J Cutan Pathol 2008: 35: 889–898
Blackwell Munksgaard. Printed in Singapore
Perspectives in Dermatopathology
Copyright # Blackwell Munksgaard 2008
Continuing Medical Education Article
Nevi with site-related atypia: a review of
melanocytic nevi with atypical histologic
features based on anatomic site
A subset of melanocytic nevi share features with melanoma and
nevi with architectural disorder but are biologically inert and to date
do not appear to portend an increased risk for the development of
malignancy. These benign nevi with certain atypical histologic features
cluster among specific anatomic sites and are thus designated nevi with
site-related atypia. We categorize these lesions into four main groups:
acral, genital, special site and conjunctival, based on anatomy and
relative prevalence of specific atypical histologic features. As the
literature and our recognition of these lesions continue to grow, our
understanding of their biology has not kept pace.
Hosler GA, Moresi JM, Barrett TL. Nevi with site-related atypia:
a review of melanocytic nevi with atypical histologic features based
on anatomic site.
J Cutan Pathol 2008; 35: 889–898.#Blackwell Munksgaard 2008.
Gregory A. Hosler1,2,
Jean Margaret Moresi3
and Terry L. Barrett1,2
1Department of Dermatology and Pathology,
University of Texas Southwestern Medical
Center, Dallas, TX, USA,
2ProPath Dermatopathology, Dallas,
TX, USA, and3Department of Dermatology,
The Johns Hopkins Hospital, Baltimore,
Gregory A. Hosler, MD, PhD
8267 Elmbrook Drive,
Dallas, TX 75247, USA
Tel: 214 237 1667
Fax: 214 237 1743
Accepted for publication March 25, 2008
Clinical differences between melanocytic nevi from
different anatomic sites have been recognized for
decades,1,2and our understanding of the correlate
changes in their histology continues to grow.3–6
Recognition of these various features as ?site related’
overwhelming majority of biopsied lesions in these
sites are benign. This specific question has become
a significant portion of our consultation practice and
others4,7and continues to expand, reflecting the
diagnostic challenges faced in the dermatopathology
Anatomic sites that have been implicated in har-
boring histologically atypical but benign nevi include
acral locations, genitals, breast, scalp, ear, flexural
regions and the conjunctiva. Nevi from other sites,
including oral and facial (Miescher) nevi, may show
characteristic features but are not included in this
discussion as they are not to date associated with any
specific or reproducible atypical histology concerning
While several of these anatomic sites may offer
a physical explanation for the atypical features of the
nevi, for example the thick stratum corneum and
dermatoglyphs of palms and soles, this is largely
speculative. The majorityof the nevi in these sites are
indistinguishable clinically and histologically from
otherwise banal nevi from the torso or other sites.
Only a small percentage shows atypical features,
which overlap with those of nevi with architectural
disorder or melanoma, and therefore, anatomic ar-
guments or hormonal influences or the effects of
constant friction are notsufficient explanations. Until
the molecular pathways are better understood and
and physical influences, this will likely remain a mere
observation, important only in our ability to distin-
guish these nevi from melanoma.
being, in our experience, one of the most common
sites for both over- and underdiagnosis of melanoma.
The frequent and at times striking upward migration
of melanocytes contributes to the former, while sam-
pling artifact (inability to evaluate the entire lesion) is
the primary contributor to the latter.
population2,8and consist primarily of nevi,3,9with
a minority of macules, lentigines and melanomas.
These include lesions on the palms, soles, volar
surfaces of fingers and toes and ungual (nail matrix
andbed)regions.Othersexpand acralsitesto include
often uniform in pigmentation, with irregular but
sharp borders (Fig. 1A). These can have a character-
istic appearance by dermoscopy because of the
pigment distribution in relation to the deep furrows
of the dermatoglyphs, with pigmentation in the sulci
more characteristic of a benign process.10
Similar to their clinical appearance, acral nevi
usually show symmetry histologically. The symmetry
can be masked, however, by problems with embed-
ding or tangential cutting11or, more commonly, by
incomplete excision. The nevus can be junctional,
compound or intradermal. Pigment in the stratum
corneum is a common finding and may be physio-
logically related to the upwardly migrating cells as
a transepidermal elimination pattern, given the
constant trauma to these sites (Fig. 1B). When a
often characteristic, with benign nested melanocytes
showing ?skip’ areas with syringotropism (Fig. 1C).
The dermal component will show maturation, bland
lacking, the lesion should be heavily scrutinized for
more aggressive features.
Nevi from the nail bed or matrix can be eye-
catching, both clinically and histologically, largely
appear asymmetric, and prominent hyperpigmenta-
Fig. 1. Acral nevi. Clinically, acral nevi often
have irregular borders but uniform pigmen-
tation (A, courtesy: Dr Kenneth Greer,
Charlottesville, VA). The pigment in the
stratum corneum gives the appearance of
transepidermal elimination in this lesion
from the sole of a 1-year-old boy (B,
1003). A different lesion shows dermal
syringotropism (C, 1003). Lesions from the
nail bed are often junctional and may show
prominent pigment (with dermal melano-
phages) and nuclear hyperchromasia (D,
2003). This example from the sole has
striking upward migration of melanocytes,
considered at the upward limit of normal for
acral lesions (E, 1003).
Hosler et al.
tion and nuclear hyperchromasia are common find-
ings (Fig. 1D). Angulation and distortion of the
junctional nests may be seen, but this appearance of
confluent growth should not be overinterpreted as
a feature of malignancy.
The epidermal component of acral lesions may
have atypical features. Boyd et al. performed a
retrospective histologic analysis of 158 acral lesions
and 148 benign, and they found that 75 (50.7%)
benign lesions had bridging of retia, 58 (39.2%) had
fibroplasia and 59 (39.9%) had a significant inflam-
acral nevi share with nevi with architectural disorder.
Acral nevi often have more lentiginous growth than
the typical benign nevus and upward migration into
the epidermis is a common finding (38.5%).12A
diagnosis of ?compound melanocytic nevus with
ascending cells (acral nevus)’ is an appropriate sign-
out to convey this feature. While fully evolved
pagetoid growth is concerning, often times the
upward migration is dramatic (Fig. 1E) and has led
some authors to use the acronym MANIAC (mela-
to describe these lesions.13
some acral nevi, one should be cautious not to
overdiagnose nevi with architectural disorder or
melanoma. This is not to say that nevi with archi-
scant evidence that acral lesions with one or several of
increased risk for a patient developing melanoma as
sites. When considering melanoma, circumscription,
symmetry and lack of cytologic atypia or mitoses are
reassuring findings.12When upwardly migrating cells
are present, they are located centrally and are not
cytologically atypical. Melanoma at acral sites will
typically have a lentiginous in situ, or precursor,
of most non-acral melanomas, and melanoma arising
at the site of an acral nevus is an unusual find.
Although mild lentiginous growth is expected in
acral nevi, its presence at the specimen margin raises
melanoma. This is a particular problem with nail bed
and matrix biopsies. Although acral nevi are more
common than acral melanoma14and acral surgeries
have an increased risk of morbidity, re-excision to
ensure complete histologic evaluation and removal
should be recommended in such cases.
Vulvar (genital) nevi
Despite the alarming clinical appearance of a subset
of vulvar pigmented lesions, vulvar melanoma is
in overdiagnosing melanoma in the vulvar region,
potentially leading to radical and unnecessary
Nevi from the vulva, to include both hair-bearing
areas and the labia minora and clitoris, account for
the majority of genital nevi. Also included in this
group by some authors are mons pubic, perineal,
primarily discussed here, although the principles can
largely be extrapolated to these other anatomic sites.
Pigmented lesions of the vulva are present in 10–
lentigines, nevi and rarely melanoma. Lentigines are
most common, while 2% of the population have
vulvar nevomelanocytic nevi.17Most pigmented
lesions are biopsied or removed from young women
at routine obstetric/gynecologic visits and are
unaware of their presence. Most lesions are benign.
There is a minority, or subset, of vulvar nevi that
occur in young, premenopausal women and have
atypical histologic features.7,15,20These atypical nevi
have features common with each other but fairly dis-
tinct from nevi with architectural disorder, leading
nevus, genital type’ to describe them. Christensen
were compared histologically with 200 nevi from the
torsos of women. Clinically, the lesions with histolog-
ically atypical features may be slightly larger or
hyperpigmented but are otherwise indistinguishable
from those with bland histology, and the cause is
In a recent outcome study by Gleason et al., 56
The study included nevi from the vulva, mons pubis
and perineum. The 39 vulvar lesions included nevi
or mucosal sites (14 or 36%). In contrast, vulvar nevi
hair-bearing regions. As an aside, in children, the
labia minora and clitoral regions are the most
common anatomic sites for atypical genital nevi.7,20
and event free for over 11 years following the re-
excision. Interestingly, 12 of 55 (22%) patients in
this study were reported to have either a personal or
family history of atypical nevi or melanoma. To our
knowledge, this is the first study suggesting a possible
link between an atypical genital nevus (or any nevus
with site-related atypia) and an increased risk for
melanoma, but more work is required in this area
before firm conclusions are drawn.
Nevi with site-related atypia
The histology of these atypical vulvar nevi can be
striking at low power, often with a large nodular and
cellular lesion, raising concern for a nodular mela-
noma (Fig. 2A). The theques, or nests, have marked
variability in size and shape, including large irregular
and fusiform forms (Fig. 2B). These are characteris-
tically located at all positions along the retia, not
restricted to their tips as is seen in nevi at most other
anatomic sites (Fig. 2C). Another characteristic fea-
ture is loss of cellular cohesion, with artifactual sep-
aration of nested melanocytes, giving them a
pseudovascular appearance (Fig. 2D). Unlike the loss
of cohesion associated with confluent lentiginous
nests. A component of lentiginous growth may be
growth is not characteristic.
dermis and the appearance of multiple cell popula-
tions is not uncommon. The cytologic atypia of these
vulvar nevi is, at times, severe (Fig. 2E). Atypia in this
the nuclear : cytoplasmic ratio is often intact. Nucle-
atypia is often uniform across the lesion. Often times,
the cytoplasm is abundant, with tan-gray dusty
intracytoplasmic melanin pigment. Elongation of
the cytoplasm into a spindled morphology is not
uncommon. Unfortunately, rare dermal mitoses have
been observed and cannot be relied upon for dis-
tinction from melanoma.
In the Gleason study, the authors identified prom-
inent irregular junctional nests, loss of cellularcohesion
and some degree of cytologic atypia as the dominant
This study also showed the frequency of dermal
maturation (100%), a co-existing common dermal
migration of melanocytes (18%) and the presence of
nevi with architectural disorder were variably present.
The stromal reaction patterns of these nevi have
Fig. 2. Genital nevi. This vulvar nevus from
a young woman has a nodular pattern (A,
403). Similar pleomorphic nesting patterns
are present in this different lesion from the
mons pubis (B, 1003). The positioning of
theques along the sides of retia and crests of
papillae is a common finding, shown in this
vulvar lesion (C, 403). Scattered melano-
cytic nests may show lack of cellular
cohesion, with the appearance of floating
melanocytes or pseudovascular structures
(D, 1003). A degree of melanocytic atypia
is an expected finding. Note the lack of
stromal change (E, 2003).
Hosler et al.
retrospectively reviewed 56 atypical melanocyticnevi
of the genital type (AMNGT) referred for consulta-
from those of nevi with architectural disorder and
melanoma. Melanomas more commonly show fibro-
plasia with a diffuseplaque-like lymphocyticinfiltrate
disorder have reproducible concentric and lamellar
fibroplasia. AMNGT have a telling inconspicuous
stroma, helpful in allowing distinction.7Diffuse fib-
rosis is also occasionally seen, perhaps more common
in polypoid lesions. A stroma of lichen sclerosus has
also been described invulvar nevi, likely representing
a collision of separate processes. In this setting, the
melanoma or pseudomelanoma (recurrent nevus
It must be emphasized that the incidence of vulvar
melanoma in young women is very low, but not
zero.22,23Vulvar melanoma more commonly occurs
on hair-bearing areas. It is often superficial spreading
as opposed to the more nodular appearance of vulvar
their distinction from melanoma include symmetry,
lack of an in situ precursor lesion, maturation in the
dermis, low proliferation index (rare mitoses are
acceptable) and lack of stromal changes described
above. In cases that are incompletely excised, even
when the features point to an atypical nevus, genital
type, re-excision should be strongly considered.
Additionally, in postmenopausal women, one’s
threshold for melanoma should be lowered as the
positive predictive value rapidly increases with age.
Nevi with site-related atypia, the special site nevi
(breast, flexural, scalp and auricular)
There has been a recent increase in the number of
publications describing atypical melanocytic nevi
specific to anatomic sites, with some authors using
the designation ?special site nevi’.24–28Like genital
nevi, these lesions are usually clinically indistinguish-
able from other nevi (Fig. 3A). A multitude of
histologically atypical features has been compara-
tively analyzed in these studies, among them asym-
metry, lentiginous growth, pagetoid growth, lamellar
and concentric fibroplasia, stromal response and
cytologic atypia, to name a few. These features are
the assessment for nevi with architectural disorder
The results of these studies indicate the close
relationship these nevi share with each other and to
a lesser extent with acral and genital nevi, although
the lines of distinction are blurred partly because of
loose definitions by different authors for what
constitutes an acral or genital or flexural site. In our
includes the breast, flexural regions, scalp and ear,
deserve a separate heading as their shared histologic
features differ somewhat from the prevalent features
of cytologic, architectural and stromal descriptors,
presence of pagetoid growth and atypical nesting
patterns, respectively. Nevi from the above special
anatomic sites also occasionally show these features,
but only in a subset and only to a degree. Other
atypical histologic features are seen with equal or
greater prevalence, in different proportions, and the
presence of junctional and dermal melanocytic
cytologic atypia is seen with relative frequency
the primary concern is excluding superficial spread-
This is in contrast to acral and genital nevi, which
more closely mimic acral lentiginous melanoma and
nodular melanoma, respectively.
On a more practical note, there are differing
opinions on the need to re-excise these atypical nevi.
In our practice, for non-special site nevi, we use the
term atypical compound nevus (as most are com-
pound) to describe nevi with both junctional and
dermal atypia, in the absence of diagnostic mela-
noma. Torso and extremity lesions with this designa-
tionare concerning, astheyare infrequentlyseenand
their biology is uncertain. Complete excision is
recommended in these cases. With lesions from the
aforementioned special anatomic sites, however, the
junctional and dermal atypia is an expected finding,
or site-related, and we do not suggest the need for
additional surgery. We generically term these lesions
nevi with site-related atypia.
not suspected by submitting clinicians. Anatomically,
they may occur anywhere, including on and around
the nipple, and on occasion are submitted in more
general terms as ?chest’, both in male and in female
patients. The so-called ?breast nevus’ (a term used
colloquially in our practice) can be at least suspected
at low power. There is a characteristic garland-like
appearance of loosely interconnecting nested mela-
nocytes (Fig. 3B). The nests are variably sized and
reside along the junction. The melanocytes are en-
larged but uniform. The most reproducible cytologic
feature is the voluminous clear-to-dusty cytoplasm,
thus maintaining an acceptable nuclear:cytoplasmic
ratio (Fig. 3C). Melanocytic atypia spills into single
but maturation to deeper, smaller forms is the rule.
The stromal findings are variable.
Nevi with site-related atypia
Ronglioletti et al. performed an interinstitutional
study on the histologic features of 101 breast nevi
compared with 97 nevi of the torso and extremities to
look at the prevalence of histologically atypical
features in both groups.24Specifically, theyexamined
the presence of asymmetry, lateral circumscription,
lentiginous growth, suprabasal melanocytes, hair
follicle involvement, pleomorphic and confluent
nests, cytologic atypia, stromal reaction and matura-
tion. Using their scoring method, atypical features
were more commonly found in breast nevi than in
their control counterparts. Atypia, stromal response
(papillary dermal fibroplasia) and the presence of
suprabasal melanocytes showed the greatest separa-
tion between the two groups (p ¼ 0.005, 0.005,
Although the impact of age was not specifically
are much more prevalent in young adults than in the
elderly. The role estrogen plays in the biology and
altered histology of breast lesions is intriguing29,30but
yet unfounded. These features are found on breast
Fig. 3. Nevi with site-related atypia, the
special site nevi. Nevi of the breast, flexural
region, scalp and ear that have atypical
histology are often clinically indistinguish-
able from histologically bland nevi and nevi
from other sites. This ear nevus has fuzzy
borders and mild variability in pigmentation
but is not concerning for malignancy (A,
courtesy: Dr Elaine Miller, Dallas, TX). This
breast nevus from a young woman has the
typical growth pattern of the loosely con-
necting variably sized melanocytic nests (B,
breast, 1003). There is junctional and
dermal cytologic atypia with nuclear
enlargement but relatively low nuclear:cyto-
plasmic ratios because of the voluminous
cytoplasm (C, breast, 2003). Atypical flex-
ural nevi share histologic features with
atypical breast nevi. Some lesions have
pleomorphic and confluent melanocytic
nests, with positioning along sides of retia
(D, inguinal, 1003). Other findings include
stromal fibrosis, an irregular nesting pattern
and dermal cytologic atypia (E, umbilical,
1003). This scalp nevus has follicular
involvement and occasional upwardly
migrating cells. The cells are uniformly
enlarged, both intraepidermally and der-
mally (F, scalp, 2003). Asymmetry and poor
lateral circumscription are commonly
observed in ear nevi but are also seen at
other special sites (G, ear, 403). Fibroplasia
and lentiginous growth of melanocytes,
features of nevi with architectural disorder,
are evident in this lesion (H, ear, 1003).
Hosler et al.
lesions of both men and women and are not restricted
to the papillomatous variety of pregnancy,31for now
also been described in so-called flexural sites, or sites
with cutaneous folds, to include axillary, umbilical,
inguinal, antecubital and popliteal fossae, pubic,
scrotal, perineal and perianal locations, and depend-
ing on body habitus, the folds of the neck and
abdomen. Some authors have lumped axillary and
the milk line, i.e. breast and perineal locations,
suggesting that their clinical appearance and histol-
ogy have embryological or hormonal influences.32
This milk line distribution may partly explain our
occasional observation of the histologic equivalent of
a site-related atypical melanocytic nevus arising on
the abdomen. The loose definitions of genital and
flexural anatomic sites between publications may
contribute to their overlap of histologic features.
from flexural sites. One pattern, more often seen in
the axillary and inguinal regions, is papillomatous,
similar to the previously described Unna nevus. This
pattern is characterized by variably sized nests,
positioned along the tips and sides of retia with an
undulating or papillomatous epidermis (Fig. 3D).
Cytologic atypia is mild in these cases and restricted
to junctional and papillary dermal portions of the
nevus. While these features are unusual, melanoma is
not often a serious consideration with this pattern. A
second pattern more closely resembles the atypical
nevi from the breast (see above), showing nesting
irregularities and cytologic atypia along the junction
(Fig. 3E). The atypia is often uniform, not pleomor-
phic. These lesions show atypia in the dermis,
generating more attention with respect to excluding
melanoma. Like their breast counterparts, cellular
pleomorphism, well-developed pagetoid growth,
dermal disorganization and dermal mitoses would
be unusual and cause for concern.
et al. performed an analysis of 40 lesions, primarily
from the axilla (13) and umbilicus (13) but also
including the scrotum (5), mons pubis (5) and perianal
region (2).25Lesions from the vulva and penis were
excluded. They identified 22 (55.5%) lesions with
atypical histology. Their findings show some overlap
with genital nevi, as these lesions also showed pleo-
Of note, all nevi from this subset were described as
having some degree of cytologic atypia. A possible
mechanical etiology was suggested based on these
On the scalp, many different types of nevi have been
nevi with architectural disorder.33,34The scalp has
more recently been added to the list of anatomic sites
with a predilection for benign but histologically
atypical nevi, differing from nevi with architectural
after extracting a subset from adolescents, identified
4 of 39 (10.3%) nevi that appear more closely related
to nevi with site-related atypia than markers for
melanoma.26As opposed to other nevi with site-
related atypia from other anatomic locations, these
scalp lesions were clinically described as atypical and,
interestingly, were not observed in young children or
older adults in this study.
Histologically, these nevi superficially resemble
nevi with architectural disorder, given the common
i.e. large pleomorphic nests with lack of cellular
ridges, follicular involvement, rare suprabasal mela-
nocytes and minimal stromal reactions (Fig. 3F).
The presence of cytologic atypia was not emphasized
in this study but is a consistent feature in our ex-
perience. In this subset of adolescents, none of these
patients had other clinically atypical nevi, developed
atypical nevi with 5–10 years of follow up or had
a relevant family history of atypical nevi or mela-
noma, suggesting these are not precursors or markers
There are two major studies examining the histologic
features of nevi of the auricular region.27,28This
region shows anatomic variability with thin skin and
rich lymphatics on the ear proper and blurring with
isnotsurprisingthatnevi fromon andaround theear
those from the scalp (and by association, breast and
by some considering the ear an acral site (Fig. 3G,H).
Lazova et al. retrospectively reviewed 101 nevi on
and around the ear and evaluated the nevi using 13
histologic criteria.27There were 42 (41.6%) nevi,
which showed atypical histologic features, and these
prevalent atypical features were poor lateral circum-
scription (92.9%), lateral extension of the junctional
component(90.5%), elongation ofrete ridges(85.7%),
retiabridging (76.2%),a dermallymphocyticinfiltrate
Nevi with site-related atypia
(76.2%) and cytologic atypia (61.9%) with a minority,
14.3%, showing pleomorphism.
Saad et al. performed a retrospective analysis of 21
auricular nevi in patients with an age range of 17–76
years.28They identified lack of lateral circumscription
(66.7%) and suprabasal melanocytes (57.1%) in the
majority of the lesions. Some degree of cytologic
atypia was present in 16 (76.2%) cases, with 10
(47.6%) described as at least moderate. In contrast to
nevi from other anatomic special sites, a much higher
proportion of auricular nevi show atypical histologic
The importance in recognizing this subset of
histologically atypical but benign nevi from the ear is
magnified by the implications of diagnosing melanoma
at this site. Melanoma of the ear is considered by some
authors to be an aggressive form, presenting at higher
stage and having lower 5-year survival rates than
melanomas at other sites.35,36Similar to other nevi of
this genre, helpful features for distinction from mela-
noma include lack of a well-developed in situ compo-
nent, overall symmetry and order to the lesion, and
maturation of the dermal component without mitoses.
histologic features may also appear atypical. In
actuality, these nevi have features that are more
versed in the anatomy of the eye. Conjunctival
pigmented lesions include melanoses, keratoses,
nevocellular nevi and rarely blue nevi, spindle cell
and epithelioid cell nevi and melanoma.37–39Nevo-
cellular nevi are fairly common, occur during
adolescence and young adulthood, usually on the
bulbar surface, and are freely mobile (Fig. 4A).
Lesions on other structures of the eye or ones fixed
to underlying structures should be thoroughly exam-
ined for malignancy.
subepithelial, with compound the most common
pattern. The mucosal epithelium is thin and charac-
teristically contains goblet cells. These mucus-secret-
ing cells are not seen in the epidermis and can be
mistaken for pagetoid growth. When a subepithelial
have cytologic atypia. Symmetry, demarcation from
the surrounding stroma and pigment stratification
with melanocytic maturation usually co-exist and are
reassuring findings (Fig. 4B). Epithelial cystic or
pseudoglandular spaces are unique to this site (Fig. 4
C,D). These are seen with regularity and likely
represent epithelial invaginations but appear inti-
mately associated with the melanocytic proliferation.
Mitotic activity is rare to absent.
The number of anatomic sites associated with benign
but histologically atypical nevi has grown to include
umbilicus, antecubital and popliteal fossae, mons
real estate for otherwise ?normal’ nevi.
Fig. 4. Conjunctival nevi. This lesion from
a young woman is on the bulbar conjunctiva,
a common location for conjunctival nevi. It
is symmetric with sharp borders and uniform
pigmentation (A, courtesy: Dr Mark Mazow,
Dallas, TX). This example is largely sub-
epithelial, with symmetry. The anatomic
location is evident by mucus-secreting cells
in the epithelium. The subepithelial compo-
nent is well demarcated from the surround-
ing stroma, is highly cellular and has
pigment stratification (B, 403). These two
separate lesions contain the typical subepi-
thelial cystic structures with goblet cells and
appear intimately associated with the mela-
nocytes (C, 2003, and D, 4003).
Hosler et al.
These sites have gained notoriety in recent years
because of the observation that a small but significant
subset of nevi consistently exhibit atypical features
despite their largely unremarkable clinical appearance.
Their prevalence at these sites appears to exceed
expectations for mere random variation,but the cause
remains unknown. Anatomic arguments for the atyp-
ical features are easier to accept for acral and
conjunctival nevi and likely make a significant contri-
bution, but their presence in only a subset of cases
distinct clinicopathologic entities or represent histo-
seen. Nonetheless, our understanding of their biology
studies showing no conclusive evidence that these nevi
a link to melanoma risk factors.
For clarity, we have divided these nevi into four
groups: acral, genital, special site and conjunctival
nevi. This grouping is made from the relative
frequencies of atypical histologic features described
in these comparative studies from the literature and
groups are somewhat arbitrarily drawn, showing
significant overlap in histologic characteristics as
illustrated conceptually in Fig. 5. While trends are
noted, for example the common observation of
pagetoid growth in acral nevi or the atypical nesting
patterns of genital nevi, there is no individual feature
specific to nevi from any individual site just as no
specific feature allows for a diagnosis of melanoma.
The importance of these nevi lies not with individual
histologic characteristics but with recognition of their
existence and their distinction from melanoma
precursors, markers for melanoma and melanoma
these nevi as premalignant or malignant, there is
potential of greater harm in the underdiagnosis of
melanoma. Until more antigens or molecular iden-
tifiers are discovered to allow for more reproducible
separation of these categories, we must heavily rely
on morphologic features for distinction, and when
in doubt, consultation or, at the very least, complete
excision is recommended.
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Fig. 5. Comparative diagram of nevi with site-
related atypia. This illustration conveys the
relative contributions of five representative
histologic features for acral, genital and
special site nevi and their relation to normal
nevi and melanoma. The area of the pentagon
is directly proportional to the probability for
aggressive biologic behavior.
Nevi with site-related atypia
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