Rosettes in actinic keratosis and squamous cell carcinoma: distribution, association to other dermoscopic signs and description of the rosette pattern
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1 DOI: /jdv JEADV ORIGINAL ARTICLE Rosettes in actinic keratosis and squamous cell carcinoma: distribution, association to other dermoscopic signs and description of the rosette pattern B. Lozano-Masdemont, 1, * I. Polimon-Olabarrieta, 1 S. Marinero-Escobedo, 1 A. Gutierrez-Pecharroman, 2 E. Rodrıguez-Lomba 3 1 Department of Dermatology, Hospital Universitario de Mostoles, Mostoles, Madrid, Spain 2 Department of Pathology, Hospital Universitario de Mostoles, Mostoles, Madrid, Spain 3 Department of Dermatology, Hospital General Universitario Gregorio Mara~non, Madrid, Spain *Correspondence: B. Lozano-Masdemont. belenmasdemont@gmail.com Abstract Background Rosettes, a dermoscopic structure characterized by four white points arranged as a 4-leaf clover, supports the dermoscopic diagnosis of actinic keratosis (AK) or squamous cell carcinoma (SCC). Objective The association of rosettes with other dermoscopic structures in AK or SCC and their distribution has not been analysed yet. Methods We conducted a prospective study of patients with histologically proven AK or SCC who presented dermoscopic rosettes at initial evaluation. Results A total of 56 tumours were collected (94.6% AK and 5.4% SCC). Thirty-seven (66.1%) lesions were non-pigmented and 19 (33.9%) pigmented. The most common dermoscopic findings were erythema (53; 94.6%) and scale (42; 75%). White circles were present in 21 lesions (37.5%); pigmented pseudonetwork in 18 (32.1%) and multiple grey to brown dots and globules in 14 (25%). Rosettes were distributed focally in 9 (16.1%) and generalized in 47 (83.9%). The rosette pattern (rosettes as the main structure) was observed only in AK (19; 35.8%). Limitations The analysis was not blinded. The distinction between focal distribution (up to 3 rosettes) or generalized could be considered arbitrary. Conclusion The rosette pattern identified in AK may be a specific pattern for AK.Accepted: 26 June 2017 Conflicts of interest None declared. Funding sources None declared. Introduction Rosettes were described in 2009 as a dermoscopic structure characterized by 4 white points arranged as a 4-leaf clover, mainly localized over the follicular openings. 1 They can be observed exclusively with polarized light dermoscopy, and are caused by polarization of concentric horn material in follicular ducts at the infundibular level and concentric fibrosis around the follicles. 2 Firstly described in actinic keratosis (AK), lichenoid AK and squamous cell carcinoma (SCC) developing from AK, they have also been detected in basal cell carcinoma, melanoma, lichen planus-like keratosis, melanocytic nevus, dermatofibroma, papulopustular rosacea and scars. 2 7 To the best of our knowledge, the association of rosettes with other dermoscopic structures in AK and SCC and their distribution has not been analysed yet. Methods We conducted a study of patients with histologically proven AK or SCC who presented dermoscopic rosettes at initial evaluation. It was carried out between October 2016 and March All dermoscopic images were taken with a DermLite (3Gen, San Juan Capistrano, CA, USA) II PRO HR dermatoscope (109 optical zoom, in polarized mode, 32 LEDs) attached to a digital camera (iphone 7). Photographs were taken using ethanol hand wash gel as immersion fluid for contact dermoscopy. The documentation form collected the following data: age, sex and anatomic subsite of the lesion on the head (scalp, forehead, temple, nose, cheek, chin) or other body region. Analysis of each lesion was performed independently by two dermatologists after histopathological confirmation of the
2 Rosettes and rosette pattern 49 diagnosis. Rosettes were assessed as present if one or more rosettes were observed. They were considered to be focally distributed if there were up to three rosettes, which were arranged in clusters. The rest were considered generalized. The rosette pattern was defined as having rosettes as the main feature, clearly visible and obvious, in addition to the red pseudonetwork and/ or the pigmented pseudonetwork. According to the latest publications, 8 14 the dermoscopic criteria included in the evaluation of AK and SCC are: scales (white or pale yellow crystalline surface); red pseudonetwork (erythema and linear-wavy telangiectasia without specific vascular structures in the interfollicular space); targetoid-like appearance or white circles (yellow to light-brown structureless centre and white outer structureless rim); pigmented pseudonetwork (structureless brown pigmentation, which is intermingled by non-pigmented follicular openings); multiple grey to brown dots and globules around hair follicles; brown structureless areas (brown colour without specific structures); erosions (small and irregularly distributed orange to red to red-brown structureless areas); keratin mass (amorphous, yellow-white to light-brown areas without any recognizable structure); Figure 2 Rosettes (arrows) in non-pigmented actinic keratosis. (a d) Generalized rosettes and white circles. Table 1 Patients demographics, type and anatomic subsite of the lesion Patient data AK SCC Total Mean age, range 70.9 (39 91) 81 (72 95) 71.4 (39 95) Female 20 (37.7%) 2 (66.7%) 22 (39.3%) Male 33 (62.3%) 1 (33.3%) 34 (60.7%) Forehead 20 (37.7%) 0 20 (35.7%) Nose 18 (34.0%) 1 (33.3%) 19 (33.9%) Scalp 8 (15.1%) 0 8 (14.3%) Cheek 4 (7.5%) 1 (33.3%) 5 (8.9%) Temple 3 (5.7%) 0 3 (5.4%) Hand 0 1 (33.3%) 1 (1.8%) Figure 3 Rosettes (arrows) in pigmented actinic keratosis. (a d) Generalized rosettes, pigmented pseudonetwork and multiple grey to brown dots and globules around hair follicles. ulceration (large irregularly shaped or roundish areas of dull red or red-brown structureless colour); and glomerular vessels (convoluted morphology, often distributed in clusters). Results Figure 1 Rosettes (arrows) in non-pigmented actinic keratosis. (a d) Generalized rosettes, erythema and scaling surface. Patients demographics and clinical characteristics A total of 56 tumours were collected. Table 1 summarizes the patients demographics, type and anatomic location of the lesion. The mean age of all patients was 71.4 years (range: years). Patients with SCC were slightly older (81 years, range: years) compared to patients with AK (70.9 years, range: years). Of the 56 patients, 34 (60.7%) were men and 22 (39.3%) were women. Fifty-three (94.6%) lesions were
3 50 Lozano-Masdemont et al. Figure 4 Focally distributed rosettes (arrows) in non-pigmented actinic keratosis (a c) and a pigmented squamous cell carcinoma. Rosettes and brown structureless areas. Figure 5 Rosettes (arrows) in a squamous cell carcinoma. Rosettes, ulceration, keratin mass and glomerular vessels. diagnosed as AK and 3 (5.4%) as SCC. Most lesions were located on the forehead (35.7%), followed by the nose (33.9%), scalp (14.3%) cheek (8.9%), temple (5.4%) and hand (1.8%). Dermoscopic features Dermoscopically, 37 (66.1%) lesions were non-pigmented (Figs 1 and 2), and 19 (33.9%) lesions were pigmented (Fig. 3). The most common dermoscopic findings were erythema (53; 94.6%) and scaly surface (42; 75%) (Fig. 1). Twenty-one (37.5%) revealed targetoid-like appearance (Fig. 2). The pigmented dermoscopic features were pigmented pseudonetwork (Fig. 3) in 18 (32.1%), multiple grey to brown dots and globules around hair follicles (Fig. 3) in 14 (25%) and brown structureless areas (Fig. 4d) in 1 (1.8%) case. Erosions (Fig. 3d) were observed in 3 (5.4%) and keratin mass (Fig. 5), ulceration (Fig. 5), and glomerular vessels (Fig. 5) in 1 (1.8%) each one. Rosettes were distributed focally (Fig. 4) in 9 (16.1%) and generalized (Figs 1-3, 5 and 6) in 47 (83.9%). The rosette pattern (rosettes as the main feature) was observed only in 19 (35.8%) AK (Fig. 6) but not in any SCC. These results are collected in Tables 2-4. Discussion White shiny structures, defined as structures which exhibit a bright white shiny colour, are seen exclusively under polarized light, contact or non-contact dermoscopy. They may present with three different morphologies: white shiny lines, white shiny areas and the mentioned rosettes. 3 White shiny lines are defined as whitish linear and orthogonal lines; and white shiny areas are characterized as white shiny clods or larger structureless areas with a shiny, bright white colour. Rosettes are defined as four closely aggregated bright white dots or points arranged as a four-leaf clover or four-dot clods arranged in a square corresponding to follicular opening. 1 Recently, it has been proposed that they are caused by polarization of concentric horn material in adnexal openings (smaller rosettes) and concentric fibrosis around the follicles (larger rosettes). 2 Individual or multiple in a given lesion, rosette is not, in itself, diagnostic of any particular lesion. Their presence speaks in favour of the diagnosis of AK (46.3%) or SCC (27%). 3 (e) Figure 6 Rosette pattern (a-e). Rosette as the main feature, clearly visible and obvious, in addition to the red pseudonetwork and/or the pigmented pseudonetwork.
4 Rosettes and rosette pattern 51 Table 2 Frequency of pigmented and non-pigmented lesions Pigmented Non-pigmented Total AK 18 (34%) 35 (66%) 53 (94.6%) SCC 1 (33.3%) 2 (66.7%) 3 (5.4%) Total 19 (33.9%) 37 (66.1%) 56 Table 3 Frequency of dermoscopic features AK SCC Total Erythema/red pseudonetwork 51 (96.2%) 2 (66.7%) 53 (94.6%) Scales 39 (73.6%) 3 (100%) 42 (75%) Targetoid-like appearance/white circles 21 (39.6%) 0 21 (37.5%) Pigmented pseudonetwork 18 (34%) 0 18 (32.1%) Multiple grey to brown dots 14 (26.4%) 0 14 (25%) and globules around hair follicles Erosions 3 (5.7%) 0 3 (5.4%) Keratin mass 0 1 (33.3%) 1 (1.8%) Ulceration 0 1 (33.3%) 1 (1.8%) Glomerular vessels 0 1 (33.3%) 1 (1.8%) Structureless brown areas 0 1 (33.3%) 1 (1.8%) Figure 7 Rosettes of different sizes in an actinic keratosis. Asterisk: four-dots rosette. Hash or pound sign: four white narrower dots within the follicular openings. Table 4 Frequency of the distribution of rosettes Distribution AK SCC Total Focal 8 (15.1%) 1 (33.3%) 9 (16.1%) Generalized 45 (84.9%) 2 (66.7%) 47 (83.9%) They also can be seen in melanoma (6.5%), 3 basal cell carcinoma (14.1%), 3 lichen planus-like keratosis (17.3%), 3 lichenoid AK1, melanocytic nevus 2, dermatofibroma 2, papulopustular rosacea 5 and scars. 6 The aim of this study was to describe the distribution of rosettes and their association with other dermoscopic signs. As expected, the most common features were erythema (94.6%) and scales (75%), as these are the most common dermoscopic signs in AK, followed distantly by targetoid follicles 37.5%. In pigmented lesions, they are observed intermingled with pigmented pseudonetwork, in combination with normal follicular openings or within brown structureless areas. Erosions were observed in three AK (5.7%) although we believe they may be caused by scratching or shaving. Keratin mass, ulceration and glomerular vessels were only present in SCC, consistent with the recently published progression model of AK actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma. 11 The distribution of rosettes in a generalized way was more common, making its identification easier (83.9% vs 16.1%). The rosette pattern identified in the present study only in AK (35.8%) has not been identified in other types of lesions (squamous cell carcinoma, basal cell carcinoma, melanoma, papulopustular rosacea or scars), so it may be a specific pattern of actinic keratosis, although future studies which support this hypothesis are needed. Figure 8 Rosette variants in an squamous cell carcinoma. Asterisk: four-dots rosette. Arrow: five-dot rosettes. Arrowhead: crosslike rosette. Figure 9 Schematic representation of the rosette variants. Upper left corner: four-dot or classic rosette. Upper right corner: five-dot rosette. Lower left corner: cross-like rosette. Lower right corner: four white narrower dots within the follicular openings. The size of rosettes may vary (Fig. 7). In fact, they may look more like a targeted follicle or white circle (Fig. 7), meaning that both signs could be a progression of the same feature. Moreover, some five white-dot structures and cross-like structures can be seen next to four-point rosettes (Fig. 8), a finding that would change or expand the definition of rosettes. The schematic representation of the rosette variants can be seen in Fig. 9. Rosettes, visible only when using polarized light dermoscopy, may be the key to the diagnosis of AK or SCC, due to their easy
5 52 Lozano-Masdemont et al. recognition, wide distribution and association with other common structures in these tumours. The rosette pattern identified in AK may be a specific pattern for AK. References 1 Cuellar F, Vilalta A, Puig S, Palou J, Salerni G, Malvehy J. New dermoscopic pattern in actinic keratosis and related conditions. Arch Dermatol 2009; 145: Haspeslagh M, No e M, De Wispelaere I, et al. Rosettes and other white shiny structures in polarized dermoscopy: histological correlate and optical explanation. J Eur Acad Dermatol Venereol 2016; 30: Liebman TN, Rabinovitz HS, Dusza SW, Marghoob AA. White shiny structures: dermoscopic features revealed under polarized light. J Eur Acad Dermatol Venereol 2012; 26: Liebman TN, Scope A, Rabinovitz H, Braun RP, Marghoob AA. Rosettes may be observed in a range of conditions. Arch Dermatol 2011; 147: Marques-da-Costa J, Campos-do-Carmo G, Ormiga P, Ishida CE, Cuzzi T, Ramos-e-Silva M. Rosette sign in dermatoscopy: a polarized finding. Skinmed 2011; 9: Rubegni P, Tataranno DR, Nami N, Fimiani M. Rosettes: optical effects and not dermoscopic patterns related to skin neoplasms. Australas J Dermatol 2013; 54: Perez-Perez L, Garcıa-Gavın J, Allegue F, Zulaica A. The rainbow pattern and rosettes in cutaneous scars. Actas Dermosifiliogr 2014; 105: Lallas A, Tschandl P, Kyrgidis A, et al. Dermoscopic clues to differentiate facial lentigo maligna from pigmented actinic keratosis. Br J Dermatol 2016; 174: Zalaudek I, Argenziano G. Dermoscopy of actinic keratosis, intraepidermal carcinoma and squamous cell carcinoma. Curr Probl Dermatol 2015; 46: Lee JH, Won CY, Kim GM, Kim SY. Dermoscopic features of actinic keratosis and follow up with dermoscopy: a pilot study. J Dermatol 2014; 41: Zalaudek I, Giacomel J, Schmid K, et al. Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: a progression model. J Am Acad Dermatol 2012; 66: Ciudad C, Aviles JA, Suarez R, Lazaro P. Diagnostic utility of dermoscopy in pigmented actinic keratosis. Actas Dermosifiliogr 2011; 102: Akay BN, Kocyigit P, Heper AO, Erdem C. Dermatoscopy of flat pigmented facial lesions: diagnostic challenge between pigmented actinic keratosis and lentigo maligna. Br J Dermatol 2010; 163: Peris K, Micantonio T, Piccolo D, Fargnoli MC. Dermoscopic features of actinic keratosis. J Dtsch Dermatol Ges 2007; 5:
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