control study was included with the
caveat that a prospective study is preferred over a casecontrol study for our particular assessment.
Three studies pertaining to small, medium, and large
CMN met our inclusion criteria. The results are shown
in Table 1.
The first article reviewed is by Rhodes and Melski (1982):
Small congenital nevocellular nevi and the risk of cutaneous melanoma. This case-control study was created
to determine the odds ratio of melanoma for persons
with small congenital nevi (SCN). This was done by
comparing the frequency of SCN in unselected cases of
melanoma to the frequency of SCN in newborn infants.
Postpubertal patients with all histological types of cutaneous melanoma invasive to at least the papillary dermis
were included and divided into three groups.
The first group was composed of 134 patients who
reported a detailed history of preexisting pigmented
lesions (PPLs) at the tumor site, but whose tumors were
not histologically examined for melanoma-associated
nevocellular nevi. The 134 patients included 67 males
and 67 females with an age range of 1678 years (mean
= 47.9 years) with histological documentation of primary
cutaneous melanoma diagnosed between April 1960
and September 1979 at the Pigmented Lesion Clinic of
Massachusetts General Hospital. In this study group, 33

patients were diagnosed at the time of interview, 40

patients were interviewed within one year of diagnosis, 23 patients were interviewed between one and two
years of diagnosis, and 38 patients were interviewed
later than two years after diagnosis. Interviews included
questions to assess the first appearance and morphological characteristics of the PPLs, along with the source of
the information obtained (parents versus patient).
The second group was composed of 234 patients who
did not report a detailed history of a PPL at the tumor
site, but whose tumors were histologically examined for
the presence of melanoma-associated nevocellular nevi.
The 234 patients included 119 males and 115 females;
1 patient was black and 233 were white, with an age
range of 12 to 90 years (mean = 47.9 years). Histology
was determined in 234 unselected melanoma specimens
entered into the Harvard Melanoma Registry within 30
days of diagnosis during the period from September
1, 1972, to May 30, 1977. Tumor-associated nevi were
examined to determine whether they were nevocellular
nevi with congenital features based on the presence of
nevus cells in the dermis.
Data on the third group of patients were obtained
from a previous study by Walton et al. (1976) in order
to determine the prevalence of congenital nevocellular
nevi by histology in 841 white newborn neonates examined within 72 hours of birth.
Finally, the data from all the groups were used to calculate an odds ratio for primary cutaneous melanoma
associated with SCN. This was done by dividing the exposure odds of SCN among patients with melanoma by the
exposure odds of SCN among neonates.
Results of the Rhodes and Melski (1982) study were
determined based on the sample groups. Of the 134
patients with melanoma in the first group, 20 (14.9%)
gave a detailed history of the existence of a PPL at the
tumor site present since birth. Out of these 20 cases, 5
were ascertained by direct interview with parents (2 of
which cases had photographs during the first 6 months
of life), whereas the other 15 were ascertained indirectly by parental statements in the past. Among these
20 patients, the estimated greatest diameter for the PPL
ranged from 3 to 15 mm (mean = 9 mm +/- 4 mm). Out of
the 234 melanoma specimens in the first group who did
not report a detailed history of a PPL at the tumor site,
19 (8.1%) were designated tumor-associated nevocellular nevi with congenital features. Furthermore, out of
these 19 cases, a total of 6 (2.6%) had nevus cells in the
lower two thirds of the reticular dermis (a highly sensitive indicator of congenital nevi). Of the 30 patients who
were included in both groups, 2 patients were among
the 20 PPLs in the first group, and 2 different patients
were among the 19 tumor-associated nevocellular nevi
with congenital features specimens in the second group.
Of the Walton et al. (1976) third study group, 7 patients

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Congenital Melanocytic Nevi and the Risk of Malignant Melanoma: Establishing a Guideline for Primary-Care Physicians

TABLE 1. AN OVERVIEW OF LITERATURE ON MELANOMA AND CONGENITAL MELANOCYTIC NEVI

(CMN Type according to Kopf et al. [1979]. CMN[n] Number of subjects with CMN in study. MM Malignant melanoma)

(0.83%) had nevocellular nevi confirmed by biopsy, all of

which were 3.0 cm in greatest diameter. Based on these
results, the study determined an odds ratio for cutaneous melanoma in persons with SCN to be 20.9 based
on history (95% confidence interval 11.0 to 39.9) and
10.5 based on histology (95% confidence interval 5.1 to
21.6). The odds ratio was 3.1 for the 6 specimens taken
from the 19 nevocellular nevi with congenital features.
The authors concluded that congenital nevi of any size
may be precursors to cutaneous melanoma.
The Rhodes and Melski (1982) study was among the first
studies to address the risk of malignant melanoma in
patients with SCN. The study methodology of distinguishing three different subject groups further aided in
minimizing confounding effects of various other parameters that were not controlled. In addition, by separating patients based on history versus tissue diagnosis, the
authors were able to note a difference in the odds ratio,
possibly raising the issue that PPL history alone may
overestimate the odds ratio of melanoma.
Although the authors conclusion may ultimately be
supported by their data, the methodology in calculating the odds ratio is inherently flawed. Information

62 EJBM, Copyright 2012

from the patients in the first subject group was in some

cases not obtained directly from the patients or families.
Among those cases in which information was directly
obtained, only two had photographic evidence of the
PPL. Thus, great subjectivity in the form of recall bias
during patient interviews is likely to confound the estimation of PPL size. In the second subject group, nearly
two times more patients were present than in the first
group. Though more subjects contribute to the power of
the study results, it is optimal to have close to an equal
number of subjects in both groups in order to minimize
the effects of statistical outliers. Among the 30 patients
in the third subject group, 2 reported a history of PPL
(6.66%) and 2 others had positive histology (6.66%).
These results were substantially different from those in
the first group (14.9%) and the second group (2.6%),
raising the issue of the accuracy of the study results.
Finally, the authors chose to use the study by Walton et
al. (1976) to estimate the prevalence rate of SCN. This
is also represents a flaw in study design because the
authors make the assumption that prevalence of SCN in
newborn infants is constant and that the prevalence of
SCN in adults is comparable to that in neonates.
The second report considered here, Risk of melanoma

4 MEDICAL REVIEWS
Congenital Melanocytic Nevi and the Risk of Malignant Melanoma: Establishing a Guideline for Primary-Care Physicians

in medium-sized congenital melanocytic nevi: A followup study, by Sahin et al. (1998), is a prospective, clinical
cohort study created to assess the risk for melanoma in
individuals with medium-sized melanocytic nevi clinically judged to be congenital. Methodology consisted
of a chart review of patients first seen from November
1955 to September 1996 in a private dermatology clinic
in order to identify cases of medium-sized CMN. The following data were taken from the chart: each patients
age at initial visit and last follow-up and the anatomic
location, shape, size, elevation, surface characteristics
(presence of hair), and color of the patients lesion.
The only inclusion criterion established was a Polaroid
photograph taken of the CMN for clinical diagnosis.
Lesions smaller than 1.5 cm in greatest diameter and
those greater than 19.9 cm in greatest diameter were
excluded, without an attempt to predict adult sizes of
CMN smaller than 1.5 cm in greatest diameter. In total,
16,871 charts were reviewed, yielding 329 patients with
Polaroid photographs of lesions that met inclusion criteria for CMN. These patients or parents of the patients
were contacted and asked whether there had been a
change in the CMN, whether a malignant melanoma had
developed within the CMN or elsewhere, and when and
how the CMN had been treated. Out of the 329 patients,
102 patients with less than one year of follow-up were
excluded. The remaining 227 patients (230 CMN) were
enrolled in the study. An additional follow-up via telephone was carried out with 174 of these patients.
Results of the Sahin et al. (1998) study were based on
demographic data and clinical characteristics of the CMN
entered into the study. CMN were first seen at an average age of 19 years (median, 12 years) with an average
age at last follow-up of 25.5 years (median, 19 years).
The average follow-up period was 6.7 years (median, 5.8
years). The largest diameters of CMN ranged from 15 to
190 mm, with an average of 40 mm. No patients developed malignant melanoma in medium-sized congenital
nevi during follow-up. However, three patients who met
the inclusion criteria developed melanoma at anatomic
sites other than those were the CMN were located. One
of these patients developed melanoma during followup, another patient had melanoma before the initial
visit, and a third patient had been diagnosed with three
melanomas, two before his first visit and one during
follow-up. Based on these results, the authors concluded
that medium-sized congenital nevi are not at increased
risk of developing into melanoma.
Several methodological attributes of the study by Sahin
et al. (1998) contributed to the soundness of the authors
conclusion and limited the confounding factors. First,
the patient data taken from the chart review allowed
the authors to define the characteristics of medium CMN
and melanoma. Second, each nevus was documented by a
Polaroid photograph, providing evidence of a skin lesion
preceding a melanoma. Third, the relatively large initial
sample size of 329 patients with medium CMN increased

the power of the study results. However, certain flaws in

the study design did exist. First, the authors determined
whether the nevus was congenital by clinical characteristics. These are inherently subjective inclusion criteria, as nevi are known to evolve with respect to clinical
appearance. Second, among the 227 patients ultimately
enrolled in the study, only 174 received follow-up; while
those patients lost to follow-up were not known to have
developed melanoma, the loss of this potentially valuable data from the study is considerable. Furthermore,
the average length of follow-up was merely 6.7 years
from an average patient age of 19 years, an interval
that may not be adequate to observe transformation of
medium CMN to melanoma. Finally, among the patients
with follow-up, the authors mentioned that they were
asked whether an MM [malignant melanoma] had
developed within the CMN or elsewhere. Once again,
without tissue diagnosis, this introduced subjectivity and
bias into the study design because patients may have
had undiagnosed melanoma, or, conversely, may mistakenly have stated that they had melanoma without an
actual diagnosis.
The third article reviewed, Giant pigmented nevi:
Clinical, histopathologic, and therapeutic considerations, by Ruiz-Maldonado et al. (1992), is a prospective, clinical cohort study created to assess the clinical
and histopathologic features, as well as the treatment of
giant CMN. This was done by entering all patients clinically diagnosed with giant pigmented nevus (defined
therein as cutaneous hamartomas of nevomelanocytes
measuring 20 cm in diameter) during the period from
January 1971 to December 1990 at the Department of
Dermatology at the National Institute of Pediatrics in
Mexico City. The sole inclusion criterion was the presence of a giant pigmented nevus. Each of the 80 patients
enrolled in the study received a physical examination,
routine laboratory tests (blood cell counts, chemistry
studies, urinalysis), and nevus biopsy. Patients with nevi
involving the skin overlying the head or upper portion
of the vertebral column received an electroencephalogram. Patients with extracutaneous abnormalities were
examined by appropriate specialists.
Results of the Ruiz-Maldonado et al. (1992) study
included data for various parameters not mentioned in
the methods section. The incidence of giant pigmented
nevi was determined to be 1 in 4,150 among general
pediatric outpatients, and 1 in 405 among pediatric
dermatology outpatients (with 21% of patients lost to
follow-up). The age of patients at the time of consultation ranged from 2 days to 16 years (mean = 20 months).
The prevalence of giant pigmented nevi in girls (65% of
sample size) was found to be significantly greater than
in boys (35% of sample size) (p <0.001), which was not
due to disparities in normal ratios in the population or
in the study subjects. In addition, the prevalence of large
nevi in second-degree relatives was found to be significantly higher than the expected frequency in the popu-

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Congenital Melanocytic Nevi and the Risk of Malignant Melanoma: Establishing a Guideline for Primary-Care Physicians

TABLE 2. MALIGNANT TRANSFORMATION (Adapted with permission from Ruiz-Maldonado et al., 1992)
Histopathologic Diagnosis

Age of Patient

Follow-Up

Malignant Melanoma

8 months

Deceased

Malignant Melanoma

2 years, 4 months

Deceased

Neuroblastoma

7 months

Deceased

Minimal
Deviation Melanoma

14 years

Alive & Well after 1 Year

lation (p <0.001). About 80% of nevi were observed to

be black in color, and 86% of nevi were pigmented and
hairy. Predominant locations of nevi included the trunk
(47%), limbs (30%), and head (22%). Histopathological
features of the 62 of 80 (78%) patients thus examined
with giant pigmented nevi were: 64% predominantly
intradermal, 12% predominantly compound, and 22%
cellular blue nevi. Finally, four malignancies were found
among the 80 patients. Two of the patients diagnosed
with malignant melanoma at the ages of 8 months and
28 months died of metastasis despite chemotherapy and
surgery. One patient diagnosed with neuroblastoma
at the age of 7 months died as well. Another patient
was diagnosed with minimal deviation melanoma at
the same position; the nevus was previously treated by
chemical peel, and the patient was alive and well one
year after the diagnosis (Table 2). The authors concluded
that there is a high risk of malignant transformation of
GPN [giant pigmented nevi].
The Ruiz-Maldonado et al. (1992) study has several
strong points. The inclusion criteria were clearly defined
and relatively simple, thus improving generalization of
results. The mean age of patients was 20 months, which
is closer to the ideal age of birth in assessing lifetime risk
of malignant melanoma. Additionally, this study made
an attempt to further quantify the prevalence of giant
pigmented nevi according to patient gender and family
history. Nonetheless, imperfections in the study design
did exist. The authors reported the average length
of follow-up time to be 4.7 years, leaving readers to
question whether long-term risk is properly addressed
in such a short period of time. Moreover, the authors
briefly mention that 21% of patients enlisted were lost
to follow-up. Not only does this limit the power of the
study results, but it also lends greater weight to outlier
effects and miscalculation of melanoma risk since those
lost to follow-up may have developed malignancy.

DISCUSSION
Both worldwide and in the United States, the incidence
of melanoma is increasing more rapidly than that of any
other cancer (Lens and Dawes, 2004; Tsao et al., 2004).
On average, one person dies every hour from metastatic
melanoma in the United States (Lens and Dawes, 2004;

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Tsao et al., 2004). Among these deaths, melanomas arising from CMN compose a portion, but the rate of this
risk remains a matter of controversy.
Several studies have suggested a vast array of risks associated with CMN, but the level and nature of the risks
uncovered often varies among individual studies. These
disparities may well be due to a lack of standardization
in defining CMN, as several differing criteria have been
employed, such as greatest size in diameter (Kopf et
al., 1979), the amount of body surface area covered by
the nevus (Lanier et al., 1976), and ease of excision and
primary closure without deformity (Kaplan, 1974). The
adoption of a standard definition is particularly important for primary-care physicians, as they are most likely
to be the first medical professionals to interact with
patients with CMN. Therefore, we chose the Kopf model
to define CMN in our literature review due to its wide
acceptance among clinicians and its relative ease of use
in practice. Subsequently, our literature review focused
primarily on ascertaining what size of CMN increases the
risk of malignant melanoma in the affected patients.
The study conducted by Rhodes and Melski (1982) determined an odds ratio for cutaneous melanoma in persons
with SCN of 20.9 based on history and 10.5 based on histology, leading the authors to conclude that congenital
nevi of any size may be precursors to cutaneous melanoma. The calculation of the odds ratio was inherently
flawed due to faulty assumptions made by the authors,
along with poor evidence in determining a history of
PPL in patients with cutaneous melanoma. Sahin et al.
(1998) reported no incidence of malignant melanoma in
227 patients arising from medium CMN, and concluded
that medium-sized CMN did not reveal an increased risk
for melanoma. Their study, however, is limited by subjective inclusion data, loss of many patients to followup, and an inadequate follow-up interval to observe
transformation of medium CMN to melanoma were it
to occur. Finally, Ruiz-Maldonado et al. (1992) studied
giant CMN in 80 patients and concluded that there exists
a high risk of malignant transformation for this type of
CMN. Although the statistical power of the study was
weakened by a substantial loss of patients to follow-up,
the diagnosis of melanoma in four patients is remarkable in view of the diminished sample size. Moreover,
the death of three patients younger than four years of

4 MEDICAL REVIEWS
Congenital Melanocytic Nevi and the Risk of Malignant Melanoma: Establishing a Guideline for Primary-Care Physicians

FIGURE 1. DIAGRAM SUMMARIZING RECOMMENDATIONS FOR PATIENTS WITH CONGENITAL MELANOCYTIC NEVI (CMN)
BASED ON SIZE.

age in this study highlights the potential catastrophic

harm that CMN possess in the event of malignant transformation.

risk of malignant transformation (Figure 1). This plan of

treatment does not take into account resectability, cosmesis, or age, since these factors are beyond the scope
of this article.

CONCLUSIONS

Further research is needed to enhance our understanding of this critical issue. Most importantly, efforts should
be made to establish evidence-based standard guidelines for primary-care physicians to confidently address
the issue of CMN in their patients. The adoption of such
guidelines is imperative in underserved areas because
the consequences of CMN are preventable and ultimately lifesaving. Thus, we have attempted to address
this issue and provide clinical recommendations in an
effort to establish standard guidelines for primary-care
physicians when dealing with CMN. In the future, morespecific evidence-based clinical recommendations should
be possible pending more original data and epidemiological studies.

Considering the results of this literature review, we have

come to the following conclusions. First, the odds ratio
calculated by Rhodes and Melski (1982) constitutes an
important initial attempt to quantify the risk of small
CMN transforming into melanoma, but more evidence
is needed to properly evaluate the risk. Second, several
shortcomings present in the Sahin et al. (1998) study
likely limit the authors claim that medium-sized CMN
do not impart an increased risk for melanoma. Third,
despite the suboptimal methodology present in the
Ruiz-Maldonado et al. (1992) study, the evidence presented therein is substantial and corroborates the risk of
melanoma from giant CMN.
Based on this analysis, clinicians may consider several
points in treating a patient with CMN. The consensus
remains that each patient should receive a total body
skin and mucosal surface exam for skin lesions upon
initial presentation. Those patients with small CMN
measuring <1.5 cm in largest diameter and medium
CMN measuring 1.5 cm to 19.9 cm in largest diameter
should be photographed and observed for any changes
throughout the patients lifetime, or given the option
for specialist referral upon initial presentation. This flexibility may be beneficial in the absence of unequivocal
indications of melanoma, particularly because patients
should be given the autonomy to make their own decisions in the context of possible melanoma transformation. Lastly, patients with large CMN measuring 20 cm
should be referred to specialists upon initial presentation
in view of the strong evidence supporting the increased

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4 MEDICAL REVIEWS
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Corresponding Author: Address correspondence to Jeremy Nikfarjam, MD

(jenikfar@montefiore.org).

Conflict of Interest Disclosures: The authors have completed and submitted
the ICMJE Form for Disclosure of Potential Conflicts of Interest. No conflicts
were noted for either author. Dr. Nikfarjam, a member of the EJBM Staff, was
not involved in the review of this manuscript.
Acknowledgements: The authors would like to thank Lorenzo Agoni, MD, MS
for designing the figures in this manuscript.