Extensive regression in pigmented skin lesions: a dangerous confounding feature

Spontaneous regression in melanomas is not an uncommon phenomenon, as it has been described in 10–35% of primary cutaneous lesions [1]. Regression does not appear to predict a more favorable course, since even fully regressed melanomas may progress into metastatic disease [2]. Several dermoscopic features have been correlated with the regression process, including white scar-like depigmented areas and gray-blue, pepper-like granules, which correspond to dermal scarring, pigment incontinence and presence of melanophages [3,4]. Regression may occur not only in melanomas, but also in melanocytic nevi, which similarly may exhibit white areas and gray-blue granules or areas under dermoscopy [5]. Overall, white areas have been proposed to be associated with the fibrosis type of regression and gray-blue areas to the melanosis type of regression of melanocytic tumors [3]. Lichen planus like keratosis (LPLK) is considered to represent a regressed solar lentigo or seborrheic keratosis. Dermoscopy of LPLK at the late stage of the regression process reveals a diffuse gray-blue granular pattern, similar to that observed in regressed melanocytic lesions [6]. In this context, when evaluating skin lesions that exhibit high degree of regression, interpretation of dermoscopic findings may be problematic, especially when no other dermoscopic clues can be recognized.

Spontaneous regression in melanomas is not an uncommon phenomenon, as it has been described in 10-35% of primary cutaneous lesions [1]. Regression does not appear to predict a more favorable course, since even fully regressed melanomas may progress into metastatic disease [2]. Several dermoscopic features have been correlated with the regression process, including white scar-like depigmented areas and gray-blue, pepper-like granules, which correspond to dermal scarring, pigment incontinence and presence of melanophages [3,4]. Regression may occur not only in melanomas, but also in melanocytic nevi, which similarly may exhibit white areas and gray-blue granules or areas under dermoscopy [5]. Overall, white areas have been proposed to be associated with the fibrosis type of regression and gray-blue areas to the melanosis type of regression of melanocytic tumors [3]. Lichen planus like keratosis (LPLK) is considered to represent a regressed solar lentigo or seborrheic keratosis. Dermoscopy of LPLK at the late stage of the regression process reveals a diffuse gray-blue granular pattern, similar to that observed in regressed melanocytic lesions [6]. In this context, when evaluating skin lesions that exhibit high degree of regression, interpretation of dermoscopic findings may be problematic, especially when no other dermoscopic clues can be recognized.

Case presentation
The fully regressed melanoma in Figure 1 was found on the arm of a 50-year-old man, who was recently diagnosed with metastatic melanoma of the ipsilateral axillary lymph nodes ( Figure 1A). Dermoscopic examination revealed a diffuse blue-gray granular pattern, scar-like, depigmented areas, and a roundish ulceration in the absence of any specific features of melanoma ( Figure 1B). Histopathologic examination showed hyperplasia of the epidermis, prominent scar-like fibrosis of the dermis (corresponding dermoscopically to scar-like depigmented areas), vascular hyperplasia, moderately dense inflammation, pigment incontinence and accumulation of melanophages (observed as blue-gray granularity under dermoscopy) ( Figures 1C,D). The latter resulted in a fuzzy appearance of the dermis, obstructing the recognition of residual melanocytes, which were finally highlighted by immunohistochemistry, as slight positivity in S100 and HMB45 stains.
In addition, we present a melanocytic nevus ( Figure 2) and a LPLK (Figure 3

Conclusions
Zalaudek et al proposed that the management of melanocytic lesions exhibiting dermoscopic features of regression may be The dermoscopic diagnosis of a LPLK may be assisted by the identification of areas reminiscent of a solar lentigo or a seborrheic keratosis within the lesion [7]. However, at the end-stage of the regression process, when such features have disappeared and the lesion is characterized only by the presence of blue-gray granules, LPLK may strikingly mimic regressive melanoma [6].
In the three lesions reported here, the presence of prominent regression features did not allow a confident differential diagnosis. Under this scenario, an otherwise benign lesion, as a melanocytic nevus, or even a LPLK, may be virtually indistinguishable on clinical and dermoscopic examination from a melanoma and vice versa. In such cases, even histopathologic examination may fail to establish a definite diagnosis.
Thus, in lesions exhibiting high degree of regression under dermoscopy, complete excision and careful clinicopathologic evaluation is mandatory to reach a reliable final diagnosis.