Skin tumors arising in tattoos: coincidental or upcoming public health issue?

Permanent tattooing has gained tremendous popularity in the past 20 years among the western population, especially the young [1]. Although this practice has been performed since the beginning of mankind by almost all civilizations, the first complications were only reported at the end of the 19th Century [2]. Various complications may occur after tattooing: bacterial and viral infections; hypersensitivity reaction to pigments and dyes; and localization of various dermatoses by a Koebner phenomenon [3]. For the last 20 years, we have also witnessed an increase in reports of cutaneous tumors developing within tattoos [4]. Thus, cases of melanoma [4], basal cell carcinoma (BCC) [4] and squamous cell carcinoma (SCC) [5–7] have been reported. In addition, anecdotal cases of cutaneous lymphoma over pseudolymphoma [8], dermatofibrosarcoma protuberans [9] and leiomyosarcoma have been described [10]. Lastly, other ‘benign’ SCC-like lesions, such as pseudo-epitheliomatous hyperplasia (PH) [7,11–13] and keratoacanthomas (KAs) [14–20] may develop. The latter are borderline lesions, the true malignancy of which is still a matter of debate between dermatologists and pathologists. Interestingly, from a pathophysiological point of view, we can provide as many arguments in favor of a potential carcinogenic risk related to tattoos as we can against such a hypothesis.

Arguments in favor of potential carcinoma risk

Role of trauma & the scarring process

Tattooing is a traumatizing act characterized by the introduction of exogenous pigments in the dermis. Trauma, scars and chronic inflammation are known to be, in some cases, responsible for the occurrence of cutaneous malignancies, such as burn scars (Marjolin’s ulcer) or suppurativa hidradenitis. From a clinical point of view, a tattoo remains inert during the person’s life. The tattooed patient only sees some slight changes of the borders and the tattoo slowly fading as a result of the macrophage intake of pigments and its migration in the skin. In reality, inflammation occurs throughout the whole life of the patient as an attempt to degrade all the remaining pigment [21]. Therefore, chronic inflammation may, by an unknown mechanism, take part in the development of local cellular proliferation.

Pigments/dyes

The composition of tattoo inks is not known and none currently have US FDA approval for use in tattooing. The data we currently have are usually old, dating from the 1970s to the 1980s. In France, legislation has very recently made it mandatory to provide the precise composition of the inks. Composition of the inks has changed in the last 20 years, metallic salts have been replaced by organic dyes, but inks are often still a mix of metallic salts, dyes and other additives [22]. It is difficult to know if the inks are more or less carcinogenic than before. It has been demonstrated that tattooed ink may contain some compounds with potential procarcinogenic properties [23].

Sun exposure

Sun is a risk factor for skin cancer. Some authors have postulated that tattoo pigment may alter UV absorption in the dermis and play a role in increasing the carcinogenic effect of UV [4]. Moreover, UV may also increase production of procarcinogenic ink byproducts [24].

Other factors?

Other factors, which are yet unknown, also need to be accounted for. Thus, as specific genetic background predisposes some patients to develop cancer, it is not unlikely that such background may also predispose to cancer on tattoos.

Arguments against potential carcinoma risk

Interestingly, the arguments developed earlier can be used as arguments against potential carcinoma risk.

Trauma & scarring process

The tattoo scar is not a burn scar and the role of the chronic inflammation in a potential carcinogenesis is not clear. Trauma, scarring and chronic inflammation are responsible for the development of skin cancer in a few cases, but this is not always the case. Kaskel et al. showed that trauma was not a risk factor for melanoma [25], while it is by far the most ‘frequent’, or at least the most frequently reported, skin cancer on tattoos compared with SCC [4].

Pigments/dyes

As clearly demonstrated by the team of Baümler et al., components such as 3,3-dichlorobenzene, which are procarcinogenic compounds, are absent in the ink, but do appear as byproducts after the ink is degraded under certain circumstances (e.g., UV exposure or laser removal) [22–24]. Moreover, these are in vitro data. We clearly do not really know the biological relevance of such data, how the skin reacts in vivo to the presence of such components or the potential ability of the skin to ‘detoxify’ such components.

Sun exposure

We must admit that we do not currently have any data regarding the sun habits of tattooed patients. It is indeed known among tattooists and tattooed customers that chronic sun exposure will increase the alteration of the tattoo design [4]. Moreover, heavily tattooed people are advised to be rarely exposed to the sun. Articles reporting cases of skin cancer on tattoos rarely mention the sun habits of the patient. In some cases, patients clearly did not have any ‘at risk’ behavior relating to sun exposure and/or the tattoo was located on a hidden place. On the other hand, some patients with a long history of chronic sun exposure (past history of actinic keratoses or of prior skin cancer) developed skin cancer on a tattoo, which tends to prove that lesions occur randomly on tattoos [4].

Epidemiology of skin cancers

Lastly, crucial data against a relationship are, thus far, statistics. Indeed, we have witnessed case reports of less than 30 patients with skin cancers on tattoos, out of the millions of people tattooed, at least in western countries. In 1985, Goldstein predicted an increased incidence of skin cancer on tattoos [26]. However, epidemiology of skin cancers is changing. Melanoma, but also BCC and SCC affect younger patients. It is rare, but not exceptional, to have a 30–40-year-old patient with BCC. As the popularity of tattooing increases, the likelihood of having a coincidental lesion at the same location as a tattoo is mathematically increasing [4].

Keratoacanthomas in tattoos are increasing

In 1973, Cipollaro described the first case of KA on a tattoo [14]. Just 30 years later, Balfour reported a case of PH on a tattoo [11]. These two conditions are very similar from a pathological point of view. Moreover, both require the pathologist to discuss a potential SCC [27,28]. Cases of KA and PH on tattoos have increased rapidly in recent years for unclear reasons (e.g., better recognition, publishing bias and true increase) and, until now, cases of SCC on tattoos were rare. As there is a debate on the true malignancy of KA and its relationship with SCC, everything may change. Recently, Fraga and Prossick reported the largest series of 11 KAs in tattoos [20]. If we consider that KAs are SCC, the latter suddenly becomes the first cancer on tattoos. Of note, this statement becomes more ‘rational’ when also taking into account the aforementioned data concerning skin cancer and scars.

However, clinicians should not be fooled and must consider two different entities: trauma-induced KA that occurs rapidly after the procedure, usually within a week to a year [29] and classical SCC, which develops within years after tattooing. Indeed, delay of onset after the procedure is a crucial data item: most of the reported cases of KAs on tattoos occur within a year after tattooing. In only one case, diagnosis of KA is doubtful, as the lesion occurred 7–8 years after tattooing [18]. PH is also a lesion that occurs rapidly after tattooing [11–13] and may be difficult to distinguish from SCC [27,28].

Three cases of note

• • McQuarrie reported the first case of SCC on a 20-year-old tattoo [5];

• • Cipollaro diagnosed KA on a biopsy performed by shaving, which again raises doubt regarding the real nature of the lesion [14];

• • Ortiz and Yamauchi described the case of a 47-year-old woman who developed PH and a rapidly growing KA-like SCC within a week after a permanent makeup tattoo of the lips [7].

Conclusion

Physicians should be alerted by any acute or chronic growing lesion occurring within a tattoo. Nevertheless, full-thickness biopsy and/or surgical removal of the entire lesion followed by thorough histological examination, rather than punch biopsies, are mandatory to distinguish SCC, KA and PH [27,28]. Even with complete excision, precise diagnosis is not always possible, and a long-term follow up should be suggested to the patient [27,28]. SCC should be considered in case of a PH or KA occurring in an old tattoo. Fast-occurring lesions are more likely to be PH or KA [28].

According to the data in hand, a tattoo is most likely not a risk factor for skin cancer. However, we may witness an increased number of tattoo-associated skin cancers in the next few years if the popularity of tattooing increases further. We may be wrong and in several years attend an explosion of cancers on tattoos. To prevent such a situation, we must continue investigating the effects of the pigments and their byproducts in the skin; establish standards for the usage of tattoo inks; continue reporting cases and series of skin cancers arising in tattoos; and, if possible, prospectively follow a large series of tattooed people to assess whether or not tattooing is a risk factor for skin cancer. Patients with a prior personal history of skin cancer, especially melanoma, should be discouraged from getting a tattoo because surveillance of pre-existing lesions will be made more difficult, especially if the tattoo is large with wide areas tattooed in dark colors [30].

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.