1.   Introduction

Epidermolysis Bullosa (EB) represents a heterogeneous group of hereditary bullous dermatoses due to intrinsic defects of the basement membrane zone structural components [1]. Those patients often develop large, irregular, rapidly growing nevi with clinical features of atypical melanocytic proliferations on sites of pre-existing vesiculo-bullous eruption [2]. The pigmented lesions often show clinical and dermoscopic features of malignancy, such as asymmetry, irregular borders, and color variegation, however, a malignant transformation has been randomly described [3]. Thus, the hypothesis of “EB nevi” that recommends a more conservative management strategy of close clinical, dermoscopic and occasionally histologic examinations for EB patients, was introduced [4]. Herein, we present a case of malignant melanoma, arising in a patient with EB simplex, to highlight the importance of critically approach all patients, irrelevant to previous clinical entity labels and controversy.

2.   Case Report

A 26-year-old Caucasian female with multiple dysplastic nevi referred to our Department for routine examination. The patient was clinically, histologically and immunofluorescently diagnosed with EB simplex since birth. She experienced multiple vesiculo-bullous eruptions on sites of mechanical trauma. Most of her melanocytic lesions appeared on such previously affected areas. In the last six months she noticed an enlarging and changing color mole on the right subscapular zone (Figure 1). Dermoscopy showed multicomponent pattern with irregular form and structure of the lesion, uneven net with sharply outlined borders and globules with different calibers. Multiple colors of red, light brown, dark brown, blue and white, were also seen(Figure 2). Histological sample displayed a wide non-circumscribed melanocytic lesion presented by atypical fusiform melanocytes with vertical, upward, pagetoid spreading, and horizontal bridging that penetrated into the papillary dermis (Figure 3). Nests of pre-existing dermal nevus were seen at the periphery of the specimen.

A superficial spreading melanoma (Clark II, Breslow 0,25mm), without ulceration and active stromal reaction, arising on the site of pre-existing dermal melanocytic nevus, was concluded. Immunohistochemical markers confirmed the pigmented character of the lesion and showed medium to high proliferative index. On account of the localization, size, clinical and dermatoscopic features, the lesion was radically removed.

3.   Discussion

EB is an inherited mechano-bullous disorder with multiple variations, characterized by chronic relapsing course and numerous complications such as infections, joint and gastro-intestinal damage, non-melanoma skin tumors, etc[5]. Large, eruptive, asymmetrical nevi have been described to appear on sites of vesicules and blisters in EB patients[6]. Initially reported in generalized atrophic benign EB, multiple nevi seem to be a frequent phenomenon in all EB patients, thus suggesting the hypothesis of “EB nevi” [7]. Two pathogenetic mechanisms seem to play crucial role in the development of the pigmented lesions. First, the higher proliferation index of the affected keratinocytes on the sites of repetitive disruption, promote local nevus cell nests or individual melanocytes to undergo simultaneous proliferation. Second, the free-floating melanocytes in the cavity of the EB blister migrate and settle at its periphery to proliferate in the micro environment of the surrounding regenerating keratinocytes. A burst of cytokines and growth factors have been detected at the sites of such vesiculo-bullous defects – hepatocyte growth factor, interleukin 8, granulocyte-macrophage colony-stimulating factor, prostaglandin E2, and leukotriene 4, thus potentially enhancing melanocytic proliferation [8].The eruption of various melanocytic lesions is of significant clinical importance, since they may act as simulators and precursors of malignant melanoma. Of note, some clinical and dermoscopic observations have shown more benign character of EB nevi [9]. A 24-month follow-up of EB patients showed that suspected lesions undergo clinically and dermoscopic spontaneous involution [10].

4.   Conclusions

Based on the clinical, dermoscopic and histologic features, EB nevi can be considered a peculiar group of melanocytic proliferations. An expertise dermatologist has to be aware of their specificity in order not to be tempted to establish a more aggressive diagnosis and treatment. A close clinical and dermoscopic review is more secure and convenient strategy for these fragile dermatological patients. On the other hand, mislead by the benign prognosis of EB nevi, the clinician risks to underestimate some melanocytic lesions with malignant nature. This is highly relevant to EB cases with pre-existing history of benign nevi with spontaneous regression. Therefore, we recommend an attentive clinical and dermoscopic follow-up for each pigmented lesion arising in EB patient.

Figure 1: Irregular, asymmetrical lesion on the right subscapular area of the patient.

Figure 2: Dermoscopic features of the pigmented lesion.

Figure 3: Histological findings of superficial spreading melanoma.

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