C h a p t e r 1 1
Disorders of White Blood Cells and Lymphoid Tissues
255
remain localized for prolonged periods and to follow an
indolent course. Extranodal marginal B-cell lymphomas
of the MALT type are curable by radiation or surgery
when localized. Mucosa-associated lymphoid tissue
lymphomas that occur in the stomach secondary to
H.
pylori
infection often respond to treatment with appro-
priate antimicrobial agents.
Clinical Manifestations.
The manifestations of NHLs
depend on lymphoma type (i.e., indolent or aggres-
sive) and the stage of the disease. Persons with indo-
lent or slow-growing lymphomas usually present with
painless lymphadenopathy, which may be isolated or
widespread. Involved lymph nodes may be present in
the retroperitoneum, mesentery, and pelvis. The indo-
lent lymphomas are usually disseminated at the time of
diagnosis, and bone marrow involvement is frequent.
With or without treatment, the natural course of the
disease may fluctuate over 5 to 10 or more years. Many
low-grade lymphomas eventually transform into more
aggressive forms of lymphoma/leukemia.
Persons with intermediate or more aggressive forms
of lymphoma usually present with accompanying consti-
tutional symptoms such as fever, drenching night sweats,
or weight loss. Frequently, there is increased susceptibil-
ity to bacterial, viral, and fungal infections associated
with hypogammaglobulinemia and a poor humoral
antibody response, rather than the impaired cellular
immunity seen with Hodgkin lymphoma. Because of
their high growth fraction, these lymphomas tend to be
sensitive to radiation and chemotherapy. Hence, with
intensive combination chemotherapy, complete remis-
sion can be achieved in 60% to 80% of cases.
41
Diagnosis and Treatment.
A lymph node biopsy is
used to confirm the diagnosis of NHLs and immu-
nophenotyping to determine the lineage and clonal-
ity. Lymphomas can be grouped according to surface
markers or phenotypic markers (e.g., CD20).
43
Staging
of the disease is important in selecting a treatment for
persons with NHL. Bone marrow biopsy, blood stud-
ies, chest and abdominal CT scans, magnetic resonance
imaging (MRI), positron emission tomography (PET),
gallium scans, and bone scans may be used to determine
the stage of the disease.
39
Newer technologies, such
as deoxyribonucleic acid (DNA) microarray analysis,
which identifies genes that are either overexpressed or
underexpressed by tumor cells, may be used to further
classify patients into distinct risk groups.
Treatment of NHLs depends on the histologic type,
stage of the disease, and clinical status of the person.
40
For early-stage disease with single or limited node involve-
ment, localized radiation may be used as a single treatment
modality. However, because most people who present with
indolent lymphomas have disseminated disease at the time
of diagnosis, combination chemotherapy, combined adju-
vant radiation therapy, or both are recommended. Persons
with lymphomas that carry a risk of CNS involvement
usually receive CNS prophylaxis with high doses of che-
motherapeutic agents or cranial irradiation.
Hodgkin Lymphoma
Hodgkin lymphoma, previously known as
Hodgkin dis-
ease,
is a specialized form of lymphoma that features the
presence of an abnormal cell called a
Reed-Sternberg
cell.
4,7,39,44
Because of improved treatment methods, death
rates have decreased by more than 60% since the early
1970s. Distribution of the disease is bimodal; it occurs
more frequently in two separate groups, the first in early
adulthood (15 to 40 years) and the second in older adult-
hood (55 years of age or older).
39,44
About 10% to 15%
of cases are diagnosed in children and teenagers.
44
Hodgkin lymphoma differs from NHLs in many
aspects. First, HL usually arises in a single node or chain
of nodes and spreads first to anatomically contiguous
lymphoid tissues, while NHLs frequently originates at
extranodal sites and spreads in an unpredictable fash-
ion. Therefore, the staging of HL is much more impor-
tant in guiding therapy than it is for NHLs. Second, HL
also has distinctive morphological features. It is charac-
terized by the presence of large, atypical, mononuclear
tumor cells, called
Reed-Sternberg cells
(Fig. 11-9).
These cells release factors that induce the accumulation
of reactive lymphocytes, macrophages, and granulo-
cytes, which typically make up greater than 90% of the
tumor cells.
7
The origin of the neoplastic Reed-Sternberg cell of
Hodgkin lymphoma has been difficult to study, in large
part because these cells do not express many of the
markers found on lymphocytes. It is only recently that
methods have been developed that allow for the micro-
analysis of these cells and their variants. These stud-
ies have shown that the Reed-Sternberg cells of most
individual cases harbor identical immunoglobulin genes
that show evidence of mutation, establishing the cell of
origin as a germinal center or postgerminal center B cell.
FIGURE 11-8.
Burkitt lymphoma. A tumor of the jaw distorts
this child’s face. (FromValdez R, Zutter M, Dulau FA, et al.
Hematopathology. In: Rubin R, Strayer DS, eds. Rubin’s
Pathology: Clinicopathologic Foundations of Medicine. 6th ed.
Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &
Wilkins; 2012:1012).
