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Print version ISSN 0365-0596
On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.3 Rio de Janeiro May/June 2004
Halo nevus spilus*
Flávio Barbosa LuzI; Beatriz França da MataII; Mayra Carrijo RochaelIII
IEffective Member SBD/SBCD; M.Sc.
in Dermatology - UFF; Ph.D. in Dermatology - UFRJ; Responsible for the Department
of Surgical Dermatology and Cutaneous Oncology - GRJ/IPGMCC
IIDermatology Specialist - UFF
IIICollaborating Member of the SBD; Adjunct Professor, Department of Pathology - UFF; Ph.D. in Pathologic Anatomy - UFF; Post-Doctorate in Dermatology - A. B. Ackermann - Institute of Dermatopathology - Thomas Jefferson University
A patient with a junctional component from a nevus spilus surrounded by an achromic halo on the right thigh is reported. The link between the immune response to melanoma and the mechanism responsible for halo nevus is closely related. There is evidence that the halo phenomenon results from a mediated cell immunologic reaction against an unknown antigen present in melanocytic lesions. Antibodies are also found in these lesions.
Key words: immunity; melanoma; nevus, pigmented
Halo nevus is a relatively common phenomenon that occurs mainly in adolescents, especially in the back and can be multiple. Its clinical course is characteristic: a preexisting melanocytic nevus is surrounded by a depigmented halo that gradually disappears with the nevus. Table 1 shows this progression from the histopathological standpoint. Frank and Cohen1 reported that at least 50% of the halo nevi disappear spontaneously. However, areas of depigmentation can persist for months and even years or become totally repigmented.2,3
The malignant potential of nevus spilus lesions has been recognized. Fifteen cases were found in the literature of melanoma originating from this type of lesion.4-18
Nevus spilus is a special type of congenital melanocytic nevus. Some authors believe that small melanocytic nevi present an increased risk of coursing to melanoma. The risk of becoming malignant increases after puberty, the cumulative probability in patients aged over 60 years is considered to be between 0.8 and 4.9%.19,20
Adolescent 15 years old, mixed race, student and single, presenting from infancy a hyperchromic stain with precise though irregular margins, located in the subsequent face of the right thigh (Figure 1). A more meticulous exam revealed punctiform and blackened stains in the surface of the lesion. Six months previously she had noticed the appearance of an achromic nummular stain with very well defined edges within the lesion. Histopathological exam demonstrated that this was a Sutton's halo nevus type lesion in a junction nevus surrounded by lentigo simplex.
Halo nevus type lesion is clinically characterized by the appearance of a nonpigmented patch bordering a melanocytic tumoral lesion, resembling a vitiligo stain. From the histopathological point of view, this lesion is formed by a mononuclear infiltrate around nevoid cells, which are progressively destroyed.
In 1952, Ito and Hamada19 described nevus spilus as a light-chestnut patch with precise but irregular edges and with blackened spots inside. Histopathologic exam shows that the light-chestnut area corresponds to a lentigo simplex and the darker points to junctional or compound nevi. Nevus spilus is a congenital melanocytic lesion. The lesion tends to appear within the first year of life and the darker points between six and 39 years of age.
In such a Sutton's nevus type vitiliginous lesion within a nevus spilus lesion there are no histological signs of atypia. Such a finding could represent both an effective response against a very initial melanoma and a strong argument against the hypothesis that this type of response means a defense mechanism against a malignant process.
The presence of immunological mechanisms in the pathogenesis of halo nevus can be demonstrated by two factors: mononuclear cell infiltrate progressively involving the nevoid cells in degeneration and the presence of antibodies directed to the antigens that react in vitro with nevoid and melanocytic cells.21
The immunity mediated by T cells in the development of halo nevus can be demonstrated by immunohistochemical studies, which reveal that the majority of the lymphocytes of the infiltrate are derived from the T lymphoid lineage and it is estimated that the largest part of which, are CD8+ T cells.22
Natural killer cells were found in small amounts and the lymphokines they activate have little influence in the cytotoxicity of the melanocytes in vitiligo,23 enabling the supposition that the same are not involved in the immune reactions that lead to the depigmentation.
Although no direct demonstration of death of the melanocytes due to the effector cells present in the halo has been observed, the abundance of antigen presenter cells within the nevus in regression and the presence of T lymphocytes in the site of the depigmentation suggest the participation of these cells in the halo phenomenon. Within the latter population of cells, evidence points to the involvement of CD8+ T cells as important destructive agents of melanocytic nevi. Possible factors unchaining the migration and activation of lymphocytes in nevi apparently without alterations have yet to be clarified.21 Mooney et al.,24 studying 142 halo nevi, observed that the depigmentation phenomenon occurs in a variety of types of histologically atypical nevi. This study demonstrates that there can be a broad spectrum of atypia among the halo nevi and in those with intense atypia it can be difficult to differentiate them from the rare phenomenon of malignant halo melanoma.
Research into the halo phenomenon in melanoma is of fundamental importance for the understanding of its regression, as well as that of halo nevus. Copeman and Eliot25 demonstrated the presence of antibodies against cytoplasmatic components of melanoma cells in patients with halo nevus in involution. They concluded that circulating antibodies contribute to the occurrence of halo nevus and that this fact suggests the vitiligous reaction could signify a rejection of the organism to an initial melanoma that is growing in a nevoid lesion. Grispan et al.26 have also suggested that this phenomenon occurs against dysplastic lesions of nevus spilus.
Tyrosinase is an auto-antigen in potential involved in the response against melanocytes in the auto-immune vitiligo27 and malignant melanoma cells.28 Another study has demonstrated that in both diseases there is a production of antibodies due to the antigens common to both the melanocytes and melanoma.29 As is well known in clinical practice, antibodies directed against the melanoma are also cytotoxic to normal melanocytes and can unchain vitiligo lesions in patients with melanoma.
Although there is a relationship between depigmentation of the halo nevus and production of antibodies against nevoid cells, regression of the nevus does not occur simultaneously with the appearance of circulating reactive antibodies against the cytoplasm of the melanoma cells. Krebs et al.30 have suggested that the immunologically mediated cytotoxicity could destroy nevoid cells that, in turn, would produce antibodies. Lesion of the cell targeted by cytotoxic T lymphocytes appears to be the primary event in the formation of the halo nevus.
After studying 46 cases of halo nevus and melanomas in regression, based on immune and histopathological aspects, Campos31 concluded that the halo phenomenon appears to be determined by antigens that do not specify the type nor benign or malignant character of the lesions, since the halo nevus, melanoma and normal melanocytes share some of the molecular targets responsible for the regression phenomenon.
The authors report the case of a patient with nevus spilus in which the clinical and histopathological halo phenomenon was observed. The possibility of an auto-immune reaction against atypical or even typical cells present in these lesions together with the similarity to that whichj occurs in the melanoma, has been presented by some authors, although its cause continues to be unexplained.
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Flávio Barbosa Luz
Rua Desembargador Izidro, 28 / 606 - Tijuca
20521-160 Rio de Janeiro RJ
Tel.: (21) 2298-2013 / 2570-5841
Received in January, 07th of 2002.
Approved by the Consultive Council and accepted for publication in October, 05th of 2002.
* Work done at "the services of Dermatology and Pathologic Anatomy, Fluminense Federal University - UFF".