ARTICLE
The genetic basis of atypical mole and melanoma syndrome has not yet
been established, despite much recent progress in this area [1-3]. The
existence of cases of unilateral atypical mole syndrome, caused by a single
dominant mutation, strongly supports the concept of an autosomal dominant
genetic mechanism, although only 2 such cases (including the present case)
have been observed thus far [4, 5]. In addition, given that melanoma occurred
in both of the cases, a close genetic relationship is implied between
susceptibility to melanoma and the atypical mole syndrome phenotype.
During the follow-up of this patient with unilateral atypical mole syndrome
following excision of a malignant melanoma, we observed the appearance
of an atypical mole on the grafted skin in the atypical mole syndrome
region. We herein report this unique case and discuss the pathogenesis
of atypical moles.
Case report
A 41-year-old man had numerous moles intermingled with clinically atypical
nevi, which showed a unilateral localization, being exclusively located
dorsally on the patient's left upper quadrant. Only a few small and banal
moles were observed elsewhere on the patient's skin. A pigmented, nodular
lesion had developed on the left upper back. It was excised with a 5-cm
margin, and skin grafting was performed at our clinic, using the patient's
right buttock as the donor site. The pigmented nodular lesion was histologically
revealed to be a superficial spreading melanoma, Clark level IV, with
a maximal tumor thickness of 8 mm. Several, clinically atypical moles,
removed at the same time, were found histologically to meet recent criteria
for atypical moles [6]. Screening of the patient's first-degree relatives
revealed that there was sporadic melanoma and atypical mole syndrome (Kraemer's
type C [7]). This case was reported previously [5].
Immediately after the skin graft, there were
no moles on the grafted skin (Fig.
1, A and B).
The patient was followed up for 5 years, and no evidence of metastasis
or recurrence of melanoma was observed. Neither apparent change of the
atypical moles in the atypical mole syndrome area nor new development
of atypical moles in other areas was observed. However, we noticed the
appearance of a clinically atypical mole, 3 x 2 mm in size, with slight
elevation and a peripheral macular tan zone, in the grafted skin near
the left side of the graft margin (Fig.1,
C and D).
We excised this atypical mole. Although this mole did not present clinical
features as florid as a common atypical mole, the histologic features
were appropriate for an atypical mole, manifesting architectural disorder
and moderate melanocytic atypia (Fig.
2).
Discussion
A recent clinical investigation has shown that atypical moles remain
clinically dynamic, and the appearance of new nevi in adulthood is common
in individuals with atypical moles [8]. Considering this finding, the
characteristics in the present case are not surprising. However, it is
of interest that in this patient a new, atypical mole appeared on the
grafted skin obtained from his buttock; the skin of the buttock itself
did not present the atypical mole syndrome phenotype.
Patients with atypical mole syndrome phenotype are thought to have a
genetically abnormal melanocytic system as well as a predisposition to
the development of melanocytic nevi over the whole body area [9, 10].
In the present patient, the abnormal melanocytic system may well be confined
to the dorsal side of the left upper quadrant. The absence of atypical
moles in areas other than this one during the 5 years of follow-up supports
this contention.
It is generally accepted that a complicated
interaction between local genetic factors and direct sunlight is important
to the development of atypical moles [10, 11]. Some authors have suggested
that, in the formation of atypical moles, direct sunlight exposure has
a strong influence, given the absence of atypical moles in the sun-protected
areas in patients with atypical mole syndrome [10], while others have
pointed out the primacy of local genetic factors in the skin based on
the evidence that the distribution pattern of atypical moles is clearly
different from that of common nevi in both patients with melanomas and
controls [11].
Concerning the appearance of the atypical mole on the grafted skin in
our patient, two possibilities may be considered. In one, a melanocyte,
predetermined to form an atypical mole, migrates from the atypical mole
syndrome-affected area to the grafted skin, where the atypical mole develops.
In the other, some unknown local genetic factors, within the affected
dermal area [12], may influence the normal melanocytes distributed in
the epidermis of the grafted skin, resulting in the development of the
atypical mole. Whatever the possibilities, cutaneous cytokines or neuropeptides
released during wound healing should also be considered as promoters acting
on potentially initiated melanocytes in the grafted skin [12, 13].
REFERENCES
1. Meyer LJ, Zone JH. Genetics of cutaneous melanoma. J Invest Dermatol
1994; 103: 112s-6s.
2. Bergman W, Gruis NA, Sandkuijl LA, Frants RR. Genetics of seven Dutch
familial atypical multiple mole-melanoma syndrome families: a review of
linkage results including chromosomes 1 and 9. J Invest Dermatol 1994;
103: 122s-5s.
3. Goldstein AM, Dracopoli NC, Engelstein M, Fraser MC, Clark WH Jr,
Tucker MA. Linkage of cutaneous malignant melanoma/dysplasic nevi to chromosome
9p, and evidence for genetic heterogeneity. Am J Hum Genet 1994;
54: 489-96.
4. Sterry W, Christophers E. Quadrant distribution of dysplasic nevus
syndrome. Arch Dermatol 1988; 124: 926-9.
5. Misago N, Takahashi M, Kohda H. Unilateral dysplasic nevi associated
with malignant melanoma. J Dermatol (Tokyo) 1991; 18: 649-53.
6. NIH Consensus Conference. Diagnosis and treatment of early melanoma.
JAMA 1992; 268:1314-9.
7. Kraemer KH, Tucker M, Tarone R, Elder DE, Clark WH Jr. Risk of cutaneous
melanoma in dysplastic nevus syndrome type A and B. N Engl J Med 1986;
315: 1615-6.
8. Halpern AC, Guerry D IV, Elder DE, et al. Natural history
of dysplastic nevi. J Am Acad Dermatol 1993; 29: 51-7.
9. Bataille V, Boyle J, Hungerford JL, Newton JA. Three cases of primary
acquired melanosis of the conjunctiva as a manifestation of the atypical
mole syndrome. Br J Dermatol 1993; 128: 86-90.
10. Abadir MC, Marghoob AA, Slade J, Salopek TG, Yadav S, Kopf AW. Case-control
study of melanocytic nevi on the buttocks in atypical mole syndrome: role
of solar radiation in the pathogenesis of atypical moles. J Am Acad
Dermatol 1995; 33: 31-6.
11. Stierner U, Augustsson A, Rosdahl I, Suurküla M. Regional distribution
of common and dysplastic naevi in relation to melanoma site and sun exposure:
a case-control study. Melanoma Res 1991; 1: 367-75.
12. Gilhar A, Gershoni-Baruch R, Margolis A, Benderly A, Brandes JM.
Dopa reaction of fetal melanocytes before and after skin transplantation
on to nude mice. Br J Dermatol 1995; 133: 884-9.
13. Matsumoto K, Robb E, Warden G, Nordlung J. Hyperpigmentation of
human skin grafted on to athymic nude mice: immunohistochemical study.
Br J Dermatol 1996; 135: 412-8.
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