The term "birthmark" is an allinclusive appellation for a wide variety of pigmented, vascular, or epidermal cellular malformations that may be congenitally present or acquired as a developmental phenomenon predetermined by embryologie errors. Most of these lesions can be classified as hamartomas, a term first used by Albrecht1 in 1904 to designate benign-tumor-like malformations of an organ composed of inappropriate admixtures of its histologic components. Subsequently, this term has been used synonymously with the generic name "nevus" to encompass a wide variety of cutaneous lesions of dermal or epidermal origin. What follows is a brief compendium of the most commonly encountered pigmented, vascular, and epidermal hamartomas and their origin, treatment, and significance.
The pigmented melanocytic nevus, or mole, represents a hereditary malformation of melanocyte-directed embryonic neuroectodermal cells arrested at the dermoepidermal junction or below. These cells, designated nevus cells, aggregate in groups or nests, the predominant site of which determines their histologic classification. Intradermal moles are composed of nevus cell nests and cords primarily within the dermis, although a few of the nevus cell elements may be found at the dermoepidermal junction. Junctional nevi, also called intraepidermal nevi, are composed of nevus cell clusters at the dermoepidermal junction or slightly above. A few additional aggregates may be found on the dermal side of the junction or free within the upper dermis. Compound moles show an approximately equal distribution of nevus cells between the dermis and dermoepidermal junction. Each has certain clinical characteristics that allow a presumptive diagnosis, and for practical purposes it is unnecessary to make an absolute diagnosis of each lesion. The natural history of these nevi is represented in Table 1.
With few exceptions, pigmented melanocytic nevi are not present at birth. They usually develop between the second and sixth years and may appear in crops at puberty. The latter phenomenon may occur in association with darkening of previously existing melanocytic nevi. They may occur on any body surface, including the nail beds and mucous membranes. There is no greater significance to palmar, plantar, genital, or mucous membrane lesions in terms of malignant potential. Similarly, the histologic type of nevus bears no significance regarding malignant degeneration, with the singular exception that intradermal moles become melanomas only in extraordinary cases. The individual risk of eventual malignant transformation in acquired melanocytic nevi is extremely low when certain facts are considered: (1) the per capita average number of pigmented nevi is between 20 and 30, and many patients have hundreds; (2) the incidence of melanoma is truly rare in childhood (but rises appreciably after puberty) and in all age groups is approximately 9,300 per year2 in the United States; and (3) less than 50 per cent of melanomas arise in pre-existing melanocytic nevi.3 Congenital melanocytic nevi of the giant or garment type do, however, show a significantly increased potential for malignant degeneration (see below).
THE NATURAL HISTORY OF ACQUIRED MELANOCYTIC NEVI
Excisional biopsy and histologic examination of melanocytic nevi are rarely indicated in children. Suspected malignancy would be the sole motivating factor for such a procedure. Clues to de novo melanoma or malignant transformation of melanocytic nevi include (1) rapid growth associated with wide diffusion of pigment with irregular margins, (2) irregular darkening of pigmented lesions associated with bluish discoloration, (3) partial loss of pigment associated with apparent spontaneous scarring, (4) erythematous halo in the absence of trauma, (5) spontaneous bleeding or increased fragility, and (6) development of nodular components. It should be emphasized that the continuing presence of hairs within an otherwise suspect pigmented lesion is no guarantee of benignity. When indicated, biopsy should always be done by excisional surgery or, if this is impractical because of size or location, by deep punch biopsy. Shave biopsies are never indicated because of the thin specimens obtained, impossibility of evaluating the deep dermal aspects of the lesion, and the confusing clinical picture of the lesion after healing has occurred. The dogma of never violating pigmented lesions for biopsy purposes has finally died.4 Such procedures may obviate sacrificial surgery and definitely are not associated with adverse survival statistics should the lesion be malignant. The only major difficulty with less than total excisions is the limited specimen available for histopathologic examination.
Figure 1. Junctional nevus.
Figure 2. Compound nevus.
Junctional nevi are usually flat or very slightly raised and measure approximately 1 cm. or less (Figure 1). The color varies from light tan to dark brown-black and may be darker centrally than at the periphery. The shape is regular and symmetrical, and the surface reveals perservation of the usual skin lines. Junctional nevi are most common in childhood and tend to be a transient phase of development of compound nevi (Table 1). The exceptions to this phenomenon are palmar, plantar, and genital nevi, which usually remain as junctional lesions.
Compound nevi as seen in childhood rarely project more than a millimeter above the normal surrounding skin (Figure 2). With increasing age they may become papillomatous, or they may remain as flattened dome shapes or as thickened plaques. The color is highly variable, some showing irregular flecks of pigmentation or a diffuse dark halo at the periphery. Adolescent changes of papillomatosis, hair growth, hyperkeratosis, and increased depth of pigmentation may occur without any increased malignant liability.
The histologic changes that accompany conversion to intradermal nevi are not associated with significantly altered gross morphology. Thus, intradermal nevi are highly variable in appearance, from domeshaped to polypoid or papillomatous, with a wide color spectrum. Most are smooth, round tan or brown nodules with distinct borders and uniform pigmentation.
Congenital (Giant Hairy Nevus)
A great deal of confusion exists regarding the definition and significance of congenital pigmented (melanocytic) nevi. When the physician is confronted with any large pigmented lesion in a pediatric patient, the single most important determination is whether or not the lesion was present at birth. Frequently, parents describe a nevus as being "present since birth," but on further questioning it becomes evident that the lesion developed within the first few months of life. Conversely, a truly congenital nevus should have its history dating to the time of the child's birth.
This information is of greatest importance when one is dealing with relatively small or medium-size nevi (1.5-6 cm.); these may not have all the clinical characteristics of the giant hairy nevus, which commonly covers an entire anatomic region. The larger lesions are so remarkable that no confusion exists regarding their origin. However, there is no consensus regarding what physical dimensions constitute a "giant" congenital melanocytic nevus. Therefore, it is probably more appropriate to ignore size alone and allow therapy to be guided by whether the lesion was congenital or acquired. This may seem to be a minor point, but the incidence of malignant melanoma arising early in congenital melanocytic nevi may, according to some authors,5·6 approach 10 per cent. Therefore, the history will significantly affect the therapeutic decision-making process in any given case. As indicated above, acquired melanocytic nevi are innocuous and require no specific therapy other than optional cosmetic removal at an appropriate age.
Fortunately, the garmentlike congenital melanocytic nevus is rare (Figure 3). They are dark brown and have an uneven papillomatous surface and irregular margins, frequently exhibiting smaller satellite nevi at the periphery. Over 95 per cent of such lesions have a hairy component that consists of large, coarse terminal hairs. When the nevus covers the vertebral column, there may be underlying myelodysplasia. Similarly, hypertrophy or atrophy may affect a limb extensively involved with the nevus.
Treatment is directed towards total excision and grafting, when necessary, to cover the resultant defect. This eliminates the malignant potential and serves to partially alleviate the adverse cosmetic impact.
Unusual Melanocytic Nevi
Halo nevus. Halo nevus is the term designating an otherwise ordinary intradermal or compound nevus around which a collar of depigmentation develops (Figure 4). The process is seen most commonly on the trunk in the second decade. The centrally located nevus usually disappears as the depigmentation advances. In most cases, the normal pigmentation eventually returns to the area when the process is complete. Halo nevi may be multiple or occur as successive events.
The entire phenomenon probably represents a local autoimmune phenomenon directed against specific pigment-producing nevus cells and secondarily involving the normal epidermal melanocytes. The histologic picture shows a dense inflammatory infiltrate composed of small lymphocytes, but none of the usual clues to inflammation are present clinically.
Pigmented nevi are not the only lesions subject to the halo phenomenon. Blue nevi, neurofibromas, and malignant melanomas (both primary and metastatic) are subject to similar changes. The likelihood of malignant change accompanying a typical halo nevus seen in childhood is extremely remote. Therefore, no specific therapy is indicated unless there is evidence overtly suggesting malignancy.
Blue nevus. The blue nevus is a hamartoma composed of a cluster of dermal melanocytes arrested in situ during embryonic development. Two types are commonly recognized.
The blue nevus (of JadassohnTièche) is a dome -shaped, wellcircumscribed, small slate-blue or blue-black nodule (Figure 5). It begins in early life and may eventually reach 6-7 mm. These nevi persist throughout life with a negligible malignant potential.
The cellular blue nevus is a larger blue or blue-black nodular or plaquelike lesion that frequently appears at birth on the low back. The surface may be smooth or irregular; in rare instances, malignant degeneration has been reported.
Spitz nevus (juvenile melanoma). "Juvenile melanoma" is a dermatologic misnomer to the extent that the name connotes malignancy. This is a benign melanocytic tumor usually occurring on the face in early childhood, but composed of cells of bizarre morphology and arrangement. Indeed, melanin may be scarce or absent.
Figure 3. Congenital garment nevus.
Figure 4. Halo nevus.
Figure 5. Blue nevus.
Figure 6. Spitz nevus
Figure 7. Spitz nevus.
The lesion presents as a firm red or reddish-brown nodule that rapidly reaches a diameter up to 2 cm. (Figures 6 and 7), then remains stationary. The surface is usually smooth with a thin delicate epithelium, but verrucous changes may spontaneously occur. Because the surface epidermis is fragile, minor trauma may cause bleeding and result in a crusted or scaling appearance. The easy bleeding and red color attest to the highly vascular component of the lesion.
Simple local excision is the only indicated therapy. This is most easily done when the lesion is small, but arguments for mere observation are persuasive when the correct diagnosis is suspected and the patient is very young. Fortunately, de novo malignant melanoma is a very rare disease in childhood; the risks of observation are therefore minimal, especially when the alternatives are general anesthesia and excisional surgery on the face of a young child. Actual malignant degeneration of the Spitz nevus does not occur, but this does not prevent an error in pathologic interpretation of the specimen resulting in subsequent sacrificial surgery. Therefore, a high index of suspicion will facilitate the correct diagnosis.
Mongolian spot. The most common of all birthmarks is the Mongolian spot (Figure 8). It is truly congenital (i.e., present at the time of birth) and represents melanocytes of neural crest derivation that fail to migrate from the dermis to the epidermis and are arrested between collagen fibers and about neurovascular bundles. In black and Asian infants the incidence is greater than 90 per cent, whereas in Caucasians it is below 10 per cent.7 Clinically, these lesions present as uniform blue-gray bruiselike, round or oval macules, most frequently in the lumbosacral, flank, or buttocks area. The natural history of the lesion is one of progressive fading and almost invariable disappearance by adolescence. Biopsy is rarely indicated, and treatment is unnecessary.
Other Pigmented Lesions
Freckles. Ephelides, or freckles, are the most common of all pigmented cutaneous lesions. The tendency for freckling is probably inherited as an autosomal dominant trait, perhaps closely linked to the gene(s) determining the increased incidence of melanocytic nevi. These two phenomena seem to occur simultaneously in blond and red-haired persons.
Figure 8. Mongolian spot.
There is no increase in the number of melanocytes within freckles; rather, the individual melanosomes in the melanocytes are larger. This results in flat tan or brownish spots that predominate in light-exposed locations and begin to appear after the fifth year. They darken quickly following sun exposure and tend to fade or disappear during winter months.
These lesions are generally insignificant, although axillary freckling in neurofibromatosis and dark freckling of sun-exposed areas of young brunet patients that persists through the winter may have diagnostic relevance and may indicate xeroderma pigmentosum.
No therapy is indicated or desirable for ordinary freckles; however, young patients with fair skin who tend to freckle may benefit from topical sun screens as a general measure to protect the skin from excessive ultraviolet exposure, which leads to severe sunburn and cumulative actinic injury. This is especially true at low latitudes and high elevations, where sunlight reaches the earth's surface with less atmospheric filtration and therefore with greater ultraviolet energy.
Lentigines. Physically, the least developed and most highly differentiated of all benign melanocytic lesions of the skin is the lentigo. Lentigines are tan to brown macules containing focally increased numbers of normal melanocytes at the dermoepidermal junction without any indication of proliferation. Several types are recognized.
Lentigines may first appear in early childhood, either singly or in generalized eruptive bursts on any cutaneous or mucous membrane surface. They vary from 1-2 mm. to coalescent lesions measuring up to 5 mm. The pigmentation is uniform and darker than freckles, and the color is unaffected by sunlight exposure. They are also more randomly distributed and sparser than freckles. They remain indefinitely but may fade in the adult years. The adult forms are distinguished by their onset with advanced age and sharp localization to areas of greatest actinic skin damage - i.e., dorsal hands, forearms, face, and neck.
Several syndromes have lentigines as a component. The best known is the Peutz-Jeghers syndrome (Figure 9). Another is the so-called leopard syndrome, in which /entigines occur early and profusely in association with electrocardigraphic changes, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness.
Café-au-lait spots. The birthmark with the greatest array of possible significant associations is the caféau-lait spot (Figure 10). These spots are usually present at birth or appear in early childhood as light-tan macules 2-5 cm. in length and approximating an oval outline. Up to five such lesions may be present on any skin surface in approximately 10 per cent of normal persons; when six or more are present, however, the probability of neurofibromatosis is markedly increased. Café-au-lait spots are usually the first, and one of the most significant, cutaneous signs of neurofibromatosis, occurring in about 90 per cent of cases.
Similar pigmented lesions occur in Albright's syndrome, but they have a more irregular outline ("coast of Maine") and more limited distribution on the trunk, buttocks, and thighs. There may be unilateral localization favoring the side with the greatest bony involvement.
Café-au-lait spots are also associated with other syndromes and visceral diseases, including tuberous sclerosis, pulmonary stenosis, and temporal lobe dysrhythmias.
Becker's nevus. Becker's nevus is not of melanocytic derivation but first appears at, or shortly after, puberty as a tan-to-brown macule on the upper trunk or proximal extremities. Males are more commonly affected. The lesion gradually hyperpigments, and coarse terminal hair eventually populates the immediate area of the nevus (Figure 11).
Figure 9. Lentigenes in Peutz-Jeghers syndrome.
Figure 10. Café-au-lait spot.
Histologically, there are no dermal changes. The epidermis may be hyperplastic, with increased basal layer pigmentation and large hair follicles. No treatment other than camouflage is indicated, and no malignant potential exists. In the early stages of development, before the evolution of the hair, the tan color of the lesion may cause confusion with café-au-lait spots. The fact that Becker's nevus evolves after the first decade distinguishes it clinically from the giant hairy (garment) nevus, which is present at birth.
Among newborns, the second most frequent type of birthmark involves vascular malformations. In a recent study by Jacobs and Walton,7 43 per cent of a large series of newborns had some type of vascular lesions, exceeded only by the incidence of the melanocytic Mongolian spot (95.5 per cent) in blacks.
Figure 11. Becker's nevus.
Figure 12. Salmon patch.
Figure 13. Port-wine stain.
Salmon Patch (Telangiectatic Nevus)
The vast majority of vascular nevi are of the salmon patch type (Figure 12). These are congenitally present without any sex predilection and most frequently involve the nape of the neck, forehead, glabella, or eyelids. The appearance is usually that of a dull-pink macule with fine telangiectasias. Usually, fading occurs within the first year of life; however, the central facial and nuchal lesions may clear more slowly.
Salmon patches are composed of distended dermal capillaries that represent the persistence of fetal circulatory patterns in the skin. No treatment is indicated, since fading and disappearance are almost universal.
The more familiar type of telangiectatic nevus, or nevus flammeus, is the port-wine stain (Figure 13). This lesion is also present at birth but shows no tendency to resolve. Port-wine stains are usually unilateral, in which case they respect the midline, but occasionally there is a contralateral component in the same or adjacent dermatome distribution. It enlarges in proportion with growth and may appear on any area of the body, but the face and neck are the most commonly encountered sites. The color varies from faint pink to a dull erythrocyanotic hue or purple. Initially the surface is quite smooth; however, with increasing age the lesion may show an irregular surface that is thickened or frankly cobblestonelike.
Microscopically, the lesion is composed of dilated mature capillaries in the dermis. There may be associated connective-tissue hypertrophy when deeper vessels are involved.
No uniformly acceptable therapy exists for the cosmetically disfiguring port-wine stain. All of the usual physical modalities (excisional surgery, tattooing, radiation, cryosurgery, and dermabrasion) have been employed without convincing success. Only the smallest of lesions can successfully be excised. Tattooing with insoluble light-colored pigments usually produces a mottled appearance and does not affect the irregular surface contours. The other physical methods are similarly fraught with disadvantages and contraindications. Certainly x-irradiation should be mentioned, but only by way of condemning its use in any benign, functionally uncompromising condition affecting children. Camouflaging cosmetics with opaque bases are still the best treatment available for port-wine nevi on exposed areas.
One syndrome that includes facial port-wine stains deserves special mention. This is encephalotrigeminal angiomatosis, or Sturge-Weber syndrome, in which there is involvement of the skin, eyes, and leptomeninges with angiomas. An important clinical feature of the port-wine stain is that it diffusely involves the skin area innervated by the first branch of the trigeminal nerve (Figure 14). The centrai nervous system involvement is not seen if the port-wine stain is entirely below the palpebral fissure.8 Port-wine stains that fail to satisfy this criterion are rarely associated with underlying ocular and CNS angiomas. Additionally, skull films taken of neonates with facial portwine stains have a very poor yield in terms of delineating CNS calcifications. This is true even if CNS angiomas are present, since they generally require years to calcify. Ocular examination for angiomatosis, glaucoma, and retinal detachment and EEGs showing abnormal electrical activity are much more reliable diagnostic maneuvers.
Figure 14. Port-wine stain (Sturge-Weber syndrome).
Figure 15. Hemangioma in a newborn.
Lesions characterized by angioblastic proliferation are subject to the vagaries of confused nomenclature, based on their variety of clinical features and histologic components. The superficial capillary type is usually referred to as a strawberry nevus. The cavernous hemangioma is basically the same pathologic process but is deeper and is made up of larger vessels. Most lesions seen in infants and children are made up of various degrees of both types.
Involuting hemangiomas are usually not apparent at birth but appear during the first three or four weeks of life. Occasionally they are apparent in the newborn infant as faint telangiectasias surrounded by a pale halo (Figure 15). These become solid red and elevated during the subsequent weeks (Figure 16).
Capillary and cavernous hemangiomas are quite common, occurring in about 10 per cent of all babies under one year of age.8 They may be single or multiple and vary considerably in ultimate size. Any area of the body may be involved. There is no sexual or genetic predilection. The lesion begins as an erythematous macule that rapidly enlarges and becomes elevated with a bosselated surface. The color soon becomes bright red or erythrocyanotic as the tumefacient evolution proceeds. Hemangiomatous elements may remain histologically superficial or penetrate into the subcutaneous tissues, in which case considerable anatomic distortion may result. The surface epithelium is usually thin and delicate, but it may be of normal thickness if the hemangioma is composed exclusively of deep elements. Ulceration with secondary infection may occur following minor trauma. Significant hemorrhage is, however, uncommon. The rapid growth and associated cutaneous changes described above may erroneously suggest malignancy. After a variable period of months, the surface shows a mottled bluish-white appearance indicative of scarring. This is the hallmark of spontaneous involution, which is usually complete after the second or third year. A relatively loose, atrophic pale scar is the only residual clinical defect unless extensive ulceration and infection supervene during the course. In that case, scarring may be more significant, but no restorative procedures should be undertaken until complete and unequivocal resolution has occurred. In most cases of involuted extensive hemangiomas, excision of the redundant scar is all that is required.
Figure 16. The natural history of a hemangioma. A: Three weeks of age. B: Three months of age. C: Six months of age. D: Eighteen months of age. E: Five years of age.
No specific treatment is indicated for capillary hemangiomas unless a vital function (i.e., sucking, vision, etc.) is disturbed by their presence. In these cases, small doses of x-irradiation (with appropriate protective shielding of surrounding structures) are effective in initiating resolution.
The final group of embryonic errors producing cutaneous defects comprises epithelial nevi. This is often a confusing group of lesions, owing to the descriptive terminology selected to designate these aggregates of epithelial tissue derived from epidermis or epidermal appendages (i.e., apocrine, eccrine, or sebaceous glands or hair follicle elements). Individual lesions show mixed histologic components, but one basic element usually predominates, thereby determining the name. The most common of these hamartomas are the verrucous, or epidermal, nevus and the sebaceous nevus.
Figure 17. Linear verrucous epidermal nevus.
The verrucous nevus either is congenital or appears in early infancy on any skin surface, although the extremities are most frequently involved. These nevi tend to be unilateral, and there is no genetic or sex predilection. The initial appearance is that of a flesh-colored or yellowbrown rough, warty oval or linear plaque (Figure 17). Frequently, a multiplicity of tiny individual warty papules form the familiar linear streaks seen on the extremities or the horizontal or gyrate configurations seen on the trunk. If the lesions are extensive and involve intertriginous sites, the surface may become macerated and foul-smelling. Enlargement may be noted at intervals during childhood, but this occurs most commonly at puberty.
The term nevus unius lateris is applicable when an extremity is extensively involved with linear or spiral lesions or when transverse patterns are present on the trunk. Bilateral lesions are uncommon; thus the confusion with cases that actually represent late partial manifestations of bullous ichthyosiform erythroderma or ichthyosis hystrix, both of which have a symmetrical distribution. These conditions are etiologically unrelated to epithelial nevi.
Treatment is directed towards alleviation of the cosmetic handicap but should not be undertaken until after puberty, when the lesion will have attained its maximum size. Excision is preferable for small lesions or moderate-size linear ones. Curettage with electrodessication or dermabrasion can be helpful, but recurrences are frequent. Bowen's disease and squamous cell carcinoma have been reported in pre-existing epithelial nevi in only the rarest of circumstances,10 in spite of frequent textbook citations to the contrary.
It should be recalled that nevus unius lateris occasionally may be associated with hypoplasia of the affected anatomic part, skeletal defects, and neurologic abnormalities.11
The sebaceous nevus is frequently present at birth or develops within the first year. Only rarely does it appear after adolescence. The lesion is most commonly encountered on the scalp or face as an isolated elevated waxy yellowish-orange or brown plaque (Figure 18). The lesions may reach up to 10 cm. in greatest dimension and are devoid of hair. They evolve through childhood with slow growth; at puberty they become thickened and develop a multiplicity of relatively uniform papillomatous projections from the surface12 (Figure 19).
Figure 18. Sebaceous nevus in an intant.
Figure 19. Sebaceous nevus in an adult.
Total surgical excision is the treatment of choice, since basal cell carcinoma may result in 6.5 to 22 per cent of cases.13,14 Such degeneration usually occurs in middle life, but it has been recorded in childhood.
1. Albrecht, E. Weber Hamartome. Verh. Dtsch. Ges. Pathol. 7 (1904), 153.
2. Seidman, H., Silverberg, E., and Holleb, A. I. Cancer statistics 1976: A comparison of white and black populations. CA 26 (1976), 2-29.
3. Sanderson, K. V. Tumors of the skin. In Rook, A. (ed). Textbook of Dermatology. Oxford, England: Blackwell Scientific Publications. 1972.
4. Walton. R. G.. and Cox, A. J. Electrodessication of pigmented nevi. Arch. Dermatol. 87 (1963), 342349.
5. Reed, W. B., et al. Giant pigmented nevi, melanoma and leptomeningeal malanocytosis. Arch. Dermatol. 91 (1965), 100-119.
6. Mark, G. J., et al. Congenital melanocytic nevi of the smaH and garment type. Hum. Pathol. 4 (1973), 395-418.
7. Jacobs, A. H.. and Walton, R. G. The incidence of birthmarks in the neonate. Pediatrics 58 (1976), 218222.
8. Alexander. G. L., and Norman, R. M. The Sturge-Weber Syndrome. Bristol. England: John Wright and Sons, 1960.
9. Jacobs, A. H. Strawberry hemangiomas - The natural history of untreated lesions. Calif. Med. 86 (1957), 8-10.
10. Swint, R. B., and Klaus, S. N. Malignant degeneration of an epithelial nevus. Arch. Dermatol. 101 (1970). 56-58.
11. Solomon. L M., Fretzin, D. F., and Dewald, R. L. The epidermal nevus syndrome. Arch. Dermatol. 97 (1968), 273-285.
12. Mehregan, A. H., and Pinkus. H. Life history of organoid nevi. Special reference to nevus sebaceus of Jadassohn. Arch. Dermatol. 91 (1965). 574-588.
13. Jones, E. W., and Hey I, T. Naevus sebaceus: A report of 140 cases with special regard to development of secondary malignant tumours. Br. J. Dermatol. 82(1970). 99-117.
14. Michalowski, R. Naevus sébacé de Jadassohn - un état précancéreux. Dermatologica 124 (1962), 326-340.
THE NATURAL HISTORY OF ACQUIRED MELANOCYTIC NEVI