Pathogenesis, Diagnosis and Management of Squamous Cell Carcinoma and Pseudoepithelial Hyperplasia Secondary to Red Ink Tattoo: A Case Series and Review

Abstract

The increasing popularity of tattooing has paralleled an increase in associated cutaneous reactions. Red ink is notorious for eliciting cutaneous reactions. A common reaction is pseudoepitheliomatous hyperplasia (PEH), which is a benign condition closely simulating squamous cell carcinoma (SCC). Differentiating PEH from SCC is challenging for pathologists and clinicians alike. The exact pathogenesis of these lesions secondary to red ink is not known, and there are no sources outlining diagnostic and treatment options and their efficacy. We present four study cases with different pathologies associated to red ink tattoos including lichenoid reaction, granulomatous reaction, PEH, and an SCC. Additionally, an extensive review of 63 articles was performed to investigate pathogenesis, diagnostic approaches, and treatment options. Hypotheses surrounding pathogenesis include but are not limited to the carcinogenic components of pigments, their reaction with UV and the traumatic process of tattooing. Pathogenesis seems to be multifactorial. Full-thickness biopsies with follow-up is the recommended diagnostic approach. There is no evidence of a single universally successful treatment for PEH. Low-dose steroids are usually tried following a step up in lack of clinical response. For SCC lesions, full surgical excision is widely used. A focus on clinicians’ awareness of adverse reactions is key for prevention. Regulation of the unmonitored tattoo industry remains an ongoing problem.

Pink and Orange Tattoo Pigments: Two Occurrences of Squamous Cell Neoplasms

“…A study of multiple tattoo inks showed high levels of heavy metals and other carcinogenic compounds, including azo dyes, which are used to make pigmented tattoo inks [7]. The red pigment has the highest association with squamous neoplasms [1,7,9,11], with some studies reporting up to 75% of squamous neoplasms occurring in red tattoo ink [3]. Previously, red ink in the tattooing industry contained high levels of mercury sulfide, which was thought to contribute to carcinogenesis [5,7,9].…”

“…The red pigment has the highest association with squamous neoplasms [1,7,9,11], with some studies reporting up to 75% of squamous neoplasms occurring in red tattoo ink [3]. Previously, red ink in the tattooing industry contained high levels of mercury sulfide, which was thought to contribute to carcinogenesis [5,7,9]. A shift has been made toward using organic dyes containing azo pigments, a known carcinogen, and instances of malignancy continue to be reported with the organic dyes [1,5,7,9,11].…”

“…Previously, red ink in the tattooing industry contained high levels of mercury sulfide, which was thought to contribute to carcinogenesis [5,7,9]. A shift has been made toward using organic dyes containing azo pigments, a known carcinogen, and instances of malignancy continue to be reported with the organic dyes [1,5,7,9,11]. In this case, the orange and pink pigments are made from a red base by mixing red with white to obtain pink and red with yellow to make orange.…”

“…The tattoo pigments used were originally intended for industrial use, not for human use [3,[5][6][7][8]. A number of adverse reactions to tattoos have been reported in the literature and include infections, allergic hypersensitivity reactions, foreign body granuloma, sarcoidosis, pseudoepitheliomatous hyperplasia, verruca, keloids, and malignancy [1,6,7,9].…”

“…The most common malignancy that is reported in tattoos is squamous neoplasms including keratoacanthoma (KA) and squamous cell carcinoma (SCC) [1,7]. Other malignancies associated with tattoos include melanoma, basal cell carcinoma, and lymphoma [3,6,8,9]. A review literature in 2021 yielded 42 cases of squamous neoplasms occurring within tattoos.…”