Dermoscopic Features of Different Forms of Cutaneous Mastocytosis: A Systematic Review

The term mastocytosis refers to a heterogeneous group of disorders characterised by accumulation of clonal mast cells in different organs, most commonly in the skin. Little is known about the role of dermoscopy in the diagnostics of mastocytosis. To date, no systematic review on the dermoscopic features of cutaneous mastocytosis has been performed. The aim of this study was to summarise the current knowledge in the field as well as to identify the knowledge gaps to show possible directions for further studies, based on a systematic search of PubMed, Scopus, and Web of Science databases and related references published before 3 January 2022. Dermoscopic features, type of dermoscope, polarisation mode, magnification, and number of cases were analysed. In total, 16 articles were included in this review (3 case series and 13 case reports), analysing 148 patients with different variants of cutaneous mastocytosis; all of the studies analysed had a low level of evidence (V). The main dermoscopic features of urticaria pigmentosa included brown structureless areas, brown lines arranged in a network, and linear vessels distributed in a reticular pattern, with this last finding also being typical of telangiectasia macularis eruptiva perstans. The presence of either circumscribed yellow structureless areas or diffuse yellowish background was a constant pattern of mastocytoma, while nodular, pseudoangiomatous xanthelasmoid, and plaque-type mastocytosis were typified by light-brown structureless areas and/or pigment network, though the first two variants also showed yellow/yellow-orange structureless areas. Finally, pigmented streaks of radial distribution surrounding hair follicles were described to be a pathognomonic dermoscopic feature of pseudoxanthomatous mastocytosis. Although this review shows that the various clinical forms of cutaneous mastocytosis may feature diagnostic dermoscopic clues, it also underlines the need for further investigation as several relevant data are missing, including evaluation of dermoscopic pattern according to anatomical locations or “lesion age”, studies on rare mastocytosis variants, evaluation of the prognostic role of dermoscopy in the context of systemic involvement, and comparative analyses with common clinical mimickers.


Introduction
The term mastocytosis refers to a heterogeneous group of disorders characterised by accumulation of clonal mast cells in different organs, most commonly in the skin, bone marrow, liver, spleen, and lymph nodes. Cutaneous involvement may be either the only manifestation of the disease (Cutaneous Mastocytosis, CM) or it may be associated with systemic disease (Systemic Mastocytosis, SM) [1][2][3]. In contrast to adults, CM predominates in children [4].
Main differential diagnoses of CM include urticaria, juvenile xanthogranuloma, arthropod bites, bullous impetigo, autoimmune bullous skin disorders, epidermolysis bullosa, staphylococcal scalded skin syndrome, and café-au-lait macules (Supplementary  Table S1) [14,15]. Dermoscopy is a supportive tool in the diagnosis of different cutaneous disorders [16]. In recent years, new papers describing the dermoscopic features of mastocytosis have been published. The aim of this study was to summarise current data on the diagnostic utility of (video) dermoscopy of skin involvement in patients with mastocytosis.

Materials and Methods
A comprehensive search of the literature using the PubMed, Scopus, and Web of Science electronic databases using the keywords 'dermoscopy' OR 'dermatoscopy' OR 'trichoscopy' OR 'videodermoscopy' OR 'videodermatoscopy' in combination with 'mastocytosis' OR 'urticaria pigmentosa' OR 'mastocytoma' OR 'teleangiectasia macularis eruptiva perstans' was performed by two investigators (M. Sławińska., A. Kaszuba) over a time period from inception to 2 January 2022. After the initial search was performed, two reviewers independently screened titles and abstracts for inclusion and exclusion criteria. In doubtful cases, decision on inclusion was based on the opinion of the third investigator (M. So). Based on title and abstract analysis, researchers selected the articles concerning dermosopic features of mastocytosis. At this step, we excluded records not related to the topic, non-English language manuscripts, review articles, and duplicates. In the relevant articles assessed full-text, references were searched for additional records. Finally, articles not containing quantitative data on dermoscopic observations were excluded. In addition to dermoscopic features, type of dermoscope, polarisation mode, magnification, and number of cases were analysed and summarised. The Oxford 2011 Levels of Evidence was used to classify the level of evidence of each article [17]. As the analysed papers concerned diagnostic studies single case reports were labelled as level of evidence V. Additionally, corresponding terminology based on the International Dermoscopy Society consensus paper has been added [18].

Results
Of the 245 records found initially in PubMed, Scopus, and Web of Science databases, a total of 17 articles were assessed full-text after title and abstract screening. Of these 17 articles, one was excluded as it did not meet the inclusion criteria, and none were included after reference screening. Thus, in total, 16 articles were included in this review (3 case series and 13 case reports), analysing 148 patients with different CM variants. The flow chart reporting the study selection process is presented in Figure 1.
The type of dermoscope used in the study was mentioned in seven records, magnification in eight (seven used ×10 magnification and one ×50 and ×200 magnification), polarisation was mentioned in five records (polarised light was applied in all of them), and information concerning the use or not of an immersion interface was not provided in any of the analysed studies. The type of dermoscope used in the study was mentioned in seven records, magnification in eight (seven used ×10 magnification and one ×50 and ×200 magnification), polarisation was mentioned in five records (polarised light was applied in all of them), and information concerning the use or not of an immersion interface was not provided in any of the analysed studies. Table 1 presents the details of the analysed studies.  Table 1 presents the details of the analysed studies.

Maculopapular Cutaneous Mastocytosis (UP Clinical Subtype)
The systematic review revealed 99 cases in seven studies. Most data on dermoscopy of this mastocytosis variant came from a study by Vano-Galvan et al. [9], who analysed 90 patients with MPCM. The most prevalent dermoscopic findings were light-brown blots (structureless areas) (43/90; 47.8%), pigment networks (36/90; 40.0%), and vascular patterns including linear vessels in reticular distribution-described as reticular vesselsand dotted vessels (11/90; 12.2%). Interestingly, the study showed that the vascular dermoscopic pattern was an independent predictive factor for the need for daily antimediator therapy. The remaining data from smaller case reports/case series (six studies, nine patients) confirmed the presence of pigment network (brown reticular lines) in all cases (in two of them associated with a red or light-brown background) [9,10,[19][20][21][22][23] (Figure 2

Maculopapular Cutaneous Mastocytosis (UP Clinical Subtype)
The systematic review revealed 99 cases in seven studies. Most data on dermoscopy of this mastocytosis variant came from a study by Vano-Galvan et al. [9], who analysed 90 patients with MPCM. The most prevalent dermoscopic findings were light-brown blots (structureless areas) (43/90; 47.8%), pigment networks (36/90; 40.0%), and vascular patterns including linear vessels in reticular distribution-described as reticular vesselsand dotted vessels (11/90; 12.2%). Interestingly, the study showed that the vascular dermoscopic pattern was an independent predictive factor for the need for daily anti-mediator therapy. The remaining data from smaller case reports/case series (six studies, nine patients) confirmed the presence of pigment network (brown reticular lines) in all cases (in two of them associated with a red or light-brown background) [9,10,[19][20][21][22][23] (Figure 2).

Maculopapular Cutaneous Mastocytosis (TMEP Clinical Subtype)
When it comes to TMEP, a systematic review revealed 13 cases from five studies, including one case limited only to acral areas. The three main dermoscopic patterns were reticular vascular pattern (thin reticular telangiectasias) observed in all cases, in three cases associated with an erythematous background, in two cases with pigment network (brown reticular lines), and in one with brownish background [9][10][11][12] (Figure 3).

Maculopapular Cutaneous Mastocytosis (TMEP Clinical Subtype)
When it comes to TMEP, a systematic review revealed 13 cases from five studies, including one case limited only to acral areas. The three main dermoscopic patterns were reticular vascular pattern (thin reticular telangiectasias) observed in all cases, in three cases associated with an erythematous background, in two cases with pigment network (brown reticular lines), and in one with brownish background [9][10][11][12] (Figure 3).
Considering pseudoangiomatous xanthelasmoid mastocytosis, only one dermoscopic case of this rare entity was published revealing a pigment network (brown reticular lines) and yellow blots (structureless areas) [7].
Finally, an instance of pseudoxanthomatous localised mastocytosis involving the vulva showed pigmented streaks with radial distribution surrounding hair follicles, and this pattern was considered pathognomonic by the authors [6].
Finally, an instance of pseudoxanthomatous localised mastocytosis involving the vulva showed pigmented streaks with radial distribution surrounding hair follicles, and this pattern was considered pathognomonic by the authors [6].

Discussion
The aim of this review was to summarise the current knowledge on the role of dermoscopy in diagnosis of mastocytosis. The analysis of published studies revealed that almost all data (127 out of 148 patients) came from one large case series, and the remaining were small case series/case reports. All of the analysed studies showed a low level of evidence (V).
Based on this review, the main dermoscopic features of UP included brown structureless areas, brown lines arranged in a network, and linear vessels distributed in a reticular pattern. The first two findings were due to basal cell layer hyperpigmentation, a typical histological feature of this form of mastocytosis, while the vascular pattern was the result of dermal vessel dilation. This last histological finding was also responsible for the main dermoscopic feature of TMEP-the so-called "vascular reticular pattern" (thin

Discussion
The aim of this review was to summarise the current knowledge on the role of dermoscopy in diagnosis of mastocytosis. The analysis of published studies revealed that almost all data (127 out of 148 patients) came from one large case series, and the remaining were small case series/case reports. All of the analysed studies showed a low level of evidence (V).
Based on this review, the main dermoscopic features of UP included brown structureless areas, brown lines arranged in a network, and linear vessels distributed in a reticular pattern. The first two findings were due to basal cell layer hyperpigmentation, a typical histological feature of this form of mastocytosis, while the vascular pattern was the result of dermal vessel dilation. This last histological finding was also responsible for the main dermoscopic feature of TMEP-the so-called "vascular reticular pattern" (thin reticular telangiectasias). By contrast, the presence of either circumscribed yellow structureless areas or diffuse yellowish background was a repetitive dermoscopic pattern of mastocytoma histologically resulting from a compact mast cell infiltration of the dermis. Moving to nodular, pseudoangiomatous xanthelasmoid, and plaque-type mastocytosis, all of them may be typified by light-brown structureless areas and/or pigment network as a result of basal cell layer hyperpigmentation, yet only the first two variants may also show yellow/yellow-orange structureless areas, likely due to a denser cellular infiltration. Finally, pigmented streaks of radial distribution surrounding hair follicles were described as being a pathognomonic dermoscopic feature of pseudoxanthomatous mastocytosis, though this observation needs to be confirmed in further studies as it came from a single report [28].
Importantly, most of the remaining mentioned findings were not specific to mastocytosis and thus, should be interpreted carefully along with clinical and histopathological findings. Brown lines arranged in a network should be differentiated from melanocytic lesions or dermatofibroma, while in cases of yellow-orange structureless areas, diagnosis of juvenile xanthogranuloma, xanthoma, solitary reticulohistiocytoma, sebaceous tumours, keratin accumulation or scaly disorders, elastic fibres disorders, and others should be considered [29].

Conclusions
Despite several articles being published on the dermoscopy of CM, there is still a need for further investigations in this regard as the current evidence was from low-quality studies. Additionally, there were various aspects that have not been investigated so far, including evaluation according to anatomical locations or "lesion age", studies on rare mastocytosis variants, evaluation of the prognostic role of dermoscopy in the context of systemic involvement, and comparative analyses with common clinical mimickers. Based on current knowledge, it seems that dermoscopy will remain a complementary technique in mastocytosis diagnosis, as potential overlap with structures observed in other entities exists.