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CHAPTER 103 Considering the overall protracted course of the disease, its indolent charac-

CUTANEOUS T-CELL ter, immunocompromised status of the patients, and absence of definitive
therapy, aggressive multiagent chemotherapy contributing to immunosup-
LYMPHOMA (MYCOSIS pression should be reserved for end-stage palliation or as a bridge to stem
cell transplantation with the goal of definitive cure. There are several
6–8
FUNGOIDES AND SÉZARY FDA-approved single agents for therapy of MF, which are safe and effective
against the disease and may be used in the therapeutic ladder prior to mul-
ti-agent regimens. Several single agents and combinations of new and
9–11
SYNDROME) older agents are in clinical trials now to test for efficacy in MF and SS. Because
no single therapy is considered to be the standard of care for MF and SS, clin-
ical trials remain a viable option for most patients. The goal of therapy is to
Larisa J. Geskin induce long-term remissions without compromising patients’ immunity and
improvement of the quality of life.

SUMMARY
DEFINITION AND HISTORY
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of malignant
lymphomas that share the propensity for malignant T lymphocytes express- In 1806, Baron Jean-Louis Alibert described a patient who presented
ing cutaneous lymphocyte antigen to infiltrate the skin. Mycosis fungoides with skin patches that grew into plaques and mushroom-like tumors
12
(MF) is the most common variant of CTCL, representing approximately 50 per- and first coined the term mycosis fungoides (MF). In 1938, Sézary and
cent of all cases. Sézary syndrome (SS) is a leukemic variant of MF, affecting Bouvrain described a syndrome of pruritus, generalized exfoliative
erythroderma, and abnormal hyperconvoluted lymphoid cells in the
1
approximately 5 percent of patients with MF. MF and SS are the most com- blood. Today this condition is referred to as Sézary syndrome (SS), a
13
mon malignant proliferations of mature memory T lymphocytes of the helper condition seen in a subset of patients with MF.
phenotype (CD4+CD45RO+), which renders patients immunocompromised Prior to the 1970s, cutaneous lymphomas were believed to be cuta-
2
even at the earliest stages of the disease. Advanced stages are associated with neous counterparts of the systemic lymphomas. In 1975, Lutzner and
severe immune suppression. Diagnosis is established by skin biopsy, followed associates suggested the term cutaneous T-cell lymphoma (CTCL),
14
by staging work up which includes radiologic imaging and pathologic evalua- recognizing that despite the significant similarities of malignant cell
tion of the lymph nodes, internal organs, blood, and marrow, as appropriate, morphology and phenotype to systemic T-cell lymphomas, the cuta-
according to presenting manifestations of the disease. neous lymphomas represented distinct entities. Although this defini-
MF is divided into early and advanced stages for therapeutic and prog- tion has helped to distinguish cutaneous lymphomas from systemic
nostic reasons. In early stages, the disease follows an indolent course and disease, it has also led to inappropriately using the umbrella term
has a favorable prognosis. In advanced stages, the prognosis is poor. There CTCL interchangeably with MF. Common World Health Organization
(WHO)–European Organisation for Research and Treatment of Can-
are numerous therapeutic options. No treatment has been definitively cer (EORTC) classification was first developed in 2005 to resolve dif-
15
proven to improve survival, but newer studies suggest that survival is lon- ferences between various classifications (Table 103–1) and is currently
ger than historically documented. Multiagent chemotherapy is not a useful accepted as the standard for CTCL staging and classification. 16
3,4
option because it is inferior to immune modulating and biologic therapies. 5
EPIDEMIOLOGY

MF is twice as common in males as in females. The median age at diag-
nosis is 55 years. Americans of African descent have a higher incidence
Acronyms and Abbreviations: ALCL, anaplastic large cell lymphoma; ALK-1, of MF and a poorer prognosis than Americans of European descent.
anaplastic lymphoma kinase-1; ATRA all-trans retinoic acid; BCNU, bis-chloroethyl- MF occurs least often in Asians and Hispanics. Evidence for a genetic
nitrosourea or carmustine; CLA, cutaneous lymphocyte antigen; CT, computed predisposition (germline transmission of susceptibility) in patients
tomography; CTCL, cutaneous T-cell lymphoma; DD, denileukin diftitox; ECP, extra- with CTCL is inconclusive. An approximately 6 percent increase in
corporeal photopheresis; EORTC, European Organisation for Research and Treatment incidence of CTCL per decade was documented from the early 1970s
of Cancer; HDACi, histone deacetylase inhibitor; HTLV-1, human T-lymphotropic virus to 1998, but the incidence subsequently leveled off and stabilized, with
type 1; Ig, immunoglobulin; IL, interleukin; LEBT, localized electron beam therapy; a current incidence of approximately one per 100,000. Incidence is
17
LyP, lymphomatoid papulosis; MF, mycosis fungoides; MMAE, monomethyl auristatin highly age-dependent, with the highest incidence of 3.6 per 100,000 of
E; NBUVB, narrow band UVB; NCCN, National Comprehensive Cancer Network; NK, adults after the age of 70 years. Approximately 3000 new cases of MF are
natural killer; PCALCL, primary cutaneous anaplastic large cell lymphoma; PCR, reported annually, comprising approximately 3 percent of all lympho-
polymerase chain reaction; PET, positron emission tomography; PUVA, psoralen with mas. The mortality rate varies widely according to the stage of disease.
UVA; RXR, retinoid X receptor; SDT, skin-directed therapy; SS, Sézary syndrome; TCR, Stage I mortality does not differ from the mortality of age-matched con-
T-cell receptor; Th2, T-helper type 2; TNMB, tumor, node, metastasis, blood; TSEBT, trols. However, stage IV patients have a 27 percent 5-year survival and
total-skin electron beam therapy; UV, ultraviolet; UVA, ultraviolet A; UVB, ultraviolet 10 percent 15-year survival. Median survival of patients with SS is 1.5
B; WHO, World Health Organization. years. The mortality rate of MF in the United States has been declining,
possibly because of earlier diagnosis of the disease. 1,18

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