Tattoo Ink-Related Cutaneous Pseudolymphoma: A Rare but Significant Complication. Case Report and Review of the Literature

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1 Aesth Plast Surg (2014) 38: DOI /s C AS E R E POR T EXPERIMENTAL/SPECIAL TOPICS Tattoo Ink-Related Cutaneous Pseudolymphoma: A Rare but Significant Complication. Case Report and Review of the Literature Andrea Marchesi Pier Camillo Parodi Marco Brioschi Matteo Marchesi Barbara Bruni Maria Giulia Cangi Luca Vaienti Received: 5 February 2013 / Accepted: 31 January 2014 / Published online: 26 February 2014 Ó Springer Science+Business Media New York and International Society of Aesthetic Plastic Surgery 2014 Abstract Background The demand for decorative tattoos is steadily growing worldwide, and in the US it is estimated that up to 24 % of adults has one or more tattoos. Subsequently, the number of tattoo-related complications is increasing. Among these, lymphoproliferative disorders play a minor but important role. The aim of this article is to arouse the awareness of plastic surgeons and dermatologists about this rare but serious complication and to stimulate stricter clinical control of their tattooed patients. Methods We report a new case of tattoo-related cutaneous pseudolymphoma (CPL) and perform a review of the last 30 years of literature on the topic in PubMed. Results Apart from this new case, only 18 cases of CPL have been reported in PubMed so far. In contrast to the classic knowledge, the T cell was the predominant phenotype in 68 % of cases. Red is confirmed to be the most involved ink. Topical and intralesional steroids, laser therapy, and surgery were used for treatment of CPL. Conclusions Even if CPL is a very rare and benign complication, we should not forget that in rare cases A. Marchesi (&) M. Brioschi L. Vaienti Dipartimento di Chirurgia Plastica Ricostruttiva, I.R.C.C.S. Policlinico San Donato, Università degli Studi di Milano, Via Morandi 30, San Donato Milanese, Milan, Italy ilmarchesiandrea@gmail.com M. Brioschi marco.brioschi1@studenti.unimi.it L. Vaienti luca.vaienti@unimi.it P. C. Parodi Department of Plastic and Reconstructive Surgery, University of Udine, Udine, Italy piercamillo.parodi@uniud.it pseudolymphoma may evolve into a true lymphoma. Diagnosis is still difficult and is based on anamnestic, clinical, and histopathological data. From the review of the literature, the T cell predominance suggests a reclassification of tattoo-induced CPL and there is not a gold standard treatment yet. Finally, once a pseudolymphoma is diagnosed, there must be a long follow-up because of the possibility to transform into a malignancy. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors Keywords Tattoo Complications Cutaneous pseudolymphoma Lymphoma Introduction The art of body-painting has become increasingly popular in recent years, and in the Western countries, the M. Marchesi Dipartimento di Scienze Biomediche per la Salute Sezione di Medicina Legale e delle Assicurazioni, Università degli Studi di Milano, Milan, Italy matteo.marchesi@unimi.it B. Bruni Servizio di Anatomia Paologica, I.R.C.C.S. Policlinico San Donato, Milan, Italy barbara.bruni@grupposandonato.it M. G. Cangi Pathology Unit, San Raffaele Scientific Institute, Milan, Italy cangi.mariagiulia@hsri.it

2 472 Aesth Plast Surg (2014) 38: Table 1 The reported cases of tattoo-related cutaneous pseudolymphoma (CPL) in the last 30 years of literature on PubMed Case Study Sex, age, ethnicity Time of onset Tattoo ink Clinical presentation Allergic test Histology Treatment Outcome 1 Gutermuth [27] 2 Chiang and Romero [20] 3 Muñoz [28] 4 Cruz [26] 5 Campolmi [19] 6 Shin [25] 7 Kahofer 8 Blumental (Case 1) [10] 9 Blumental (Case 2) [10] 10 Blumental (Case 3) [10] 11 Zinberg [32] M, 57, M, 67, F, 36, M, 30, M, 65, F, 46, F, 34, F, 49, white F, 40, white M, 32, M, 28, 6 months Red Erythematous plaques, 42 years Blue, green Pruritic erythematous papules developed Red Embossing of the areas of the tattoo, pruritic 1 year Red Hyperkeratotic nodulations, 10 years Black Swelling and micronodular lesions, 1 year Red Red-colored and indurated swelling, 6 years Red Red nodular infiltrate, 27 years Blue, green Several pruritic nodules 20 years Red Red nodule, 17 years Red Several nodules, Red Nodular masses, Patch test?: nickel Intradermal test?: Premium 2000 red Lymphoid infiltrate consisted Lymphoid infiltrate consisted Patch test?: metallic mercury 0.5 % in petrolatum Pseudolymphoma with diffuse lymphocytic dermal infiltrate Dense lymphocytic infiltrate around the pigment, compatible with pseudolymphoma Pseudolymphoma with T cell predominant features Lymphoid infiltrate consisted Intermingled small lymphoid cells and histiocytes Spiegler-Fendt pseudolymphoma Small lymphoid cells and histiocyte Wait and see Complete remission after 3 years Q-switched Nd:YAG laser and concomitant intralesional triamcinolone Improvement months later Surgical excision Complete remission after 3 years. Topical occlusive clobetasol Response was poor Systemic methylprednisolone acetate (40 mg) and Q-switched Nd:YAG laser 595-nm pulsed dye laser and intralesional triamcinolone injections Topical steroids and surgical excision Intralesional triamcinolone acetonide Recurrence after steroids; complete resolution with laser Partial recurrence after 1 year Complete remission Complete resolution after 2 years Complete resolution after 2 years Complete resolution after 2 years Lymphohistiocytic infiltrate Intralesional triamcinolone Several recurrences

3 Aesth Plast Surg (2014) 38: Table 1 continued Case Study Sex, age, ethnicity 12 Chave [31] M, 28, 13 Patrizi [21] F, 35, 14 Cristaudo (Case 1) 15 Cristaudo (Case 2) 16 Cristaudo (Case 3) 17 Camilot (Case 1) 18 Camilot (case 2) 19 Present case F, 32, F, 36, M, 49, F, 39, M, 46, M, 35, Time of onset Tattoo ink Clinical presentation Allergic test Histology Treatment Outcome 28 years Red and blue Asymptomatic nodules, indurated plaque 3 years Green Multiple domeshaped papules, 1 year Red Papulonodular lesions 15 months Red Linear nodular lesions Lymphoid infiltrate consisted 2 years Red Nodular lesions 5 months Red Nodular lesions Lymphoid infiltrate consisted 4 months Red Nodular lesions Lymphoid infiltrate consisted 6 months Red Red pruritic plaques Topical clobetasol propionate 0.05 % cream Flattening of the indurated areas Hydroxychloroquine sulfate Complete resolution after 1 year Topical clobetasol propionate 0.05 % cream Topical clobetasol propionate 0.05 % cream Topical clobetasol propionate 0.05 % cream No response No response No response Surgical excision No follow-up Surgical excision No follow-up Surgical excision Complete resolution at 3 month

4 474 Aesth Plast Surg (2014) 38: estimated percentage of adolescents and adults with one or more tattoos now varies from 4 to 24 % [1 3]. Concurrently, plastic surgeons and dermatologists are frequently called upon to treat tattoo-related complications or even remove the entire tattoo. In such a setting, it is fundamental to keep up to date with this growing field. With respect to tattoo-related complications, infectious diseases have been studied extensively and more sophisticated tattooing techniques have lowered but not abolished the risk of transmission of syphilis, tuberculosis, and hepatitis. Even allergic and granulomatous complications in connection with the process of tattooing have been described. Other diseases such as lupus erythematosus discoid, sarcoidosis, psoriasis, lichen planus, and skin tumors such as basal cell carcinoma, squamous cell carcinoma, and melanoma may be localized to only the tattooed area [4, 5]. Despite the wide popularity of tattoos, the relationship between tattooed pictures and lymphoproliferative disorders has not been studied in depth and only a few cases of tattoo ink-related cutaneous pseudolymphoma (CPL) have been reported in the last 30 years; no data are available about the overall incidence and prevalence of tattoorelated CPL. CPL represents a benign T- or B-cell lymphoproliferative disorder. Historically, the B-cell pattern has been more correlated to tattoo ink than the T-cell pattern [6]. The most involved pigment is red and the mechanism of development of CPL is still unknown. It is generally wise to be guarded in the diagnosis of CPL because in a number of cases clear progression from apparent CPL to true cutaneous lymphoma have been recorded and one case was related to tattoo ink. We describe here a new case of tattoo-related CPL and review all reported cases in the literature. The aim of this article was to increase the awareness of plastic surgeons about this possible diagnosis, which can easily be confused with more banal conditions such as hypertrophic or keloid scarring. Moreover, once CPL is diagnosed, it requires a long and strict follow-up. Materials and Methods Tattoo-induced CPL is really a rare complication. We report one case and found 18 cases of tattoo-induced CPL in the last 30 years in the English literature in PubMed (Table 1). Patients general characteristics, the anatomical site of the tattoo, delay of onset of symptoms from tattooing, clinical appearance of the lesion, the tattoo ink responsible for reaction, the allergic tests performed, the predominant lymphocyte population on histology, the type of management used, and the effectiveness of treatment were reviewed. Fig. 1 A tattoo-related cutaneous pseudolymphoma localized only on reddish areas of the tattoo Case Report A 35-year-old white male presented with a skin lesion localized to a tattoo gotten 1 year before on his right forearm. Clinical examination detected a multicolored tattoo of a little house. Closer inspection revealed several linear reddish plaques, nonulcerated, with regular borders corresponding exactly to the underlying red-colored areas of the tattoo, i.e., the roof of the little house (Fig. 1). The lesion was indurated, nontender, and solidly in place, and lymphadenopathy was not appreciable upon palpation. The lesions were noted by the patient 6 months after tattooing and slowly increased in size; mild itching was referred to the plaques and worsened in the heat and when sweating. The patient did not report any previous trauma, intervention, or bleeding episodes at the lesion site, and medical history did not show personal or family allergic diseases. It was not possible to discover the constituents used in the tattoo dyes. Epicutaneous patch testing using the European standard series, supplemented with various metal haptens, yielded negative results. Incisional biopsy of the lesion was performed under local anesthesia. Histopathological examination revealed a lymphoid infiltrate compatible with CPL (Fig. 2), with a predominant T-cell phenotype, including CD3?, CD5?, and CD7? (Fig. 3), and the CD4:CD8 ratio was 1.1:1 (Fig. 2). CD20? cells were rare (Fig. 3). PCR analysis of T-cell receptor gene (TCRG) rearrangements confirmed the diagnosis of a reactive lymphocytic disease (Fig. 4). Chest radiography, liver function tests, and complete blood count showed no

5 Aesth Plast Surg (2014) 38: Fig. 2 a Tattoo pigment in the superficial reticular dermis and diffuse lymphoid infiltrate (hematoxylin and eosin; original magnification, 910). Lymphoid cells are almost equally positive for CD4 (b) and CD8 (c) (original magnification, 910), with an abnormal CD4:CD8 ratio of 1.1:1 abnormalities. Due to the unique well-defined and limited lesion, treatment consisted of two-stage surgical excision using the tissue expansion technique. Complete resolution of the clinical condition, with no early relapses, was verified at 8 weeks after intervention. Discussion CPL is a heterogeneous group of benign reactive T- or B-cell lymphoproliferations clinically and/or histologically similar to cutaneous lymphomas. The term pseudolymphoma does not involve a specific cause or disease but simply refers to a process of infiltration of in the skin in response to a variety of known and unknown causes. CPLs are divided into two major immunologic categories: mixed B and T cell (i.e., cutaneous lymphoid hyperplasia, Kimura disease, angiolymphoid hyperplasia with eosinophilia, and Castlemann s disease) and T cell (i.e., pseudomycosis fungoides, lymphomatoid contact dermatitis, and Jessner s lymphocytic infiltration of the skin). Mixed B- and T-cell CPL may arise in the course of Lyme disease with Borrelia burgdorferi infection [7], after vaccination [8] or traumatic acupuncture [9], and in tattoos as a reaction to certain pigments [10]. Most T-cell CPLs are idiopathic but some may arise as a form of adverse drug reaction or after persistent contact dermatitis. Persistent nodular scabies and arthropod bites may also cause a T-cell pseudolymphomatous histology [11], possibly due to retained foreign material stimulating a persistent antigenic reaction [12]. Clinically, both T- and B-cell CPL may present as multiple cutaneous plaques or nodules. The T-cell subtype may also present as persistent erythema that sometimes develops into an exfoliative erythroderma, especially in those cases caused by a reaction to a drug or contact dermatitis. The mixed B- and T-cell subtype may also be

6 476 Aesth Plast Surg (2014) 38: Fig. 3 a The dermal infiltrate is composed primarily of T cells (original magnification, 94). b Rare B cells in the dermal infiltrate (original magnification, 94). c CD5 expression among T-cell infiltrates (original magnification, 910). d CD7 expression in dermal and epidermal infiltrating T (original magnification, 9200) associated with palpable lymphadenopathy, adding to diagnostic confusion. It is fundamental to give the pathologist a good clinical history to help distinguish between true lymphoma and pseudolymphoma because the pathological, phenotypic, and molecular differentiations are not absolute. The inflammatory infiltrate may be bandlike, nodular, or diffuse and composed predominantly of and eventually with other inflammatory cells (i.e., plasma cells, eosinophils, mast cells, neutrophils, and histiocytic giant cells). Benign or reactive processes are usually considered polyclonal, whereas the presence of monoclonality generally implies a malignant process. Thus, PCR analysis of TCRG is usually recommended to distinguish between reactive and neoplastic cutaneous lymphocytic diseases. This distinction, however, is not always true. It is possible to find clonal T- or B-cell populations in CPL and maybe a subset more likely to develop into lymphoma [13 15]. Indeed, it is estimated that lymphomas develop in % of patients affected by CPL, typically many years after the original diagnosis [16]. This may explain the one published case of tattoo-induced CPL malignant transformation [17]. Even if unlikely, physicians should be alerted to this occurrence and routinely follow patients for extracutaneous manifestations or local relapses. Unfortunately, malignant evolution cannot be predicted by clinical or histologic features, TCRG rearrangement, or DNA flow cytometry [18]. Nevertheless, in our case we found an abnormal CD4:CD8 ratio of 1.1:1, whereas normally it is approximately 2 3:1. This suggests that this patient should be followed to exclude the possibility of an evolving tattoorelated T-cell lymphoproliferative disorder. From the review of the literature (our case is included), 10 men and 9 women, all white and with a median age of

7 Aesth Plast Surg (2014) 38: Fig. 4 Profile of gene-scanning analysis of T-cell receptor gene (TCRG) rearrangements (x axis, length of PCR product; y axis, fluorescence intensity). a Polyclonal pattern of TCRG rearrangements of the case, showing typical polyclonal Gaussian curve. b Positive control of monoclonal TCRG rearrangements. PCR analysis was performed as described in van Dongen [33] 41 years, were evaluated. The mean time of onset of CPL after tattooing was 9 years (range = 4 months to 42 years). It is confirmed that red ink was the most common causative agent (15 cases, 79 %), but black [19] and blue and green [20, 21] dyes also were able to induce CPL. Classical tattoo dyes contain metal compounds reddish areas are mainly cinnabar, blue mainly cobalt salts, and green mainly chrome salts but organic substances, including synthetic azo-dyes, are used in modern tattoo dyes. Even if the pathogenesis is not completely clear, it has been suggested that these components are the leading elicitors of delayed hypersensitivity; indeed, allergic reactions to red mercury-based dyes have been reported [22]. A photosensitive reaction to cadmium yellow occurs occasionally [23], and when photosensitive reactions to red tattoos are investigated, it is found that the cause is sometimes a cadmium salt [24]. In only one case were the constituents of tattoo ink provided by the manufacturer [25]: metal iron, copper fumes, metal manganese, and metal cobalt. In most cases the infiltrate is localized to the tattoo area where pigment is deposited. It appears like erythematous nodules or plaques, sometimes causing itching, or a photosensitive reaction [26]. From the precise location on only specific-colored areas and its uniform appearance, CPL can be clinically distinguished from pathologic scarring or granulomatous reactions. However, diagnosis of CPL is based on histologic features, architecture of infiltration, and the results of immunophenotyping and genotyping of the. Thirteen of 19 cases (68 %) showed T-cell preponderance on histology, and the other six were described without using immunochemistry. In contrast to the literature, B-cell predominance was not demonstrated in the collected cases. This suggests that adjustment or reclassification of tattooinduced CPL may be necessary. To evaluate the evidence for a delayed hypersensitivity reaction to the pigment, patch testing was performed in eight cases. During the tattooing process, the dyes are pushed directly into the dermis: because the epidermal Langerhans cells are avoided in this way, some of the allergic tests given in such cases may be negative. An intradermal reaction test was also performed in one case [27]. There is no standard treatment for tattoo-induced pseudolymphoma since none of those proposed has yet been successful. As cautioned by Muñoz [28], even if malignant transformation is rare, surgical excision of the tattoo should be performed whenever possible [27, 28, 31], including only excision of smaller tattoos or reconstruction with tissue expansion for larger tattoos. For those patients in whom a surgical option is not feasible (e.g., lip-liner tattoo), a wait-and-see approach can be proposed [25]. However, regular follow-up is mandatory as progression of CPL to lymphoma has been reported [17]. Laser treatment, especially Nd:YAG, has been used with success [19, 20, 29] but the risk of spreading dyes in the dermis, worsening the hypersensitivity response, must be considered. Moreover, treatment with a laser may not remove the pigment completely and is therefore not recommended [30]. Topicals such as clobetasol propionate 0.05 % [31] or intralesional injection of corticosteroids like triamcinolone [32] have been used but the results are variable. The use of different strengths and doses of steroids does not allow a standardized comparison and recurrences are common [26]. However, if nonsurgical treatment modalities are chosen, regular follow-up visits are advised [29]. Conclusions With the increasing popularity of tattoos, reactions to them are more likely to occur. Even if it is less common compared to lichenoid and granulomatous reactions in the

8 478 Aesth Plast Surg (2014) 38: tattoo area, CPL is a rare skin lesion to consider, since it can be easily confused with a pathologic scar or a granulomatous reaction and can, in rare cases, evolve into a malignancy. Different from previous data reported in dermatology textbooks, in our case and in most of the cases in PubMed, the T-cell pattern seems to be predominant and so further studies are needed. Finally, considering the long time between tattooing and the onset of lymphoproliferative disorders, we should expect to see a higher rate of tattoo-induced pseudolymphomas in the future. Conflict of interest disclose. References The authors have no conflicts of interest to 1. Bosello R, Favaro A, Zanetti T, Soave M, Vidotto G, Huon G, Santonastaso P (2010) Tattoos and piercings in adolescents: family conflicts and temperament. 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