Page 1431 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 79

MARGINAL ZONE LYMPHOMAS (EXTRANODAL/

MALT, SPLENIC, AND NODAL)

Carlos A. Ramos

The term marginal zone refers to a histologic compartment located Antiglobulin tests and reticulocyte count may be useful to rule out
at the periphery of lymphoid follicles immediately outside their autoimmune hemolytic anemia. Serum protein electrophoresis and
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mantle zone. The marginal zone is especially evident in the spleen, immunofixation may demonstrate a monoclonal immunoglobulin.
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although identical areas have been observed in other lymphoid β 2 -microglobulin levels may have prognostic value as in other
structures, including mesenteric lymph nodes and mucosa-associated indolent lymphomas. Viral hepatitis (B and C) and HIV studies to
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lymphoid tissue (MALT) (Fig. 79.1). Ordinarily, it is composed exclude coexisting infections that affect therapeutic approaches
predominantly of B cells that are slightly larger than mantle zone should be obtained.
lymphocytes and strongly positive for surface immunoglobulin (Ig) Depending on the primary site of disease, specific procedures may
M, but weakly positive for IgD (in contrast to mantle zone cells, be indicated. Gastrointestinal MZLs may require repeat staging
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which are strongly positive for IgD). Marginal zone B lymphocytes endoscopies, during which an adequate number of biopsies should
are thought to be involved in fast protective responses against patho- be obtained. For gastric ENMZL, the European Gastro-Intestinal
genic encapsulated bacteria that do not trigger classical T-cell–depen- Lymphoma Study (EGILS) group recommends a mapping procedure
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dent humoral immunity. They are also assumed to be the physiologic with a minimum of 10 biopsies taken from visible lesions and
counterpart of a group of non-Hodgkin lymphomas (NHL) that are additional ones from macroscopically normal mucosa; the same
currently referred to as marginal zone lymphomas (MZLs). procedure should be repeated to assess treatment response. 11–17
Although MZLs share a common denomination, arising from Because endoscopic biopsies are not transmural, endoscopic ultra-
histologic similarities, new genetic findings and longer follow-up sound (EUS) is a useful way to assess the depth of involvement, which
studies have established that the currently recognized subtypes of has prognostic implications. 12–17 For head primaries, such as ocular
MZLs, initially described in the Revised European-American Lym- adnexal ENMZL, appropriate directed examination and imaging
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phoma (REAL) classification, are different diseases. In the most studies (CT or magnetic resonance) are indicated.
recent WHO classification of tumors of the hematopoietic and
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lymphoid tissues, these disorders comprise three distinct entities:
extranodal MZL of MALT type (ENMZL), splenic MZL (SMZL) STAGING OF MARGINAL ZONE LYMPHOMA
and nodal MZL (NMZL). Immunoproliferative small intestinal
disease (IPSID), formerly known as alpha heavy chain (or Seligmann) Imaging studies of the chest, abdomen, and pelvis, usually CT scans,
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disease, has been recently recognized as a variant of ENMZL. In should be obtained to adequately stage the disease. Positron emission
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aggregate, MZLs represent approximately 10% of all NHL. Clini- tomography (PET) scan has been increasingly used for staging and
cally, they behave indolently and have a prolonged course. Therefore, evaluation of response to therapy in NHL, but it may be less useful
management strategies share similarity with other low-grade lympho- in MZL because up to 60% of these lymphomas may be PET-
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mas, although specific biologic characteristics and particular patho- negative, especially in early-stage gastric ENZML. Some MZL
physiologic mechanisms determine unique therapeutic approaches in series, however, document a PET-positivity rate of up to 80%, 19–23
some of the subtypes. This chapter will summarize the clinical with better detection rates seen for head and neck and bronchial
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characteristics and current management strategies for the different versus gastric or ocular MZL. Also for staging and, occasionally, for
types of MZL. diagnostic purposes, bone marrow biopsy and aspirate are usually
advocated, even in cases in which the likelihood of systemic disease
is low, because any positive result has important implications for
INITIAL EVALUATION OF MARGINAL ZONE LYMPHOMA therapy.
Staging of MZL is similar to that of other lymphomas; the Ann
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As for other lymphomas, biopsy of an adequate amount of tissue with Arbor system, or an adapted version, is used most frequently (Table
review by a hematopathologist with expertise in the field is essential 79.1). Nonetheless, specific staging systems have been adopted for
to establish the diagnosis. Excisional or incisional biopsies of a lymph particular sites. Gastrointestinal MZL is often staged according to a
node or suspicious mass, obtained by endoscopic or conventional modified Ann Arbor scheme, commonly known as the Lugano
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means, are preferred. In patients without easily accessible nodes or staging system, which incorporates indices corresponding to depth
masses, computed tomography (CT) or ultrasound-guided core of mucosal invasion and proximity of affected lymph nodes to the
needle biopsy is usually well tolerated and may be adequate for primary lesion (see Table 79.1). Of note, the Lugano system has no
diagnosis. Fine-needle aspiration is not appropriate for diagnosis; stage III, and its stage IIE may refer to lesions that extend by contigu-
sufficient material must be obtained for proper histologic examina- ity to adjacent organs and not necessarily to secondary involvement
tion and required immunophenotypic and genetic studies. of lymph nodes. Recently, arguing that the dissemination patterns of
Physical examination with special attention to peripheral lymph extranodal lymphomas are essentially different from those of primary
nodes and the abdomen should be performed. Initial laboratory nodal lymphomas, the EGILS group has proposed a new staging
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evaluation should include a complete blood count (cytopenias may system (the Paris staging system) that is based on the TNM scheme
be evidence of marrow infiltration or of autoimmunity) with evalu- used for solid tumors (see Table 79.1). The International Society for
ation of a peripheral blood smear (to exclude leukemic involvement) Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task
and basic biochemical studies, including lactate dehydrogenase force of the European Organization of Research and Treatment of
(LDH) level, which is an important prognostic factor and a potential Cancer (EORTC) have also recently suggested a new, TNM-based
indicator of transformation from indolent to aggressive lymphoma. staging system for cutaneous lymphomas other than mycosis
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