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1284 Part VII Hematologic Malignancies

A B C

Fig. 79.3 SPLENIC MARGINAL ZONE LYMPHOMA, VILLOUS LYMPHOCYTES, AND PRIMARY
NODAL MARGINAL ZONE LYMPHOMA. (A) Splenic marginal zone lymphoma is characterized by an
expansion of the marginal zone cells (left) and their spilling into the red pulp (right). (B) These cells can also
become leukemic and can be recognized on the peripheral blood smear. Note the polar distribution of the
cytoplasmic projections. (C) Primary nodal marginal zone lymphoma is rare, and involvement of a node by
extranodal disease must always be ruled out. NMZL is histologically characterized by an expansion of marginal
zone cells (formerly referred to as monocytoid B cells) in between reactive germinal centers.

these patients can achieve CR after successful treatment of the infec- 14q32, different from those seen in ENMZL, occurred in 12% of
tion. 183,184 This raises the possibility that, like ENMZL, this disease patients. The translocation t(11;18) was not seen in SMZL. More
is associated with chronic antigenic stimulation. However, no other than 50% of cases had three or more cytogenetic aberrations. Dele-
infections have been described in clear connection to SMZL, despite tions of 8p and 17p (TP53) have been seen in approximately 15%
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a suggested association with Plasmodium, and thus the etiology of of cases analyzed with DNA microarrays. The biologic significance
most cases is unknown. of these chromosomal abnormalities is unclear at this point, although
there are ongoing efforts at clarifying it. 188
Approximately 50%–60% of SMZL have evidence of somatic
Histology hypermutation of the immunoglobulin genes, 181,188–190 and there is
some evidence that, similar to CLL, these cases may have better
189
The classic histology of SMZL includes a population of small lym- overall prognosis. Both mutated and unmutated tumors display
phocytes that surrounds or replaces the germinal centers of the bias in variable region usage, with predominance of VH1-2 family
lymphoid follicles of the white pulp, effacing their mantle zone, and genes. Intraclonal variation has also been described, which suggests
progressively merging peripherally with larger, marginal zone–like the presence of ongoing mutational events in these lymphomas. 191
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cells. These cells expand to the interfollicular zones and invariably In contrast to hairy cell leukemia, the V600E BRAF variant has
192
invade the red pulp (see Fig. 79.3A). A few scattered lymphoblasts not been detected in SMZL. In addition, the L265P MYD88
are usually present, and as in ENMZL, plasmacytic differentiation mutation commonly observed in Waldenström macroglobulinemia/
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can occur. Bone marrow involvement usually gives rise to nodular lymphoplasmacytic lymphoma is rare in SMZL. These findings
interstitial lymphoid infiltrates that resemble the histology of the may help distinguish these disorders when the diagnosis is in doubt.
spleen, although the cell types are usually admixed, without distinct
zones. Peripheral blood involvement is typically associated with
lymphocytes that have short polar villi (see Fig. 79.3B), as mentioned Therapy
earlier, although the villi may be absent.
Because SMZL behaves indolently, in asymptomatic patients without
significant or progressive cytopenias, expectant observation is a rea-
Immunophenotype sonable approach. The 5-year overall survival rate of 32 patients with
asymptomatic SMZL who never received treatment was 86% in one
194
The phenotype of SMZL is similar to that of ENMZL (see earlier), published series. In another series, 10 out of 14 untreated patients
but in contrast to the latter, SMZL is usually IgD-positive. The same were alive between 1 and 6 years after diagnosis. 195
differential diagnosis considerations apply; additionally, because this Indications for lymphoma treatment are similar to those for
disease behaves as a chronic B-cell leukemia, it is of interest that advanced-stage ENMZL, including symptomatic splenomegaly. As
SMZL is negative for annexin A1 and CD25 and usually negative for for other forms of MZL, there are no data from randomized trials
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CD103 (in contrast to hairy cell leukemia). Rare cases may be guiding selection of therapy, and most recommendations come from
CD5-positive. 187 consensus opinions of experts in the field. 9

Genetics Anti-HCV Therapy

A substantial amount of genetic data on SMZL has been accumulated In patients with evidence of active HCV infection, anti-HCV therapy
during the last decade. A recent review of 330 patients with SMZL is recommended. A study of the effects of interferon-α (IFN-α) in
documented del(7q) (affecting different loci in regions q21 to q36) SMZL showed eight complete and one partial hematologic responses
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as the most frequent cytogenetic abnormality (≈40% of patients). in nine HCV-positive patients after clearance of HCV (with two of
Gains of genetic material from chromosomes 3 (≈25%), 8 (≈10%), them requiring addition of ribavirin), versus no responses in six
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and 12 (≈8%) were also seen frequently. Translocations involving HCV-negative individuals. One patient in CR treated initially only