Dermoscopic Findings in Cases of Cutaneous Metastases

Cutaneous metastases (CM) are cancerous cells in any layer of the skin, originating from primary cancer [1]. These tumor cells metastasize through haematogenous, lymphatic, and direct tissue invasion. Even some cases of iatrogenic malignant implantation have been reported [2]. Regarding the frequency of skin metastasis formation, it correlates with the frequency of primary cancer [3]. The most common types of cancers to produce CM are melanoma, breast cancer, lung cancer, colon cancer and others, but theoretically, every type of cancer can form metastases in the skin (Table 1) [4]. As 1-10%


INTRODUCTION
Cancer remains a crucial public health issue worldwide. A major problem with the management and treatment of malignancies is their ability to produce metastases.
Cutaneous metastases (CM) are cancerous cells in any layer of the skin, originating from primary cancer [1]. These tumor cells metastasize through haematogenous, lymphatic, and direct tissue invasion. Even some cases of iatrogenic malignant implantation have been reported [2]. Regarding the frequency of skin metastasis formation, it correlates with the frequency of primary cancer [3]. The most common types of cancers to produce CM are melanoma, breast cancer, lung cancer, colon cancer and others, but theoretically, every type of cancer can form metastases in the skin (Table 1) [4]. As 1-10% of all cancer patients with metastatic disease will develop cutaneous metastases, they are quite rare in everyday practice but of great importance. Skin involvement in the metastatic process is considered a poor prognosis for the overall patient condition [5].

MATERIALS AND METHODS
This review was prepared by performing a comprehensive search of the literature using keywords related to cutaneous metastases and their dermoscopic findings. The search was run on January 2021, in EBSCOhost, ScienceDirect, Wiley Online Library and ClinicalKey databases. Book chapters, case studies, case reports and literature reviews were included.
Inclusion criteria included the articles on the topic of cutaneous metastases formed by internal malignancy, melanoma or lymphoma, and those containing clinical and/or dermoscopic images of the cutaneous metastases. Exclusion criteria involved report on primary skin tumors, non-English studies, and if full articles are not available.
A total of 580 citations were generated from the literature search, of which twenty-two (n=22) met the inclusion criteria. For the analysis of dermoscopic patterns in cutaneous metastases, only papers that provided dermoscopic images were considered. Ten (n=10) of the analysed reports were used to provide a summary of the available data on dermoscopic features in cutaneous metastases. Pictures from the author's private collection were added for additional visual purposes.

Clinical Features
The most common clinical presentation of cutaneous metastases involves painless, firm nodules located in the dermis, anatomically near the primary tumor site, metastatic lymph node or surgical scar [1,5,6] (Fig. 1). These nodules usually appear suddenly and show a rapid enlargement. The average size of a nodule is between 1 to 3 cm, but much larger and smaller lesions have been reported [7]. Various other clinical forms of skin metastases have been reported as well. For example, cutaneous metastases can mimic dermatitis [8] and even chancres [9]. The migration of the malignant cells can also cause lymphatic obstruction, presenting as facial swelling and elephantiasis [7].
The color of the newly formed lesion varies from fleshcolored to pink, red, purple, and even black. In breast cancer, such specific forms as induration (peau d'orange), erysipelaslike formations and erythematous papules that resemble vascular proliferation are described. In leukemia and lymphoma patients, papular and nodular pink-to-brown lesions have been described as a form of cutaneous metastases [5, 10 -12].
It is also worth mentioning that cutaneous metastases can become infected by various pathogenic and/or opportunistic bacteria (such as S. aureus, P. aeruginosa), causing discomfort, pain, malodor, and other complications [13].

The Role of Dermoscopy in Diagnostics Of Cutaneous Metastasis
There are no specific steps for acquiring the diagnosis of skin metastasis. The appearance and anatomical site of the newly formed lesion as well as the patient's history can play an important role in the diagnostic process. Although lesion biopsy is considered the most effective diagnostic method, an additional, non-invasive diagnostic approach would be dermoscopy.
Dermoscopy (or epiluminescence microscopy, ELM) is a widely used method in clinical practice to mainly inspect benign and malignant nevomelanocytic lesions. A study carried out in 2017 by Christoph Sinz et al. suggests that dermoscopy also improves the diagnosis and management of nonpigmented skin cancers and should be used as an adjunct method to the basic examination of suspicious lesions [14].
The available information on the dermoscopic patterns of cutaneous metastasis is limited; we found ten publications on this topic ( Table 2).  In a case report of cutaneous metastasis of renal carcinoma, dermoscopy revealed purple-red colour lesions with multiple linear vessels that were distributed in a parallel pattern in the centre of the lesion. White lines in the periphery of the lesion were also described [16].
In reports on cutaneous melanoma metastases, the main dermoscopic patterns reported are homogenous, saccular, amelanotic, vascular and polymorphic [17,18]. Rubegni et al. suggest that the vascular patterns are related to tumor thickness; corkscrew vessels are more often found in thick lesions while punctate vessels predominate in thinner ones. Vascular structures are more often found in melanoma metastases than in primary lesions, thus they could be a valid diagnostic tool for distinguishing primary melanoma from its metastases [18]. Vascular patterns (serpentine, hairpin, and other types of vessels) are also reported by Jaimes et al. in nonpigmented melanoma metastases. Other dermoscopic patterns include peripheral grey spots/globules, pigmentary halo, and perilesional erythema [17 -19].
The main dermoscopic findings in cutaneous forms of lymphomas include various presentations of vessels (ex., linear, dotted, arborizing), structureless areas and yellow areas, as well as scaling [12].
Some examples of dermoscopic images from cutaneous metastases are presented in (Figs. 2-4).
Overall, the use of dermoscopy increases yearly, but case reports and studies on the specific dermoscopic features of cutaneous metastases are not that common. This could be due to the uncommonness of secondary cutaneous malignancies in general or the lack of dermoscopy skills and use in other specialties, excluding the dermatology field. The most structured information in the literature on the dermoscopic findings in specific tumor metastases is related to melanoma [17, 18] and cutaneous lymphomas [12]. This could be due to the fact that these patients are often overseen by dermatologists, who tend to use dermoscopy as a diagnostic tool more than any other specialists.
The main reported characteristics of skin metastases in dermoscopy overall are various forms of vascular patterns (ex. linear, dotted, arborizing, corkscrew-like and others, as well as a mix of various patterns or polymorphous vessels) [1, 12 -22]. The vascular patterns may be related to the thickness of the secondary metastases [18]. Other dermoscopic signs include structureless areas, white lines, and the presence of peripheral globules or spots. Changes in color (hyperpigmentation, pink, yellow and orange patches) are also described [1, 12 -22].
As breast cancer is one of the most common types of cancer to metastasize the skin in the female population [3], we think that more in-depth information should be gathered regarding the various clinical forms and their dermoscopic patterns, as the data varies in case reports. Clinical variants from the pink nodular lesion with erythema and polymorphic vessels with bright white lines seen in dermoscopy [15] and structures with pigmentation and globules of irregular distribution with a blue-white veil [1,21], mimicking melanoma appearance, are reported. These patterns should be analysed more thoroughly and characterized accordingly.
The results of this review are of importance to dermatologists and oncologists and other specialists, whose patients have a clinical suspicion of cutaneous metastases, to verify or deny their concerns before receiving lesion biopsy results. Limitations of these results include the factor that most of the results were obtained from case reports and case series studies (Oxford Level of Evidence 5 and 4). Multicentric studies on large populations with cutaneous metastases would be useful to better distinguish the dermoscopic characteristics of cutaneous metastasis.

CONCLUSION
Cutaneous metastases are rare in everyday practice but are crucial to recognize. Their main clinical characteristics are pink to erythematous nodules with vascular patterns seen on dermoscopy, though other variants with different types of primary lesions and color patterns are reported. As the use of dermoscopy rises yearly, a better understanding of the dermoscopic features in cutaneous metastases should be obtained and reported, performing larger studies with standardized description criteria.

CONSENT FOR PUBLICTION
Not applicable.

FUNDING
None.