Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (369 page)

   Additional karyotypic abnormalities are associated with a poor prognosis.

Suggested Readings

Ghielmini M, Zucca E. How I treat mantle cell lymphoma.
Blood.
2009;114:1469–1476.

Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with advancedstage mantle cell lymphoma.
Blood.
2008;111:558–565.

Perez-Galan P, Dreyling M, Wiestner A. Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era.
Blood.
2011;117:26–38.

MARGINAL ZONE LYMPHOMA (MZL)

   Definition

MZL includes three distinct entities that originate from memory B lymphocytes, normally present in the marginal zone of secondary lymphoid follicles: splenic MZL (±villous lymphocytes); extranodal MZL of mucosa-associated lymphoid tissue (MALT); and nodal MZL. These three lymphoma subtypes account for 5–17% of all non-Hodgkin lymphomas. They are clinically distinct.

   The first two types will be presented in this section.

A.   Splenic marginal B-cell lymphoma is an indolent lymphoma composed of small lymphocytes that surround and replace the splenic white pulp germinal centers. The condition may be associated with villous lymphocytes in the peripheral blood. Splenic hilar lymph nodes and the bone marrow are often involved.

B.   MALT lymphoma is a low-grade lymphoma originating in sites normally devoid of lymphoid tissues, such as stomach (the most prevalent), salivary glands, small bowel, lung, and thyroid. It is often preceded by chronic inflammation of the affected site or is associated with autoimmune diseases such as Sjögren syndrome and Hashimoto thyroiditis. Bacterial infection with
Helicobacter pylori
is associated with 92% of gastric MALT lymphomas. Usually, MALT presents as a localized disease.

   Who Should Be Suspected?

Splenic marginal B-cell lymphoma
: Elderly patients with abdominal discomfort due to splenomegaly, lymphocytosis, and cytopenias. Peripheral lymphadenopathy and involvement of extralymphatic organs–except bone marrow—are uncommon. The course is extremely indolent, but it has the potential to transform into a highgrade lymphoma.

MALT lymphoma: A patient (median age 60) with GI symptoms not otherwise diagnosed or with demonstrated
H. pylori
infection of the stomach and a gastric lesion. The majority of patients present with stage I or II disease.

   Laboratory Findings

Splenic B-Cell Marginal Zone Lymphoma

   
CBC
: Anemia, thrombocytopenia (both may have an autoimmune etiology), and neutropenia are commonly present; lymphocytosis is frequently present, but not essential for diagnosis. The lymphocytes have a round nucleus, condensed chromatin, and abundant basophilic cytoplasm with small surface “villous” projections. A combination of hemoglobin <12 g/dL, elevated LDH, and serum albumin <3.5 g/dL is predictive of short survival.

   
Coagulation
: PTT may be prolonged due to an acquired inhibitor, such as the lupus anticoagulant.

   
Bone marrow or lymph node biopsy
is indicated in the absence of diagnostic peripheral blood findings or available spleen histology. Bone marrow involvement may be mild and difficult to identify.

   
Immunophenotype
: The neoplastic lymphocytes express surface immunoglobulins (IgM or IgD), B-cell antigens (CD19, CD20, CD22), and BCL-2. They are CD5, CD10, CD43, CD23, CD25, and CD103 negative. Negative CD10 and BCL6 help exclude follicular lymphoma.

   
Cytogenetics and molecular genetics
: The majority of the patients show an abnormal karyotype; recurrent aberrations include gain of 3q and deletion of 7q22-36. Deletion of 17p is associated with an aggressive clinical course. A gene expression profile, different from other B-cell lymphomas, has been described.