Page 1516 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 85

T-CELL LYMPHOMAS

Owen A. O’Connor, Govind Bhagat, Karthik A. Ganapathi, Jason Kaplan,
Paolo Corradini, Joan Guitart, Steven T. Rosen, and Timothy M. Kuzel

The T-cell lymphomas are a heterogeneous group of diseases. They (Canada), for example, was roughly 1.6%, compared with the 18.3%
are generally divided into those that predominantly arise within the frequency in Hong Kong.
skin, and are thus referred to as the cutaneous T-cell lymphomas Although rare in the West, subtypes of PTCL are not uncommon
(CTCLs), and those that do not primarily arise in the skin, namely, in the Eastern hemisphere and in Central and South America.
the mature or peripheral T-cell lymphomas (PTCLs). Like the B-cell Geographic and ethnic variability have been cited as reasons for the
malignancies, each of these subcategories of T-cell lymphoma can be differences in the prevalence of some types of PTCL. Exposure to
divided into indolent and aggressive diseases, each associated with its certain infectious or environmental agents is thought to account for
own characteristic biology and treatment principles. Although CTCL some of the geographic variation, especially with regard to human
is considered a mature T-cell lymphoma, these diseases are for the T-lymphotropic virus-1 (HTLV-1) infection and occurrence of adult
most part indolent in nature. They are characterized by a variety of T-cell leukemia/lymphoma (ATLL), as well as Epstein-Barr virus
clinical entities, each with its own unique biology and presentation. (EBV) infection and the development of natural killer (NK)/T-cell
The mature or peripheral T-cell lymphomas typically arise in lymph lymphoma (NKTCL) in Asia, the Caribbean, and Central and South
nodes, extranodal sites, or with a leukemic disease, and are for the America. Globally the three most common subtypes of PTCL are
most part very aggressive diseases. The separation of the T-cell lym- PTCL-NOS (25.9%), AITL (18.5%), and ALCL (12%). PTCL-
phomas into cutaneous or noncutaneous is largely intended to NOS is recognized as being slightly more common in North America,
highlight some of the general differences in behavior, although clearly with a lower incidence in Europe and Asia, whereas AITL appears to
there is overlap. Some forms of CTCL can involve nodal and extra- be more common in Europe compared with Asia or North America.
nodal sites, and some forms of PTCL can involve the skin. Given the Enteropathy-associated T-cell lymphoma (EATL) is associated with
marked differences in biology, clinical behavior, and treatment of celiac disease, which itself is associated with human leukocyte antigens
these two categories of T-cell lymphoma, in this chapter we have DQ2 or DQ8, both being more common in European populations.
organized them into different sections. Similarly, EBV-associated lymphomas are primarily seen in Japan,
Korea, and northern China, as well as immigrant populations from
THE PERIPHERAL T-CELL LYMPHOMAS South America in North America. These data suggest that there may
be a variety of both genetic and environmental factors that may
(NONCUTANEOUS) predispose to T-cell lymphomas, many of which are only now being
identified in larger epidemiologic studies.
The mature or peripheral T-cell lymphomas are a heterogeneous
group of diseases. Most PTCL entities are highly aggressive diseases
that respond poorly to conventional chemotherapy. Among the Classification
most common subtypes are PTCL, not otherwise specified (NOS),
angioimmunoblastic T-cell lymphoma (AITL), and the anaplastic The classification of PTCLs has evolved substantially over the past
large-cell lymphomas (ALCLs). Although these diseases are consid- several decades. Older classification schemes failed to incorporate all
ered to carry an unfavorable prognosis compared with their B-cell the necessary immunophenotypic, cytogenetic, morphologic, and
counterparts, select molecular entities, such as anaplastic lymphoma clinical data to subclassify these diseases, as now presented in the
kinase (ALK)-positive ALCLs, are associated with a highly favorable context of the World Health Organization (WHO) classification
prognosis, comparable to or better than diffuse large B-cell lymphoma system. The WHO classification published in 2008 recognizes more
(DLBCL). than 22 different subtypes of T-cell lymphoma distributed among
It is estimated that there were approximately 66,360 cases of four different subcategories. As shown in Table 85.1 and Fig. 85.1,
non-Hodgkin lymphoma (NHL) in the United States in 2011, of these subcategories are divided into nodal, extranodal, cutaneous, and
which the T-cell lymphomas account for approximately 5%–10% of leukemic, each based on the predominant clinical behavior of that
all cases. The median age at diagnosis is 59 years, which is lower than disease entity.
the median age of 66 for patients with NHL in general. Like other The nodal group consists of PTCL-NOS, which is the most
forms of lymphoma, T-cell lymphomas are diseases of older adults, common subtype of PTCL, accounting for roughly one-quarter of
with approximately 40% of cases occurring between the ages of 55 all PTCL cases. Other subtypes include ALCL and AITL. In ALCL
and 74 years, and only about 5% of cases occurring after the age of there is a significant impact of specific cytogenetic features on prog-
85 years. Between 2004 and 2008, Surveillance Epidemiology and nosis. The ALK-positive forms of ALCL (Fig. 85.2), which are
End Results (SEER) reported the age-adjusted incidence rate of T-cell characterized by the nucleophosmin (NPM)-ALK translocation
lymphoma as approximately 1.8 per 100,000 men and women. The [t(2;5)] have a highly favorable prognosis, whereas those variants that
incidence rates among all races in males and females are approximately are ALK negative carry a relatively poor prognosis. Other than the
2.3 and 1.4 per 100,000 individuals, respectively, in contrast to 24 presence of the ALK translocation as determined by fluorescence in
and 16.5 cases per 100,000 males and females, respectively, for NHL. situ hybridization (FISH), there is no way to differentiate these dis-
The disease is almost twice as frequent in males as females. In general, eases on strictly morphologic or immunophenotypic grounds. As
PTCLs are far more common in Asia. For example, the International such, the appropriate therapeutic recommendations for these two
Peripheral T-Cell and Natural Killer/T-Cell Lymphoma Study noted diseases obligatorily involve an understanding of this specific cytoge-
that T-cell lymphomas accounted for only 5%–10% of all NHL cases netic feature. Each of these ALCL variants accounts for about 5%–6%
in Western countries and about 10%–20% in Asian countries. of all cases of PTCL. Similarly, it is often a significant diagnostic
Rudiger et al have reported that the frequency of PTCL in Vancouver challenge to discriminate ALK-negative ALCL from PTCL-NOS.

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