With any experience with melanocytic lesions it is clear to the pathologist that a proportion of
melanomas histopathologically resemble melanocytic nevi (Table 1). Many of these melanomas are only
diagnosed in retrospect, e.g., after metastases have occurred. The ability of the pathologist to
distinguish such melanomas from nevi varies with experience and the use of rather subjective criteria in
many instances (Table 2). It must be emphasized that a subset of lesions prove to be impossible to
diagnose as clearly benign or malignant and are most appropriately designated as borderline or
biologically indeterminate, until ancillary studies become available to aid in their classification.
In this presentation various types of melanoma simulating nevi will be discussed acknowledging that
many of the categories show overlap and their designation may be rather arbritary.
The term nevoid melanoma probably encompasses a number of entities that have previously or are currently
designated as "minimal deviation" melanoma, small cell melanoma, verrucous (or verrucous and keratotic)
melanoma, spitzoid melanoma, and potentially any melanoma diagnosed in retrospect that may resemble any
type of nevus. Nonetheless the term has primarily been used to identify melanomas resembling closely
common nevi such as compound or dermal nevi. The extent to which such "melanomas" resemble nevi of
course varies, and it can be honestly stated the diagnosis of such lesions is truly in the eyes of the
beholder. Thus the spectrum of such lesions probably ranges from atypical nevi overdiagnosed as melanoma
to lesions that some would consider obvious melanomas. As mentioned above a proportion of such lesions
prove so difficult that they can only be recognized in retrospect.
With respect to clinical features, in the original report by Schmoeckel, Castro, and Braun-Falco
there were no distinctive features observed by the authors that separated NM from other forms of
melanoma. In reality the clinical features may vary enormously.
In order to consider a histopathological diagnosis of NM the author believes that such lesions should
definitely suggest a common nevus at scanning magnification. Thus such lesions may appear reasonably
symmetrical and well-circumscribed. In general, pagetoid spread is not a prominent feature, the tumor
may be mostly dermal, and there may be the perception of some maturation (diminution in cellular and
nuclear sizes with depth). The melanocytes are generally of sufficiently small size to suggest nevus
The immediate features that should raise the possibility of melanoma from this author's experience
include any degree of pagetoid spread, confluence and high cellular density of melanocytes in the dermis,
some cytological atypia, and mitotic figures in the dermal portion of the lesion (the greater the number
and the greater the depth, the higher the probability of melanoma). When such an impression is reached,
the pathologist must scutinize the lesion for the number of abnormal features (Table 2) present and the
extent to which they are present before arriving at a judgement as to whether the lesion is melanoma, not
melanoma, or indeterminate.
Some particular features favoring NM over a nevus include large size, asymmetry, heterogeneity of
melanocytes in the lesion, confluence of melanocytes continuing to the base of the specimen and pari
passu the lack of maturation, cytological atypia of melanocytes in the deepest part of the lesion, easily
found mitoses in the dermal component, and finally mitoses in the deepest portion of the lesion.
Junctional Nested Variants of Nevoid Melanoma
A particular problem is the occurrence of lesions with predominately nested patterns of melanocytes in
the epidermis, a finding that strongly suggests a nevus. Often these lesions demonstrate
well-circumscribed junctional nesting at their peripheries and are fairly symmetrical. Useful findings
suggesting melanoma are thinning and effacement of the epidermis, dermal-epidermal cleavage, the large
size of such nests frequently replacing the epidermis spatially, variation in the size and shape of such
nests, and the propensity to confluence and discohesion of these nests. If one also observes some degree
of pagetoid spread, pronounced cytological atypia, and abnormalities of the dermal portion of the lesion
(Table 2), these are additional factors in supporting an interpretation of melanoma. A proportion of
these proliferations cannot be reliably diagnosed as melanoma or nevus and must be designated as
Since size is a major criterion in diagnosing melanoma versus benign lesions, the occurrence of primary
melanomas with a diameter under 5 to 6 mm may present a major diagnostic challenge. Such melanomas also
may lack other features such as asymmetry, heterogeneity, poor circumscription, etc., that could aid in
confirming a diagnosis of melanoma (Table 2). In any event when faced with the possibility of a melanoma
of unusually small size, one must rely more heavily on other criteria in order to confidently confirm
melanoma versus a benign lesion or one of uncertain nature. The possibility of metastatic melanoma must
always be kept in mind and probably is a major consideration much more commonly than has been
Thus one must search for significant asymmetry, heterogeneity, pagetoid spread, poor circumscription,
confluent discohesive nesting of melanocytes, lack of maturation, prominent cellularity and confluence in
the dermis, dermal mitoses, and cytological atypia to add support for malignancy.
We have previously published a classification of melanomas presenting with a majority (>50%) of
melanoma cells having a size less than or equivalent to nearby basilar keratinocytes (Table 1). In
addition to metastatic melanoma which may have a small-cell phenotype with some frequency, melanomas
developing in congenital nevi or de novo in children and adults or in
markedly sun-damaged skin (often with lentiginous nevus precursors) may be composed of small melanoma
cells resembling small round cell tumors or lymphoma. Although some authors have suggested that this
subtype of melanoma is simply a variant of nevoid melanoma, this author would counter that small-cell
melanomas are fairly distinctive based on the cell size of melanoma cells; nonetheless some probably
would qualify as NM based on a resemblance to a nevus.
The subgroup of small-cell melanomas in children is fairly unique in this author's experience because
of their frequent localization to the scalp, significant Breslow thickness, and highly aggressive
course. Histologically, these tumors contain a significant component of relatively small cells with
round or oval nuclei and generally scant cytoplasm, usually disposed in sheets. The general impression
is a monomorphous population of cells, suggesting lymphoma, a small round-cell tumor, or a melanocytic
nevus. In general, the nuclei exhibit some clumping of chromatin and hyperchromatism. The amount of
cytoplasm is minimal or a small rim of eosinophilic, bluish, or clear material. These melanomas may
display a papillomatous or verrucous epidermal surface, resembling a papillomatous nevus, frequently with
highly cellular aggregates of cells filling the dermal papillae of the verrucous processes.
Some of these melanomas may have intra-epidermal components or be entirely dermal. The
intra-epidermal components may show variable basilar proliferation of melanocytes with no evidence of
pagetoid spread. This intraepidermal pattern may be minimal in the "verrucous" melanomas and
insufficient for conventional melanoma in-situ.
SCM developing in markedly sun-damaged skin of adults are often associated with atypical lentiginous
nevus precursors. Clinically these lesions do not seem to differ significantly from other melanomas
developing in adults. They are thus common on the backs of (older men) and the lower extremities of
women and often are at least 1 cm in diameter. Histologically, they are characterized by small melanoma
cells that seem to vary little in size and shape but nonetheless show some pleomorphism and
hyperchromatism. There is usually pagetoid spread of these small cells in the context of an epidermis
that is frequently thinned and effaced. In many instances there is a lentiginous proliferation of
melanocytes and an associated lentiginous nevus. The invasive component may be comprised of nests of
monomorphous cells suggesting a nevus; however, cytological atypia, deep melanin synthesis, and lack of
maturation are commonly present. In this author's experience mitoses are often few in number or absent
in the dermal component.
If nevoid melanomas constitute a poorly defined group of lesions, then "Spitzoid" melanomas are even a
less coherent group. The reason for the latter conclusion is that Spitz tumors and melanoma per se share
many features in common and a percentage of cases clearly cannot be categorized as either Spitz tumor or
melanoma. Thus melanomas classified as Spitzoid will range between Spitz tumors misdiagnosed as melanoma
and lesions some observers would characterize as typical melanomas. The largest proportion of lesions
will include atypical Spitz tumors, proliferations that occupy an indeterminate category and display
Spitz-like features, and finally melanomas with Spitz-like features, some of which are diagnosed only
after metastasis. The latter group includes rare tumors reported in the literature as metastasizing
Spitz tumors. In this author's experience the latter group of lesions generally have Spitz-like
features, fall into in a borderline category, and require conservative management and follow-up. Such
lesions are usually of large size (often >1 cm), may be ulcerated, demonstrate involvement of the deep
reticular dermis or subcutis, show confluent sheets or aggregates of melanocytes, and have mitoses in the
dermal component. We have introduced a grading protocol that may be utilized to assess atypical Spitz
tumors in children and adolescents for their metastatic potential.
Spindle Cell Melanoma of Sun-Exposed Skin
There are a group of melanomas developing in sun-exposed skin that may closely mimic pigmented spindle
cell nevi (PSCN) and some closely related lesions with Spitz-like features. These melanomas usually
originate from lentiginous melanomas (so-called lentigo maligna variants) of markedly sun-damaged skin.
The most common location in this author's experience is the ear. The striking resemblance to PSCN and
Spitz tumors is based on the presence of fairly uniform and slender pigmented spindle cells or somewhat
larger plump spindle cells that are arranged in intraepidermal fascicles. Such lesions may be reasonably
well-circumscribed and symmetrical. In order to diagnose melanoma one must try to find other abnormal
features including some degree of pagetoid spread, large junctional nests or fascicles, and convincing
cytological atypia. A percentage of lesions will fall into an indeterminate category and should be
managed as melanoma.
Blue Nevus-Like Melanoma (Malignant Blue Nevus)
There has been recognition with increasing frequency of melanomas, both primary (malignant blue nevi
[MBN]) and metastatic, that resemble benign blue nevi. Although some malignant melanomas resembling blue
nevi have straighforward features of malignancy, others are diagnosed with difficulty or only after
metastasis or having clinical information. A particular problem is the concept of atypical cellular blue
nevi (ACBN) and their distinction (or lack of distinction from melanoma). At present criteria for ACBN
are poorly defined and fail to distinguish a proportion of such lesions from melanoma. Criteria
generally have included any number of the following: large size often >1 or more cm, asymmetry,
infiltrative margins, cytological atypia, 1-2 mitoses/10 high power fields, focal necrosis, and
inflammation. It is clear that the greater the number of abnormal features, the greater the likelihood
of malignancy. Nonetheless a subset of lesions may suggest a benign tumor based on features such as
small size, subtle or low-grade atypia, lack of necrosis, and low mitotic rate. One must rely on other
factors that increase concern such as older age of the patient, location such as the scalp, any degree of
atypia or mitotic activity, or history of recurrence.
It has recently been clearly documented that metastatic melanoma may rarely mimic ordinary blue
nevus. Features such as asymmetry, cytological atypia, mitoses, and necrosis should raise concern for
about metastatic melanoma along with critical clinical information.
Epidermotropic Metastatic Melanoma
Metastatic melanoma may not only mimic primary melanoma but also various types of melanocytic nevi
including banal compound and dermal nevi, atypical ("dysplastic") nevi, blue nevi (see above), pigmented
spindle cell nevi, and Spitz tumors. The initial impression at scanning magnification may suggest a
benign nevus based often on the small size of the lesion and in many cases sharp circumscription,
symmetry, and even some maturation. However at higher magnification one can usually detect a
monomorphous appearance of melanocytes; high cellular density and confluence of melanocytes; cytological
atypia as exemplified by nuclear pleomorphism, hyperchromatism of a proportion of nuclei, and easily
found nucleoli; and usually some number of mitoses. Although not always present, the intraepidermal
component may be very limited. Furthermore, the diameter of the dermal component of the lesion may be
greater than that of the intraepidermal portion of the lesion.
- Barnhill RL. The Pathology of Melanocytic Nevi and Malignant Melanoma. Butterworth-Heinemann,
- Schmoeckel C, Castro CE, Braun-Falco O. Nevoid malignant melanoma. Arch Dermatol Res
- McNutt NS, Urmacher C, Hakimian et al. Nevoid malignant melanoma: Morphologic patterns and
immunohistochemical reactivity. J Cutan Pathol 1995;22:502-517.
- Kossard S, Wilkinson B. Small cell (naevoid) melanoma: A clinicopathologic study of 131 cases.
Austral J Dermatol 1997; 38 (Suppl.):S54-S58.
- Kamino H, Kiryu H, Ratech H. Small malignant melanomas: Clinicopathologic correlation and DNA ploidy
analysis. J Am Acad Dermatol 1990;22:1032-1038.
- Gonzalez A, West A, Pitha J, Taira J. Small-diameter invasive melanomas: clinical and pathologic
characteristics. J Cutan Path 1996;23:126-132.
- Hendrickson MR, Ross JC. Neoplasms arising in congenital giant nevi: Morphologic study of seven
cases and a review of the literature. Am J Surg Pathol 1981;5:109–35.
- Barnhill RL, Flotte TJ, Fleischli M, Perez-Atayde A. Cutaneous melanoma and atypical Spitz tumors in
childhood. Cancer 1995;76:1833-1845.
- Spatz A, Ruiter D, Hardmeier T, et al. Melanoma in childhood: an EORTC-MCG multicenter study on the
clinico-pathological aspects. Int J Cancer 1996;68:317-324.
- Spatz A, Barnhill RL. Small cell melanoma in childhood. Pathology Case Reviews 4:102-106, 1999.
- Spitz S. Melanomas of childhood. Am J Pathol 1948;24:591-609.
- Reed RJ, Ichinose H, Clark WH Jr, Mihm MC Jr. Common and uncommon melanocytic nevi and borderline
melanomas. Semin Oncol 1975;2:119–47.
- Busam KJ, Barnhill RL. Spitz nevus and Spitzoid melanoma. In: Kirkham N, Lemoine N. Progress in
Pathology, Vol. 2. Churchill Livingstone, 1995.
- Barnhill RL, Argenyi ZB, From L, Glass LF, Maize JC, Mihm MC Jr, Rabkin MS,Ronan SG, White WL,
Piepkorn M. Atypical Spitz nevi/tumors: lack of consensus for diagnosis, discrimination from melanoma,
and prediction of outcome. Hum Pathol. 1999;30:513-20.
- Spatz A, Calonje E, Handfield-Jones S, Barnhill RL. Spitz tumors in children: A grading system for
risk stratification Arch Dermatol 135:282-289, 1999.
- Smith K, Skelton H, Lupton G, Graham J. Spindle cell and epithelioid cell nevi with atypia and
metastasis (malignant Spitz nevus). Am J Surg Pathol 1989;13:931-939.
- Tran TA, Carlson JA, Basaca PC, Mihm MC.Cellular blue nevus with atypia (atypical cellular blue
nevus): a clinicopathologic study of nine cases. J Cutan Pathol. 1998 May;25:252-258.
- Busam KJ. Metastatic melanoma to the skin simulating blue nevus. Am J Surg Pathol. 1999;23:276-82.
- Abernethy JL, Soyer HP, Kerl H, Jorizzo JL, White WL. Epidermotropic metastatic malignant melanoma
simulating melanoma in situ. A report of 10 examples from two patients. Am J Surg Pathol. 1994
Melanomas simulating nevi
- Nevoid melanoma
- Junctional nested variant
- Small-diameter melanoma
- Small-cell melanoma
- development in congenital nevi
- de novo
- development in congenital nevi
- -de novo
- development in markedly sun-damaged skin
- mucosal melanoma
- Spitzoid melanoma
- Metastasizing Spitz tumor
- Spindle cell melanoma
- Blue-nevus like melanoma (malignant blue nevus)
- Epidermotropic metastatic melanoma
Histopathological features employed in the distinction of melanoma from a benign melanocytic
BENIGN LESION |
≥ 6mm, often ≥ 10mm < 6mm small-diameter melanoma, metastatic melanoma ||
<5 or 6mm often |
Usually asymmetrical ||
Usually symmetrical |
Often poorly-circumscribed at peripheries with single-cell intraepithelial patterns ||
Often well-circumscribed with well-defined nests at periphery |
Often heterogenous with two or more cellular phenotypes, or variable cellular populations ||
Often homogeneous |
Single-cells reaching confluence along dermal epidermal junction; loss of rete-oriented pattern; cells scattered in pagetoid pattern; irregular and haphazard nesting; discohesive, large nests ||
Single-cells on elongated rete ridges little or no pagetoid spread regular, uniform nesting, cohesive, relatively small nests |
DERMAL PATTERNS ||
Confluence of cells with little or no maturation and disregard of stroma ||
Regular spacing and maturation with depth |
High cellular density, crowding Of cells ||
Lower cellular density |
MELANIN SYNTHESIS ||
Variable or no loss of synthesis with depth ||
Loss of synthesis with depth |
EPIDERMAL REACTION ||
Hyperplasia, thinning, ulceration; variable ||
Often uniform |
Melanoma cells track along skin appendages, nerves, blood vessels/lymphatics ||
Usually no tropisms, except congenital nevi, Spitz and pigmented spindle cell nevi |
Likelihood of melanoma increases with absolute Number in dermis and depth or mitoses ||
Usually not present in dermal component |
Single cells or confluent necrosis ||
Usually not present |
HOST RESPONSE ||
Often band-like infiltrates with superficially invasive melanoma; Diminished inflammation with increasing tumor thickness ||
Little or no inflammation, perivascular infiltrates, band-like infiltrates in halo nevi |
Often all stages: early, intermediate, late; multifocal common in thin melanoma; often asymmetrical ||
Uncommon, often symmetrical |
CYTOLOGICAL FEATURES |
Uniform atypia epithelioid cells: Abundant pink granular or "dusty" cytoplasm; nuclear enlargement; nuclear pleomorphism; dispersed chromatin with prominent nucleoli; hyperchromatism. |
Spindle or cuboidal cells: often retraction of cytoplasm and high nuclear to cytoplasmic ratios; nuclear enlargement; pleomorphism; hyperchromatism
Small cells: often uniformity of cell type; pleomorphism; hyperchromatism
Little or no, or variable atypia |