NON-NEOPLASTIC 1 HYPERPIGMENTATIONS EPHELIDES (FRECKLES) Ephelides are small, circumscribed, focally and donation compared with the surrounding pigmented lesions in which, despite their in- skin. Since freckles occur preferentially in in- creased and persistent pigment synthesis, the dividuals with fair skin that is easily damaged constituent melanocytes have not acquired the by the sun, they may be viewed as a localized, neoplastic characteristics of nevus cells. The albeit incomplete, protective response induced hyperpigmentation that characterizes these le- by ultraviolet (UV) light. sions is observed histologically as an increased Microscopic Findings. At scanning magni- content of melanin in the keratinocytes, with fication, there is a small circumscribed area of little or no evidence of melanocytic prolifera- epidermal hyperpigmentation without obvious tion. These lesions may represent acquired func- melanocytic proliferation. The epidermal archi- tional derangements in the epidermal melanin tecture is normal, with perhaps slight rete ridge unit involving keratinocytes as well as melano- elongation. The excess pigment may be recog- cytes. Although these lesions are not generally nizable only by careful comparison with adja- of great clinical importance, it is occasionally cent, normally pigmented “internal control” necessary to distinguish them clinically from skin. Although confirmation that melanocytes nevi, and some also may simulate melanoma, are not increased in number may require im- thus prompting biopsy. munohistochemical confirmation in occasional cases, normal basal melanocytes generally are SIMPLE EPHELIS (FRECKLE) distinguished from adjacent keratinocytes by Definition. Simple ephelis is a circumscribed their slightly smaller cell bodies, which often area of hyperpigmentation typically located on bulge downward into the basement membrane sun-exposed skin, less than about 4 mm in size, zone (fig. 1-1), their round to ovoid uniformly and not associated with significant melanocytic hyperchromatic nuclei, and a thin clear mantle proliferation. devoid of intercellular junctions that envelops Clinical Features. Simple ephelides are light the cell. There are no large epithelioid mela- tan, fairly uniform, pigmented lesions with nocytes, no rows of contiguous melanocytes, slightly irregular and indefinite borders. They and no nests of melanocytes in the dermis or are usually approximately 2 mm in diameter, epidermis. Simple ephelis are most often seen almost always less than 4 mm, and are distrib- in melanoma or other skin resection specimens uted on light-exposed areas of skin, especially as an incidental finding. on the shoulders and upper limbs. There is no Higher magnification reveals only coarse alteration of skin surface marking patterns, pigment granules in keratinocytes that are in- and the lesions are not palpable. In susceptible creased by comparison with adjacent skin, but individuals (those with skin that can burn in are otherwise unremarkable. There is no obvi- the sun and that tans poorly), freckles begin to ous morphologic abnormality of melanocytes, appear in childhood, while their numbers gener- which, if anything, tend to be reduced in num- ally remain fairly constant in adulthood unless ber by comparison with surrounding skin (1). heavy exposure continues. They often darken Differential Diagnosis. Clinically, ephelides with sunlight exposure and fade in winter. The overlap with simple lentigines, but histologic freckle appears to represent a localized area distinction is easy, based on the absence of evi- of skin in which the epidermal melanin unit dence of melanocytic proliferation. There is also has become more or less permanently altered, considerable overlap with the lesion described resulting in more abundant pigment synthesis next, the actinic (solar) lentigo. Melanocytic Tumors of the Skin Clinical Features. Actinic lentigines are poorly circumscribed, tan or brown, slightly variegated pigmented lesions, usually measur- ing about 4 to 10 mm in diameter. Larger le- sions, especially those with marked pigmentary variation or dark colors, may overlap with lentigo maligna, occasionally prompting biopsy. The lesions are distributed on sun-exposed skin in individuals with fair (type I) skin, especially on the shoulders, and there is sometimes a history of their relatively sudden appearance after a blistering sunburn. Some lesions have a slight scale, or a scale can be elicited by light rubbing or scratching. Actinic lentigines are probably representatives of a heterogeneous and poorly characterized group of conditions that are all associated with epidermal hyperplasia with or without atypia, with hyperkeratosis, and with hyperpigmenta- tion. There is a spectrum of morphologic overlap with pigmented actinic keratoses, pigmented seborrheic keratoses, and the freckles induced by psoralen and UV therapy (PUVA freckles) (2). Because they are indicators not only of exposure to UV light, but also of sensitivity to its effects, the presence of moderate to many actinic lentigines on the skin is associated with an increased relative risk for melanoma in case- Figure 1-1 control studies (3,4). LENTIGINES, FRECKLES, AND SMALL JUNCTIONAL Microscopic Findings. The keratinocytic NEVI IN CHRONICALLY SUN-DAMAGED SKIN epithelium shows elongation and variable The multiple lesions are clinically consistent with thinning of the rete ridges in association with a lentigines, freckles, and small junctional nevi. These small slightly noncontiguous lentiginous melanocytic macular lesions are indistinguishable from one another proliferation (figs. 1-2, 1-3). There is usually ob- clinically. Together, they constitute risk factors for the development of cutaneous melanoma. viously increased pigment, mainly in the basilar keratinocytes. The papillary dermis may contain a few patchy lymphocytes and melanophages, ACTINIC (SOLAR) LENTIGO or be unremarkable. Often, there is obvious Definition. Variously known as actinic len- actinic elastosis. Although melanocytes in the tigo, solar lentigo, sunburn freckle, age spot, liver basal layer may be normal in number or slightly spot, and so on, these common lesions present, increased, as assessed by morphometry, this especially in middle age and beyond, as poorly may or may not be recognizable histologically circumscribed focal areas of hyperpigmentation when compared with the surrounding skin, and that are larger and more irregular than most in any case, there is never any florid evidence simple ephelides (fig. 1-1). Although morpho- of melanocytic proliferation. The melanocytes metric studies have revealed a subtle increase in are neither contiguous nor nested, and show no melanocytic number compared to control skin, atypia. Pigment in keratinocytes is increased by this proliferation is subtle and noncontiguous, comparison with the surrounding epidermis. unlike that of a true lentigo. Strictly speaking, Moreover, these keratinocytes may appear the term “lentigo” may be inappropriate, but it somewhat enlarged and demonstrate incom- is hallowed by tradition. plete or slightly disordered maturation, at times Non-Neoplastic Hyperpigmentations Figure 1-2 ACTINIC LENTIGO Top: In a region of chronically sun-damaged skin, there is an area where the rete ridges are elongated. Bottom: Hyperpigmentation of basal keratinocytes is seen in the region of elongated rete ridges. In this region, the number of melanocytes is measurably increased compared to adjacent skin, leading to the use of the term “lentigo” rather than “freckle.” suggesting some overlap with the pigmented strikingly jet black borders with a reticulated variants of actinic keratosis (fig. 1-4). surface pattern (fig. 1-). Once formed, they Differential Diagnosis. A darkly pigmented are stable. The clinical appearance occasion- variant, which we term the reticulated lentigo in ally leads to some clinical concern, but the our clinic, occasionally leads to patient or physi- lesions histologically are quite banal and not cian concern because it presents as a variegated at all alarming. The keratinocytic epithelium jet black patch with a finely reticulated pattern shows lentiginous elongation of rete ridges that may suggest melanoma. The lesion occurs without obvious melanocytic hyperplasia. There on intermittently sun-exposed skin, especially is markedly increased pigment in the basilar the shoulders, and may appear suddenly after a keratinocytes, distributed in a patchy pattern. sunburn. The affected patient usually has skin The dermis may be normal or show a few patchy type I (always burns, never tans). The lesions, lymphocytes and/or melanophages. The me- which are sometimes multiple, are about 4 lanocytes in the basal layer are unremarkable to 10 mm in diameter, poorly circumscribed, in number or morphology, with pigment in and impalpable, and have highly irregular, keratinocytes increased by comparison with the Melanocytic Tumors of the Skin Figure 1-3 ACTINIC LENTIGO Left: Rete ridge elongation, basal hyperpigmentation, and an increased number of melanocytes (right) are seen in a localized area along the dermal-epidermal junction. Right: The greater increase in number of melanocytes is unusual for an actinic lentigo, bordering on the appearance of a lentigo simplex; however, the melanocytes are not in contiguity, which is consistent with the diagnosis of actinic lentigo. Figure 1-4 Figure 1-5 ACTINIC LENTIGO RETICULATED LENTIGO Hyperpigmentation of basal keratinocytes, without This highly characteristic lesion appears to