Simulators of malignant melanoma of the skin

ARTICLE

Early recognition of malignant melanoma is crucial in order to remove lesions at a stage when complete cure can still be achieved. Over the last few years, several studies have focused on criteria for the diagnosis of melanoma, in an attempt to improve early detection and increase survival chances. As a result of these efforts, widely accepted guidelines are now available for the clinical [1-3] and histopathological [4, 5] diagnosis of cutaneous malignant melanoma, allowing the correct identification of most lesions. Unfortunately however, some melanoma defy clinical and/or histopathological recognition [6, 7], and some benign lesions (melanocytic or non-melanocytic) can present with clinical and/or histopathological aspects simulating malignant melanoma [8-13]. Awareness of these simulators is important to avoid useless (and potentially dangerous), aggressive treatments. In this article we illustrate the clinico-pathological features of the most important benign simulators of malignant melanoma of the skin.

Several benign cutaneous non-melanocytic tumours can present with clinical aspects similar to those of malignant melanoma (Fig. 1) [8]. A list of the most common lesions is provided in Table I. Simple excision and subsequent examination of routinely fixed sections of tissue allow the correct diagnosis in most cases. Immunohistochemical staining of neoplastic cells helps in identifying the few cases where histological examination may not be sufficient for a definitive diagnosis (e.g., Paget's disease and pigmented epidermotropic metastasis of breast carcinoma among others) [14, 15].

A more important group of simulators of malignant melanoma is represented by benign melanocytic lesions showing clinical and/or histopathological aspects mimicking malignancy. A list of these lesions is provided in Table II. The main clinicopathological criteria to distinguish them from malignant melanoma will be reviewed for each of these lesions. Melanosis of mucosal regions, pigmented streaks in melanoma scars and reticulated (ink-spot) lentigo have been included in this group, although they do not represent true proliferations of melanocytes.

Melanocytic nevi located on the palms and soles may simulate melanoma clinically by being asymmetrical and showing irregular pigmentation. Histopathologically, they often reveal melanocytes arranged in solitary units or small nests within the entire thickness of the epidermis including the horny layer. Features allowing the correct histopathological diagnosis are the sharp circumscription and symmetry of the lesion, the maturation of melanocytes with progressive descent into the dermis, and the absence of atypical melanocytes and mitoses. A helpful clue for distinguishing benign from malignant melanocytic lesions on acral regions is the columnar disposition of melanocytes and melanin within the epidermis and horny layer in the nevi, as opposed to the diffuse pattern seen in malignant melanoma. This peculiar architectural feature may be explained by the particular anatomical location. In fact, it has been demonstrated recently that acral nevi cut perpendicular to the skin ridges show involvement of upper layers of the epidermis restricted to the site of the ridges (that is, columnar arrangement of melanocytes and melanin within the epidermis and horny layer), whereas those cut parallel to the skin ridges present melanocytes in the epidermis and horny layer throughout the entire length of the lesion. This finding suggests a role of the peculiar anatomy of these regions in the genesis of the atypical histopathological features of acral melanocytic nevi.

Ancient nevi have been described recently as benign histopathological simulators of malignant melanoma. They are characterized by the presence of dilated, sometimes thrombosed blood vessels, hyalinized collagen, fibrosis and sclerosis, and by the finding of atypical melanocytes and the presence of mitotic figures. The term "ancient nevus" has been derived from the so-called "ancient schwannoma", which shows similar degenerative aspects and atypical features. Criteria that favour benignancy in ancient nevi are the absence of changes of melanoma in situ within the epidermis, and the presence of melanocytes of a "normal" nevus beneath the atypical melanocytes.

This variant of melanocytic nevi is characterized clinically by small, hypermelanotic lesions located on sun-exposed areas. Histopathologically there is marked elimination of melanin through the epidermis and horny layer (pigmented parakeratosis), thus mimicking malignant melanoma. However, lesions are small, symmetrical and sharply circumscribed. Melanocytes are arranged mostly at the dermo-epidermal junction, and there are neither atypical features nor mitoses. Black (hypermelanotic) nevi are probably related to so-called "new nevi of midlife" and "nevoid lentigo" [21].

Some blue nevi may mimic malignant melanoma clinically by being large, heavily pigmented tumours, sometimes with smaller lesions in the surrounding area simulating satellite metastases. In most cases histological examination reveals features of a "common" blue nevus. Occasionally, dense nodules of melanocytes extending into the subcutaneous fat (so-called "neuronevus of Masson") are found. These histopathological features may be misinterpreted as those of a malignant melanoma. Criteria that allow distinction are the symmetry, sharp circumscription and vertical orientation of the lesion, the lack of atypical features of melanocytes, and the absence of mitoses. Another variant of blue nevi that can be mistaken for a melanoma is the so-called "blue nevus with benign lymph node metastases", usually characterized by a cellular blue nevus in the skin associated with the finding of melanocytes within a regional lymph node [23-25]. In contrast to melanoma, cells of the blue nevus within lymph nodes are confined to the capsule, and do not show atypical features or mitoses. It has been suggested that the presence of cells of a blue nevus within a lymph node is due to an "error" during migration of melanocytes from the neural crest to the skin.

Combined nevi are characterized either by the combination of histopathological features of two different benign melanocytic nevi, or by the presence of more than one population of melanocytes within a single lesion. They may simulate malignant melanoma clinically by being asymmetrical and revealing markedly irregular pigmentation. Features that allow distinction from melanoma are the sharp circumscription and the overall appearance of the lesion, showing a well circumscribed, hyperpigmented spot surrounded usually by a less pigmented area. Histopathologically, there are several types of combined nevi, characterized by the combination of any morphological expression of congenital and/or acquired nevi. A typical variant presents with epithelioid and spindle cells of a Spitz's nevus together with a dysplastic nevus. Another type features small melanocytes admixed with large balloon cells, simulating balloon cell melanoma. Combined nevi can be distinguished from malignant melanoma by the absence of features of melanoma in situ in the intraepidermal portion of the neoplasm, the maturation of melanocytes with progressive descent into the dermis, and the absence of nuclear atypia (with the exception of cells of Spitz's nevi).

Some congenital nevi biopsied shortly after birth may show a pagetoid intraepidermal growth of melanocytes which is virtually indistinguishable from that observed in malignant melanoma. These lesions usually present clinically with plaques characterized by irregular pigmentation. Histopathologically, melanocytes arranged in nests or as solitary units are present within the entire thickness of the epidermis including the horny layer. Helpful criteria for differentiation from malignant melanoma are the monomorphism of the intraepidermal melanocytes and the presence of melanocytes of a congenital nevus without atypical features in the dermis.

This benign melanocytic nevus can simulate melanoma histopathologically by virtue of a dense nodular infiltrate of melanocytes extending into the subcutaneous fat and showing some atypical features and rare mitoses. However, the neoplasm is sharply circumscribed, top-heavy, and lacks the intraepidermal features of melanoma in situ. Deep penetrating nevi have been interpreted as a peculiar variant of the combined nevi, being characterized by a plexiform pattern with populations of melanocytes with different morphological features [24]. The difficulties in the correct interpretation of these lesions are well illustrated by the recent description of a deep penetrating nevus with metastases [37].

Dysplastic nevi were first described in 1978 as a marker of familial melanoma [38]. In more recent years, it has become evident that they represent one of the several morphological expressions of acquired melanocytic nevi [42]. Clinically, they can simulate melanoma by being larger than 6 mm, asymmetric, poorly circumscribed and irregularly pigmented. Histopathological features mimicking malignant melanoma are the presence of atypical cells (melanocytes with larger, pleomorphic nuclei, sometimes with prominent nucleoli) and a few solitary melanocytes over the dermo-epidermal junction. Features that allow diagnosis of these lesions as benign are the symmetry, the predominance of melanocytes arranged in nests over those arranged as solitary units, and the presence of maturation of cells with progressive descent into the dermis. In 1992, in the report of a Consensus Conference organized by the National Health Institute of the United States of America, it was suggested that the term "dysplastic nevus" be abandoned because of unclear definitions and lack of repeatable criteria for diagnosis [43].

Halo nevi are defined as melanocytic nevi surrounded by an area of depigmentation caused by an immunological reaction directed against the melanocytes of the nevus. Clinically, they are easily diagnosed as benign. Histopathology, however, may pose problems in the classification of such lesions. The dense infiltrate of inflammatory cells in a melanocytic lesion, in fact, may be confused with the immune response caused by a melanoma (a "halo nevus" variant of so-called minimal deviation melanoma was described in 1990 by Reed and coworkers [45]). The inflammatory cells may at times completely obscure the nests of melanocytes, and atypical nuclear features can be observed in single cells. Features that favour benignancy are the distribution of lymphocytes throughout the entire neoplasm in a symmetrical fashion (in melanoma, by contrast, there is a tendency for focal aggregation of reactive lymphocytes), and the benign aspect of melanocytes with nests situated mainly at the dermo-epidermal junction and predominating over solitary melanocytes. Once completely regressed, halo nevi can be very difficult to differentiate from completely regressed malignant melanoma. Features that favour benignancy in completely regressed pigmented lesions are the size (i.e., regressed melanoma are larger as a rule) and shape, halo nevi being usually dome-shaped in contrast to regressed melanoma, which presents with flat macules.

Melanocytes in sun-damaged skin may be increased in number and show slight nuclear atypia. A similar picture can be observed in the epidermis overlying some intradermal melanocytic nevi or other benign cutaneous tumours (i.e., dermatofibroma). These features can be mistaken for those of a melanoma in situ. However, melanocytes are arranged only at the dermo-epidermal junction, do not tend to confluence and form nests, and are relatively equidistant from one another.

Longitudinal melanonychia may be due to a lentigo simplex, a benign melanocytic nevus, or a malignant melanoma. It is characterized clinically by a brown or black longitudinal streak within the nail plate. Benign forms can be very difficult to distinguish from melanoma in situ of the nail matrix. A helpful clinical clue is the presence in melanoma of the so-called Hutchinson's sign, characterized by periungueal spread of the pigmentation on the proximal or lateral nail fold. Histopathology of benign lesions may show either features of a benign melanocytic nevus, or just a hyperpigmentation of the epidermis with no increase of melanocytes. By contrast, melanoma in situ shows intraepidermal spread of atypical melanocytes arranged in nests or as solitary units. A familial occurrence of benign pigmented streaks in the nails has recently been documented [47].

This condition may occur on the genital, labial or oral mucosa. Clinically lesions are often similar to those of melanoma in situ in these regions, being asymmetrical, poorly circumscribed, and irregularly pigmented. Histopathologically, there is an increase of melanocytes with long dendrites at the dermo-epidermal junction. There are neither cellular atypia, nor melanocytes above the dermo-epidermal junction, nor nests of melanocytes. A few melanophages, but no melanocytes, are found in the dermis.

Nevi exposed to UV radiation [50]

Benign melanocytic nevi exposed to UV radiation may show intraepidermal features simulating melanoma in situ (e.g., solitary melanocytes disposed not only at the dermo-epidermal junction but also in upper epidermal layers). However, intraepidermal melanocytes do not show atypical features, and the dermal component does not reveal any aspect of malignancy. Architectural features return to normality within a few weeks after UV-irradiation.

These melanocytic lesions can be located on the vulva, the penis, the nipple, the umbilicus, and the perianal region. Clinically, they can simulate melanoma showing asymmetry and poor circumscription. Histopathologically there is an intraepidermal proliferation of melanocytes that can be mistaken for melanoma in situ, with some melanocytes and nests located in the upper layers of the epidermis. Features that allow classification of genital nevi as benign are the predominance of nests over solitary melanocytes within the epidermis, the presence of an intradermal component showing discrete nests of melanocytes maturing with a progressive descent into the dermis, and the absence of atypical melanocytes and mitoses.

The onset of a new melanocytic lesion on a pre-existing nevus has been designated in the French literature as "nevus sur nevus" (nevus on nevus). A typical example is represented by a common nevus or a Spitz's nevus arising on a pre-existing nevus spilus. Clinically, differentiation from malignant melanoma arising in a melanocytic nevus can be difficult. Histopathologically, one can observe the features of the two components of the lesion, sometimes with the picture of a combined nevus.

Rarely, pigmented linear streaks develop in scars of malignant melanoma. Although these lesions may clinically simulate local recurrence of the melanoma, histological examination reveals only basal layer hyperpigmentation without proliferation of melanocytes within the epidermis or dermis.

These lesions simulate a melanoma clinically as well as histopathologically, and are one of the most vexing problems in the realm of melanocytic lesions in newborns. Clinically, there is a nodule within a giant congenital nevus, which may be more or less pigmented than the neighbouring nevus. Histopathologically, there are sheets of melanocytes larger than those in the surrounding nevus, and there can be mitoses and necrotic melanocytes. Although the epidermis usually lacks the features of melanoma in situ, it is often impossible to distinguish these lesions from a so-called "dermal" melanoma developing in a giant congenital nevus. Features that are helpful in the diagnosis are the sharp circumscription, the superficial location of the nodule, and the monomorphism of the large melanocytes. Children presenting with such lesions, how-
ever, should be closely and carefully followed to rule out malignant melanoma.

Recurrent (persistent) nevi may simulate melanoma clinically by being asymmetric, poorly circumscribed, and irregularly pigmented. They occur after incomplete excision of a benign melanocytic nevus, usually after "shaving" biopsies that fail to remove cells in the deeper part of the lesion. Complete clinical history and review of the original sections are crucial for the diagnosis, in order to rule out the possibility of a melanoma recurring after incomplete excision. Recurrent nevi are characterized histopathologically by the proliferation of melanocytes above a scar. Intraepidermal melanocytes are arranged mainly as solitary units disposed in all levels of the epidermis, thus simulating malignant melanoma. However, the atypical growth of melanocytes is strictly confined to the area where scar tissue is present in the dermis (by contrast, melanocytes of recurrent melanoma extend beyond the lateral margins of the scar). In addition, complexes of the pre-existing nevus are often detectable below the scar and/or at the side of the lesion. Review of the original section, as already mentioned, is crucial for the final diagnosis.

These lesions have been recently described on the upper trunk on sun-exposed area in young adults. They are characterized clinically by a heavily pigmented, reticulated lesion. Lack of symmetry and the amount of pigmentation make the differentiation from melanoma in situ very difficult. On histopathological examination, however, they reveal hyperpigmentation of the epidermis without any increase in the number of melanocytes.

Spindle and/or epithelioid cell nevi (Spitz's nevi) were described as "juvenile melanoma" by Sophie Spitz in 1948 [66]. They were subsequentely identified as benign melanocytic tumours occurring mainly, but not exclusively, in children and adolescents. Clinically, Spitz's nevi sometimes simulate melanoma by virtue of marked hyperpigmentation (so-called Reed's tumour). However, in contrast to melanoma, lesions are symmetrical, sharply circumscribed, homogeneously pigmented, and do not measure more than 1 cm as a rule. Histopathologically, Spitz's nevi often present with some features of melanoma including scattered melanocytes arranged as solitary units within all levels of the epidermis, confluence of nests, growth of melanocytes along adnexal structures, marked cellular atypia, and the presence of a few mitoses. In spite of these worrying aspects, Spitz's nevi are wholly benign neoplasms; histopathological features that allow them to be distinguished from malignant melanoma are the symmetry and sharp circumscription of the lesion, the presence of a maturation of melanocytes with progressive descent into the dermis, and the absence of mitoses in the lower portion of the melanocytic infiltrate. Although differentiation of Spitz's nevi from malignant melanoma is possible in most instances, it is at times impossible to reach a definitive diagnosis. In such cases, careful follow-up of the patients is mandatory.

We have presented the main clinicopathological characteristics and differential diagnostic features of benign melanocytic simulators of malignant melanoma. These lesions may pose a formidable threat to the diagnosis and management of patients with pigmented melanocytic tumours. Knowledge of their features allows avoidance of the diagnostic "pitfalls" in most cases. It must always be remembered, however, that in some cases a definitive diagnosis cannot be reached on the basis of the clinicopathological features alone. These patients, of course, should be carefully and regularly followed. Finally, in recent years, epiluminescence microscopy (EM) and digital epiluminescence microscopy (DEM) have provided new criteria for the clinical diagnosis of pigmented (melanocytic and non-melanocytic) skin lesions. Detailed EM diagnostic criteria have been described in specific studies [67]. The most important EM criteria for differential diagnosis of pigmented skin lesions are summarized in Table III.

REFERENCES

1. Clark WH Jr. Clinical diagnosis of cutaneous malignant melanoma. JAMA 1976; 236: 484-5.

2. Mihm MC Jr, Clark WH Jr, From L. The clinical diagnosis, classification and histogenetic concepts of the early stages of cutaneous malignant melanomas. N Engl J Med 1971; 284: 1078-82.

3. Ackerman AB. Clinical diagnosis of malignant melanoma in situ. In: Pathology of malignant melanoma. Ackerman AB (ed.), New York, Masson Pub., 1983; 57-8.

4. Maize JC, Ackerman AB. Pigmented lesions of the skin. Lea & Febiger, Philadelphia, 1987.

5. Ackerman AB. The concept of malignant melanoma in situ. In: Pathobiology of malignant melanoma. Elder DE (ed.): Basel, Karger, 1987, 205-10.

6. Andersen WK, Silvers DN. Melanoma? It can't be melanoma! JAMA 1991; 266: 3463-5.

7. Wong TY, Suster S, Duncan LM, Mihm MC Jr. Nevoid melanoma: a clinicopathologic study of seven cases of malignant melanoma mimicking spindle and epithelioid cell nevus and verrucous dermal nevus. Hum Pathol 1995; 26: 171-9.

8. Ackerman AB, Cerroni L, Kerl H. Pitfalls in the histopathologic diagnosis of malignant melanoma. Lea & Febiger, Philadelphia, 1994.

9. Connors RC, Ackerman AB. Histologic pseudomalignancies of the skin. Arch Dermatol 1976; 112: 1767-80.

10. Mihm MC Jr, Googe PB. Problematic pigmented lesions. Philadelphia, Lea & febiger, 1990.

11. Barnhill RL, Rous GC. Histopathological spectrum of clinically atypical melanocytic nevi. Arch Dermatol 1990; 126: 1315-8.

12. LeBoit PE. Simulants of malignant melanoma: a rogue's gallery of melanocytic and nonmelanocytic impostors. Pathology: State of the Art Reviews 1994; 2: 195-258.

13. Barnhill RL. Pathology of melanocytic nevi and malignant melanoma. Boston, Butterworth-Heinemann, 1995.

14. Shamai-Lubovitz O, Rothem A, Ben-David E, Sandbank M, Hauben D. Cutaneous metastatic carcinoma of the breast mimicking malignant melanoma, clinically and histologically. J Am Acad Dermatol 1994; 31: 1058-9.

15. Gillham SL, Morrison RG, Hurt MA. Epidermotropic neuroendocrine carcinoma. Immunohistochemical differentiation from simulators, including malignant melanoma. J Cutan Pathol 1991; 18: 120-7.

16. Kerl H, Trau H, Ackerman AB. Differentiation of melanocytic nevi from malignant melanomas in palms, soles, and nail beds solely by signs in the cornified layer of the epidermis. Am J Dermatopathol 1984; 6 (suppl.): 159-61.

17. Botet MV, Caro FR, Sanchez JL. Congenital acral melanocytic nevi clinically simulating acral lentiginous melanoma. J Am Acad Dermatol 1981; 5: 406-10.

18. Haupt HM, Stern JB. Pagetoid melanocytosis. Histologic features in benign and malignant lesions. Am J Surg Pathol 1995; 19: 792-7.

19. Kerl H, Soyer HP, Cerroni L, Wolf I. "Ancient" nevus ­ A benign simulator of melanoma. J Cut Pathol 1993; 20: 550.

20. Cohen L, Bennion S, Johnson T, Golitz L. Benign black nevus: clinical, histopathologic and ultrastructural features in 316 cases. J Cut Pathol 1995; 22: 55.

21. Clark WH Jr, Elder DE, Guerry D, IV, Epstein MN, Greene MH, Van Horn M. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol 1984; 15: 1147-65.

22. Cerroni L, Soyer HP, Kerl H. Pseudomelanoma nei neonati: lesioni melanocitiche benigne che simulano il melanoma maligno. G It Dermatol Ped 1992; 4: 71-4.

23. Sterchi JM, Muss HB, Weidner N. Cellular blue nevus simulating metastatic melanoma: report of an unusually large lesion associated with nevus-cell aggregates in regional lymph nodes. J Surg Oncol 1987; 36: 71-5.

24. Azzopardi JG, Ross CMD, Frizzera G. Blue naevi of lymph node capsule. Histopathology 1977; 1: 451-61.

25. Lambert WC, Brodkin RH. Nodal and subcutaneous cellular blue nevi. A pseudometastasizing pseudomalignancy. Arch Dermatol 1984; 120: 367-70.

26. Pulitzer DR, Martin PC, Cohen AP, Reed RJ. Histologic classification of the combined nevus: analysis of the variable expression of melanocytic nevi. Am J Surg Pathol 1991; 15: 1111-22.

27. Cooper PH. Deep penetrating (plexiform spindle cell) nevus: a frequent participant in combined nevus. J Cut Pathol 1992; 19: 172-80.

28. Fletcher V, Sagebiel RW. The combined nevus: mixed pattern of benign melanocytic lesions that must be differentiated from malignant melanomas. In: Pathology of malignant melanoma. Ackerman AB (ed.), New York, Masson Pub., 1981; 273-83.

29. Rogers GS, Advani H, Ackerman AB. A combined variant of Spitz's nevus. How to differentiate them from malignant melanomas. Am J Dermatopathol 1985; 7 (suppl.): 61-78.

30. Baas J, Bergfeld WF. Melanoma-like changes in benign congenital nevi. J Cut Pathol 1986; 13: 436.

31. Cullity G. Intra-epithelial changes in childhood nevi simulating malignant melanoma. Pathology 1984; 16: 307-11.

32. Kamino H, Ackerman AB. The problems of interpreting the meanings of atypical melanocytes and unusual pattern of melanocytes within the epidermis. In: Pathology of malignant melanoma. AB Ackerman (ed.), New York, Masson Pub., 1981; 129-57.

33. Kerl H, Smolle J, Hödl S, Soyer HP. Kongenitales Pseudomelanom. Z Hautkr 1989; 64: 564-8.

34. Silvers DN, Helwig EB. Melanocytic nevi in neonates. J Am Acad Dermatol 1981; 4: 166-75.

35. Seab JA, Graham JH, Helwig EB. Deep penetrating nevus. Am J Surg Pathol 1989; 13: 39-44.

36. Mehregan DA, Mehregan AH. Deep penetrating nevus. Arch Dermatol 1993; 129: 328-31.

37. Graham J. Malignant deep penetrating nevus. J Cut Pathol 1996; 23: 76.

38. Clark WH Jr, Reimer RR, Greene M, Ainsworth AM, Mastrangelo MJ. Origin of familial malignant melanomas from heritable melanocytic lesions. "The B-K mole syndrome". Arch Dermatol 1978; 114: 732-8.

39. Elder DE, Goldman LI, Goldman SC, Greene MH, Clark WH Jr. Dysplastic nevus syndrome: a phenotypic association of sporadic cutaneous melanoma. Cancer 1980; 46: 1787-94.

40. White IR, MacDonald DM. Familial multiple melanocytic naevi: the
B-K mole syndrome. Clin Exp Dermatol 1981; 6: 549-53.

41. Ackerman AB, Magana-Garcia M. Naming acquired melanocytic nevi. Am J Dermatopathol 1990; 12: 193-209.

42. Ackerman AB. What nevus is dysplastic, a syndrome and the commonest precursor of malignant melanoma? A riddle and an answer. Histopathology 1988; 13: 241-56.

43. Ackerman AB. Critique of definitions about melanocytic proliferations formulated by an NIH panel. Am J Dermatopathol 1992; 14: 238-44.

44. Wayte DM, Helwig EB. Halo nevi. Cancer 1968; 22: 69-90.

45. Reed RJ, Webb SV, Clark WH Jr. Minimal deviation melanoma (halo nevus variant). Am J Surg Pathol 1990; 14: 53-68.

46. Baran R, Haneke E. Longitudinal melanonychia. In: Diseases of the nails and their management. Baran R, Dawber RPR (eds.) London, Blackwell Scientific Pub., 1994; 485-92.

47. Colver GB, Beveridge GW. Familial acquired pigmented streaks in the nail. Clin Exp Dermatol 1991; 16: 158-9.

48. Sison-Torre EQ, Ackerman AB. Melanosis of the vulva. A clinical simulator of malignant melanoma. Am J Dermatopathol 1985; 7 (suppl.): 51-60.

49. Barnhill RL, Albert LS, Shama SK, Goldenhersh MA, Rhodes AR,
Sober AJ. Genital lentiginosis: a clinical and histopathologic study. J Am Acad Dermatol 1990; 22: 453-60.

50. Tronnier M, Wolff HH. UV-irradiated melanocytic nevi simulating melanoma in situ. Am J Dermatopathol 1995; 17: 1-6.

51. Gonzalez SB. Histopathologic diagnosis of pigmented lesions of the skin. Path Res Pract 1991; 187: 387-431.

52. Christensen WN, Friedman KJ, Woodruff JD, Hood AF. Histologic characteristics of vulvar nevocellular nevi. J Cut Pathol 1987; 14: 87-91.

53. Hofmann-Wellenhof R, Soyer HP, Smolle J, Kerl H. Spitz's nevus arising on a nevus spilus. Dermatology 1994; 189: 265-8.

54. Ho VC, Sober AJ. Pigmented streaks in melanoma scars. J Dermatol Surg Oncol 1990; 16: 663-6.

55. Carroll CB, Ceballos P, Perry AE, Mihm MC Jr., Spencer SK. Severely atypical medium-sized congenital nevus with widespread satellitosis and placental deposits in a neonate: the problem of congenital melanoma and its simulants. J Am Acad Dermatol 1994; 30: 825-8.

56. Angelucci D, Natali PG, Amerio PL, Ramenghi M, Musiani P. Rapid perinatal growth mimicking malignant transformation in a giant congenital melanocytic nevus. Hum Pathol 1991; 22: 297-301.

57. Kornberg R, Ackerman AB. Pseudomelanoma. Arch Dermatol 1975; 111: 1588-90.

58. Dwyer CM, Kerr RE, Knight SL, Walker E. Pseudomelanoma after dermabrasion. J Am Acad Dermatol 1993; 28: 263-4.

59. Park HK, Leonard DD, Arrington JH, Lund HZ. Recurrent melanocytic nevi: clinical and histologic review of 175 cases. J Am Acad Dermatol 1987; 17: 285-92.

60. Bolognia JL. Reticulated black solar lentigo ("ink spot" lentigo). Arch Dermatol 1992; 128: 934-40.

61. Kaddu S, Soyer HP, Wolf IH, Rieger E, Kerl H. Reticulated lentigo. Hautarzt 1997; 48, 181-5.

62. Paniago-Pereira C, Maize JC, Ackerman AB. Nevus of large spindle and/or epithelioid cells (Spitz's nevus). Arch Dermatol 1978; 114: 1811-23.

63. Barnhill RL, Barnhill MA, Berwick M, Mihm MC Jr. The histologic spectrum of pigmented spindle cell nevus. Hum Pathol 1991; 22: 52-8.

64. Requena L, Sanchez Yus E. Pigmented spindle cell nevus. Br J Dermatol 1990; 123: 757-63.

65. Smith NP. The pigmented spindle cell tumour of Reed: an underdiagnosed lesion. Semin Diag Pathol 1987; 4: 75-87.

66. Spitz S. Melanoma of childhood. Am J Pathol 1948; 24: 591-609.

67. Wolf IH, Kerl H, Soyer HP, Binder M, Pehamberger H, Fritsch P, Wolff K. Epilumineszenzmikroskopie zur Diagnose pigmentierter Hauttumoren. Hautarzt 1997; 48: 353-62.