III.10
III.10.1 Definition
Halo nevus (synonyms: Sutton nevus; leuko- derma acquisitum centrifugum; albinismus perinaevicus) is a melanocytic nevus surround- ed by a rim of depigmentation, resembling a
“halo”. The lesion was originally identified as a distinct entity by Sutton in 1916, whereas in 1874 Hebra and Kaposi had described it as viti- ligo [1].
III.10.2 Clinical Features
Clinically, halo nevus typically appears as a cir- cumscribed, homogeneously coloured, 3–6 mm in size, evenly shaped nevus surrounded by a peripheral sharply defined symmetrical depig- mented area. The central nevus usually is a common benign compound nevus [2]. The en- circling halo of hypomelanosis has a uniform radial distance from the central nevus and var- ies in size from a few millimetres up to some centimetres (Fig. III.10.1).
Chapter III.10
Halo Nevus
Alessandro Di Stefani and Sergio Chimenti III.10
Contents
III.10.1 Definition . . . .124
III.10.2 Clinical Features . . . .124
III.10.3 Dermoscopic Criteria . . . .126
III.10.4 Relevant Clinical Differential Diagnoses . . . .126
III.10.5 Histopathology . . . .126
III.10.6 Management . . . .127
References . . . .127
The incidence of halo nevus in the popula- tion is estimated to be around 1%, and a familial occurrence has also been reported [3]. It is more common in children and young adults, with an average age of onset at 15 years, and has no gen- der or racial predilection. Preferential site of in- volvement is the trunk, although it may occur anywhere on the body. The presence of two or more halo nevi has been described in 25–50% of affected individuals. Occasionally, a high num- ber of halo nevi may develop simultaneously or sequentially.
Over a period of months or years, halo nevi typically show a characteristic clinical course that can be divided into four clinical stages:
(a) stage I, in which the white halo around the central nevus appears; (b) stage II, with lightening and reddening of the central nevus;
(c) stage III, which is characterized by progres- sive involution and subsequent complete re-
Fig. III.10.1. Typical clinical presentation of a halo ne- vus: note the papular, uniformly colored, evenly shaped central nevus with a symmetrical, peripheral rim of depigmentation resembling a halo
Halo Nevus
Alessandro Di Stefani and Sergio Chimenti III.10
gression of the central nevus, leaving a circular area of non-pigmented skin; and (d) stage IV, in which the depigmentation may persist for years before melanocytes from the surrounding skin eventually re-popularize the area (Fig.
III.10.2) [4]; however, unusual clinical evolu- tion of halo nevus has also been reported, with progressive darkening of the nevus component [5]. The coexistence of a halo nevus and vitiligo has been reported in about 20% of cases, although the relationship between these two types of acquired leucoderma has not been fully elucidated [6]. Occasionally, halo nevus is observed in patients with a personal or family
history of melanoma [7]. Association with me- lanoma has been also supported by detection of circulating antibodies reactive against ne- vus cells as well as melanoma cells in the serum of patients with halo nevus [8]. In addition, the prevalence of halo nevi in patients with Turner’s syndrome has been reported to be higher as compared with the general population [9]. The aetiology of halo depigmentation is un- known: most often it is idiopathic, but some- times it follows sunburns (Fig. III.10.2). T-lym- phocytes are believed to play a key role in the progressive destruction of nevus cells [2].
Fig. III.10.2. a Clinical image of the back of a 10-year- old child with a recent history of sunburn. b Three months later, dermoscopic examination of the nevus in the left lumbar region reveals a subtle halo of depigmen- tation surrounding the central nevus. c Clinical image of
the same patient 12 months later shows a more evident halo nevus. d Dermoscopic examination (at the same time of c) demonstrates involution of the central nevus and a width-surrounding halo
126 A. Di Stefani, S. Chimenti
III.10
III.10.3 Dermoscopic Criteria
The dermoscopic features that characterize halo nevi have not yet been described in detail. The most frequently observed pattern is the homo- geneous-globular pattern, followed by the ho- mogeneous pattern and the globular pattern, while the reticular pattern is uncommon (Fig. III.10.3) [10]. Brown homogeneous pig- mentation, brown globules and pigment net- work are generally associated with benign mela- nocytic nevi, especially if they are regularly distributed within the lesion [11–10]. The pe- ripheral halo does not display any peculiar der- moscopic criteria, with the exception of a whit- ish colour. Dermoscopy may reveal the presence of other dermoscopic criteria within the halo le- sion in order to establish a definite diagnosis and/or rule out a regressing melanoma [11]. In addition, dermoscopic monitoring of halo ne- vus allows to better appreciate involution pro- cess during follow-up visits [10].
III.10.4 Relevant Clinical Differential Diagnoses
Halo nevus usually is a common benign com- pound or intradermal nevus [2], but an encircl- ing halo is also described in association with congenital nevus, blue nevus, Spitz nevus and, very rarely, with melanoma [7, 12–15]; thus, the
most important differential diagnosis is with a melanoma showing halo-like regression. Clini- cally, the halo surrounding a regressive mela- noma is usually more asymmetrical and, in most cases, the central lesion is more irregular in shape, borders, and coloration [7, 14–15]. In addition, melanoma with halo-like regression may display a dermoscopic multicomponent pattern (i.e. the simultaneous presence of atypi- cal pigment network, blue white veil, irregular dots/globules, regression structures) [10].
Other differential diagnoses include melano- cytic lesions such as atypical nevus, recurrent nevus, Meyerson nevus, targetoid hemosiderot- ic nevus, cockade nevus and melanoma metas- tases, as well as non-melanocytic lesions as seb- orrheic keratosis, neurofibroma, and basal cell carcinoma [16]. When the nevus component is completely regressed, halo Nevus must be dis- tinguished from unilesional vitiligo: both disor- ders present, clinically, a pure white colour of the otherwise unchanged surface of the skin [2, 6].
III.10.5 Histopathology
Halo nevus is histopathologically defined by the presence of a striking dense, band-like lympho- cytic infiltrate among dermal nevus cells and loss of pigment at the dermo-epidermal junc- tion at the periphery of the nevus [2, 16]. Some nevi with a lymphocytic infiltrate of the type seen in halo nevus (“halo phenomenon”) do not show an obvious clinical depigmented halo;
therefore, clinical correlation is important in rendering a diagnosis of halo nevus [16]. The number of remnant nevus cells depend on the stage at which the biopsy is taken. Mitotic fig- ures usually are not present, although occasion- al apoptotic cells may be identified. Macro- phages may be seen within the infiltrate, some of which are loaded with melanin.
Immunohistochemical staining for S-100, HMB45 or Melan-A, may be useful to identify residual nevus cells when a dense lymphocytic infiltration obscures surviving melanocytes. Im- munohistochemistry shows positivity of lympho- cytic cells for CD1a, CD68, CD3 and CD8 [17]. A clonal expansion of T lymphocytes has been demonstrated in cases of halo nevi [17]. There is
Fig. III.10.3. Dermoscopy of a halo nevus shows a ho- mogeneous-globular pattern and a whitish, peripheral depigmented area. (Inset: clinical image)
also evidence of activated lymphocytes in the pe- ripheral blood as well as anti-nevic IgM antibody production in affected individuals [2, 8]. These data suggest that cytotoxic T cells may be in- volved in the regression of the nevus and that the destruction of melanocytes in the halo phenom- enon could be view as the lysis of a distinctive cell type through an autoimmune-like process medi- ated by an oligoclonal T-cell response [17].
III.10.6 Management
Halo nevus is a benign lesion, and no treatment is required. Reassurance of the concerned pa- tient is a relevant issue. If a typical halo lesion is observed in children, no further examinations are needed and it may be of only cosmetic sig- nificance. A clinical and dermoscopic follow-up may be performed in order to monitor the char- acteristic evolution of halo nevi. Despite clini- cally benign features, the presence of a new halo lesion in an adult individual should be regarded with a high index of suspicion and an excisional biopsy is mandatory. Surgical excision should be performed also in all halo nevi showing clin- ico-dermoscopic atypical features in order to rule out a regressive melanoma.
C
Core Messages
■ Halo nevi usually show a characteristic clinical appearance and course.
■ Regression may be explained by direct cytotoxic effects of lymphocytes on melanocytes.
■ The most important differential diagnosis is the rare case of a mela- noma revealing a halo-type of regres- sion.
■ Halo nevi are benign lesions and treatment is not necessary in typical lesions in children.
■ Surgical excision and subsequent histopathological examination should be performed in halo nevi showing clinico-dermoscopic atypical features.
References
1. Sutton RL (1916) An unusual variety of vitiligo (leucoderma acquisitum centrifugum). J Cut Dis 34:797–800
2. Elder DE, Xu X. Halo naevus (2006). In: Le Boit PE, Burg G, Weedon D et al. (eds) World Health Orga- nization classification of skin tumors. Pathology and genetics of skin tumors. IARC Press, Lyon 3. Herd RM, Hunter JA (1998) Familial halo naevi.
Clin Exp Dermatol 23:68–69
4. Barnhill RL, Fitzpatrick TB, Fandrey K et al. (1995) Color atlas and synopsis of pigmented lesions. Mc- Graw-Hill, New York
5. Inamadar AC, Palit A, Athanikar SB et al. (2003) Unusual course of a halo nevus. Pediatr Dermatol 20:542–543
6. Schallreuter KU, Kothari S, Elwary S et al. (2003) Molecular evidence that halo in Sutton’s naevus is not vitiligo. Arch Dermatol Res 295:223–228 7. Fishman HC (1976) Malignant melanoma arising
with two halo nevi. Arch Dermatol 112:407–408 8. Tokura Y, Yamanaka K, Wakita H et al. (1994) Halo
congenital nevus undergoing spontaneous regres- sion. Involvement of T-cell immunity in involution and presence of circulating anti-nevus cell IgM an- tibodies. Arch Dermatol 130:1036–1041
9. Brazzelli V, Larizza D, Martinetti M et al. (2004) Halo nevus, rather than vitiligo, is a typical der- matologic finding of Turner’s syndrome: clinical, genetic, and immunogenetic study in 72 patients.
J Am Acad Dermatol 51:354–358
10. Kolm I, Di Stefani A, Hofmann-Wellenhof R, et al. (2006) Dermoscopy patterns of halo nevi. Arch Dermatol 142:1627–1632
11. Argenziano G, Soyer HP, Chimenti S et al. (2003) Dermoscopy of pigmented skin lesions: results of a consensus meeting via the Internet. J Am Acad Der- matol 48:679–693
12. Itin PH, Lautenschlager S (2002) Acquired leuko- derma in congenital pigmented nevus associated with vitiligo-like depigmentation. Pediatr Derma- tol 19:73–75
13. Harvell JD, Meehan SA, LeBoit PE (1997) Spitz’s nevi with halo reaction: a histopathologic study of 17 cases. J Cutan Pathol 24:611–619
14. Saida T, Tsuchiya S (1984) Spontaneous partial re- gression of primary melanoma with death due to metastases. Arch Dermatol 120:1494–1496 15. Pantoja E, Wendth AJ, Beecher TS (1977) Perile-
sional vitiligo in melanoma. Cutis 19:51–53 16. Mooney MA, Barr RJ, Buxton MG (1995) Halo ne-
vus or halo phenomenon? A study of 142 cases. J Cutan Pathol 22:342–348
128 A. Di Stefani, S. Chimenti
III.10
17. Musette P, Bachelez H, Flageul B et al. (1999) Im- mune-mediated destruction of melanocytes in halo nevi is associated with the local expansion of a lim- ited number of T cell clones. J Immunol 162:1789–
1794
