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Melanocytic Nevi. These lesions show typical network (A) and regular globules (D), on dermoscopy. RCM mosaic image (B, 161 mm) at the level of the DEJ shows rings of bright polygonal cells surrounding roundish to oval dark areas corresponding to dermal papillae at DEJ. Transverse section (C) shows isolated melanocytes arranged around the dermal papillae and there are nevus cells nests within the epidermis. RCM mosaic image (E, 1,561,5 mm) at the level of the DEJ and dermis shows compact aggregates of large polygonal cells similar in morphologic features and reflectivity, forming polyhedral structures. Transverse section (F) shows dense nests composed of nevus cells within the dermis surrounded by a narrow band of epidermis. doi:10.1371/journal.pone.0081205.g003
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Histopathologic interpretation of dermoscopic and reflectance confocal microscopy (RCM) features of cutaneous melanoma was timidly carried out using perpendicular histologic sections, which does not mimic the same plane of the image achieved at both techniques (horizontal plane). The aim of this study was to describe the transverse histologic secti...
Contexts in source publication
Context 1
... typical network ( Figure 3A), on RCM it was characterized by rings of bright polygonal cells (small melanocytes and melanin-rich keratinocytes) surrounding roundish to oval dark areas corresponding to dermal papillae at dermoepidermal junction. Rings were clearly outlining the papillary contours and were separated by a thin, structureless, slightly refractive space that sharply contrasted with the dark background (edged papillae) ( Figure 3B). ...
Context 2
... typical network ( Figure 3A), on RCM it was characterized by rings of bright polygonal cells (small melanocytes and melanin-rich keratinocytes) surrounding roundish to oval dark areas corresponding to dermal papillae at dermoepidermal junction. Rings were clearly outlining the papillary contours and were separated by a thin, structureless, slightly refractive space that sharply contrasted with the dark background (edged papillae) ( Figure 3B). No atypical cells were detectable. ...
Context 3
... the transverse histologic sections, an increased number of isolated melanocytes were arranged around the dermal papillae that accounted for the higher brightness of the cells within the rings at RCM examination. (Figure 3C). ...
Context 4
... the globular nevus, an accurate correspondence in shape was observed between brown globules on dermoscopy ( Figure 3D) and the dense melanocytic clusters on RCM ( Figure 3E), appearing as compact aggregates with sharp margin of large polygonal cells similar in morphologic features and reflectivity, forming polyhedral structures (dense clusters). Routine histologic examination revealed a predominance of well-circum- scribed melanocytic nests and cords of typical, monomorphous nevocytes, mainly located within the dermal papillae, and separated by thin epidermal cristae. ...
Context 5
... the globular nevus, an accurate correspondence in shape was observed between brown globules on dermoscopy ( Figure 3D) and the dense melanocytic clusters on RCM ( Figure 3E), appearing as compact aggregates with sharp margin of large polygonal cells similar in morphologic features and reflectivity, forming polyhedral structures (dense clusters). Routine histologic examination revealed a predominance of well-circum- scribed melanocytic nests and cords of typical, monomorphous nevocytes, mainly located within the dermal papillae, and separated by thin epidermal cristae. ...
Context 6
... histologic examination revealed a predominance of well-circum- scribed melanocytic nests and cords of typical, monomorphous nevocytes, mainly located within the dermal papillae, and separated by thin epidermal cristae. Transverse histologic sections revealed mostly large dense nests composed of large cohesive nevus cells within the dermis surrounded by a narrow band of epidermis ( Figure 3F). ...
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Citations
... RCM may not detect invasive melanoma because of limited penetration beyond the upper reticular dermis. 36 ...
Lentigo maligna (LM) is a melanoma in situ with distinct clinical features and histology. It commonly affects males after the sixth decade of life. Incidence rates of LM have increased based on early 21st century data from different countries, however data are suboptimal. Data from England show a plateauing crude incidence between 2013-2019. By comparison, invasive melanoma and other types of melanoma in situ commonly appears in younger age groups (median age 58 and 67 years old, respectively) and incidence is rising. The most important risk factors for LM include fair skin and cumulative ultraviolet solar radiation exposure. Although LM is limited to the epidermis and connected skin adnexa, it may progress to invasive lentigo maligna melanoma. The reported rate of malignant progression varies, reflecting a challenge for LM epidemiology research, as often lesions are removed on diagnosis. LM poses a challenge in diagnosis and management. While it can be diagnosed clinically or dermoscopically, the gold standard remains histopathological assessment of biopsied skin tissue. Reflectance confocal microscopy allows for better appreciation of the complexity of LM at a cellular level, often progressing beyond clinical margins. Management of LM may involve Mohs micrographic surgery or excision, although recurrence may occur even with 5 mm clinical margins. Imiquimod cream may be effective, but incomplete treatment and recurrence has been reported. Conservative management with observation or radiotherapy may be used in selected cases. 5-year net survival rates are excellent. This paper reviews the natural history, epidemiology, aetiology, pathogenesis, diagnosis and management of LM.
... The terms are listed in Tables 1, 2, 3, 4 and 5, along with the corresponding description of the confocal microscopy findings and correlation with histology, for normal skin, melanocytic and non-melanocytic lesions. 11 Fig. 1 shows the terms used to describe the dif- ferent aspects of collagen in the papillary dermis and the number of participants using each of the mentioned terms. Fig. 2 illustrates the main terms considered for the description of melanocytic and non-melanocytic lesions. ...
Background
Currently, there is no uniform and official terminology in Portuguese for reflectance confocal microscopy analysis, despite the increasing number of Brazilian dermatologists using this new tool.
Objective
To present the terminology in Brazilian Portuguese for the description of reflectance confocal microscopy and establish the first Brazilian consensus on terms related to normal skin and cutaneous tumors.
Methods
10 Brazilian specialists from different institutions and states of Brazil were selected to evaluate the best corresponding terms in Portuguese for normal skin, melanocytic and non-melanocytic tumors. The terms used were translated from international consensuses in the English language. The modified Delphi method was used to create the consensus in 3 steps.
Results
The terms considered the most appropriate in the Portuguese language to describe the findings of normal skin, melanocytic and non-melanocytic lesions in the reflectance confocal microscopy analysis were presented.
Study limitations
The limitations of the present study include the number of participants and limited regional representation (only two of the five Brazilian regions were represented).
Conclusion
This Brazilian consensus represents an opportunity for dermatologists and physicians specializing in cutaneous oncology to become familiar with reflectance confocal microscopy, propagating the technique in clinical and research environments to stimulate national and international publications on this subject.
... 13 This technique has been applied for diagnosis of melanoma and basal cell carcinoma (BCC) and may reduce unnecessary biopsies of benign lesions. 14,15 Despite these applications, RCM imaging of the vulvar area has only been described in a few pilot studies to date. [16][17][18][19][20][21] Therefore, the primary objective was to explore the technical feasibility and patient acceptability of RCM imaging on the vulva. ...
Incorrect and delayed diagnosis of vulvar high-grade squamous intraepithelial neopla-sia (vHSIL) and lichen sclerosus (LS) increases malignant progression risks and negatively impacts prognosis and quality of life. There is a need to improve diagnosis and monitoring. Reflectance confocal microscopy is a non-invasive imaging tool that visualizes skin structures at cellular resolution. The objectives were to explore feasibility and patient acceptability of vulvar RCM imaging and to identify RCM characteristics that are discriminative for vulvar HSIL and LS. This was a prospective, cross-sectional, observational clinical trial in patients with vHSIL and LS compared to healthy volunteers. RCM images and vulvar tissue samples were obtained. Five (5) patients with vHSIL, 10 patients with LS and 10 healthy volunteers were enrolled. In total, 100 image series of vulvar skin were obtained, including lesional and nonlesional sites. The RCM technique was considered acceptable for application by patients and healthy controls. Healthy vulvar skin was characterized by a homogenous, normal honeycomb patterned epidermis and a clear epidermal-dermal junctions. Vulvar HSIL and LS displayed an atypical honeycomb pattern of the epidermis and lymphocytic influx with presence of melanophages. Distinct features specifically observed in LS included the presence of hyalinised vessels and sclerotic areas in the dermis. RCM is a non-invasive imaging technique that is feasible and clinically acceptable to apply on vulvar skin, both in patients with premalignant lesions and healthy controls. Recognition and validation of disease-specific characteristics could make reflectance confocal microscopy a clinical tool to non-invasively aid identification of vulvar premalignancies. K E Y W O R D S genital disease, lichen sclerosus, reflectance confocal microscopy, vulva
... The examination was carried out in a step-by-step manner, with complete image documentation for subsequent analyses blinded from anatomopathological results. The RCM evaluation was based on features previously described (Table 1) [3][4][5]. ...
Some melanocytic lesions do not present enough clinical and dermoscopic features to allow ruling out a possible melanoma diagnosis. These “doubtful melanocytic lesions” pose a very common and challenging scenario in clinical practice and were selected at this study for reflectance confocal microscopy evaluation and subsequent surgical excision for histopathological diagnosis. The study included 110 lesions and three confocal features were statistically able to distinguish benign melanocytic lesions from melanomas: “peripheral hotspot at dermo-epidermal junction”, “nucleated roundish cells at the dermo-epidermal junction” and “sheet of cells”. The finding of a peripheral hotspot (atypical cells in 1mm ² ) at the DEJ is highlighted because has not been previously reported in the literature as a confocal feature related to melanomas.
... RCM opened a new era of optical biopsies, with an evident application in the diagnosis of skin cancer due to the high reflective index of melanin and keratin. The mosaic formed during RCM imaging allows a direct correlation between dermoscopy and cytological patterns in the diagnosis of melanoma and non-melanoma skin cancer (NMSC) [2][3][4]. ...
... Recently, studies testing the usefulness of combining RCM with digital dermoscopy monitoring have shown a reduction in the number of lesions excised to diagnose skin cancer, reflecting a 2-fold reduction in unnecessary biopsies [4]. ...
Background:
Different techniques for non-invasive skin examination and early diagnosis of skin lesions are available nowadays, being dermoscopy and reflectance confocal microscopy (RCM) the most diffused ones. Several studies supported the complementary use of dermoscopy and RCM that improves diagnostic accuracy when dealing with melanocytic lesions.
Objectives:
To analyze RCM diagnostic accuracy in the differential diagnosis between melanocytic and non-melanocytic lesions.
Methods:
This is a cohort selected cross-sectional study conducted at the Dermatology Unit of the University of Campania L. Vanvitelli, Naples, Italy, from 2012 to 2020. We searched the image database for all excised lesions for which the clinical and dermatoscopic differential diagnosis was between melanocytic and non-melanocytic and for which an RCM examination was performed. Sensitivity, specificity, and diagnostic accuracy values were estimated.
Results:
The study included 53 cases that were found to have disagreement between clinical, histological and RCM diagnosis, of which, in 31 cases the differential diagnosis was melanocytic vs non-melanocytic lesion. The RCM reached a specificity of 87% (95% CI: 0.73-1) and a sensitivity of 62.5% (95% CI: 0.29-0.96) in the present sample. Diagnostic accuracy was 80.6% (95% CI: 0.67-0.94).
Conclusion:
RCM has a high specificity in differentiating between difficult-to-diagnose melanocytic and non-melanocytic lesions.
... The diagnostic criteria for these dermoscopic and RCM features has been mostly inferential, based on the empirical observations and in some cases routine vertical histopathologic sections [2,[24][25][26]. The initial clinical-dermoscopy-RCM-histopathologic correlation was performed with a gross whole-image to whole-sample correlation and without a precise one-to-one direct correlation [27][28][29]. Few studies have evaluated the dermoscopic and RCM correlation of most structures [30] and some of the described features still lack a specific histopathologic counterpart that is needed for better understanding of what we are visualizing with the aforementioned imaging devices. ...
... Few studies have evaluated the dermoscopic and RCM correlation of most structures [30] and some of the described features still lack a specific histopathologic counterpart that is needed for better understanding of what we are visualizing with the aforementioned imaging devices. Furthermore, since dermoscopy and RCM visualize 'en face' details, it might be difficult or impossible to match the findings seen on histopathologic vertical sections (i.e., perpendicular to the skin surface) [3,29]. To the best of our knowledge, only one histopathologic interpretation study has correlated dermoscopy and RCM features with horizontal sections, but the biopsies were not image-guided, possibly not including the specific feature under evaluation [29]. ...
... Furthermore, since dermoscopy and RCM visualize 'en face' details, it might be difficult or impossible to match the findings seen on histopathologic vertical sections (i.e., perpendicular to the skin surface) [3,29]. To the best of our knowledge, only one histopathologic interpretation study has correlated dermoscopy and RCM features with horizontal sections, but the biopsies were not image-guided, possibly not including the specific feature under evaluation [29]. ...
Dermoscopy and reflectance confocal microscopy (RCM) are two noninvasive, optical imaging tools used to facilitate clinical diagnosis. A biopsy technique that produces exact correlation with optical imaging features is not previously reported. To evaluate the applications of a novel feature-focused ‘precision biopsy’ technique that correlates clinical–dermoscopy–RCM findings with histopathology. This was a prospective case-series performed during August 2017 and June 2019 at a tertiary care cancer. We included consecutive patients requiring a precise dermoscopy–RCM–histopathologic correlation. We performed prebiopsy dermoscopy and both wide probe and handheld RCM of suspicious lesions. Features of interest were isolated with the aid of paper rings and a 2 mm punch biopsy was performed in the dermoscopy- or RCM-highlighted area. Tissue was processed either en face or with vertical sections. One-to-one correlation with histopathology was obtained. Twenty-three patients with 24 lesions were included in the study. The mean age was 64.6 years (range 22–91 years); there were 16 (69.6%) males, 14 (58.3%) lesions biopsied were on head and neck region. We achieved tissue-conservation diagnosis in 100% (24/24), 13 (54.2%) were clinically equivocal lesions, six (25%) were selected for ‘feature correlation’ of structures on dermoscopy or RCM, and five (20.8%) for ‘correlation of new/unknown’ RCM features seen on follow-up. The precision biopsy technique described herein is a novel method that facilitates direct histopathological correlation of dermoscopy and RCM features. With the aids of optical imaging devices, accurate diagnosis may be achieved by minimally invasive tissue extraction.
... Pagetoid distribution of large pleomorphic cells is seen across all layers of the epidermis as LM progresses, causing epidermal disarray. At the dermal-epidermal junction, poorly defined dermal papillae and atypical cells may form bridges that resemble mitochondrial structures [38]. In comparison to nonmelanocytic skin neoplasms, resembling caput medusae, junctional swelling with penetration of the hair follicle was found to be representative of LM/LMM, with an overall specificity of 83% and sensitivity of 96% [39,40]. ...
Lentigo maligna (LM), also known as Hutchinson's melanotic freckle, is a form of in situ melanoma characterized by the proliferation of atypical melanocytes along the basal epidermis in sun-damaged skin. If left untreated, LM will progress to lentigo maligna melanoma (LMM), a form of invasive melanoma with the same prognosis as other forms of invasive melanoma. LM is more common in the elderly, with a peak occurrence between the ages of 65 and 80 years. LM, however, is rarely present on the trunk and extremities. The diagnosis of LM, confirmed by histopathological and biopsy examination, is based on clinical and dermoscopic features. It typically begins as a tan-brown macule or patch, but it can progress to a variegated pigmentation with dark black color or even amelanotic characteristics. The risk factors involved in the LM development include a history of sunburns, lighter skin types, advanced age, history of nonmelanoma skin cancers, and tendency to form solar lentigines. This article explains the clinical presentation of LM, also reviews the available information on the diagnosis and management of LM, and discusses the potential of such information in facilitating the future prospective.
... The possibility of optimally comparing horizontal histopathology and RCM images represents a relatively new trend, and quite a few papers have been published in this field regarding both inflammatory and neoplastic disorders (11)(12)(13)(14)(15)(16)(17). The purpose of this review paper is to establish the "state of the art" on RCM and HHS findings in skin tumors, emphasizing how well horizontal histopathology reflects the images provided by RCM. ...
... RCM of the second MM with an atypical pigmented network showed at dermoepidermal junction atypical nests of both rounded and elongated hyperreflective melanocytes combined to an architectural disarray of dermal papillae and some bright cells or small dots within dermal papillae; vertical histopathology revealed an in situ melanoma, and RCM findings were confirmed by HHS showing pleomorphic melanocytes arranged in nests and presence of lymphocytes within dermal papillae. Based of RCM, Braga et al. (17) were also able to discriminate dermoscopic globules in nevi and melanomas on the basis of morphological atypia: both RCM and HHS showed small nests of monomorphous non-atypical bright melanocytes nonconnected with epithelium in nevi and larger nests of pleomorphic neoplastic melanocytes in MMs. Lastly, pseudopods were not characterized by morphological atypia on RCM, corresponding to peripherally visible, confluent clusters of pigmented neoplastic melanocytes on horizontal histopathology. ...
In dermatopathological daily practice, vertical histopathology sections are classically used to analyze skin biopsies. Conversely, horizontal histopathological sections are currently used for the diagnosis of some types of alopecia. In the last years the morphological findings obtained by horizontal histopathology have been correlated to those obtained by in vivo reflectance confocal microscopy which provides the same “point of view” of the skin. This review paper emphasizes the strong matching and correlation between reflectance confocal microscopy images and horizontal histopathology in cutaneous neoplasms, further demonstrating the strong reliability of this innovative, non-invasive technique in the management of skin tumors.
... These features may be revealed with non-invasive skin imaging techniques, such as capillaroscopy and reflectance confocal microscopy (RCM), avoiding skin biopsies. RCM provides in vivo high-resolution imaging of horizontal sections of the skin at different layers [17], and it can be applied to the evaluation of vascular structures, hematic flow, and speed [18,19]. ...
... For each examination, sequences of high-resolution individual images were acquired following a standardized protocol [17]. Briefly, four 4 mm × 4 mm mosaics, starting from the stratum corneum up to the papillary dermis (with a resolution of about 350 μm of depth), with a step of 30 μm, were acquired. ...
Port-wine stains (PWS) are frequently refractory to laser treatments. Although previous data highlight prognostic factors and biological events related to poor outcomes, no previous publications correlate their capillaroscopic and architectural features. The aim of the present study is to describe refractory port-wine stains performing capillaroscopy and reflectance confocal microscopy (RCM) to describe their morphological and microscopic aspects. This is a prospective cohort study. All the consecutive patients with PWS poor responsive to previous treatment were included. Clinical assessment, capillaroscopy, and reflectance confocal microscopy were performed. A total of 65 patients were included, 12 with a capillaroscopic Type II pattern patients and 53 with Type III. At RCM examination, PWS with a capillaroscopic Type III pattern showed deeper-located blood vessels (p < 0.001) with a higher diameter (p < 0.042) compared with Type II. At the dynamic evaluation, 3 RCM patterns can be distinguished: Subset A, characterized by linear vessels with reduced diameter; Subset B, formed by enlarged vessels; and Subset C, characterized by deep and large aneurysmatic dilatation connected to small vessels. We defined 3 RCM patterns of refractory PWS.
... Analogously, we hypothesize that nevus patterns emerge from nonlinear dynamical microscopic systems of cell-cell and cell-matrix interactions that can be simulated by abstracted mathematical models of basic cellular functions. We developed a mathematical model and simulation approach that connect abstracted microscopic dynamics of individual melanocytes in a realistic three-dimensional geometric model of the physiologic microenvironment with the morphologic appearance of nevi observed by dermatoscopy [41,42] and histopathology [43]. ...
Spatio-temporal patterns of melanocytic proliferations observed in vivo are important for diagnosis but the mechanisms that produce them are poorly understood. Here we present an agent-based model for simulating the emergence of the main biologic patterns found in melanocytic proliferations. Our model portrays the extracellular matrix of the dermo-epidermal junction as a two-dimensional manifold and we simulate cellular migration in terms of geometric translations driven by adhesive, repulsive and random forces. Abstracted cellular functions and melanocyte-matrix interactions are modeled as stochastic events. For identification and validation we use visual renderings of simulated cell populations in a horizontal perspective that reproduce growth patterns observed in vivo by sequential dermatoscopy and corresponding vertical views that reproduce the arrangement of melanocytes observed in histopathologic sections. Our results show that a balanced interplay of proliferation and migration produces the typical reticular pattern of nevi, whereas the globular pattern involves additional cellular mechanisms. We further demonstrate that slight variations in the three basic cellular properties proliferation, migration, and adhesion are sufficient to produce a large variety of morphological appearances of nevi. We anticipate our model to be a starting point for the reproduction of more complex scenarios that will help to establish functional connections between abstracted microscopic behavior and macroscopic patterns in all types of melanocytic proliferations including melanoma.
