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C H A P T E R 82

DIAGNOSIS AND TREATMENT OF DIFFUSE LARGE B-CELL

LYMPHOMA AND BURKITT LYMPHOMA

Kieron Dunleavy and Wyndham H. Wilson

Diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma this confers a much worse prognosis compared with MYC-negative
(BL) are the most common types of aggressive B-cell lymphoma. cases when CHOP-type (cyclophosphamide, doxorubicin [Novan-
Although they share many clinical and biologic features, the approach trone], vincristine [Oncovin], and prednisone) regimens are used.
to their management is different; therefore, an accurate histologic Recently, gene expression profiling has defined a new molecular
diagnosis is of utmost importance. There have been several recent taxonomy for DLBCL. Morphologically indistinguishable tumors
therapeutic advances in the management of these diseases, and both can show marked heterogeneity in gene expression, and these pat-
DLBCL and BL have high cure rates with current treatment terns of expression may be classified into signatures that correspond
approaches. Therefore, it is imperative to promptly evaluate patients to the cellular origin of the lymphoma according to its stage of
with these diseases and expeditiously institute appropriate therapy. B-cell differentiation; on the basis of these signatures, DLBCL can
be divided into at least three different subtypes: germinal center
B-cell (GCB)-like, activated B-cell (ABC)-like, and primary medi-
DIFFUSE LARGE B-CELL LYMPHOMA astinal B-cell lymphoma (PMBL). Importantly, these subtypes of
2
DLBCL have disparate outcomes following standard therapy with
Epidemiology the ABC subtype having an inferior survival in many retrospective
studies. 3
DLBCL is the most prevalent histologic subtype of non-Hodgkin
lymphoma (NHL) (of which there are approximately 72,000 new
cases in the United States each year) and comprises 30% to 40% of Clinical Features
these diseases. Although the median age at diagnosis is in the seventh
decade of life, DLBCL affects children and adults of all ages, and it The clinical presentation of DLBCL is variable and depends on a
is slightly more common in males than females. Though the etiology number of factors, including histology, patient age, and immune
of DLBCL is unknown in most cases, it can arise from transformation status. The disease typically presents with lymphadenopathy that can
of an indolent lymphoma. A history of immunodeficiency is a sig- range from relatively asymptomatic to causing pain (Fig. 82.2),
nificant risk factor, and individuals who are human immunodeficiency causing organ compromise such as ureteral obstruction or spinal cord
virus (HIV) positive have in the range of 100 times higher incidence compression. The involvement of bone marrow (BM) is much less
of developing DLBCL over those who do not have HIV. frequent than with indolent lymphomas and is present in approxi-
mately 20% of cases.
Patients may have constitutional manifestations from the produc-
Pathobiology tion of inflammatory molecules and a variety of other cytokines and
chemokines produced by the lymphoma cells or host tissues. Such
The pathobiology of DLBCL is very heterogeneous, and within manifestations include weight loss, malaise, fevers, night sweats, and
DLBCL, there are several morphologic variants that include centro- loss of appetite. Of these, unexplained weight loss of more than 10%
blastic, immunoblastic, T-cell rich or histiocyte-rich, (see E-Slide of body weight and temperature higher than 38°C as well as drench-
VM03959) and anaplastic subtypes. Recent progress using techniques ing night sweats are referred to as “B” symptoms.
such as molecular profiling and other high-resolution genetic tech-
nologies are further advancing this taxonomy. There are also several
clinical-pathologic variants of DLBCL. Primary mediastinal B-cell Investigation
lymphoma (PMBL), for example, commonly presents in young
women and usually remains localized to the mediastinum (Fig. 82.1). History and Physical Examination
Primary central nervous system lymphoma (PCNSL) is another rare
subtype of DLBCL that rarely disseminates to extraneural sites and Patients should be questioned about systemic symptoms, and their
is much more commonly observed in HIV-positive individuals. It is performance status should be assessed (Table 82.1). It is important
important to recognize that DLBCL can also arise as a result of to determine if there is a history of potential causative factors such
histologic transformation from an indolent lymphoma. Although this as prior malignancy, chemotherapy or radiation treatment, or auto-
differentiation may not affect treatment choice initially, it will affect immune or immunodeficiency diseases. A history of infection with
prognosis and natural history, and therefore needs to be recognized or exposure to various pathogens, including HIV and hepatitis B and
at diagnosis. 1 C, should be excluded. A detailed physical examination should be
The neoplastic cells of DLBCL express pan B-cell markers, includ- performed with particular attention to lymph node (LN) regions.
ing CD20, and surface or cytoplasmic immunoglobulin is often Skin involvement by DLBCL is rare (Fig. 82.3).
demonstrated. CD10, BCL6, and IRF4/MUM1 are variably An accurate histologic diagnosis is imperative to determine the
expressed, and the proliferation index as measured by Ki67 staining patient’s prognosis and treatment; therefore, the single most impor-
is typically high. Approximately 30% of cases show abnormalities tant diagnostic test is a technically adequate and properly evaluated
involving the BCL6 gene, and translocation of the BCL2 gene, a excisional tissue biopsy. With few exceptions, fine-needle aspiration
hallmark of follicular lymphoma, is present in 20% to 30% of cases. is inadequate for diagnosis. Aggressive lymphoma should be diag-
Approximately 10% of cases of DLBCL harbor a t(8:14) MYC nosed by an experienced hematopathologist familiar with the nuances
translocation, and recently, several groups have demonstrated that and pitfalls of lymphoma diagnosis.

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