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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.86 no.4 Rio de Janeiro July/Aug. 2011
Epidermolysis bullosa nevus: case report and literature review*
Carolina Porto CotrimI; Fernanda Tolstoy de SimoneII; Ricardo Barbosa LimaIII; Carlos Baptista BarcauiIV; Maria Auxiliadora Jeunon SousaV; Gabriela LowyVI
IPhysician graduated from the State University of Montes Claros (Universidade Estadual de Montes Claros - UNIMONTES) - Graduate course in Dermatology at the Teaching Hospital Gaffree and Guinle, Federal University of the State of Rio de Janeiro (Hospital Universitario Gaffree e Guinle, Universidade Federal do Estado do Rio de Janeiro - HUGG - UNIRIO) - Rio de Janeiro (RJ), Brazil
IIResidency in Dermatology at the Teaching Hospital Gaffree and Guinle, Federal University of the State of Rio de Janeiro (Hospital Universitario Gaffree e Guinle, Universidade Federal do Estado do Rio de Janeiro - HUGG - UNIRIO) - Rio de Janeiro (RJ), Brazil
IIIGraduate course in Dermatology at the Teaching Hospital Gaffree and Guinle, Federal University of the State of Rio de Janeiro (Hospital Universitario Gaffree e Guinle, Universidade Federal do Estado do Rio de Janeiro - HUGG - UNIRIO) - Rio de Janeiro (RJ), Brazil. Assistant Professor at the Dermatology Service of the Graduate course in Dermatology at the Teaching Hospital Gaffree and Guinle, Federal University of the State of Rio de Janeiro (Hospital Universitario Gaffree e Guinle, Universidade Federal do Estado do Rio de Janeiro - HUGG - UNIRIO) - Rio de Janeiro (RJ), Brazil
IVPhD in Dermatology from the University of São Paulo (Universidade de São Paulo - USP) - Associate Professor at the Institute of Dermatology Professor Rubem David Azulay, Santa Casa de Misericordia do Rio de Janeiro (Instituto de Dermatologia Professor Rubem David Azulay da Santa Casa de Misericordia do Rio de Janeiro - IDPRDA - SCMRJ) - Rio de Janeiro (RJ), Brazil
VRetired Professor of the Medical Science School of the State University of Rio de Janeiro (Faculdade de Ciencias Medicas da Universidade Estadual do Rio de Janeiro - UERJ) - Medical Director of Investigation at Dermatologia S/C Ltda. - Rio de Janeiro (RJ), Brazil
VIDistinguished Professor (Livre Docencia) in Dermatology from the Federal University of the State of Rio de Janeiro (Universidade Federal do Estado do Rio de Janeiro - UNIRIO) - Retired Full Professor of the Dermatology Service, Teaching Hospital Gaffree and Guinle, Federal University of the State of Rio de Janeiro (Hospital Universitario Gaffree e Guinle, Universidade Federal do Estado do Rio de Janeiro - HUGG - UNIRIO) - Rio de Janeiro (RJ), Brazil
Acquired melanocytic lesions resembling malignant melanoma have been described in all major categories of Epidermolysis bullosa and referred to as "Epidermolysis bullosa nevi''. They easily induce to diagnostic error, although no malignant transformation has been reported. We report the development of a large acquired melanocytic nevus at a site of recurrent blisters in a 5-year-old child with Epidermolysis bullosa simplex. The global dermoscopic pattern was suggestive of benignity, and the histopathological findings were compatible with a compound melanocytic nevus. This is the first published case of Epidermolysis bullosa nevi in Brazilian literature. Despite their benign behavior, we emphasize the importance of regular clinical and dermoscopic monitoring, since a malignant course still cannot be totally excluded.
Keywords: Biopsy; Dermoscopy; Epidermolysis bullosa; Melanoma; Nevus, pigmented
Epidermolysis bullosa (EB) nevus is the name given to the acquired melanocytic nevus that develops in Epidermolysis bullosa (EB).1 Despite its benign course, this nevus is particularly important for being clinically indistinguishable from melanoma, according to the ABCD rule.1-6 As it simulates melanoma, this may induce to unnecessary aggressive treatment.
Our review of the literature revealed that it occurs predominantly in dystrophic forms of EB. The case presented below will be the fourth case published in the international literature of EB nevus in an Epidermolysis bullosa simplex patient, and it is the first case published in Brazilian literature.
A white, 5-year old female patient diagnosed with Epidermolysis bullosa simplex (EBS) was referred for evaluation of a pigmented lesion with progressive growth, for approximately three months, located on the fourth left toe, the site of recurrent bullous lesions. The daughter of non-consanguineous healthy parents, she had presented recurrent bullous lesions since the first days of life, mainly on the extremities.
Upon clinical examination, the patient presented flaccid blisters and eroded areas on the soles of feet and between the toes. On the fourth toe there was a pigmented macula affecting almost its whole extension, asymmetrical, with irregular margins and a few satellite lesions on its periphery (Figure 1). There was pigmentation variation with black, light brown and dark brown colors. The dermoscopic aspect of the macula included irregular dark brown dots on its surface and aggregated globules on its periphery (Figures 2 and 3). On the plantar surface were observed fibrillar or parallel furrow patterns, with some isolated black dots on the periphery (Figure 4). No vascular structures were observed. The global dermoscopic pattern of the pigmented lesion suggested benignity and was compatible with the homogeneous globular pattern.
Histopathology of a dense pigmented area revealed the presence of nests of regular melanocytes located on the upper and middle dermis and on the dermoepidermal junction, without cellular or architectural atypical structures (Figure 5). No upper pagetoid migrations of melanocytes and mitotic figures were observed. Therefore, the histopathological findings were compatible with a compound melanocytic nevus.
The clinical and histopathological findings led to an EB nevus diagnosis.
Considering the benign behavior of these nevi described in the literature, we opted for periodical follow-up of this patient.
Epidermolysis bullosa represents an heterogeneous group of mechanobullous diseases, genetically determined and secondary to an intrinsic defect in the structural component of the basement membrane zone (BMZ). It is characterized by cutaneous fragility and bullous lesions that appear as result of trivial traumas. 1-5
Uncommon large and eruptive melanocytic nevi have been described in EB patients.1-6 Their similarity with melanoma easily induces to diagnostic error.
The EB nevi term was proposed by Bauer and collaborators in 2001 to designate acquired melanocytic lesions that have a peculiar combination of clinical, histopathological and biologic criteria.1 In their case study with 86 EB patients, they found 12 patients affected in the three main EB groups, suggesting that EB nevi are not so rare among EB patients.
The onset of EB nevi usually occurs in childhood and appears as a large, eruptive and pigmented lesion on areas of recurrent bullous lesions. It has marked asymmetry, pigmentation variation, cicatricial areas and regression focuses.1,3-6 Such characteristics suggest a false impression of malignancy, reinforced when the pigmented lesion shows continuous and sometimes sudden growth, with onset of satellite lesions, as occurred in our patient. 2
The EB nevus has a dynamic evolution, with fast growth and possible changes on its surface. 1-5 Bauer and collaborators described two patients with generalized atrophic EB, in whom similar lesions lost their pigmentation and their surfaces became papillomatous in a period between seven and eight years. 1 Cash and collaborators described another patient who had dystrophic EB and an EB nevus that lost pigmentation after 18 months of follow-up. 4
Considering that morphological alterations in pigmented lesions are described as significant predictors of malignancy, it was suggested that the EB nevus could be an exception to this rule, since continuous clinical modifications of these nevi have been documented for 25 years, and cutaneous melanoma was excluded through repeated histological evaluation. 1,2, 7
Lanschuetzer and collaborators analyzed the dermoscopic characteristics of 23 EB nevus lesions in 11 patients. 2 This study found a high frequency of dermoscopic criteria associated with melanoma as multicomponents (20 of 23), atypical pigmented network (17 of 23), globules and irregular dots (16 of 23), irregular pigmentation (22 of 23) and atypical vascular pattern (7 of 23). However, strong indicators for invasive cutaneous melanoma such as gray-blue areas, black dots and blue-white veil were not common characteristics of EB nevi. They observed a new vascular pattern similar to glomerular vessels, suggesting that it could be specific of EB nevi, representing an exaggerated neovascularization during the skin repair process. In the same study, most lesions presented false-positive results when the ABCD rules and Seven-Point method of dermoscopy were applied. Likewise, in our patient the EB nevus presented a false-positive result when dermoscopic algorithms were calculated, but the global dermoscopic pattern was compatible with the homogeneous globular pattern, which is suggestive of benignity. This means that the EB nevus represents an exception to diagnostic dermoscopic algorithms, although the global dermoscopic evaluation frequently permits an estimation of a benign nature. 2
The histopathological pattern of the EB nevus may be compatible with a compound/ junctional nevus, or a persistent nevus. 1-6 The first pattern was described in three EBS cases in the literature, and was also observed in the case here described.1,4,5 The persistent nevus pattern is more frequent in recessive dystrophic EB patients. 1,4,5 A challenge related to the EB nevus histopathology is the difficulty in distinguishing a persistent melanocytic nevus pattern from a melanoma pattern. 4 Monomorphous melanocytes, absence of mitotic figures, normal proliferative rates and knowledge about the EB nevus phenomenon may help distinguish them. 4
The EB nevus pathogenesis is not completely understood. The most accepted hypothesis is that repeated traumas to the basal layer where recurrent blisters appear could induce proliferation of melanocytes, according to inflammation and reepithelization processes.1-6 The phenomenon of Koebner, represented as the expansion of an incipient nest of nevic cells, or of melanocytes present in the epidermis or in the follicular epithelium, could be involved. 1,4,5,6, 8 In addition, in EBS the lysis of basal keratinocytes, which is associated with the complete destruction of melanocytes, could modify the normal relationship between these two cells, and residual melanocytes would proliferate freely.3 The disordered arrangement of these melanocyte clones could explain the dermoscopic characteristics seen in EB nevi. 2,3, 4
Although large and eruptive melanocytic nevi have already been described in the main EB categories, there is predominance of dystrophic and junctional forms of the disease. 1-5 The complete loss of a specific protein of the basement membrane zone (BMZ) in the recessive forms of EB would favor development of these nevi. 1,3, 5 Note that the EB nevus was reported in only three EBS patients; our case is the fourth one described in the international literature, and the first described in Brazilian literature.
Similar cases of eruptive melanocytic nevi were described following Stevens-Johnson syndrome episodes, erythema multiforme and associated with lichen sclerosus and atrophicus 9-12. The proposed pathogenesis is similar to that related to EB nevus.3,9-12
There is only one report describing a child with bullous pemphigoid located on the a vulva, where recurrent blisters developed, an atypical melanocytic nevus with clinical and dermoscopic characteristics of melanoma.13 This was the first case where a melanocytic nevus developed on the site of bullous lesions, in bullous autoimmune and subepidermal disease in childhood.
Monitoring EB nevus patients for over 25 years did not make any malignant alteration evident.1,2 Considering the benign course of these nevi, we adopted a conservative therapy, with periodical follow-up of our patient.
In conclusion, we emphasize the importance of clinical, dermoscopic and histopathological studies of these nevi to avoid diagnostic error and unnecessary interventions. Despite their benign course, we point out that it is very important to make a differential diagnosis in comparison with melanoma, as well as regular monitoring, since malignant evolution cannot be completely excluded.
1. Bauer JW, Schaeppl H, Kaserer C, Hantich B, Hinter H. Large Melanocytic nevi in hereditary epidermolysis bullosa. J Am Acad Dermatol. 2001;44:577-84. [ Links ]
2. Lanschuetzer CM, Emberger M, Laimer M, Diem A, Bauer JW, Soyer HP, et al. Epidermolysis bullosa naevi reveal distinctive dermoscopic pattern. Br J Dermatol. 2005;153:97-102 [ Links ]
3. Gallardo F, Toll A, Malvehy J, Mascaró-Galy JM, Lloreta J, Barranco C, et al. Large atypical melanocytic nevi in recessive dystrophic epidermolysis bullosa: clinico pathological, ultrastructural, and dermoscopic study. Pediatr Dermatol. 2005;22:338-43. [ Links ]
4. Cash SH, Dever TT, Hyde P, Lee BJ. Epidermolysis Bullosa Nevus. Arch Dermatol. 2007;143:1164-7. [ Links ]
5. Stavrianeas NG, Katoulis AC, Moussatou V, Bozi E, Petropoulou H, Limas C, et al. Eruptive large melanocytic nevus in a patient with hereditary epidermolysis bullosa simplex. Dermatology. 2003;207:402-4. [ Links ]
6. Natsuga K, Akiyama M, Sato-Matsumura KC, Tsuchiya K, Shimizu H. Two cases of atypical melanocytic lesions in recessive dystrophic epidermolysis bullosa infants. Clin Exp Dermatol. 2005;30:636-9. [ Links ]
7. Kittler H, Seltenheim M, Dawid M, Pehamberger H, Wolff K, Binder M. Morphologic changes of pigmented skin lesions: a useful extension of the ABCD rule for dermatoscopy. J Am Acad Dermatol. 1999;40:558-62. [ Links ]
8. Soltani K, Pepper MC, Simjee S, Apatoff BR. Large acquired nevocytic nevi induced by the Kobner phenomenon. J Cutan Pathol 1984;11:296-9. [ Links ]
9. Shoji T, Cockerell CJ, Koff AB, Bhawan J. Eruptive melanocytic nevi after Stevens-Johnson syndrome. J Am Acad Dermatol. 1997;37:337-339. [ Links ]
10. Kirby JD, Darley CR. Eruptive melanocytic naevi following severe bullous disease. Br J Dermatol. 1978;99:575-80. [ Links ]
11. Carlson JA, Mu XC, Slominski A, Weismann K, Crowson AN, Malfetano J, et al. Melanocytic proliferations associated with lichen sclerosus. Arch Dermatol. 2002;138:77-87. [ Links ]
12. El Shabrawi-Caelen L, Soyer HP, Schaeppi H, Cerroni L, Schirren CG, Rudolph C, et al. Genital lentigines and melanocytic nevi with superimposed lichen sclerosus: a diagnostic challenge. J Am Acad Dermatol. 2004;50:690-694. [ Links ]
13. Lebeau S, Braun RP, Masouyé I, Perrinaud A, Harms M, Borradori L. Acquired melanocytic naevus in childhood vulval pemphigoid. Dermatology. 2006;213:159-162. [ Links ]
Mailing address: Received on 04.05.2010. * Study carried out at the Dermatology Service, Teaching Hospital Gaffree and Guinle, Federal University of the State of Rio de Janeiro (Hospital Universitario Gaffree e Guinle, Universidade Federal do Estado do Rio de Janeiro - HUGG - UNIRIO) - Rio de Janeiro (RJ), Brazil.
Carolina Porto Cotrim
Rua João Rebelo, 376, Cândida Câmara
39.401-036 Montes Claros - MG, Brazil
Approved by the Advisory Board and accepted for publication on 12.07.10.
Conflict of interest: None
Financial funding: None
Received on 04.05.2010.
* Study carried out at the Dermatology Service, Teaching Hospital Gaffree and Guinle, Federal University of the State of Rio de Janeiro (Hospital Universitario Gaffree e Guinle, Universidade Federal do Estado do Rio de Janeiro - HUGG - UNIRIO) - Rio de Janeiro (RJ), Brazil.