Recent Advances in the
Management of Cutaneous Lymphomas
L. Frank Glass,
and Reinhard Dummer
The treatment options for patients with primary cutaneous B- and T-cell lymphomas are as diverse
as the diseases themselves, including both skin-directed and systemic therapies. Long-term remis-
sion can be attained in many cases; however, no treatment is curative with the possible exception
of allogeneic stem cell transplant. Improved insight into the molecular biology and pathophysiology
of these diseases has led to the development of novel drugs and targeted therapies, including
monoclonal antibodies and antimetabolites, as well as improved radiotherapeutic techniques. We
aim to summarize these new and emerging treatment modalities, and to outline how they may be
integrated into the clinical management of patients with primary cutaneous lymphoma (CL).
Semin Oncol 39:150-162 © 2012 Elsevier Inc. All rights reserved.
rimary cutaneous lymphomas (CLs) are a heter-
ogeneous group of malignancies derived from
skin homing lymphocytes. In general, they are
characterized by an indolent course, but there is po-
tential for ultimate progression to nodal or systemic
disease. Reported incidence rates have been steadily
increasing over the last 30 years and are currently
estimated at 0.3 to 1.0 per 100,000, with a male-to-
female ratio of nearly 2:1.
An exception to this trend
is diffuse large B-cell lymphoma,
which shows a clear
predilection for women. Most commonly, patients
present with CL between the sixth and eighth decade
of life, and diagnosis prior to the age of 20 years is rare.
In contrast to other non-Hodgkin lymphomas, which
are predominantly B-cell– derived, approximately 75%
of all CLs are cutaneous T-cell lymphomas (CTCLs) and
25% are cutaneous B-cell lymphomas (CBCLs). Distinc-
tion between primary CLs and involvement of the skin
secondarily by nodal or systemic lymphomas is crucial,
due to important differences in both the clinical behav-
ior and management of these entities.
CLASSIFICATION AND DIAGNOSIS
In 2008, the World Health Organization (WHO) and
European Organization for Research and Treatment of
Cancer (EORTC) published a revised classiﬁcation for
lymphoid neoplasms (Table 1)
based on cell of ori-
gin, immunophenotype, and genetic characteristics.
The diagnosis of cutaneous lymphomas requires a
high index of suspicion, as presentation in early stages
may be largely nonspeciﬁc. CTCL, in particular, may
evolve into patches and plaques over the span of years
to decades, whereas CBCL more often presents with
the rapid development of nodules or tumors. Current
National Comprehensive Cancer Network (NCCN)
guidelines recommend the evaluation of all slides by a
pathologist with expertise in primary CLs, with ade-
quate immunohistochemical analysis.
ment and cytogenetics also may be useful in select
instances; the rapidly increasing knowledge of T-cell
biology and molecular genetics has the potential to
further advance diagnostic methods, as well as expand
the opportunities for targeted therapy. Following diag-
nosis of CL, a work-up including a complete physical
examination, with particular attention to node-bearing
areas and pertinent laboratory and imaging studies,
should be completed for accurate stage determination.
In 2007, the International Society of Cutaneous Lym-
phomas (ISCL) and the EORTC proposed two separate
staging guidelines for mycosis fungoides (MF)/Sézary
syndrome (SS) (Table 2) and for CLs other than MF and
SS (Table 3).
These recommendations allow for more
consistent and reproducible staging of patients with
CL, ultimately improving clinicians’ ability to adminis-
Department of Dermatology, University Hospital Zürich, Switzerland.
Department of Dermatology and Cutaneous Surgery, University of
South Florida, Tampa, FL.
Department of Cutaneous Oncology, Mofﬁtt Cancer Center, Tampa, FL.
Financial support: This work was supported in part by the Bangerter-
Rhyner-Stiftung. B. Belloni is supported by the Merck Sharp &
Dohme scholarship grant for oncologic research.
Address correspondence to Professor Dr Reinhard Dummer, Department
of Dermatology, University Hospital, Zürich, Gloriastr. 31, CH-8091
Zürich, Switzerland. E-mail: firstname.lastname@example.org
0270-9295/ - see front matter
© 2012 Elsevier Inc. All rights reserved.
Seminars in Oncology, Vol 39, No 2, April 2012, pp 150-162