—  SHORT COURSE #31  —

Precursors To Melanoma And The Problematic Nevomelanocytic Proliferation

Section 3 - Common Acquired Nevus and Other Benign Acquired Nevi

Neil Crowson, MD
Cynthia M. Magro, MD
Martin C. Mihm, Jr., MD


Introduction

Nevi are circumscribed anomalies of embryonic development that may be present at birth or may appear later during life. The term "nevus" originates from the Latin word for maternal impression; many authors consider it to be a synonym for "hamartoma" (Happle, 1995). Melanocytic nevi are collections of pigment-producing cells of melanocytic origin present in the epidermis, the dermis or both. Most nevi are acquired; less than 1% are considered to be congenital. Melanocytes are pigment-synthesizing cells normally confined to the epidermis and manifesting prominent dendritic processes; they usually do not divide. The constituent cell of the nevus is a pigment-synthesizing melanocyte, but differs from its normal counterpart by virtue of a nondendritic morphology, by having the capability for division, and by virtue of representing, in at least some cases, a clonal proliferation (Robinson et al., 1998). Using polymerase chain reaction technology to determine polymorphism of X-linked genes it has been shown that unlike melanomas, which are monoclonal, benign common acquired nevi are typically polyclonal, perhaps proof that benign nevi are hamartomata (Harada et al., 1997). The cell of origin of the nevus may be cutaneous melanocytic stem cells termed melaonoblasts, cells within nerve endings in the dermis, or mutated melanocytes that have developed the ability to proliferate (Robinson et al., 1998). One melanocyte provides melanin for approximately 5 to 20 keratinocytes.

Nevi can be classified by their onset (congenital or acquired) and by their microscopic location in the skin (junctional when confined to the epidermis, compound when involving the epidermis and dermis, or dermal when confined to the dermis). Nevi can also be classified by architecture, i.e., Miescher's nevus, Unna's nevus, or the dysplastic nevus.

Clinical features
Common acquired nevi show, in most instances, an evolutionary pattern of development, presenting as a small, flat, tan lesion 1.0–2.0 mm in diameter, which slowly assumes a dimension of up to 4.0–5.0 mm. As it progresses, it becomes slightly raised, leading to a central papule that is usually tan, with a dark brown peripheral rim. The central elevation is held to reflect the acquisition of a dermal population derived from migration of nevus cells from the epidermis to the dermis (Lund and Stobbe, 1949; Maize and Foster, 1979; Stegmaier and Montgomery, 1953). Later, the nevus becomes a papule or nodule that may be dark blue, light tan or flesh-colored. Some nevi present as flesh-colored papules from their onset that apparently are dermal and take origin in hair follicles. Common acquired nevi manifest a cephalo-caudal spread (Stegmaier and Becker, 1960; Nichols, 1973), and are thus most common on the head and neck.

The average white person will have from 20 to 100 benign acquired melanocytic nevi with the incidence climbing in proximity to the equator; there is a clear relationship to sun exposure (Gallagher et al., 1990). The peak incidence of new nevi is in the second decade of life. The number of nondysplastic nevi is an independent risk factor for the development of melanoma; the average number of nondysplastic melanocytic nevi 2 mm or greater in diameter is 97 for melanoma patients and 36 for control subjects. The relative risk was 4.4 (p = 0.01) for 26 to 50 nevi, 5.4 (p = 0.008) for 51 to 100 nevi, and 9.8 (p = 0.001) for more than 100 nondysplastic melanocytic nevi (Holly et al., 1987).

Rarely, nevi may appear as a disseminated eruption resembling a lichenoid rash. Such cases have occurred in apparently young healthy adults with no known internal organ anomalies (Eady et al., 1977).

Histology
A melanocytic nevus is composed of nevomelanocytes that derived from neural crest migrants to the skin, and are classified as type A, type B, or type C (Masson, 1951; Mihm et al, 2001) cells located in the epidermis and/or dermis, in cohesive nests or as singly disposed cells. The type A, or epithelioid nevus cell has abundant coarsely melanized cytoplasm that may be more intensely melanized around a nucleus containing a discrete nucleolus. The cells are found with the epidermis and superficial dermis. The type B or lymphocyte-like nevus cell is a round to cuboidal, nonpigmented cell with a round hyperchromatic nucleus containing an inconspicuous nucleolus and with a scant rim of cytoplasm. They are slightly larger than mature resting small lymphocytes or mast cells, i.e., in the 8–10 μm range. The type C or neuroid nevus cell has a spindled morphology with fibrillary elongate cytoplasmic processes reminiscent of a Schwann cell (Lund, 1949; Maize and Foster, 1979). Senescent change may be observed in the dermal component and can be misinterpreted as melanocytic dysplasia. The hallmarks of senescent atypia are multinucleation with close nuclear apposition and hyperchromasia with complete loss of nuclear detail that is most unlike the hyperchromasia of dysplasia. These senescent changes are most apparent centrally. Pleomorphism may be striking in different portions of the lesion, but in any one high power field there is uniformity. Balloon cell change is also thought to represent a senescent phenomenon ultrastructurally characterized by vacuolar degeneration of melanosomes. The prototypic common acquired nevi initiates as a lentiginous proliferation of single cells dispersed along the basal layer of epidermis, forming tan-colored or dark macules, sometimes with an irregular contour. These then manifest accumulations of cells as discrete junctional nests, i.e. the junctional nevus. Migration of nevus cells into the dermis then forms a compound nevus, the clinical concomitant being a palpable lesion. Complete nevus cell migration into the dermis forms a dermal nevus, manifested clinically as a palpable lesion with a tan or pale color.

The junctional nevus demonstrates discrete intraepidermal nests of nevomelanocytes (Maize and Foster, 1979) localized to the tips of slightly hyperplastic rete ridges. Pagetoid spread of nevomelanocytes may occur, especially in children's nevi or in specific anatomic locations such as acral sites, but is not the dominant form of melanocytic growth is usually orderly, emanating from basal nests and thus accentuated overlying retia. This directed pagetoid migration yields discrete columns of melanin in the stratum corneum. The junctional nevus nests may be associated with a lentiginous proliferation of nevus cells that by definition are arranged as single cells along the basal layer and do not extend at lateral edges beyond the nested component. This lesion is termed the lentiginous junctional nevus. Mirror-image symmetry is the rule. An individual section may impart an apparent intradermal location to a junctional nest, whose true epidermal residence is only demonstrable by serial sections (Kopf and Andrade, 1960).

The cells comprising the nests are cohesive with ample cytoplasm and short dendrites that may extend between keratinocytes. The nuclei are round to oval, with delicate margins containing finely dispersed chromatin and small, amphophilic nucleoli. Five or more such nevomelanocytes define a junctional thθque or nest (Mihm et al, 2001). The cells within the nests are monotonous in size and shape and have either a type A or a type B morphology. There is variable melanization with some cells being devoid of pigment and others manifesting abundant but uniform cytoplasmic pigmentation. Heterogeneity of melanization is mainly a feature of dysplastic melanocytic proliferations, and is characterized by coarse, variably sized melanin granules. Mitoses are rare.

The stroma beneath the junctional nests may exhibit mild periretal fibroplasia but not the patterned lamellar or concentric eosinophilic fibrosis seen in dysplastic nevi, nor is there inflammation or increased vascularity. Halo junctional nevi, in contrast, manifest a brisk lymphohistiocytic inflammatory response that is symmetrical; as it subsides, a uniform pattern of delicate dermal fibroplasia with neovascularization occurs.

In compound nevi, melanocytes are found in both the epidermis and dermis; the intraepidermal component of the benign acquired nevus usually is delimited by the lateral boundaries of the subjacent dermal component. Any extension beyond the dermal domain exhibits bilateral, or mirror-image, symmetry. The size of the dermal nests are usually similar to that of the intraepidermal nests. The nests are encased in a delicate stroma, and may assume a coalescent bandlike disposition but are still discernible as separate nests as opposed to an expansile nodule. The dermal component typically stops at the papillary-reticular dermal junction, without extension into the reticular or adventitial dermis, and in adulthood a stromal proliferation occurs at the base of the nevus and separates it from the papillary-reticular dermal junction. Mast cellsare then often admixed and mucin may be observed.

The intraepidermal cytology is identical to that described for the prototypic benign common acquired junctional nevus, but the dermal component has a variable morphology reflective of progressive maturation of cell type toward the base of the lesion. The superficial component comprises type A cells, while type B cells are often situated at the base and may be admixed with type C, or neurotized, nevus cells. Lipoid phanerosis, or infiltration by fat cells, is a frequent concomitant of this involuting phase. Pleomorphism of the dermal component may be observed as a random phenomenon thought to represent senescent change rather than dysplasia.

The dermal nevus has, by definition, no intraepidermal component; in practice we allow up to 2 junctional theques. The features described for the dermal component of the compound nevus apply to the dermal nevus. Maturation may be associated with striking neurotization including structures resembling Meissner corpuscles, Verocay bodies, and nerve twigs, and with senescent atypia; some neurotized nevi are indistinguishable from neurofibromata althouth the advenitia around hair follicles and eccrine ducts is spared (Mihm et al, 2001). Mucinosis with mast cell hyperplasia may be seen (Aso et al., 1988). Fibrous involution is another senescent phenomenon, particularly in nevi of the midface, and is the likely derivation of the fibrous papule and perifollicular fibroma (Stegmaier, 1959). Formation of pseudovascular spaces may be seen, due in part to a fixation artifact, whereby stroma manifests a cleft caused by shrinking of the nevus cells. Mitoses are rarely observed unless there has been an inciting factor such as trauma; the presence of more than three mitoses in one section should prompt the study of multiple levels to exclude nevoid melanoma. In truncal nevi one may see an eosinophilic homogenous collagen band separating the epidermis from the nevus. Dermal nevi may be assocated with an intraepidermal single-cell proliferation of plump melanocytes, most often disposed in a lentiginous array. This proliferation is focal, is most conspicuous centrally and is held to represent a photoactivation effect in facial nevi in particular. We incorporate microscopic descriptions in reports of melanocytic neoplasms to describe such findings but doubt that it heralds a significant risk of malignant degeneration.

References
  1. Aso M, Hashimoto K, Eto H, Fukaya T, Ishihara M, Shimao S, Shimizu Y. Expression of Schwann cell characteristics in pigmented nevus. Immunohistochemical study using monoclonal antibody to Schwann cell associated antigen. Cancer 1988;62: 938–943.

  2. Eady RA, Gilkes JJ, Jones EW. Eruptive naevi: report of two cases, with enzyme histochemical, light and electron microscopical findings. Br J Dermatol 1977;97: 267–278.

  3. Gallagher RP, McLean DI, Yang CP, et al. Anatomic distribution of acquired melanocytic nevi in white children. A comparison with melanoma: the Vancouver Mole Study. Arch Dermatol 1990;126:466–471.

  4. Happle R. What is a nevus? A proposed definition of a common medical term. Dermatology 1995;191: 1–5.

  5. Harada M, Suzuki M, Ikeda T, Kaneko T, Harada S, Fukuyama M. Clonality in nevocellular nevus and melanoma: an expression-based clonality analysis at the X-linked genes by polymerase chain reaction. J Invest Dermatol 1997;109: 656–660.

  6. Holly EA, Kelly JW, Shpall SN, Chiu SH. Number of melanocytic nevi as a major risk factor for malignant melanoma. J Am Acad Dermatol 1987;17: 459–468.

  7. Kopf AW, Andrade R. A histologic study of the dermoepidermal junction in clinically "intraepidermal" nevi, employing serial sections: I. Junctional theques. Ann NY Acad Sci 1963;100: 200–222.

  8. Lund HZ, Stobbe GD. The natural history of the pigmented nevus. Factors of age and anatomic location. Am J Pathol 1949;25: 1117–1155.

  9. Maize JC, Foster G. Age-related changes in melanocytic naevi. Clin Exp Dermatol 1979;4:49–58.

  10. Masson P. My conception of cellular nevi. Cancer 1967;51;4: 9–38.

  11. Mihm MC, Jr, Crowson AN, Magro CM. The nondysplastic acquired nevi: common acquired nevus and other benign acquired nevi. In: Crowson AN, Magro CM, Mihm MC, Jr. The melanocytic proliferations : a comprehensive textbook of pigmented lesions. New York : John Wiley and sons, 2001:73-96.

  12. Robinson WA, Lemon M, Elefanty A, et al. Human acquired naevi are clonal. Melanoma Res 1998;8: 499–503.

  13. Stegmaier OC, Montgomery H. Histopathologic studies of pigmented nevi in children. J Invest Dermatol 1953;20: 51–62.

  14. Stegmaier OC, Becker SW Jr. Incidence of melanocytic nevi in young adults. J Invest Dermatol 1960;34:125–129.

  15. Unna PG. Naevi and naevo-carcinoma. Berl Klin Wochenschr 1893;30: 14.

Other Acquired Benign Nevi

Balloon cell nevus
First described by Meischer in 1935 (Meischer, 1935), the balloon cell nevus does not deviate clinically in appearance from other common acquired nevi, manifesting as a dome-shaped, flesh-colored papule, typically less than 6 mm in diameter (Schrader and Helwig, 1967; Goette and Doty, 1978), most often in patients under the age of 30 and mainly in the head and neck.

Histology
Diagnosis hinges on the presence of so-called balloon cell change involving more than 50% of dermal nevomelanocytes. Focal balloon cell change, that is, involving less than 50% of the cellular infiltrate, occurs in 2% of nevi. In most cases the background lesion is a common acquired nevus of compound or dermal subtype (Schrader and Helwig, 1967) but one may rarely see this change in a dysplastic nevus (Smoller et al., 1991). The balloon cells manifest abundant clear, finely vacuolated cytoplasm and small hyperchromatic nuclei with a scalloped contour. Multinucleation may be observed. Electron microscopy reveals the cytoplasmic vaculoation to reflect vacuolar degeneration and confluence of melanosomes (Hashimoto and Bale, 1972). Lysosomes containing cytoplasmic remnants are present . Hence, a balloon cell nevus appears to be a distinctive morphologic subtype of the senescent/involuting nevus. An inflammatory infiltrate can be observed (Cote et al., 1986). The main differential diagnostic consideration is that of balloon cell melanoma; the distinction rests on the cytology. In balloon cell melanoma, the majority of cells manifest pleomorphism, with the nuclei appearing large irregularly-distributed chromatin, mitoses and necrosis.

References
  1. Cote J, Watters AK, O'Brien EA. Halo balloon cell nevus. J Cutan Pathol 1986;13:123–127.

  2. Goette DK, Doty RD. Balloon cell nevus. Summary of the clinical and histologic characteristics. Arch Dermatol 1978;114: 109–111.

  3. Hashimoto K, Bale GF. An electron microscopic study of balloon cell nevus. Cancer 1972;30: 530–540.

  4. Miescher G. Umwandlung von Naevuszellen in Talgdrusenzellen? Arch Derm Syph 1935;42: 1265–1273.

  5. Schrader WA , Helwig EB. Balloon cell nevi. Cancer 1967;20:1502–1514.

  6. Smoller BR, Kindel S, McNutt NS, Gray MH, Hsu A. Balloon cell transformation in multiple dysplastic nevi (letter). J Am Acad Dermatol 1991;24(2Pt1): 290–292.


Cockarde Nevus
The cockarde nevus is characterized by a distinctive variegated pattern of pigmentation. Specifically, the central portion is uniformly pink or darkly pigmented, whereas the periphery has a stippled or striped pattern of pigmentation (Guzzo et al., 1988).The differential diagnosis clinically is target blue nevus, halo nevus, and, rarely, melanoma.

The center of the Cockarde nevus manifests a junctional or compound nevus , whereas the periphery is composed of variably pigmented junctional thθques.

Reference
  1. Guzzo C, Johnson B, Honig P. Cockarde nevus: a case report and review of the literature. Pediatr Dermatol 1988;5: 250–253.


Nevus Spilus
The term nevus spilus was introduced in 1978 by Stewart et al. for a well-defined patch of uniform brown pigmentation that histologically resembles an ephilus but is distinguished mainly by its larger size (Stewart et al., 1978). Others have used the term to denote the entity of speckled lentiginous nevus, characterized by a light brown macule on which are superimposed darker macular or papular lesions. The prevalence of nevus spilus is said to be 2% (Kopf et al, 1985); there is no sex predilection. It is most often seen on the trunk and may manifest a dermatomal distribution. The lightly-pigmented foci are consistent with a lentigo simplex, while the superimposed darker spots have features of a junctional or compound nevus of common acquired or dysplastic subtype and, rarely, a dermal Spitz nevus or a blue nevus(Akasaka et al., 1993; Hoffman et al., 1994); the combined nevus of blue nevus and nevus spilus subtypes is also called Kawamura's nevus.

Reports of malignant melanoma arising in lesions of nevus spilus have led to concerns regarding its malignant potential (Weinberg et al., 1998). By 1997, 17 patients had been reported in the literature; the most common type is a superficial spreading melanoma (Grinspan et al., 1997). In some such cases, features of a dysplastic nevus were present, but most had a junctional nevus morphology. The patients were white women aged 35-56 years whose melanomas arose on the basis of prexisting congenital nevi spilus. The lesions ranged in size from 2 to 10 cm. Our current recommendation is thus to completely excise all lesions of nevus spilus that are of congenial onset. Alternatively, for large, atypical and congenital lesions, one may propose periodic examination using baseline photography and selective excision for atypical elements Nevus spilus may be a cutaneous manifestation of a phacomatosis (Du et al., 1998).

Histology
In those lesions that have uniform pigmentation, the histology is indistinguishable from a lentigo simplex, showing slight elongation of retia manifesting increased pigmentation of basilar keratinocytes and a variable increase in bland melanocytes confined to a lentiginous distribution. Such lesions also must be distinguished from a cafι au lait spot of neurofibromatosis, in which the density of melanocytes along the dermoepidermal junction is higher than is characteristic of nevus spilus; giant melanosomes can be observed in both cafι au lait and nevus spilus (Takahashi, 1976). Agminated blue and Spitz nevi with an overlying lentigo simplex-like epidermal alteration are reported (Kiene et al., 1995; Betti et al., 1997).

References
  1. Akasaka T, Imamura Y, Kon S. Multiple agminated juvenile melanoma arising on a hyperpigmented macule. J Dermatol 1993;20: 638–642.

  2. Betti R, Inselvini E, Palvarini M, Crosti C. Agminated intradermal Spitz nevi arising on an unusual speckled lentiginous nevus with localized lentiginosis: a continuum?. Am J Dermatopathol 1997;19: 524–527.

  3. Du LC, Delaporte E, Catteau B, Destee A, Piette F. Phacomatosis pigmentovascularis type II. Eur J Dermatol 1998;8: 569–72.

  4. Grinspan D, Casala A, Abulafia J, Mascotto J, Allevato M. Melanoma on dysplastic nevus spilus. Int J Dermatol 1997;36: 499–502.

  5. Hwang SM, Choi EH, Lee WS, Choi SI, Ahn SK. Nevus spilus (speckled lentiginous nevus) associated with a nodular neurotized nevus. Am J Dermatopathol 1997;19: 308–322.

  6. Hofmann-Wellenhof R, Soyer HP, Smolle J, Kerl H. Spitz's nevus arising on a nevus spilus. Dermatology 1994;189: 265–268.

  7. Kiene P, Brodersen JP, Folster-Holst R. "Blue" variant of naevus spilus. Hautarzt 1995;46:349–51

  8. Kopf AW, Levine LJ, Rigel DS, Friedman RJ, Levenstein M. Prevalence of congenital-nevus-like nevi, nevi spili, and cafe au lait spots. Arch Dermatol 1985;121: 766–769.

  9. Stewart DM, Altman J, Mehregan AH. Speckled lentiginous nevus. Arch Dermatol 1978;114: 895–896.

  10. Takahasi M. Studies on cafe au lait spots in neurofibromatosis and pigmented macules of nevus spilus. Tohoku J Exp Med 1976;118: 255–273.

  11. Weinberg JM, Schutzer PJ, Harris RM, Tangoren IA, Sood S, Rudolph RI. Melanoma arising in nevus spilus. Cutis 1998;61: 287–289.


Compound and Dermal Nevi with Mitotic Activity
Although mitoses are not typically seen in the dermal component of common acquired compound or dermal nevi and are infrequent within the intraepidermal component, we have all seen cases of completely benign-appearing nevi in which mitoses are identified. Mitoses should alert the pathologist to the possibility of a nevoid or minimal deviation melanoma. However, in an otherwise clinically and histologically banal-appearing nevus, mitotic activity should not be used as the sole criterion for rendering a diagnosis of melanoma. We then comment that no other features warranting a diagnosis of melanoma are present, i.e., there is no inherent dysplasia of the dermal component, conspicuous nucleolation of nevus cells at the base of the lesion is not observed, mitoses are typical and infrequent (i.e., no more than 3 mitoses in one section, and an expansile nodule is not observed. Multiple levels are performed through the block to assess for such features, and if any of the aforesaid are observed, we feel that the biological behavior cannot be predicted. A conservative reexcision of such cases is advised if they are not completely excised.

Effects of Exogenous or Endogenous Hormones on Nevocellular Nevi
Nevi become larger and darker during pregnancy, a phenomonon that correlates histologically to an increase in junctional melanocyte proliferation with an increase in cell size, increased chromatin content and conspicuous nucleolation. However, the chromatin remains evenly distributed, the N/C ratios are maintained and there is uniformity with respect to nuclear shape and size, particularly within a specific junctional nest. The degree of atypia and hyperplasia attributed exclusively to estrogen effect is mild, thus, marked atypia in a melanocytic lesion biopsied during pregnancy should not be so attributed. In those women who are pregnant or who are in the immediate postpartum period or those who ingest oral contraceptives, there is a striking increase in the number of estrogen- and progesterone-binding cells similar to those observed in melanomas and melanoma precursor lesions. Thus, significant atypia in melanocytic lesions excised from pregnant patients should not be discounted as a reactive estrogen effect; rather, it could unmask inherent melanocytic dysplasia induced by the altered hormonal milieu (Mihm et al, 2001). The lesion must be examined for standard cytologic and architectural features associated with dysplasia: significant variability of nuclear size and shape, irregular distribution of chromatin, and increased N/C ratios are hallmarks of dysplasia and cannot be attributed to a reactive phenomenon. prominent pagetoid growth and effacement of architecture may indicate severe melanocytic dysplasia.

Differential Diagnosis of the Common Acquired Nevus and Its Distinction from the Dysplastic Nevus
The main diagnostic dilemma is the distinction of the Acquired compound nevus from a dysplastic nevus. One hallmark of dysplastic nevi is the presence of an asymmetric shoulder comprising an intraepidermal proliferation of melanocytes extending beyond a preexisting dermal component. A similar phenomenon is seen in congenital and some otherwise banal acquired nevi, but in that setting, the intraepidermal component may manifest a lentiginous, a nested, or a mixed lentiginous and nested pattern, but is a symmetrical proliferation seen on either side of the dermal component without cytologic atypia, in contrast to the asymmetry and cytologic atypia characteristic of the shoulder in dysplastic nevi. Observation of the quality and location of the nests is an important diagnostic aid, as nests in dysplastic nevi are randomly disposed between and along the sides of the retia with variation in size and shape and with at least focal fusion of adjacent nests. Benign nevi display an orderly nesting pattern confined to the tips of the retia without confluent growth between adjacent nests. Nests in the benign nevus are generally cohesive, of similar size, and composed of monomorphous small bland cells.

Congenital nevi and the risk of malignant transformation
Congenital pigmented lesions are identified in approximately 1% of newborn infants. While the overwhelming number of these lesions are small 3-4 mm, a rare number may be several centimeters in size. These lesions have been designated giant congenital nevi or garment congenital nevi, the latter term used for lesions greater than 20cm in diameter, or lesions that cover the entire trunk or limb. Lesions less than giant in size are considered as intermediate when measuring 1.5 to 5.0 cm and small when less than 1.5 cm. The giant congenital nevus has a bimodal peak of incidence of melanoma, the first occurring in the first 5 years of life and the 2nd occurring from puberty into adulthood. Small congenital nevi, on the other hand, are not reported to undergo malignant transformation during the first 2 decades of life, but the risk of malignancy appears during late adolescence and the incidence progressively rises in adult life. In one prospective series of 160 patients with large congenital nevi, all 3 patients who developed melanomas did so in extracutaneous sites: two in the central nervous system and one in the retroperitoneum (Bittencourt et al, 2000). The 5-year cumulative risk for developing melanoma was 2.3% and the relative risk was 101 (Bittencourt et al, 2000). Lesions located in the region of the head and neck may be associated with melanocytic proliferations of the meninges with rare extension into the cisterna magni causing secondary hydrocephalus. This phenomenon, termed neurocutaneous melanosis may be associated with intracranial melanoma. Epidemiologic studies impute an incidence of malignant transformation in small congenital nevi of approximately 1%. Small- and intermediate-sized congenital nevi do not require excision, at least for the first 2 decades of life, because there appears to be no significant risk of developing malignant melanoma during this time period. Congenital nevi covering 4% or less of the body surface may not be at significant risk for malignant transformation (Swerdlow et al,1995).

The morphology of the congenital nevus changes with age, irrespective of the nevus size. There is darkening within the first 5-6 years of life and then again at puberty. The lesion is flat at birth and becomes progressively more palpable with age, gradually acquiring terminal hairs. As the patient ages, these lesions usually develop areas of hyperkeratosis, "doughy" alterations associated with mucinous degeneration, and the formation of neurofibromata. The appearance of firm nodules in congenital nevi is always of concern and any nodular proliferation should be excised for histological evaluation to exclude malignant transformation. One diagnostic consideration in this setting is the development of proliferative nodules; up to 5 mm in diameter with smooth or sometimes ulcerated surfaces, these are held to reflect self-limited, slowly-growing and often spontaneously-regressing proliferations (Lowes et al, 2000).

Histology
The following features we consider to be diagnostic of the congenital origin of a nevus. First, intramural or subendothelial nesting of nevus cells in small to medium size arteries and veins. Second, the presence of nevus cell nests replacing the papilla of the hair follicle. Third, the presence of nevus cells scattered in single cell array throughout the lower reticular dermis and the subcutaneous fat. Fourth, the presence of multiple nevus cell cells in multiple arrectores pilorum. Fifth, the presence of nevus cells in tight perivascular array mimicking an inflammatory infiltrate throughout the reticular dermis. Other features may be suggestive but are not diagnostic (Crowson et al, 2000).

Treatment
We believe that no lesion should be prophylactically removed in its entirety. Each patient is carefully followed and evaluated with gross inspection and palpation for subcutaneous nodules, changes in lesional consistency, surface topography or coloration. Should any such change occur, an excision of this area with a margin of the nevus is recommended. We recommend complete excision or partial extensive excision of a giant congenital nevus in a patient in whom biopsy shows foci worrisome for evolution into melanoma or consistent with overt melanoma. Nevi up to 5 cm in size can be excised in a 1–stage procedure, but larger lesions may mandate use of a tissue expander, sometimes with staged therapy using full- or intermediate-thickness grafts following superficial partial removal of the nevus, with the proviso that no histologic evidence of atypia is identified.

References
  1. Bittencourt FV, Marghoob AA, Kopf AW, Koenig KL, Bart RS. Large congenital melanocytic nevi and the risk for development of malignant melanoma and neurocutaneous melanocytosis. Pediatrics 2000;106: 736-741.

  2. Swerdlow AJ, English JS, Qiao Z. The risk of melanoma in patients with congenital nevi: a cohort study. J Am Acad Dermatol 1995;32: 595–599.

  3. Lowes MA, Norris D, Whiteld M. Benign melanocytic proliferative nodule within a congenital naevus. Australas J Dermatol 2000;41: 109-111.

  4. Crowson AN, Magro CM, Mihm MC, Jr. The nevomelanocytic proliferations : a comprehensive textbook of pigmented lesions. New York : Wiley-Liss, 2001: 550pp.