Abstract
The RCM criteria of most types of melanocytic nevi have been extensively described in the literature within the past years [1–4]. This chapter complements this body of knowledge by describing the RCM features of less frequent types of nevi, namely blue, “black” and recurrent nevi. Common to these nevus variants is that they are often the clinical outlier or “ugly duckling” among the patient’s moles, and as such, these nevi tend to raise some clinical concern; moreover, their dermoscopic features are often equivocal. To this end, RCM can reveal additional architectural and cellular details about these nevi, and thus can serve as a helpful adjunct for diagnosis and management decision. In the following sections, we describe the RCM features of these nevi in the context of the current technical limitations of RCM, such as the restricted depth of penetration of light and the limited cellular details.
The RCM criteria of most types of melanocytic nevi have been extensively described in the literature within the past years [1–4]. This chapter complements this body of knowledge by describing the RCM features of less frequent types of nevi, namely blue, “black” and recurrent nevi. Common to these nevus variants is that they are often the clinical outlier or “ugly duckling” among the patient’s moles, and as such, these nevi tend to raise some clinical concern; moreover, their dermoscopic features are often equivocal. To this end, RCM can reveal additional architectural and cellular details about these nevi, and thus can serve as a helpful adjunct for diagnosis and management decision. In the following sections, we describe the RCM features of these nevi in the context of the current technical limitations of RCM, such as the restricted depth of penetration of light and the limited cellular details.
1 Common Blue Nevus
Many types of blue nevi have been described in the literature, including cellular, amelanotic and combined blue nevi to name just a few [5, 6] ; this variability probably reflects the fact that nevi described as “blue” on clinical grounds, actually represent different types of congenital nevi on histopathology. For simplicity, we describe herein only the RCM features of the so-called common blue nevus, defined below.
The common blue nevus usually appears as a solitary, blue-colored macule, papule or nodule on the head and neck or the dorsum of the hands and feet. On histopathology, there is a proliferation of markedly pigmented, bipolar dendritic melanocytes that are splayed as solitary units between thickened collagen bundles in the reticular dermis. In addition, scattered, pigment-laden melanophages are usually noted. While typically common blue nevi are long standing, patient history may be indecisive or even alluding to a recent change. In these cases, the clinical differential diagnosis may include a pigmented basal cell carcinoma, a nodular melanoma, a melanoma metastasis or melanoma arising within a pre-existing blue nevus [7].
Dermoscopy is often helpful in the diagnosis of common blue nevus. The blue color noted clinically is also observed with dermoscopy; a steel-blue pigmentation lacking additional dermoscopic features is typically seen with nonpolarized dermoscopy. However, blue nevi may show at times color variegation on dermoscopy (e.g., blue-white, blue-brown or polychromatic structureless pigmentation), particularly when using polarized dermoscopy [8]. Such variegate blue nevi may be clinically and dermoscopically equivocal.
With confocal microscopy, common blue nevi characteristically show a typical honeycomb pattern of the epidermis and a preserved dermo-epidermal junction. Within the dermis, scattered bright dendritic cells corresponding to pigmented dendritic melanocytes can be observed. The demonstration of dermal melanocytes by RCM depends on their anatomic location. Only the most superficial portion of the reticular dermis is visualized by RCM at present. In addition, polygonal, plump-bright non-nucleated cells can be seen in the dermis, correlating to melanin-laden dermal melanophages; the dendritic melanocytes and the melanophages are often seen on RCM amidst thickened bright collagen bundles in the reticular dermis.
The main limitation of RCM in the assessment of common blue nevi is the restricted depth of penetration; the adequate evaluation of the entire depth of the lesion cannot be guaranteed. However, if RCM shows features that deviate from those described, the clinical diagnosis of blue nevus needs to be questioned. For example, the presence of melanocytes in pagetoid pattern within the epidermis, a disarranged DEJ and dermal cerebriform nests point to the diagnosis of melanoma[9, 10]. The detection of well-demarcated bright tumor islands at the DEJ/upper dermis, within thickened collagen with en face blood vessels, is diagnostic of pigmented basal cell carcinoma [11].
2 Black Nevus
The so-called black nevus is a recently described clinical entity [12]. On clinical examination, the black nevus presents as a dark brown to black macule or papule with an average diameter of 5 mm. This type of nevus is typically found in darker skin-typed patients (e.g., type IV skin) and is usually located on the trunk, predominantly on the back. With dermoscopy, black nevi usually display a central, sharply demarcated, dark-brown to black homogeneous area (black lamella) and a regular pigment network at the periphery; the partial removal of the black lamella with tape-stripping may enable the visualization of an underlying pigment network with dermoscopy. The dermoscopic finding of a black lamella correlates on histopathology with abundant melanin in a compact stratum corneum above a deeply pigmented junctional or compound nevus [13, 14].
Though benign, black nevi are often excised due to their worrisome clinical appearance; the black nevus is usually darker than the patient’s other nevi and hence may be perceived clinically as an outlier, “ugly duckling” nevus [15]. Compounding the clinical concern are reports that the finding of black pigmentation in clinically atypical lesion may be a predictor of early melanoma [16]. Dermoscopy may alleviate the clinical concern with black nevi if there is a symmetric distribution of colors and structures; however, equivocal dermoscopic findings, such as an eccentric black lamella, irregular black dots (due to focally denser melanin deposits within the stratum corneum) or slight network irregularities, may lead to an unnecessary excision.
With RCM, black nevi usually show a thickened cornified layer with highly reflective, homogeneous areas of varying size and shape, correlating to pigmented scales. The underlying spinous-granular layers display a regular cobblestone pattern due to the high content of melanin granules within the keratinocytes. The DEJ typically shows a regular ringed pattern (i.e., edged-papillae) and small, predominantly junctional, nests.
Thus, RCM may point the clinician to the correct diagnosis in black nevi that are clinically and dermoscopically equivocal. Irregular black dots can be identified as bright melanin deposits within the cornified layer, and differentiated from nucleated or dendritic cells in pagetoid pattern that would be seen in melanoma. A regular epidermal and DEJ architecture can be visualized with RCM in black nevi despite the extent of epidermal pigmentation; this is similar to the reassuring effect of tape-stripping showing a regular underlying network with dermoscopy.
3 Recurrent Nevus
Recurrent nevi, following an incomplete removal of melanocytic nevi (e.g., by shave biopsy), may clinically and histopathologically simulate melanoma in situ [17, 18]. On clinical examination, irregularly pigmented, asymmetric macules with indistinct borders are characteristically seen in the surgical scar. Asymmetry of colors and structures, color variegation and concerning pigment structures, such as an irregular network, irregular dots or streaks, may be observed with dermoscopy [19]. On histopathology, recurrent nevus is characterized by the presence of irregularly distributed junctional nests and melanocytes disposed as solitary units, occasionally in pagetoid pattern, above the scar; peripheral and deep to the scar, remnants of the melanocytic nevus can often be seen. The presence of nevus nests beneath the scar, as well as review of the previous biopsy specimen, can assist the pathologist to arrive at the correct diagnosis of a recurrent nevus.
With RCM, a typical honeycomb or cobblestone pattern is usually observed at the spinous-granular layers of the epidermis; focal “streaming” of basal keratinocytes (i.e., distortion and elongation of keratinocytes along a longitudinal axis) may be present due to distortion caused by the underlying scar. Single bright, nucleated cells of varying sizes and shape may be seen at suprabasal epidermal layers, correlating to melanocytes in pagetoid pattern seen on histopathology. At the DEJ, a regular ringed pattern can be observed together with irregularly shaped dermal papillae, again due to distortion caused by the underlying scarring. The flattening of the DEJ over the scar may also result in a focal loss of the ringed pattern; the presence of irregularly distributed nests and single melanocytes of varying sizes and shape may also be seen. In the upper dermis, there is an increased density of bright and thickened collagen fibers, correlating to the fibrosis on histopathology.
RCM is particularly valuable for the differentiation of recurrent nevus from hyper-pigmentation which is occasionally seen within surgical scars. In cases of hyper-pigmentation, pigmented basal keratinocytes without nests or solitary melanocytes are characteristically observed. However, at present, in most cases of recurrent nevi, the differentiation from melanoma in situ with RCM is hindered by the limited penetration of light (inability to see the regular nests in the deeper dermis, underneath the scar) and the inability to visualize nuclear details. Thus, in cases showing melanocytic proliferation above the scar with RCM, the clinician will likely opt for an excision.
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Ahlgrimm-Siess, V., Arzberger, E., Hofmann-Wellenhof, R., Scope, A. (2012). The Many Faces of Nevi: Blue, “Black” and Recurrent Nevi. In: Hofmann-Wellenhof, R., Pellacani, G., Malvehy, J., Soyer, H. (eds) Reflectance Confocal Microscopy for Skin Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21997-9_12
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