CASE REPORT

Treatment of Mycosis Fungoides with Bexarotene Results in

Remission of Diffuse Plane Xanthomas
Stamatis Gregoriou, Dimitris Rigopoulos, Christos Stamou, Vasiliki Nikolaou, and George Kontochristopoulos

Background: Cutaneous xanthomas develop as a result of intracellular and dermal deposition of lipids in either hyper- or
normolipidemic patients. Plane xanthomas may signal the presence of an underlying monoclonal gammopathy, chronic
myelomonocytic leukemia, or cutaneous T-cell lymphoma. Investigators have suggested that xanthomatized T cells may result in
induction of plane xanthomas.
Methods: We report the case of a patient with mycosis fungoides (MF) and plane xanthomas who was treated with bexarotene
for his MF.
Results: Significant improvement in the clinical signs of MF was observed within 3 months. We also observed a substantial
regression of the xanthomas after 5 months of treatment. Complete clinical remission of both the MF and xanthomas was obtained
after 6 months. The patient was still free of xanthomas after 3 years of follow-up.
Conclusion: Bexarotene led to the clearing of the cutaneous lesions of cutaneous T-cell lymphoma and plane xanthomas. This
may be due to an effect of bexarotene on the aberrant T cells that may cause xanthomatization.

Contexte: Les xanthomes cutanés sont causés par le dépôt intracellulaire et dermique de lipides chez les personnes hyper- ou
normolipidémiques. Les xanthomes plans peuvent être le signe de la présence sous-jacente d'une gammapathie monoclonale, d'une
leucémie myélomonocytaire chronique, ou d'un lymphome T cutané. Les chercheurs croient que les lymphocytes T xanthomisés
peuvent provoquer l'apparition de xanthomes plans.
Méthode: Nous faisons état, dans le présent article, du cas d'un patient atteint d'une mycose fongoïde (MF) et de xanthomes
plans, qui a été traité par le bexarotene pour la MF.
Résultats: Une diminution sensible des signes cliniques de la MF a été observée au cours des 3 premiers mois de traitement.
Nous avons également noté une diminution importante des xanthomes après 5 mois de traitement, et une rémission clinique
complète et de la MF et des xanthomes a été obtenue au bout de 6 mois de traitement. Le patient est encore exempt de xanthomes
après 3 ans de suivi.
Conclusions: Le bexarotene a permis la disparition des lésions cutanées liées au lymphome T cutané et des xanthomes plans.
Cette disparition peut être attribuable à un effet du bexarotene sur les lymphocytes T aberrants, qui peuvent causer la
xanthomisation.

C UTANEOUS XANTHOMAS develop as a resuit of

intracellular and dermal deposition of lipids in either
hyper- or normolipidemic patients. Plane xanthomas may
signal the presence of an underlying monoclonal gammo-
pathy, chronic myelomonocytic leukemia, or cutaneous T-
cell lymphoma (CTCL).^ Bexarotene is a synthetic retinoid
analogue that specifically activates retinoid X receptors and
has been approved for the treatment of CTCL refractory to at
least one previous systemic therapy.^'^ We report the case of
a patient with mycosis fungoides (MF) and plane xanthomas
that were ameliorated after treatment with bexarotene.

Case Report

From the University of Athens Medical School, Department of
Dermatology, Attikon Hospital, and the 2nd Department of
Dermatology, Andreas Sygros Hospital, Athens, Greece.
Address reprint requests to: Stamatis Gregoriou, MD, PhD, 42 Kiftsou str,
N kifisia, 14564 Athens, Greece; e-mail stamgreg@yahoo.gr.
DOI 10.2310/7750.2012.12022
© 2013 Canadian Dermatology Association
A 68-year-old patient presented with yellow-orange indu-
rated plaques on the forehead and periorbitally and slightly
indurated scaly brownish-red plaques on the trunk and
extremities with obscure borders (Figure 1). According to
the patient, the lesions had a sudden onset 6 months ago. He
had a medical history of hypertension, hyperlipidemia, and
coronary heart disease.

52 Journal of Cutaneous Medicine and Surgery, Vol 17, No 1 (January/February), 2013: pp 52-54
 Bexarotene Treatment Results in Remission of Plane Xanthonias
Figure 1. Yellow-orange indurated plane xanthonias on the forehead (A) and periorbital plane xanthomas (xanthelasma) (B) at presentation.
Biopsy specimens were obtained from the forehead
plaque, periorbitally, and from the plaques on the trunk
and extremities. Histology of the forehead lesion revealed
abundant histiocytes with foamy degeneration of their
cytoplasm and elastosis. Histology from the trunk lesion
revealed moderate dense lymphocytic infiltration by small
and medium lymphocytes with nuclear anomalies.
Immunohistochemistry showed that the neoplastic ceUs
had CD3^CD4^CD45RO''CD8" and memory T-ceU phe-
notype. Clonal T-ceU receptor gene rearrangement was
detected by polymerase chain reaction analysis. A diag-
nosis of MF affecting 20% of body surface area (BSA) for
the trunk lesions and plane xanthomas for the facial lesions
was made based on these clinical and histopathologic data.
Complete blood count and routine serum biochemistry
were within normal limits except for an abnormal lipid
profile (total lipids 561 mg/dL, triglycérides 153 mg/dL,
cholesterol 204 mg/dL, low-density lipoprotein 133 mg/dL,
high-density lipoprotein 40 mg/dL). The patient had
known dislipidemia that was treated with rosuvastatin
10 mg daily. Thyroid hormone evaluation was within
normal limits. A chest radiograph and a computed
tomographic scan of the upper and lower abdomen were
unremarkable. Cardiologie evaluation revealed an ejection
fracture (EF) of 45%. Staging of MF was determined to be
IB (T2, NO, MO).
Administration of interferon-a2b (INTRON A) was
excluded in the patient because of his decreased EF. We
decided to prescribe bexarotene 600 mg once per day.
Blood lipids and thyroid hormones were monitored
every 15 days for the first month and every month
afferward.
Significant improvement in the clinical signs of MF was
observed within 3 months. We also observed a substantial
53
regression of the xanthomas, affer 5 months of treatment,
even though the serum cholesterol and triglycéride levels
were stiU high. Complete clinical remission of both the MF
and xanthomas was obtained affer 6 months (Figure 2).
The patient was stiU free of xanthomas affer 3 years of
foUow-up. The patient showed a mild recurrence with
smaU patches of MF (stage la, 7% BSA) affer the
bexarotene dose was reduced to 300 mg due to lipid
abnormalities a year later. Narrow-band ultraviolet B
phototherapy was initiated to treat the recurrence, leading
to complete resolution of the lesions.
Discussion
Association of plane xanthomas with CTCL has rarely been
reported in the medical literature.*"^ Pathogenesis has
been suggested to be associated with lipoprotein leakage in
MF plaques and subsequent histiocyte phagocytosis,
leading to plane xanthoma formulation close to the tumor
plaques.'' Plane xanthomas in normolipidemic patients
with MF might be produced because of alteration in
lipoprotein content or structure, local tissue alteration
(trauma, infiammation, local tissue synthesis), or lympho-
proliferative disease.' Other investigators have suggested
that atypical T lymphocytes might activate macrophages
via cytokines such as interleukin-4 and interferon-y,
leading to their xanthomatization.^
Bexarotene (Tagretin) is a member of a subclass of
retinoids that selectively activate retinoid X receptors.
Once activated, these receptors bind to deoxyribonucleic
acid (DNA) and initiate transcription. Bexarotene induces
transcription of genes that control the growth and
replication of ceUs. As a likely result of this action,
bexarotene has been shown in laboratory studies to inhibit
54 Gregorioii et al
Figure 2. Marked improvement in forehead (A) and periorbital (B) plane xanthomas after 6 months on bexarotene therapy.
the growth of some tumor cell lines and decrease tumors
in cancer animal models.'"
The mode of action of bexarotene on both xanthomas
and MF plaques in our patient can only be speculative. If one
considers as valid the hypothesis that xanthomatized T cells
result in induction of plane xanthomas, bexarotene might
have a therapeutic effect on this xanthomatized T-cell
infiltrate, resulting in regression of the lesions. Studies on the
pathogenesis of plane xanthomas in patients with lympho-
proliferative disorders might shed more light on the subject.
Acknowledgment
Financial disclosure of authors and reviewers: None
reported.
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