Challenging Patterns of Atypical Dermatofibromas and Promising Diagnostic Tools for Differential Diagnosis of Malignant Lesions

Dermatofibroma (DF) or fibrous histiocytoma is one of the most frequent benign cutaneous soft-tissue lesions, characterized by a post-inflammatory tissue reaction associated with fibrosis of the dermis. Clinically DFs have a polymorphous clinical aspect from the solitary, firm, single nodules to multiple papules with a relatively smooth surface. However, multiple atypical clinicopathological variants of DFs have been reported and, therefore, clinical recognition may become challenging, leading to a more burdensome identification and sometimes to misdiagnosis. Dermoscopy is considered an important tool in DFs diagnosis, as it improves diagnostic accuracy for clinically amelanotic nodules. Although typical dermoscopic patterns are most frequently seen in clinical practice, there have also been some atypical variants described, mimicking some underlying recurrent and sometimes harmful skin afflictions. Usually, no treatment is required, although an appropriate work-up may be necessary in specific cases, such as in the presence of atypical variants or a history of recent changes. This narrative review’s aim is to summarize current evidence regarding clinical presentation, positive and differential diagnosis of atypical dermatofibromas and also to raise awareness about the importance of specific characteristics of atypical variants to better differentiate them from malignant conditions.


Results
This narrative review aimed to reevaluate the clinical and land dermoscopic pat of atypical dermatofibromas compared to the typical ones. Although the clinical diag of DFs may be simple in daily practice, in the presence of various patterns, diagno DFs can become challenging. Therefore, specific characterization of these atypical var is essential in differentiating them from malignant conditions and assessing the ri local recurrence.

Results
This narrative review aimed to reevaluate the clinical and land dermoscopic patterns of atypical dermatofibromas compared to the typical ones. Although the clinical diagnosis of DFs may be simple in daily practice, in the presence of various patterns, diagnosis of DFs can become challenging. Therefore, specific characterization of these atypical variants is essential in differentiating them from malignant conditions and assessing the risk of local recurrence.

Clinical Presentation
Clinically, DF usually presents as solitary, hyperkeratotic, small (0.3 to 1 cm) and slow-growing nodule with a red-brown surface [2,4,5,19] (Figure 2). The rate of recurrence seems to be higher in lesions initially greater than 1 cm [6]. Other clinical patterns include firm, flat, sometimes atrophic, single or multiple papules, plaques, with a variety of colors (light brown, dark brown, purple, red or yellow) [1,39] (Figure 3).
Colour may also vary depending on the Fitzpatrick fototype ( Figure 4). The overlying skin can be pink, red, purple, gray, yellow, orange, blue, brown or black [40]. On palpation DFs have the consistency of a nodule, that moves freely over the subcutis [40]. The dimple sign is valuable in the diagnosis of DFs, although it may not always assure it [41].
Besides the classical clinical presentation, there have also been described some unusual atypical variants. Rare variants may include metastasizing benign DFs, which are usually larger than typical variants (more than 3 cm) [4, 42,43]. Morphological features can be those of cellular, aneurysmal or atypical DFs and a greater number of mitosis has been noticed in this cases [4,42,43]. Extension into the subcutaneous layer and local recurrence has also been described [4,42,43]. Regarding metastatic sites, lymph nodes and lungs are the most frequent ones [4, 42,43].  Colour may also vary depending on the Fitzpatrick fototype ( Figure 4). The overlying skin can be pink, red, purple, gray, yellow, orange, blue, brown or black [40]. On palpation DFs have the consistency of a nodule, that moves freely over the subcutis [40]. The dimple sign is valuable in the diagnosis of DFs, although it may not always assure it [41].  Besides the classical clinical presentation, there have also been described some unusual atypical variants. Rare variants may include metastasizing benign DFs, which are usually larger than typical variants (more than 3 cm) [4, 42,43]. Morphological features can be those of cellular, aneurysmal or atypical DFs and a greater number of mitosis has been noticed in this cases [4, 42,43]. Extension into the subcutaneous layer and local recurrence  Colour may also vary depending on the Fitzpatrick fototype ( Figure 4). The overlying skin can be pink, red, purple, gray, yellow, orange, blue, brown or black [40]. On palpation DFs have the consistency of a nodule, that moves freely over the subcutis [40]. The dimple sign is valuable in the diagnosis of DFs, although it may not always assure it [41].  Besides the classical clinical presentation, there have also been described some unusual atypical variants. Rare variants may include metastasizing benign DFs, which are usually larger than typical variants (more than 3 cm) [4, 42,43]. Morphological features can be those of cellular, aneurysmal or atypical DFs and a greater number of mitosis has been noticed in this cases [4, 42,43]. Extension into the subcutaneous layer and local recurrence  Colour may also vary depending on the Fitzpatrick fototype ( Figure 4). The overlying skin can be pink, red, purple, gray, yellow, orange, blue, brown or black [40]. On palpation DFs have the consistency of a nodule, that moves freely over the subcutis [40]. The dimple sign is valuable in the diagnosis of DFs, although it may not always assure it [41].  Besides the classical clinical presentation, there have also been described some unusual atypical variants. Rare variants may include metastasizing benign DFs, which are usually larger than typical variants (more than 3 cm) [4, 42,43]. Morphological features can be those of cellular, aneurysmal or atypical DFs and a greater number of mitosis has been noticed in this cases [4,42,43]. Extension into the subcutaneous layer and local recurrence Giant lesions (larger than 5 cm) have also been described in the scientific literature [4, 40,43] (Figure 5). The largest tumor reported measured 17 × 9 × 4 cm [44].
A Meyerson phenomenon adjacent to the DF has been seen [70] ( Figure 6).
A Meyerson phenomenon adjacent to the DF has been seen [70] ( Figure 6).
A Meyerson phenomenon adjacent to the DF has been seen [70] ( Figure 6).

Figure 6.
A Meyerson phenomenon is adjacent to the DF.

Diagnosis and Assessment
As multiple atypical variants of DF have been reported in the literature, clinical recognition may become challenging, leading to a more burdensome identification and sometimes to misdiagnosis [2,9]. Although diagnosis is commonly based on clinical

Diagnosis and Assessment
As multiple atypical variants of DF have been reported in the literature, clinical recognition may become challenging, leading to a more burdensome identification and sometimes to misdiagnosis [2,9]. Although diagnosis is commonly based on clinical presentation and history, further diagnostic tools such as dermoscopy, variable-frequency ultrasonography, fluorodeoxyglucose positron-emission tomography (FDG-PET) scans, and confocal laser scanning microscopy are necessary.
Dermoscopy is a non-invasive procedure useful for the diagnosis and management of pigmented tumours of the skin [9,71]. Among the scientific literature, various dermoscopic structures have been mentioned. DFs typical dermoscopic appearance includes the presence of a delicate, peripheral light-to-medium brown pigment network with a sharply demarcated central white scar-like area, white network and homogeneous pigmentation [1,8,9] (Figure 7). it correlates with histopathological types of DFs [72]. As DFs proved to have intense F-1 fluorodeoxyglucose uptake on positron emission tomography-computed tomograph scan, the letter coud be a possible diagnostic alternative [73]. Although confocal lase scanning microsocopy is mainly used to evaluate melanocytic lesions, it is helpful i diagnosing DFs as their features (bright rings at the periphery, collagen structures at th center, central keratin) correlate with both dermoscopy and histopathology [74]. Although typical dermoscopic patterns are most frequently seen in clinical practice some authors described atypical types of DFs (Table 1).  For atypical variants, high definition optical coherence tomography can be useful as it correlates with histopathological types of DFs [72]. As DFs proved to have intense F-18 fluorodeoxyglucose uptake on positron emission tomography-computed tomography scan, the letter coud be a possible diagnostic alternative [73]. Although confocal laser scanning microsocopy is mainly used to evaluate melanocytic lesions, it is helpful in diagnosing DFs as their features (bright rings at the periphery, collagen structures at the center, central keratin) correlate with both dermoscopy and histopathology [74].
Although typical dermoscopic patterns are most frequently seen in clinical practice, some authors described atypical types of DFs (Table 1).  Additional clinical features may include ring-like or donut-shaped globular structures, vascular structures and sometimes ulceration, comedo-like openings, scale, crusts, or peripheral collarette fissures [8,9].
The pigment network may vary from peripheral/total/irregular delicate to peripheral/total/irregular prominent and atypical appearance [1,3,9]. Aytekin et al. evaluated dermoscopically 142 DFs of 72 patients and concluded that pigment network was found in 57% of cases, the most common subtype being irregular delicate or asymmetric pigment network [1]. Delicate pigment network seen in DFs is commonly thin, varying from light to medium brown and it is considered that it results as hyperpigmentation of rete ridges rather than the proliferation melanocytes [1]. According to the study performed by Arpaia et al., the pigment network was darker in the center, becoming gradually pale towards the periphery with brownish thin streaks [80]. In 2000, Ferrari et al. noticed that the peripheral pigment network and central white scar-like patches are more prevalent in women and among the classical histopathologic type of DFs [36]. The results may alternate due to the quality of the dermoscopy (contact/non-contact, polarized/nonpolarized light) and the difference among genders [1]. Interestingly, Zaballos et al. also identified in some DFs a significant and/or atypical pigment network [8].
Central white scar-like patches are sharply demarcated with irregular white regions, histopathologically characterized by various grades of fibrosis in the dermis [1,9] (Figure 8).
Aytekin et al. have detected white scar-like patches in 37.3% of cases, the most common subtype being the central ones [1]. This structure is considered the most widespread feature of diffuse fibrous DF with a peripheral delicate pigment network [1]. It has also been noticed that the scar structure occasionally got a white radial streaks appearance, which gave the aspect of a spitzoid pattern [1]. Zaballos et al. evaluated 412 DFs and observed that white scar-like patches are mainly localized in the center part of the lesion [8]. Moreover, Arpaia et al. concluded that the central white patch was the most frequent dermoscopic feature, observed in 91.6% of cases [80].  [36]. The results may alternate due to the quality of the dermoscopy (contact/non-contact, polarized/nonpolarized light) and the difference among genders [1]. Interestingly, Zaballos et al. also identified in some DFs a significant and/or atypical pigment network [8].
Central white scar-like patches are sharply demarcated with irregular white regions, histopathologically characterized by various grades of fibrosis in the dermis [1,9] (Figure  8). Aytekin et al. have detected white scar-like patches in 37.3% of cases, the most common subtype being the central ones [1]. This structure is considered the most widespread feature of diffuse fibrous DF with a peripheral delicate pigment network [1]. It has also been noticed that the scar structure occasionally got a white radial streaks appearance, which gave the aspect of a spitzoid pattern [1]. Zaballos et al. evaluated 412 DFs and observed that white scar-like patches are mainly localized in the center part of the lesion [8]. Moreover, Arpaia et al. concluded that the central white patch was the most frequent dermoscopic feature, observed in 91.6% of cases [80].
The white network may be central, total, irregular, or crystalline-like [1,3,9]. Zaballos et al. identified a network of white lines and brown holes, which was later considered a variation of the white scar-like patch [8]. There has been raised awareness of the importance of distinguishing this structure from dysplastic nevi, Spitz nevi and the negative pigment network encountered in melanomas [1,8].
The homogenous pigmentation may include multiple colors (brown, yellow) or it may appear as hypopigmentation [1,3,9] (Figure 9). Ferrari et al. noticed that homogeneous pigmentation was most frequently in females and DFs with sebaceous hyperplasia, whereas peripheral homogeneous pigmentation was mostly encountered in men [36]. Karaarslan et al. observed a homogeneous blueish pigmentation that was associated with the hemosiderotic type of the DF [81]. Usually, hemosiderotic variants are indicated by the green color [79]. The white network may be central, total, irregular, or crystalline-like [1,3,9]. Zaballos et al. identified a network of white lines and brown holes, which was later considered a variation of the white scar-like patch [8]. There has been raised awareness of the importance of distinguishing this structure from dysplastic nevi, Spitz nevi and the negative pigment network encountered in melanomas [1,8].
The homogenous pigmentation may include multiple colors (brown, yellow) or it may appear as hypopigmentation [1,3,9] (Figure 9). Aytekin et al. have detected white scar-like patches in 37.3% of cases, the most common subtype being the central ones [1]. This structure is considered the most widespread feature of diffuse fibrous DF with a peripheral delicate pigment network [1]. It has also been noticed that the scar structure occasionally got a white radial streaks appearance, which gave the aspect of a spitzoid pattern [1]. Zaballos et al. evaluated 412 DFs and observed that white scar-like patches are mainly localized in the center part of the lesion [8]. Moreover, Arpaia et al. concluded that the central white patch was the most frequent dermoscopic feature, observed in 91.6% of cases [80].
The white network may be central, total, irregular, or crystalline-like [1,3,9]. Zaballos et al. identified a network of white lines and brown holes, which was later considered a variation of the white scar-like patch [8]. There has been raised awareness of the importance of distinguishing this structure from dysplastic nevi, Spitz nevi and the negative pigment network encountered in melanomas [1,8].
The homogenous pigmentation may include multiple colors (brown, yellow) or it may appear as hypopigmentation [1,3,9] (Figure 9). Ferrari et al. noticed that homogeneous pigmentation was most frequently in females and DFs with sebaceous hyperplasia, whereas peripheral homogeneous pigmentation was mostly encountered in men [36]. Karaarslan et al. observed a homogeneous blueish pigmentation that was associated with the hemosiderotic type of the DF [81]. Usually, hemosiderotic variants are indicated by the green color [79]. Ferrari et al. noticed that homogeneous pigmentation was most frequently in females and DFs with sebaceous hyperplasia, whereas peripheral homogeneous pigmentation was mostly encountered in men [36]. Karaarslan et al. observed a homogeneous blueish pigmentation that was associated with the hemosiderotic type of the DF [81]. Usually, hemosiderotic variants are indicated by the green color [79].
The vascular pattern has been widely discussed. Vascular structures are used in dermoscopy to diagnose melanoma and other pigmented or vascular tumors, which mimic melanoma [1,3]. Nevertheless, DFs may have peripheral, central, or total erythema, dotted, hairpin, glomerular, comma, or linear vessels, but also polymorphic and atypical ones [1,3,9] (Figure 10). The vascular pattern has been widely discussed. Vascular structures are used in dermoscopy to diagnose melanoma and other pigmented or vascular tumors, which mimic melanoma [1,3]. Nevertheless, DFs may have peripheral, central, or total erythema, dotted, hairpin, glomerular, comma, or linear vessels, but also polymorphic and atypical ones [1,3,9] (Figure 10).   Contrary to other studies, Genc et al. found vascular structures to be the most frequent dermatoscopic feature and described a red to brown halo phenomenon in 4.9% of DFs [75]. Another study performed by Agero et al. concluded that blood vessels were seen in 44% of DFs when using polarized light [82]. Ferrari et al. described 2 DFs with dotted vessel patterns, whereas Aytekin et al. stated that the most frequent vascular structures in their study were erythema and dotted vessels [1,9,36].
Melanoma-like and pyogenic granuloma-like atypical patterns were seen mostly in the case of aneurysmal DFs [75]. Furthermore DFs may have a pinkish-red pigmentation, dotted vessels and superficial white scales resembling psoriasis [9]. A "collision tumour-like" pattern was also described having a white area with focal pigment network [9]. Particularly, collision-like patterns along with melanoma-like and vascular tumour-like patterns were most commonly noticed in men [9]. Aditionally there have been described palisading, granular cell, myxoid, lichenoid, balloon cell and signet-ring cell variants [2,6,9]. a DF with arborizing vessels, along with the central white scar-like patch and fine delicate pigment network.   [3]. They underlined the importance of a correct differential diagnosis as pink nodular lesions with erythema, vascular structures, shiny white streaks and a central white patch may suggest malignancy, mainly amelanotic/hypomelanotic melanoma [3]. Moreover, regarding the dermopathological types, non-fibrocollagenous variants of DFs were proned to have atypical patterns [36,75].
Melanoma-like and pyogenic granuloma-like atypical patterns were seen mostly in the case of aneurysmal DFs [75]. Furthermore DFs may have a pinkish-red pigmentation, dotted vessels and superficial white scales resembling psoriasis [9]. A "collision tumourlike" pattern was also described having a white area with focal pigment network [9]. Particularly, collision-like patterns along with melanoma-like and vascular tumour-like patterns were most commonly noticed in men [9]. Aditionally there have been described palisading, granular cell, myxoid, lichenoid, balloon cell and signet-ring cell variants [2,6,9].
As such, dermoscopy may be beneficial in increasing diagnosis and management accuracy, but since dermoscopic features may vary as well, it is certainly important to take into consideration other differential diagnoses [4,9,71,75].    [3]. They underlined the importance of a correct differential diagnosis as pink nodular lesions with erythema, vascular structures, shiny white streaks and a central white patch may suggest malignancy, mainly amelanotic/hypomelanotic melanoma [3]. Moreover, regarding the dermopathological types, non-fibrocollagenous variants of DFs were proned to have atypical patterns [36,75].
Melanoma-like and pyogenic granuloma-like atypical patterns were seen mostly in the case of aneurysmal DFs [75]. Furthermore DFs may have a pinkish-red pigmentation, dotted vessels and superficial white scales resembling psoriasis [9]. A "collision tumourlike" pattern was also described having a white area with focal pigment network [9]. Particularly, collision-like patterns along with melanoma-like and vascular tumour-like patterns were most commonly noticed in men [9]. Aditionally there have been described palisading, granular cell, myxoid, lichenoid, balloon cell and signet-ring cell variants [2,6,9].
As such, dermoscopy may be beneficial in increasing diagnosis and management accuracy, but since dermoscopic features may vary as well, it is certainly important to take into consideration other differential diagnoses [4,9,71,75]. As such, dermoscopy may be beneficial in increasing diagnosis and management accuracy, but since dermoscopic features may vary as well, it is certainly important to take into consideration other differential diagnoses [4,9,71,75].
Moreover, the epidermis usually exhibits elongated rete ridges containing hyperpigmented basal keratinocytes, aspect known as "dirty feet" sign [2]. There is also a proliferation of spindle-shaped fibrous cells mixed with histiocytoid cells at the level of the dermis [22,89,90]. Collagen bundles are commonly seen between the spindled fibrous Moreover, the epidermis usually exhibits elongated rete ridges containing hyperpigmented basal keratinocytes, aspect known as "dirty feet" sign [2]. There is also a proliferation of spindle-shaped fibrous cells mixed with histiocytoid cells at the level of the dermis [22,89,90]. Collagen bundles are commonly seen between the spindled fibrous cells along with the unaffected layeser, known as the "Grenz zone" [2,[89][90][91].
A histologic review performed by Alves et al. on 192 dermatofibromas stated that common fibrous hystiocitoma was the most frequent type, observed in 80% of cases [2]. Individual collagen bundles encompassed by lesional cells (fibroblasts, macrophages and blood vessels) and a predominantly lymphocytic inflammatory infiltrate may be seen [2].
Atypical DFs also known as DFs with monster cells, are poorly documented variants of typical fibrous histiocytomas [88]. Besides typical findings, atypical DF are comprised of pleomorphic spindle-like, hystiocite-like cells and multinucleate giant cells. [89].
LeBoit and Barr firstly described dermatofibroma with granular cells in 1991 [87,88]. This rare histologic variant can be confused with other malignant or benign cutaneous neoplasms such as: benign granular cell tumor, malignant granular cell tumor, primitive polypoid granular cell tumor, granular cell ameloblastoma, granular cell fibrous papule of the nose, granular cell basal cell carcinoma, granular cell schwannoma, granular cell leiomyoma, granular cell leiomyosarcoma or angiosarcoma and granular cell dermatofibrosarcoma protuberans [87]. Morfology of the lesion along with immunohistochemical evaluation might sometimes be decisive for the corect diagnosis [86]. For instance, benign granular cell tumors are positive for S-100 protein, CD63, CD68 and neuron-specific enolase whereas atypical fibroxanthoma stains negatively for S100 protein, Melan-A, human melanoma black (HMB)-45 pan-cytokeratin (CK) and actin and positively for CD68 and vimentin [87].
Immunohistochemistry can be useful to differentiate DFs from schwannomas, leiomyomas and leiomyosarcomas [87].
Hemosiderotic dermatofibromas, dermatoscopically characterized by a blue/red center with white lines and maybe network and vessels at the periphery may lead to a dermoscopically differential diagnosis with Kaposi sarcoma due to the intense vascularity [28,29]. Nevertheless, Kaposi sarcoma stains are positive for CD31, CD34 and D2-40, and patients are also positive for HHV-8 [19].
CK20 positive Merkel cells, present in the follicular induction, crowding, no peripheral palisading, clear cell hyperplasia, and the absence of nuclear atypia are helpful pathologic features in differentiating DFs with follicular induction from basal cell carcinomas [19].

Discussion
This narrative review aimed to reevaluate the clinical and dermoscopic patterns of atypical dermatofibromas compared to the typical ones. Moreover, there have been mentioned some not-so-common etiopathogenic factors. Dermatofibromas are prevalent cutaneous benign tumours that most frequently affect young or middle-aged adults. Clinically, dermatofibromas appear as single or multiple firm papules or nodules with a smooth surface anywhere on the body, mainly on the lower extremities. They can vary in size and colour from light brown to dark brown, yellow, purple or red. Although the clinical diagnosis of DFs may be simple in daily practice, in the presence of various patterns, diagnosis of DFs can become challenging.
Therefore, it is essential to consider the possible links between dermoscopy and histology and complete surgical excision, especially in the presence of atypical variants or a history of recent changes. Thus, the precise definition of dermoscopic patterns for this frequent benign tumour is of major interest.
In a reverse manner, the possibility of a misdiagnosis of malignant skin disorders, inlcuding non-melanoma skin cancer, is a main challenge in terms of worldwide public health management. A lot of clinicians may face it and thus malignancy-related misdiagnosis remains one of the main issues in the dermatologic field. Similar to the case of melanomas or basal cell carcinomas being misdiagnosed as diabetic foot ulcer, they can be more easily considered, even by experts, as benign lesion, such as dermatofibromas [111]. As malignant tumors may sometimes mimic benign conditions, the main focus has been on finding a non-invasive, reliable, sensible and highly specific diagnostic methods to identify specific features which suggest malignancy.

Promising Differential Diagnostic Methods
Apart from dermoscopy and digital dermoscopy, not so common diagnostic tools may include variable-frequency ultrasonography, in which DFs appear as hypoechoic solid nodules and high-definition optical coherent tomography, in which DFs can resemble malignant conditions on FDG-PET scans [73,74]. Among other studied techniques there have been mentioned reflectance confocal microscopy (RCM), multiphoton microscopy, fluorescence evaluation, Raman spectroscopy and diffuse reflectance [112][113][114][115]. Highfrequency ultrasonography has been a valuable diagnostic and prognostic tool in early detecting other types of malignancies, such as hepatocellular carcinoma, for a long time, but it recently has begun to represent a promising opportunity in dermatology by using deep learning-based algorithms to analyse automated images [77,116,117]. Complementary techniques, such as dermoscopy in conjunction with RCM, may also enhance diagnostic accuracy of melanocytic conditions [118][119][120]. Confocal laser scanning microscopy is also considered an alternative tool [118][119][120].
The use of fractal parameters and fractal analysis method in dermatology is promising in the evaluation of image parameters, independently of the adopted scale [121]. There are currently studies being carried regarding the usefulness of fractal parameters in building classes of disease units based upon pictures of cutaneous pigmented lesions [121,122]. It might provide fully automatic diagnostic systems able to determine the type of pigmented tumor and inform us regarding the most adequate management [121].
Taking into consideration that dermatology is a largely visual speciality, the high cost of travel expenses to urban centres, the long wait times to see a dermatologist and the shortage of dermatology services mainly in rural areas, several research studies analizying the role of an artificial intelligence (AI) system as a diagnostic tool for the management of skin conditions have been conducted, focusing mainly on the malignant ones [123][124][125][126][127][128][129]. Several studies proved that telehealth platforms, easily reachable through smartphone apps, could increase patients access to dermatological care, especially during COVID-19 pandemic [127,[130][131][132]. Some of the apps can use AI to provide various differential diagnoses depending on the information provided: patient demographics, lesion type, location, symptoms and progression [127,129]. Artificial neural networks, such as convolutional neural networks (CNNs), can be used to analyse visual imagery, being very effective in recognizing automated images and equal or superior than dermatologist in recognizing skin cancers [123]. Implementing AI as a diagnostic aid in the clinical practice may be safe, useful and feasible for skin lesions accurate detection and for better differentiating malignant from benign ones [123][124][125][126][127].
In order to diminish the high degree of subjectivity and variability regarding specificity, sensitivity, and diagnostic accuracy when performing RCM, a lot of artificial intelligence algorithms were created to ensure alternatives, assistance and support od dermatologists on a daily basis [118]. AI in RCM has been used so far to point out the dermal-epidermal junction, evaluate the the quality of RCM mosaics and distinguish between different skin tumors [118].
A lot of other studies have analyzed the correlation between spectrophotometric parameters of skin color and behavioral/environmental factors to predict the risk of cutaneous malignancies [133]. They concluded that the measurment of skin melanin index measured on the arm or buttock is the simplest predictor and should be added in predictive models. Regarding the environmental/behavioral factors, the total number of sunburns appear to be the most important one. As such, spectrophotometric measurements may be considered a quick screening examination method of the skin [133].
In histopathology, AI is efficient in classifying and characterizing tissues, in detecting mitosis and segment histologic primitives as epithelium, nuclei and tubules [128].
As a consequence of complexity and intransparency of deep neural networks in classifying skin cancer, explainable artificial intelligence (XAI) has also been suggested as an alternative although further research studies are needed to evaluate the influence of XAI in detecting cutaneous cancer [134].
There are lot of opportunities that lie ahead, from automated classification of cutaneous cancer through convolutional neural networks, sequential digital dermoscopy and automated total body photography to AI and automated teledermoscopy [135]. However, the potential use of AI in clinical practice remains to be addressed due to their limitations and further studies need to be conducted in order to implement it every day medical practice [135].

Conclusions
Clinical diagnosis of typical dermatofibromas is easy, with a classic dermoscopic pattern of pigmented network and central white patch. However, in current clinical situations, dermatofibromas display a wide range of presentations and histological variants that make the differentiation from other tumours, such as malignant melanoma, very difficult. Specific characterization of these atypical variants is essential in differentiating them from possibly more aggressive lesions and assessing the risk of local recurrence. As a matter of fact, the definitive diagnosis of a skin condition, especially in a doubtful clinical diagnostic scenario, demands complete surgical resection and histopathological analysis. As artificial intelligence technologies had reached an impressive precision in identifying various skin lesions, along with other inovative diagnostic methods, we can emphasise that in the future it will lead to improved safety and patient care and maybe enhance dermatologists' productivity. Institutional Review Board Statement: The study was approved by the local Ethical Committee of the "Elias" University Emergency Hospital. The research was conducted according to the Helsinki Declaration. The pictures are part of the authors' own archive and are from the patients admitted in "Elias" University Emergency Hospital in the last 2 years. They do not contain personal data.
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.

Data Availability Statement:
This review summarizes data reported in the literature and it does not report primary data.

Conflicts of Interest:
The authors declare no conflict of interest.