ARTICLE
Cutaneous pseudolymphomas represent benign reactive T- or B-cell lymphoproliferative
disorders of different causes that simulate cutaneous lymphomas clinically
or histopathologically. Depending on the predominant type of cells in
the infiltrate, they are divided into T- or B-cell pseudolymphomas. Diagnostic
immunohistology assists in differentiating pseudolymphomas from lymphomas
as well as between different types of pseudolymphomas [1]. T-cell pseudolymphomas
include idiopathic pseudolymphoma, lymphomatoid drug reaction, lymphomatoid
contact dermatitis, persistent nodular arthropode bite reaction, nodular
scabies and actinic reticuloid. Cutaneous B-cell pseudolymphomas include
idiopathic lymphocytoma cutis, Borrelia lymphocytoma cutis, post zoster
scar lymphocytoma cutis, some persistent arthropode-bite reactions and
tattoo-induced lymphocytoma cutis [2]. In general, a polymorphous infiltrate
with predominantly small lymphocytes and an admixture of a considerable
number of macrophages, eosinophils and plasma cells is considered to be
a typical feature of B-cell pseudolymphomas whereas true B-cell lymphomas
tend to be more monomorphous [3, 4].
Reactions to tattoos may present as granulomatous [5, 6], lichenoid [7],
or pseudolymphomatous reactions [8-14]. Granulomatous tattoo reactions
which usually represent hypersensitivity reactions to tattoo pigments
can also be a manifestation of systemic sarcoidosis [15].
Pseudolymphomas as a result of tattoos have occasionally been reported
in the literature. They occur mainly in reddish areas (mainly cinnabar),
but pseudolymphomas in blue (mainly cobalt salts) and green (mainly chrome
salts) areas have also been described [8].
We herein present a 34 year old woman who developed nodular infiltrates
in a tattoo on her left chest which had been administered 6 years
before. The infiltrate was excised and further histopathological and immunohistochemical
studies were performed.
Case report
A 34 year old woman presented at our outpatients clinic with a red
nodule limited to the red area of a tattoo on her right chest which had
been applied 6 years before (Fig.
1). The substances of the red and black dye were not known to the
patient. There was no pain or itching. Topical treatment with steroids
had not shown any improvement of the nodular infiltrate.
Physical examination revealed a healthy female with normal physical findings
apart from a red nodular infiltrate in the center of a black tattoo on
her right chest. The tattoo itself was done in black colors with a red
center representing a rose. There was no involvement of the regional lymph
nodes.
A punch biopsy was considered to be suspicious for cutaneous pseudolymphoma.
Finally, the entire lesion was excised.
Histology
Histopathologic findings revealed parakeratosis and irregular epidermal
hyperplasia with scattered necrotic keratinocytes. A dense diffuse infiltrate
of lymphoid cells extended from the papillary dermis to the mid-reticular
dermis. The vast majority of cells were small, inconspicuous lymphocytes
with scattered plasma cells and eosinophils. In addition, histiocytes and
histiocytic giant cells were visible. Especially at the bottom of the infiltrate
there was evidence of a dark brown, granular, non refractile foreign material
(Fig. 2). The finely granular
foreign body was noted within the cytoplasm of histiocytes as well as extracellularly
between collagen bundles.
Immunohistology
On immunohistochemical analysis the lymphoid infiltrate consisted mainly
of CD3+ T lymphocytes. CD 20 detected small clusters of B-cells which
composed approximately 20% of the lymphocytic infiltrate (Fig.
3). Analysis with kappa and lambda light chain revealed a polyclonal
pattern.
Molecular genetic analysis
Analysis of TCR and IgH gene rearrangement was carried out with a standard
polymerase chain reaction (PCR) technique on routinely-fixed, paraffin-embedded
sections of tissue [16], using primers described previously [17, 18].
With both sets of primers a polyclonal smear could be observed, indicating
that a monoclonal population of lymphocytes was not present in the infiltrate.
Discussion
The clinical findings showing an asymptomatic red nodule limited to the
red area of a tattoo as well as the histopathological features, showing
a dense diffuse infiltrate of small, inconspicuous lymphoid cells with
an admixture of scattered plasma cells, eosinophils and histiocytes suggest
the diagnosis of pseudolymphoma in our patient. The diagnosis of pseudolymphoma
was confirmed by immunohistochemical and molecular analysis. As there
were only few B-lymphocytes, no germinal centers and numerous T-cells,
a mixed B- and T-cell pseudolymphoma was suggested. Apart from the clinical
setting, malignant lymphoma was excluded because of the "top-heavy" distribution
of the infiltrate, lack of cellular atypia and by the polyclonality of
both the B- and T-cell population.
Only a few cases of tattoo-induced pseudolymphomas have been described
up to now [8-14]. The time of onset ranged from a few months up to 32 years
after administration of the tattoo. Itching has been observed in some
patients [8, 12], while in others ¯ like in our patient ¯ the lesions
were asymptomatic.
In most hitherto reported cases, the pseudolymphomatous infiltrate is
limited to the red colored area of the tattoo, with cinnabar (mercuric
sulfides) being the dye most commonly used. Histopathologically, like
in our case, a lymphohistiocytic infitrate with some eosinophils in the
infiltrate and a few plasma cells have been found in the upper dermis
or throughout the dermis [8-14]. Follicular [8, 12] and nodular structures
[11] have occasionally been encountered.
Extensive immunohistochemical examinations were performed by Rijlaarsdam
et al. in 1988 [12] showing mainly T-cells (Leu 4 + /CD3)
with an admixture of many eosinophils, polyclonal plasma cells and some
Langerhans cells in the interfollicular infiltrate, whereas in the germinal
centers B-cells (Leu 14 + /CD 22) with a considerable admixture
of T-cells (Leu 4 +) and follicular dendritic cells were found. Staining
with anti-light chain immunoglobulin sera showed equal amounts of kappa
positive and lambda positive cells. Niles et al. recognized a diffuse
infiltrate of T-lymphocytes (UCHL1, MT1), few B-lymphocytes (4KB5, L26)
and plasma cells in his case [13]. A polyclonal expression of the heavy
immunoglobulin chain as well as the gamma chain of the T-cell receptor
was reported by Aman et al. in 1997 [14].
In our patient, immunohistochemical findings showed CD 3+ T-cells
and CD 20+ B-cells (approximately 20%) in the infiltrate, similar to what
was observed by Aman et al. [14].
Remarkably, Sangueza [19] described the evolvement of an immunohistologically
monoclonal B-cell lymphoma from cutaneous polyclonal pseudolymphoma in
a tattoo. In the first biopsies the infiltrate consisted predominantly
of T-cells, with 10-20 % B-cells. In the third and fourth biopsy
samples however, atypical lymphoid cells were detected being positive
with pan B-cell antibodies and lambda light chain restriction.
The pathogenetic mechanism of the development of pseudolymphoma in a tattoo
is still unclear. The primary inflammatory reaction caused by injury of
the skin itself does not lead to development of pseudolymphoma, as only
certain areas (especially red ones) are involved. A progressive inflammatory
reaction is presumed. The inducing factor of pseudolymphoma in our patient
might have been a persistent chronic antigenic stimulus due to the red
dye, remaining in the dermis for 6 years, leading to sensitization
and a delayed hypersensitvity reaction with proliferation of lymphoid
cells.
The finding of primary and secondary follicle
centers in a case reported by Rijlaarsdam et al. suggests a follicle
center cell reaction to tattoo pigment with distinct B- and T-cell compartments
analogous to those observed in reactive lymph nodes. This assumption is
supported by the occurrence of characteristic populations of antigen presenting
cells in the compartments (Langerhans cells in T-cell compartments, follicular
dendritic cells in B-cell compartments) [12]. In our case, follicular
structures were not shown, but small clusters of B-cells within the diffuse
infiltrate of T-cells are suggesting a combined T- and B-cell response,
(Fig. 4).
To evaluate the evidence for delayed hypersensitivity reaction to the
dye, patch testing has been performed by some authors. It showed a strong
delayed hypersensitivity reaction to mercury products in some cases [12,
19] whereas in other cases patch testing was negative [10]. In our patient,
due to lack of therapeutic consequences, patch testing was not performed.
The occurrence of pseudolymphomas mostly in red areas of the tattoo is
remarkable. It might be due to high immunological potential of the widely
used mercury containing pigment (cinnabar), which can also lead to granulomatous
reactions. In 1991 Sowden et al. showed that apart from cinnabar,
other red dyes containing a variety of inorganic pigments like aluminium,
iron, calcium, titanium or silicon may also provoke a cutaneous inflammatory
response [20]. Additionally, pseudolymphoma in blue (mainly cobalt salts)
and green (mainly chrome salts) areas of a tattoo have also been observed
[8].
Intralesional steroids [8, 9, 12] and excision [11-14] have been reported
in the literature as treatment options for pseudolymphomas associated
with tattoos. Treatment with laser may not remove the pigment completely
and is therefore not recommended [21]. Although the evolution of a pseudolymphoma
into a malignant lymphoma seems to be the exception, surgical excision
or ¯ if other treatment modalities are chosen ¯ regular follow-up visits
are advised.
Article accepted on 20/1/03
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