The knowledge of histopathology and in vivo reflectance confocal microscopy correlation has several potential applications. Reflectance confocal microscopy can be performed in all skin tumors, and in this article, the most common histopathologic features of confocal microscopic findings in melanocytic skin tumors and nonmelanocytic skin tumors are described.
Key points
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Several histopathologic features of skin tumors can be characterized individually through reflectance confocal microscopy (RCM) examination.
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As a result, RCM has significant correlation with histopathologic final diagnosis.
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RCM can improve noninvasive in vivo diagnosis of skin tumors and prevent biopsy of benign lesions.
Introduction
The knowledge of histopathology and in vivo reflectance confocal microscopy (RCM) correlation has several potential applications. First, it enables the skin tissue evaluation of specific sites for a punch biopsy, improving its diagnostic accuracy and reducing the need of repetitive investigation in heterogeneous lesions. Second, it may differentiate skin tumors and reassure confidence in clinical diagnosis of doubtful lesions.
Notably, RCM evaluation of a given lesion is made in sections parallel to skin (en face), where each section is at a different skin depth. Oppositely, conventional histopathology sections are made perpendicular to the skin, and each section shows different depths of a given lesion. This technical difference makes the histopathology-RCM correlation challenging for the general pathologist/dermatologist, who is used to studying the skin according to perpendicular sections. Braga and colleagues described the value of transverse histologic sections as a tool to better understand the structures observed in dermoscopy and RCM.
In this article, the most common skin tumors observed in clinical practice as seen on RCM are described.
Introduction
The knowledge of histopathology and in vivo reflectance confocal microscopy (RCM) correlation has several potential applications. First, it enables the skin tissue evaluation of specific sites for a punch biopsy, improving its diagnostic accuracy and reducing the need of repetitive investigation in heterogeneous lesions. Second, it may differentiate skin tumors and reassure confidence in clinical diagnosis of doubtful lesions.
Notably, RCM evaluation of a given lesion is made in sections parallel to skin (en face), where each section is at a different skin depth. Oppositely, conventional histopathology sections are made perpendicular to the skin, and each section shows different depths of a given lesion. This technical difference makes the histopathology-RCM correlation challenging for the general pathologist/dermatologist, who is used to studying the skin according to perpendicular sections. Braga and colleagues described the value of transverse histologic sections as a tool to better understand the structures observed in dermoscopy and RCM.
In this article, the most common skin tumors observed in clinical practice as seen on RCM are described.
Confocal microscopy correlation in melanocytic skin tumors
Melanocytic nevi are seen in histopathology as a benign proliferation of nevus cells with monomorphic pattern. When the proliferation occurs initially at the epidermis, more precisely at the dermal-epidermal junction (DEJ), it is known as junctional nevi. On the other hand, when the nevus cells are located at the dermis, the lesion is classified as dermal nevus. Finally, when it is located in both compartments (epidermis and dermis), it is named compound nevus.
Junctional Nevi
Junctional nevi can be seen in RCM with 2 patterns: ringed and/or meshwork ( Table 1 ).
| RCM | Histopathology |
|---|---|
| Ring pattern | Junctional nevus: individual melanocytes at the DEJ, elongated papillae, and lentiginous pattern |
| Meshwork and junctional thickening (enlargement of the junctional space) | Junctional nevus: junctional nests located at the tips of epidermal ridges |
| Meshwork and junctional thickening with junctional and dermal nests | Compound nevus: nests at the DEJ and papillary dermis (more superficial) |
| Meshwork with junctional and dermal nests, predominantly with clod pattern | Compound nevus: nests at the DEJ, papillary dermis, and reticular dermis (deeper) |
| Dense or dense and sparse nests | Dermal nevus: nevus cells nests at the dermis |
The ringed pattern is the most commonly observed. It presents as edged papillae with intense bright basal keratinocytes surrounding a dark center. In histopathology, it corresponds to a lentiginous proliferation of single melanocytes at the DEJ (see Table 1 ; Fig. 1 ).
In the meshwork pattern, a proliferation of nevus cells organized in nests is seen at the interpapillary space by histopathology and, consequently, by RCM as well (see Table 1 ; Fig. 2 ).
Dermal Nevi
The main RCM characteristic of this lesion is the clod pattern that shows intradermal nests (clods) occupying at least 50% of the lesion. This pattern corresponds to the cobblestone pattern in dermoscopy, and in histopathology, this feature represents nests of melanocytes at the dermal level (see Table 1 ; Fig. 3 ).
Compound Nevi
Compound nevi can present both junctional nevus patterns and intradermal nests (clods) in the papillary dermis. The nests can be dense, observed like compact dense aggregates, or dense and sparse, observed like compact dense aggregates with large cells detectable within (see Table 1 ; Fig. 4 ).
Dysplastic Nevi
Dysplastic nevi or atypical nevi are benign lesions that might show few features of melanoma in dermoscopy, RCM, or histopathology and can be extremely challenging at all levels. Some RCM features have been described ( Fig. 5 , Table 2 ), as follows:
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Slightly irregular epidermal architecture with few sporadic pagetoid cells mainly in the center of the lesion;
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Papillae contours are mostly edged and, when nonedged papillae are observable, they rarely extend more than 10% of the lesion surface;
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Presence of some large nucleated atypical cells at the DEJ, usually found in the center of the lesion;
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Junctional and/or intradermal nests, usually observed like compact dense aggregates with large cells detectable within (dense and sparse nests);
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Junctional nests can present an elongated shape or short interconnections, which correspond to nest fusion and bridging at histopathology;
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Bright particles (corresponding to inflammatory infiltrate), plump bright round and stellate cells (corresponding to melanophages), and coarse collagen fibers. These fibers assume a bandlike disposition that corresponds in histopathology to lamellar and concentric fibrosis around epidermal ridges.
| RCM | Histopathology |
|---|---|
| Edged papillae are prevalent at the lesion (<10% nonedged papillae) | Focal disorganization at DEJ |
| Low presence of atypical cells at epidermis | Few atypical melanocytic cells at epidermis (focal atypia) |
| Atypical cells at DEJ | Few atypical melanocytic cells at DEJ (focal atypia) |
| Nests usually with dense and sparse pattern | Nests at DEJ and/or dermis |
| Short interconnections | Nest fusion and bridging at DEJ |
| Bright particles, plump bright round and stellate cells at dermis | Inflammatory infiltrate and melanophages at dermis |
| Collagen in bandlike disposition at dermis | Lamellar and concentric fibrosis around epidermal ridges at dermis |
Spitz/Reed Nevus
RCM features found in Spitz/Reed nevi are in most cases indistinguishable from melanoma, and good correlation has been found between some RCM features and histopathologic examination. Although there are several types of dermoscopy patterns for Spitz nevus, the most prevalent is the starburst pattern, and the RCM features found for this pattern are ( Fig. 6 ) as follows:
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Typical regular epidermis (honeycombed or cobblestone), sometimes with pagetoid infiltration;
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Nonedged papillae with atypical cells and junctional thickenings at DEJ;
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Spindled cells and dendritic cells at epidermis and DEJ;
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Dense regular nests at DEJ and papillary dermis;
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Sharp borders constituted by a peripheral rim of dense nests;
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Bright particles (corresponding to inflammatory infiltrate);
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Plump bright round and stellate cells (corresponding to melanophages).
Related posts:
Basics of Confocal Microscopy and the Complexity of Diagnosing Skin Tumors
Discriminating Nevi from Melanomas
Shining into the White
Application of Handheld Confocal Microscopy for Skin Cancer Diagnosis
The Role of Reflectance Confocal Microscopy in Clinical Trials for Tumor Monitoring
Fluorescence (Multiwave) Confocal Microscopy
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