Introduction
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.

Nevoid Melanoma
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 cells.

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 indeterminate.

Small-Diameter Melanoma
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 appreciated.

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.

Small-Cell Melanoma
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.

Spitzoid Melanoma
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.

References

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Table 1
Melanomas simulating nevi

Nevoid melanoma Junctional nested variant Small-diameter melanoma Small-cell melanoma Childhood development in congenital nevi de novo Adults 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

Table 2
Histopathological features employed in the distinction of melanoma from a benign melanocytic lesion.

	MELANOMA	BENIGN LESION
SIZE	≥ 6mm, often ≥ 10mm < 6mm small-diameter melanoma, metastatic melanoma	<5 or 6mm often
SYMMETRY	Usually asymmetrical	Usually symmetrical
CIRCUMSCRIPTION	Often poorly-circumscribed at peripheries with single-cell intraepithelial patterns	Often well-circumscribed with well-defined nests at periphery
HETEROGENEITY	Often heterogenous with two or more cellular phenotypes, or variable cellular populations	Often homogeneous
INTRAEPIDERMAL PATTERNS	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
CELLULARITY, CELLULAR DENSITY	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
TROPISMS	Melanoma cells track along skin appendages, nerves, blood vessels/lymphatics	Usually no tropisms, except congenital nevi, Spitz and pigmented spindle cell nevi
MITOSIS	Likelihood of melanoma increases with absolute Number in dermis and depth or mitoses	Usually not present in dermal component
NECROSIS	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
REGRESSION	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