Aesth Plast Surg DOI 10.1007/s00266-014-0287-5
CASE REPORT
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 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
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 www.springer.com/00266.
A. Marchesi (&) M. Brioschi L. Vaienti Dipartimento di Chirurgia Plastica Ricostruttiva, I.R.C.C.S. Policlinico San Donato, Universita` degli Studi di Milano, Via Morandi 30, San Donato Milanese, 20097 Milan, Italy e-mail: [email protected]
M. Marchesi Dipartimento di Scienze Biomediche per la Salute – Sezione di Medicina Legale e delle Assicurazioni, Universita` degli Studi di Milano, Milan, Italy e-mail: [email protected]
M. Brioschi e-mail: [email protected] L. Vaienti e-mail: [email protected] P. C. Parodi Department of Plastic and Reconstructive Surgery, University of Udine, Udine, Italy e-mail: [email protected]
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
B. Bruni Servizio di Anatomia Paologica, I.R.C.C.S. Policlinico San Donato, Milan, Italy e-mail: [email protected] M. G. Cangi Pathology Unit, San Raffaele Scientific Institute, Milan, Italy e-mail: [email protected]
123
123
F, 36, White
Mun˜oz et al. [28]
Cruz et al. [26]
Campolmi et al. [19]
Shin et al. [25]
Kahofer et al.
Blumental et al. (Case 1) [10] Blumental et al. (Case 2) [10]
Blumental et al. (Case 3) [10]
Zinberg et al. [32]
3
4
5
6
7
8
10
11
9
M, 67, White
Chiang and Romero [20]
2
M, 28, White
M, 32, White
F, 40, white
F, 49, white
F, 34, White
F, 46, White
M, 65, White
M, 30, White
M, 57, White
Gutermuth et al. [27]
1
Sex, age, ethnicity
Study
Case
–
17 years
20 years
27 years
6 years
1 year
10 years
1 year
–
42 years
6 months
Time of onset
Red
Red
Red
Blue, green
Red
Red
Black
Red
Red
Blue, green
Red
Tattoo ink
Nodular masses, asymptomatic
Several nodules, asymptomatic
Red nodule, asymptomatic
Several pruritic nodules
Red nodular infiltrate, asymptomatic
Red-colored and indurated swelling, asymptomatic
Swelling and micronodular lesions, asymptomatic
Hyperkeratotic nodulations, asymptomatic
‘‘Embossing’’ of the areas of the tattoo, pruritic
Pruritic erythematous papules developed
Erythematous plaques, asymptomatic
Clinical presentation
–
–
–
–
–
–
Patch testing-
–
Patch test?: metallic mercury 0.5 % in petrolatum
–
Patch test?: nickel Intradermal test?: Premium 2000 red
Allergic test
Lymphohistiocytic infiltrate
Small lymphoid cells and histiocyte
Spiegler-Fendt pseudolymphoma
Intermingled small lymphoid cells and histiocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Pseudolymphoma with T cell predominant features
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Dense lymphocytic infiltrate around the pigment, compatible with pseudolymphoma
Pseudolymphoma with diffuse lymphocytic dermal infiltrate
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Histology
Table 1 The reported cases of tattoo-related cutaneous pseudolymphoma (CPL) in the last 30 years of literature on PubMed
Intralesional triamcinolone
–
–
Intralesional triamcinolone acetonide
Topical steroids and surgical excision
Several recurrences
Complete resolution after 2 years
Complete resolution after 2 years
Complete resolution after 2 years
Complete remission
Partial recurrence after 1 year
Recurrence after steroids; complete resolution with laser
Systemic methylprednisolone acetate (40 mg) and Q-switched Nd:YAG laser 595-nm pulsed dye laser and intralesional triamcinolone injections
Response was poor
Complete remission after 3 years.
Improvement months later
Complete remission after 3 years
Outcome
Topical occlusive clobetasol
Surgical excision
Q-switched Nd:YAG laser and concomitant intralesional triamcinolone
Wait and see
Treatment
Aesth Plast Surg
Study
Chave et al. [31]
Patrizi et al. [21]
Cristaudo et al. (Case 1)
Cristaudo et al. (Case 2)
Cristaudo et al. (Case 3)
Camilot et al. (Case 1)
Camilot et al. (case 2)
Present case
Case
12
13
14
15
16
17
18
19
Table 1 continued
M, 35, White
M, 46, White
F, 39, White
M, 49, White
F, 36, White
F, 32, White
F, 35, White
M, 28, White
Sex, age, ethnicity
6 months
4 months
5 months
2 years
15 months
1 year
3 years
28 years
Time of onset
Red
Red
Red
Red
Red
Red
Green
Red and blue
Tattoo ink
Red pruritic plaques
Nodular lesions
Nodular lesions
Nodular lesions
Linear nodular lesions
Papulonodular lesions
Multiple domeshaped papules, asymptomatic
Asymptomatic nodules, indurated plaque
Clinical presentation
Patch testing-
Patch testing-
Patch testing-
Patch testing-
–
Patch testing-
Allergic test
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Histology
Surgical excision
Surgical excision
Surgical excision
Topical clobetasol propionate 0.05 % cream
Topical clobetasol propionate 0.05 % cream
Topical clobetasol propionate 0.05 % cream
Hydroxychloroquine sulfate
Topical clobetasol propionate 0.05 % cream
Treatment
Complete resolution at 3 month
No follow-up
No follow-up
No response
No response
No response
Complete resolution after 1 year
Flattening of the indurated areas
Outcome
Aesth Plast Surg
123
Aesth Plast Surg
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.
123
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
Aesth Plast Surg 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 lymphocytes 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
123
Aesth Plast Surg 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 lymphocytes (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 lymphocytes 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
123
subset more likely to develop into lymphoma [13–15]. Indeed, it is estimated that lymphomas develop in 10–20 % 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
Aesth Plast Surg
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 et al. [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 lymphocytes. 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 Mun˜oz et al. [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
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Aesth Plast Surg
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.
The authors have no conflicts of interest to
References 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. Riv Psichiatr 45(2):102–106 2. Mayers LB, Judelson DA, Moriarty BW, Rundell KW (2002) Prevalence of body art (body piercing and tattooing) in university undergraduates and incidence of medical complications. Mayo Clin Proc 77(1):29–34 3. Laumann AE, Derick AJ (2006) Tattoos and body piercings in the United States: a national data set. J Am Acad Dermatol 55(3):413–421 4. Kluger N, Koljonen V (2012) Tattoos, inks, and cancer. Lancet Oncol 13(4):e161–e1618 5. Kazandjieva J, Tsankov N (2007) Tattoos: dermatological complications. Clin Dermatol 25:375–382 6. Van Vloten WA, Willemze R (2003) The many faces of lymphocytoma cutis. J Eur Acad Dermatol Venereol 17(1):3–6 7. Garbe C, Stein H, Dienemann D, Orfanos C (1991) Borrelia burdorferi-associated cutaneous B-cell lymphoma. J Am Acad Dermatol 24:584–590 8. Lanzafame S, Micali G (1993) Cutaneous lymphoid hyperplasia (pseudolymphoma) secondary to vaccination. Pathologica 85:555–556 9. Kim K, Lee M, Choi J et al (2002) CD30-positive T-cell rich pseudolyphoma induced by gold acupuncture. Br J Dermatol 146:882–884 10. Blumental G, Okun MR, Ponitch A (1982) Pseudolymphomatous reactions to tattoos. J Am Acad Dermatol 6:485–488 11. Walton S, Bottomley WW, Wyatt EH, Bury HP (1991) Pseudo T-cell lymphoma due to scabies in a patient with Hodgkin’s disease. Br J Dermatol 124:277–278 12. Burg G, Dummer R, Kadin M (2001) From inflammation to neoplasia. Arch Dermatol 137:949–952 13. Ploysangam T, Breneman DL, Mutasim DF (1998) Cutaneous pseudolymphomas. J Am Acad Dermatol 38:877–905 14. Halevy S, Sandbank M (1987) Transformation of lymphocytoma cutis into malignant lymphoma. Acta Derm Venereol 67:172–175 15. Nakayama H, Mihara M, Shimao S (1987) Malignant transformation of lymphadenosis benigna cutis: a possibly transformed case and B-cell lymphoma. J Dermatol 4:266–269
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16. Chott A, Vonderheid EC, Olbricht S et al (1996) The same dominant T-cell clone is present in multiple regressing skin lesions and associated T-cell lymphomas of patients with lymphomatoid papulosis. J Invest Dermatol 106:696–700 17. Sangueza OP, Yadav S, White CR et al (1992) Evolution of B-cell lymphoma from pseudolymphoma: a multidisciplinary approach using histology, immunochemistry and Southern blot analysis. Am J Dermatopathol 14:408–413 18. el-Azhary RA, Gibson LE, Kurtin PJ et al (1994) Lymphomatoid papulosis: a clinical and histologic review of 53 cases with leukocyte immunophenotyping, DNA flow cytometry, and T-cell receptor gene rearrangement studies. J Am Acad Dermatol 30:210–218 19. Campolmi P, Bassi A, Bonan P et al (2011) Cutaneous pseudolymphoma localized to black tattoo. J Am Acad Dermatol 65(5):e155–E157 20. Chiang C, Romero L (2009) Cutaneous lymphoid hyperplasia (pseudolymphoma) in a tattoo after far infrared light. Dermatol Surg 35:1434–1438 21. Patrizi A, Raone B, Savoia F, Bacci F, Pileri A, Gurioli C, Neri I (2009) Tattoo-associated pseudolymphomatous reaction and its successful treatment with hydroxychloroquine. Acta Derm Venereol 89(3):327–328 22. Sowden JM, Byrne JP, Smith AG, Hiley C, Suarez V, Wagner B, Slater DN (1991) Red tattoo reactions: X-ray microanalysis and patch-test studies. Br J Dermatol 124(6):576–580 23. Bjo¨rnberg A (1963) Reactions to light in yellow tattoos from cadmium sulphide. Arch Dermatol 88:267–271 24. Yazdian-Tehrani H, Shibu MM, Carver NC (2001) Reaction in a red tattoo in the absence of mercury. Br J Plast Surg 54:555–556 25. Shin JB, Seo SH, Kim BK, Kim IH, Son SW (2009) Cutaneous T cell pseudolymphoma at the site of a semipermanent lip-liner tattoo. Dermatology 218:75–78 26. Cruz FA, Lage D, Frige´rio RM, Zaniboni MC, Arruda LH (2010) Reactions to the different pigments in tattoos: a report of two cases. An Bras Dermatol 85(5):708–711 27. Gutermuth J, Hein R, Fend F, Ring J, Jakob T (2007) Cutaneous pseudolymphoma arising after tattoo placement. Eur Acad Dermatol Venereol 21:536–578 28. Mun˜oz C, Guilabert A, Mascaro´ JM Jr, Lopez-Lerma I, Vilaplana J (2005) An embossed tattoo. Clin Exp Dermatol 31:309–310 29. Antony FC, Harland CC (2003) Red ink tattoo reactions: successful treatment with the Q-switched 532 nm Nd:YAG laser. Br J Dermatol 149:94–98 30. Zelickson BD, Mehregan DA, Zarrin AA, Coles C, Hartwig P, Olson S, Leaf-Davis J (1994) Clinical, histologic, and ultrastructural evaluation of tattoos treated with three laser systems. Laser Surg Med 15:364–372 31. Chave A, Mortimer NJ, Johnston GA (2004) Simultaneous pseudolymphomatous and lichenoid tattoo reactions triggered by re-tattooing. Clin Exp Dermatol 29:196–205 32. Zinberg M, Heilman E, Glickman F (1982) Cutaneous pseudolymphoma resulting from a tattoo. J Dermatol Surg Oncol 8(11):955–958 33. van Dongen JJ, Langerak AW, Bru¨ggemann M et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia 17:2257–2317
CASE REPORT
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 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
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 www.springer.com/00266.
A. Marchesi (&) M. Brioschi L. Vaienti Dipartimento di Chirurgia Plastica Ricostruttiva, I.R.C.C.S. Policlinico San Donato, Universita` degli Studi di Milano, Via Morandi 30, San Donato Milanese, 20097 Milan, Italy e-mail: [email protected]
M. Marchesi Dipartimento di Scienze Biomediche per la Salute – Sezione di Medicina Legale e delle Assicurazioni, Universita` degli Studi di Milano, Milan, Italy e-mail: [email protected]
M. Brioschi e-mail: [email protected] L. Vaienti e-mail: [email protected] P. C. Parodi Department of Plastic and Reconstructive Surgery, University of Udine, Udine, Italy e-mail: [email protected]
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
B. Bruni Servizio di Anatomia Paologica, I.R.C.C.S. Policlinico San Donato, Milan, Italy e-mail: [email protected] M. G. Cangi Pathology Unit, San Raffaele Scientific Institute, Milan, Italy e-mail: [email protected]
123
123
F, 36, White
Mun˜oz et al. [28]
Cruz et al. [26]
Campolmi et al. [19]
Shin et al. [25]
Kahofer et al.
Blumental et al. (Case 1) [10] Blumental et al. (Case 2) [10]
Blumental et al. (Case 3) [10]
Zinberg et al. [32]
3
4
5
6
7
8
10
11
9
M, 67, White
Chiang and Romero [20]
2
M, 28, White
M, 32, White
F, 40, white
F, 49, white
F, 34, White
F, 46, White
M, 65, White
M, 30, White
M, 57, White
Gutermuth et al. [27]
1
Sex, age, ethnicity
Study
Case
–
17 years
20 years
27 years
6 years
1 year
10 years
1 year
–
42 years
6 months
Time of onset
Red
Red
Red
Blue, green
Red
Red
Black
Red
Red
Blue, green
Red
Tattoo ink
Nodular masses, asymptomatic
Several nodules, asymptomatic
Red nodule, asymptomatic
Several pruritic nodules
Red nodular infiltrate, asymptomatic
Red-colored and indurated swelling, asymptomatic
Swelling and micronodular lesions, asymptomatic
Hyperkeratotic nodulations, asymptomatic
‘‘Embossing’’ of the areas of the tattoo, pruritic
Pruritic erythematous papules developed
Erythematous plaques, asymptomatic
Clinical presentation
–
–
–
–
–
–
Patch testing-
–
Patch test?: metallic mercury 0.5 % in petrolatum
–
Patch test?: nickel Intradermal test?: Premium 2000 red
Allergic test
Lymphohistiocytic infiltrate
Small lymphoid cells and histiocyte
Spiegler-Fendt pseudolymphoma
Intermingled small lymphoid cells and histiocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Pseudolymphoma with T cell predominant features
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Dense lymphocytic infiltrate around the pigment, compatible with pseudolymphoma
Pseudolymphoma with diffuse lymphocytic dermal infiltrate
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Histology
Table 1 The reported cases of tattoo-related cutaneous pseudolymphoma (CPL) in the last 30 years of literature on PubMed
Intralesional triamcinolone
–
–
Intralesional triamcinolone acetonide
Topical steroids and surgical excision
Several recurrences
Complete resolution after 2 years
Complete resolution after 2 years
Complete resolution after 2 years
Complete remission
Partial recurrence after 1 year
Recurrence after steroids; complete resolution with laser
Systemic methylprednisolone acetate (40 mg) and Q-switched Nd:YAG laser 595-nm pulsed dye laser and intralesional triamcinolone injections
Response was poor
Complete remission after 3 years.
Improvement months later
Complete remission after 3 years
Outcome
Topical occlusive clobetasol
Surgical excision
Q-switched Nd:YAG laser and concomitant intralesional triamcinolone
Wait and see
Treatment
Aesth Plast Surg
Study
Chave et al. [31]
Patrizi et al. [21]
Cristaudo et al. (Case 1)
Cristaudo et al. (Case 2)
Cristaudo et al. (Case 3)
Camilot et al. (Case 1)
Camilot et al. (case 2)
Present case
Case
12
13
14
15
16
17
18
19
Table 1 continued
M, 35, White
M, 46, White
F, 39, White
M, 49, White
F, 36, White
F, 32, White
F, 35, White
M, 28, White
Sex, age, ethnicity
6 months
4 months
5 months
2 years
15 months
1 year
3 years
28 years
Time of onset
Red
Red
Red
Red
Red
Red
Green
Red and blue
Tattoo ink
Red pruritic plaques
Nodular lesions
Nodular lesions
Nodular lesions
Linear nodular lesions
Papulonodular lesions
Multiple domeshaped papules, asymptomatic
Asymptomatic nodules, indurated plaque
Clinical presentation
Patch testing-
Patch testing-
Patch testing-
Patch testing-
–
Patch testing-
Allergic test
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Lymphoid infiltrate consisted mainly of CD3?T lymphocytes
Histology
Surgical excision
Surgical excision
Surgical excision
Topical clobetasol propionate 0.05 % cream
Topical clobetasol propionate 0.05 % cream
Topical clobetasol propionate 0.05 % cream
Hydroxychloroquine sulfate
Topical clobetasol propionate 0.05 % cream
Treatment
Complete resolution at 3 month
No follow-up
No follow-up
No response
No response
No response
Complete resolution after 1 year
Flattening of the indurated areas
Outcome
Aesth Plast Surg
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Aesth Plast Surg
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.
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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
Aesth Plast Surg 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 lymphocytes 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
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Aesth Plast Surg 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 lymphocytes (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 lymphocytes 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
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subset more likely to develop into lymphoma [13–15]. Indeed, it is estimated that lymphomas develop in 10–20 % 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
Aesth Plast Surg
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 et al. [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 lymphocytes. 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 Mun˜oz et al. [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
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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.
The authors have no conflicts of interest to
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