Pseudoepitheliomatous Hyperplasia in a Red Pigment Tattoo A Separate Entity or Hypertrophic Lichen Planus-like Reaction?

| December 1, 2015

Viktoryia Kazlouskaya, MD, PhD; Jacqueline M. Junkins-Hopkins, MD Ackerman Academy of Dermatopathology, New York, New York

Disclosure: The authors report no relevant conflicts of interest.

Red pigment tattoos are known to cause pseudoepitheliomatous hyperplasia in the skin, frequently simulating squamous cell carcinoma or keratoacanthoma. Herein, the authors present two additional cases of red pigment tattoo pseudoepitheliomatous hyperplasia in which they noted a lichenoid tissue reaction. They reviewed the previously published cases and observed a lichenoid reaction in the histopathological images similar to hypertrophic lichen planus. The authors suggest that these reactions might best be referred to as “lichenoid reaction with pseudoepitheliomatous hyperplasia” or “hypertrophic lichen planus-like reaction.” Accordingly, recognition of an inflammatory component may allow additional treatment options. (J Clin Aesthet Dermatol. 2015;8(12):48–52.)

Adverse reactions to tattoos are not uncommon and include hypersensitivity reactions, granuloma formation, cutaneous lymphoid hyperplasia, lichenoid tissue reaction, and infection.[1] Pseudo-epitheliomatous hyperplasia (PEH) is a rare tattoo reaction that has been described in a handful of case reports.[2–8] It is specifically characteristic of red pigment tattoos. Herein, the authors present two additional cases of PEH arising in red pigment tattoos. The proposed etiology of this reaction, which was also accompanied by a lichenoid tissue reaction, is discussed, along with its possible relationship to hypertrophic lichen planus (HLP)-like reaction.

Clinical presentation

Case 1. A 47-year-old man presented to the dermatologist with a solitary lesion on his lateral right leg which had developed in his tattoo. The heart-shaped tattoo, obtained many years ago, had initially been unassociated with adverse reactions. Seven months after tattoo re-coloring, he developed an itchy eruption and verrucous lesions, which progressed for an additional two months, until he presented to the dermatologist. Examination at the time revealed a massive exophytic verrucous plaque that strictly followed the contours of the heart-shaped tattoo (Figure 1). Squamous cell carcinoma (SCC) was clinically suspected. Initial punch biopsies were felt to possibly represent SCC. An additional larger biopsy was obtained. Both specimens were reviewed in consultation, and a diagnosis of PEH was made.

Case 2. A 44-year-old woman complained of pruritus and nodular growths within a butterfly-shaped tattoo several weeks after receiving this tattoo. On examination, there were crusted nodules noted in areas of the tattoo. Excoriations and postinflammatory pigment alteration were seen in the tattoo and the surrounding skin. The affected areas had been red; however, tattoo pigment was no longer clinically evident in the affected areas at the time of presentation (Figure 2). A biopsy of a nodule was obtained.

Histopathological features
In both cases all biopsies were characterized by marked epidermal and infundibular hyperplasia (Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8). Cytological atypia was absent. In the dermis, there was a patchy to lichenoid mixed infiltrate containing lymphocytes, histiocytes, and plasma cells admixed with course granules of red tattoo pigment. Lymphocytes were noted to disrupt the interface of the epidermis and follicle epithelium, where vacuolar interface changes, dyskeratotic keratinocytes, and focal epidermal-dermal separation were seen in the first case (Figure 4). The biopsy from Case 2 showed focal lichenoid changes and only rare red pigment granules (Figure 9).


In the first patient, therapy with topical 5-florouracil for four weeks was instituted without response. The lesion remained stable at four and eight weeks, and the patient was eventually lost to follow-up.

In the second patient, the lesions were noted to resolve without therapeutic intervention six weeks after biopsy was performed

Skin tattooing is a common practice dating back to ancient times and is widely practiced across a variety of cultures. Multiple tattoo adverse reactions with different pathogenesis have been described, including early and late hyper-sensitivity, foreign body granulomas, kerato-acanthomas (KAs), SCC, and infections. Histopathologic patterns associated with these reactions include spongiotic, psoriasiform, lichenoid, granulomatous (sarcoidal, palisading, and suppurative), pseudo-lymphomatoid infiltrate (including cutaneous lymphoid hyperplasia and lymphomatoid papulosis simulators), vesiculobullous, vasculitis, fibrosing, and panniculitis.[1]

The character of the adverse reaction depends, in part, on the color of the tattoo pigment. Red pigment tattoos have been associated predominantly with delayed hypersensitivity (lichenoid reaction is the most frequent variant), photosensitivity, and granulomatous reactions.[9],[10] Adverse reactions, developing in the red tattoos were previously attributed to the mercury salts contained in early red pigments. Mercury use in commercially available tattoo colors is now restricted. Subsequently, the reactions have been ascribed to the newer organic azo dyes.[11]

A case of epidermal hyperplasia in a red tattoo was presented at the dermatology society meeting by Sulzberger in 193712 and later PEH in a red pigment tattoo was described by Goldberg in 1959,[2] which clinically presented as multiple verrucous papules that developed in the red portion of a flag tattoo. Patch tests for mercury were positive. Later in 1967, Goldstein presented an observation on 15 subjects with red tattoos he saw in Hawaii; two of these subjects had massive PEH.[13] Reported cases of PEH in red pigment tattoos are summarized in Table 1.

Authors describing PEH in red tattoos considered this reaction “rare” and “unique.” It appears that some cases which describe lichenoid hypersensitivity reactions in red tattoos clearly show PEH in the clinical and histopathological images.[9],[14] Moreover, lichenoid tissue reaction accompanies PEH in all reported cases, including the one described herein.[2–8] Such a combination of PEH and lichenoid dermatitis is typical for hypertrophic lichen HLP or HLP-like reaction. In fact, LP has been described in red pigment tattoo.[15] This may represent a Koebner effect of otherwise classic LP involving other areas of the skin.

Sun exposure preceded PEH development in some cases of tattoo reactions.[4] Goldstein mentioned that in some patients, the reactions to the red tattoo pigment developed only after they moved to Hawaii.[13] He proposed that sun exposure may be an additional pathological factor for the adverse reactions in red pigment tattoos. Use of sunscreens was effective in some cases.[13] Similarly, sun exposure is known to aggravate certain forms of LP, in particular, but not limited to, LP actinicus. Prakash et al[16] have studied the seasonal influence on LP incidence in India and found that LP cases were more frequently reported in sunny periods of the year.

The cases presented herein exhibited prominent infundibular hyperplasia, a feature of PEH, but also of keratoacanthomas (KAs). KAs have also been reported in the red pigment tattoos,[17],[18] including multiple, rapidly evolving KAs in multicolor tattoos.[19],[20] Fraga and Prossick,[21] in describing a case series of 11 KAs developing in tattoos, mentioned that 85 percent of the lesions were strictly located in red pigment areas. Squamous cell carcinoma (SCC) adjacent to KA was described in this series. Many of these reported red tattoo-related KAs were associated with a lichenoid reaction, either by report or by figure representation. Toll et al[22] argued that eruptive KAs, which also have been described after surgery, may actually represent HPL-like reactions combined with infundibulocystic hyperplasia.[22],[23] The epidermal hyperplasia has been proposed to represent the pathway to neoplasia, given that SCC may arise in some cases.[24] Considering the prominent histologic overlap with PEH and KAs, and the diagnostic challenge in differentiating these entities,[25] the authors feel that some previously described cases of KAs developing in tattoos may represent PEH.

Additionally, given the known occurrence of lichenoid dermatitis in tattoos, and the presence of lichenoid tissue reaction that appears to be present in the figures of previously reported PEH in tattoo reactions, the authors propose the term “lichenoid reaction with PEH or HPL-like reaction,” as a more accurate term to designate this specific tattoo reaction. Highlighting the inflammatory changes may offer an additional option for management of these verruciform tattoo plaques.

Reported therapeutic interventions for this unusual reaction have included excision and topical or injected corticosteroids, but there is not enough data to accurately assess the efficacy of these treatment regimens. Approaching this lesion as an inflammatory process, in addition to topical corticosteroids, alternative therapy, previously proven helpful for lichen planus, may provide some benefit, such as calcineurin inhibitors, psoralen plus ultraviolet light therapy, ultraviolet A1, and excimer laser.[26–28] Surgical excision may be helpful and offer additional histopathologic evaluation for malignancy. Laser therapy may provide another option, if the cost is not prohibitive to the patient.

In summary, the authors have reported two additional cases of PEH tattoo reaction, and emphasize the importance of awareness of this phenomenon to avoid erroneously treating this as squamous cell carcinoma. Furthermore, they highlighted that the lichenoid tissue reaction that accompanies the PEH appears to be a consistent feature, with marked overlap with HLP.

The authors would like to thank Dr. Dennis Polley for providing clinical images, information, and follow-up on patients.

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