Seminars in Diagnostic Pathology
Volume 20, Issue 2 , Pages 121-127, May 2003

Splenic marginal zone lymphoma

  • Ahmet Dogan, MD, PhD, MRCPath

      Affiliations

    • Department of Histopathology, University College London, London, United Kingdom
    • Corresponding Author InformationAddress reprint requests to Ahmet Dogan, MD, PhD, MRCPath, Department of Histopathology, Royal Free and University College Medical School, UCL Hospitals, Rockefeller Building, University St, London WC1E 6JJ, United Kingdom
    • ,
  • Peter G Isaacson, MB ChB, DM, DSc (FRCPath)

      Affiliations

    • Department of Histopathology, University College London, London, United Kingdom

Article Outline

Abstract 

Splenic marginal zone lymphoma (SMZL) is an indolent lymphoproliferative disease accounting for approximately 1% of all lymphomas. SMZL presents with marked splenomegaly, and often accompanied by circulating atypical ‘villous lymphocytes’ and is also known as splenic lymphoma with villous lymphocytes. Histologically, the spleen in SMZL is characterised by a nodular infiltrate based on pre-existing white pulp but also involving the red pulp. Within the white pulp, the infiltrate has a biphasic morphology comprising an inner zone of small lymphocytes and a peripheral (marginal) zone of larger lymphoid cells. Usually the splenic lymph nodes and bone marrow are also involved by a vaguely nodular infiltrate of similar nature. Immunophenotypically, the tumor cells has a mature B-cell phenotype and frequently express IgM and IgD but typically lack CD5, CD23, CD43, CD10, Bcl-6 and cyclin D1. Analysis of immunoglobulin heavy-chain gene variable regions suggest that some cases of SMZL arise form postfollicular B cells but others from naı̈ve B cells. Genetic studies have shown abnormalities of a number of chromosomes however 7q31-32 allelic loss appears to be characteristic. Histological differential diagnosis include a number of entities such as lymphoid hyperplasias, other marginal zone lymphomas, mantle cell lymphoma, follicular lymphoma, and B-CLL.

Keywords:  Spleen, marginal zone lymphoma, splenic lymphoma with villous lymphocytes

 

SPLENIC MARGINAL ZONE LYMPHOMA (SMZL) is a rare disease accounting for approximately 1% of all lymphomas1 and approximately 20% of lymphoproliferative disorders in diagnostic splenectomy specimens.2 SMZL was first described by Schmid et al3 as a low-grade B-cell lymphoma of the spleen characterised by a nodular infiltrate based on pre-existing white pulp follicles which were partly or completely overrun by the neoplastic cells. The tumor cells mimicked the morphology and immunophenotype of normal splenic marginal zone cells and the tumor was assumed to be arising from these cells. It soon became apparent that the clinical and morphological features of SMZL overlapped with another entity, splenic lymphoma with villous lymphocytes (SLVL), which was described a few years earlier.4, 5, 6, 7 SLVL was characterised by splenomegaly and moderate lymphocytosis comprising small, abnormal lymphocytes with thin, short, unevenly distributed villi. Isaacson et al8 reviewed the histological and immunophenotypic features SLVL cases and concluded that SLVL and splenic marginal zone lymphoma were one and the same entity. Splenic marginal zone lymphoma was provisionally recognized as a unique clinico-pathological entity in the Revised European American Lymphoma classification9 and has been included in the current World Health Organization (WHO) classification.1 The gold standard for diagnosis of SMZL remains the histological examination of the spleen rather than morphology and immunophenotype of the peripheral blood lymphocytes, as not every case is characterized by the presence of villous lymphocytes, and other B-cell lymphoproliferative disorders may show a similar peripheral blood picture.10

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Clinical features 

Splenic marginal zone lymphoma shows a slight predilection for men compared to women (M/F = 1.3).6, 7, 8, 10, 11, 12, 13 The age range is variable (24–95) but most series report a median or average age of 63–69.8, 10, 11, 12, 13 The patients typically present with splenomegaly, B-symptoms, abdominal pain, and cytopenias.11, 13 A low level of monoclonal paraprotein can be detected in approximately half of the patients.5, 7 Lymphocytosis and circulating villous lymphocytes are seen in only two thirds of the patients whereas in most there is involvement of the bone marrow.11, 13 Other sites occasionally affected include the liver and, rarely, the abdominal lymph nodes.11 SMZL has an indolent clinical course with a mean overall survival of 8.5 years and a 5-year survival rate of 65%.11

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Morphological features 

Peripheral blood cytology 

When the peripheral blood is involved, medium sized atypical lymphocytes are seen in peripheral blood smears. These usually account for more than 30% of all lymphocytes and appear larger than the cells of B-cell chronic lymphocytic leukemia (B-CLL). They often have round or oval nuclei with clumped chromatin and sometimes distinct nucleoli. There is often a moderate amount of cytoplasm with moderate degree of basophilia. However, the most striking feature is the presence of irregularities of plasma membrane consisting of thin short villi, which are typically unevenly distributed and polarised5, 6 (Fig 1). Although these appearances are characteristic of SMZL they are not by themselves diagnostic, as similar appearances can be seen in leukaemic phase of both follicular and mantle cell lymphoma.14, 15 Furthermore, in some cases peripheral blood cytology is indistinguishable from hairy cell leukemia or B-CLL.10

Spleen 

The spleen is massively enlarged weighing well over 1000 g in most cases. Macroscopically, the infiltration appears diffuse with no identifiable tumor masses.13 Microscopically, the most striking feature is a nodular infiltrate centred on the pre-existing white pulp lymphoid follicles3 (Fig 2). The tumor has a biphasic pattern with an inner core of small lymphocytes and an outer margin of medium sized lymphocytes1 (Fig 2). The inner central zone of small lymphocytes resembles normal mantle zone cells with scanty cytoplasm and small irregular nuclei, clumped chromatin, and indistinct nucleoli. In contrast, the lymphocytes occupying the marginal zone appear similar to normal SMZL. These have well-defined clear cytoplasm and round-oval nuclei with a more open chromatin pattern and indistinct nucleoli. Variable numbers of scattered transformed blasts with prominent nucleoli are also present in the marginal zone. Occasionally plasma cell differentiation within the marginal zone or in the center of the nodules can be observed.16 In some nodules, residual reactive germinal centers in the center of the nodules are seen however a well-defined mantle zone separating the tumor cells from the follicle center is absent.

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  • Fig 2. 

    SMZL, histological features (Hematoxylin-eosin). (A) Low power view showing marked marginal zone pattern. (B) Medium power view showing the central core of small lymphocytes (c), the larger cells occupying the marginal zone (MZ) and the red pulp infiltrate (RP). (C) High power view of the marginal zone component including occasional transformed blasts (arrow). (D) High power view of central small cell component. (E) High power view of red pulp involvement with intrasinusoidal infiltration. (F) Medium power view of bone marrow trephine biopsy showing nodular lymphoid infiltrate.

The reasons for the biphasic morphology of the same tumor clone are not known. The differences are likely to be a consequence of different signals present in different microenvironments of the follicle center and the marginal zone. This is analogous to follicular lymphoma where the neoplastic cells within the follicles have different morphological and immunophenotypic characteristics compared to those infiltrating the interfollicular areas.17

Red pulp infiltration is present to a varying degree in all cases. The majority of the cells in the red pulp comprise the small lymphocytic component and infiltrate the red pulp diffusely. Infiltration of sinuses is a prominent feature of most cases (Fig 2). Typically, there are also scattered small nodules of larger cells similar to those at the periphery of the follicles in the white pulp. In a minority of cases, diffuse red pulp infiltration can be so dense as to obscure the nodular white pulp component.

Lymph nodes 

The histological appearance of the splenic hilar lymph nodes is equally characteristic.18 The lymph node architecture is partially effaced by a nodular infiltrate of lymphocytes with preserved dilated sinuses. Occasional preserved germinal centres are present in the center of the nodules suggesting that, as in the spleen, they are the basis for the nodular pattern. Again, most follicles are completely or partly overrun by small lymphocytes but, unlike the spleen, a peripheral (or marginal) zone of larger cells is not characteristic although larger cells and some blasts may be mixed in within the smaller cells. When the peripheral lymph nodes are involved, the architecture is usually completely effaced and nodularity is only partly retained. The sinuses are less conspicuous and there is often capsular infiltration.

Bone marrow 

The bone marrow is involved in most cases including those with no evidence of peripheral blood involvement. Usually there is a nonparatrabecular nodular interstitial infiltrate of small lymphocytes similar to that seen in the lymph nodes13 (Fig 2). Occasionally reactive follicle centers, partially overran by the neoplastic cells, can be seen in the centers of the nodules. Intra-sinusoidal lymphoma cells are characteristic but may be difficult to detect in routinely stained sections.19

Other organs 

Liver is involved in approximately one fifth of patients.11 There is often a nodular infiltrate of small lymphocytes within the portal tracts but also in the parenchyma. Other nonhaematopoietic organs are rarely involved.

Large cell transformation of SMZL 

SMZL invariably contains a number of transformed cells within the marginal zone compartment. Increased numbers of blasts within the marginal zone but also in the central small cell compartment has been reported to be associated with clinically aggressive disease, although objective criteria for identification of these cases has not been established.20 Approximately 10% of SMZL cases progress to a large cell lymphoma after an average of 3 years after initial diagnosis. The histological and immunophenotypic features of the large cell lymphoma are similar to other diffuse large B-cell lymphomas. The transformation is mostly seen in the peripheral lymph nodes and appears to affect the prognosis adversely.

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Immunophenotype 

The immunophenotype of SMZL is relatively uniform in tissue sections. The tumor cells have a mature B-cell immunophenotype and to a large extent mimic the phenotype of normal splenic marginal zone cell. The immunophenotype of both phases, the inner core of smaller cells, and the larger cells occupying the marginal zone are identical. They express CD20, cytoplasmic monotypic immunoglobulin, and Bcl-2 but typically lack CD5, CD10, Bcl-6, CD23, CD43, and cyclin D18, 21, 22, 23 (Fig 3). In contrast to normal splenic marginal zone cells, which mostly express IgM but not IgD, the majority cases of the SMZL cases stain for both IgM and IgD and the rest for IgM only.10 CD21 highlights follicular dendritic cell meshwork underlying the white pulp nodules. When residual germinal centers are seen in the center of the white pulp nodules, these characteristically express germinal center B-cell differentiation markers CD10 and Bcl-6, show a high proliferation fraction, but lack Bcl-2 (Fig 3). Usually, the small cell component of the SMZL rims the residual follicle center replacing the ‘mantle zone’ and no residual IgD positive polytypic mantle zone cells separating the follicle center from the tumor cells are seen. The proliferation fraction of SMZL is low with most Ki67 positive cells located at the periphery of the nodules, in the marginal zone. When a residual germinal center is present this imparts a so-called ‘target’ pattern of proliferation to the infiltrate (Fig 3).

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  • Fig 3. 

    SMZL, immunophenotype (immunoperoxidase). (A) CD20: Both the white and red pulp are infiltrated by CD20+ cells. (B) Bcl-2: The tumor cells are positive for Bcl-2 whereas the central residual follicle center is negative. (C) Ki67: The proliferating cells are within the residual reactive follicle center or in the marginal zone, ‘Target pattern.’ (D) IgD: Both components of SMZL infiltrate are IgD+ whereas the central residual follicle center is negative. (E) Ig kappa light chain: Only some of the cells within the central residual follicle center are positive. (F) Ig lambda light chain: Both components of SMZL infiltrate and some of the cells within the central residual follicle center are positive.

Involved hilar lymph nodes and bone marrow show identical phenotypic features. In bone marrow biopsies, CD20 staining is very helpful in demonstrating intrasinusoidal distribution of tumor cells.

Flow-cytometric studies performed on circulating villous lymphocytes from cases defined as SLVL have shown a much more variable phenotype with expression of CD5 and even CD10 in many cases.24 The differences between the results of flow cytometry and immunohistochemistry can be partly explained by differences in immunophenotyping technique and, possibly, the compartment and microenvironment of the cells under study. However, because the detection of villous lymphocytes is somewhat subjective, it is conceivable that cases of SMZL defined on this basis as SLVL may have included other types of lymphoma with splenomegalic presentation and peripheral blood involvement.

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Genetics 

In keeping with light chain restriction demonstrated by immunophenotyping, SMZL shows monoclonal rearrangement of immunoglobulin heavy chain genes.3, 25 The sequence analysis of the immunoglobulin heavy chain gene variable regions (VH) have showed 2 distinct groups, one with germline, unmutated VH sequences consistent with a naı̈ve B-cell origin, and the other with mutated germline VH sequences consistent with a postfollicular/memory B-cell origin.10, 26, 27, 28 Interestingly, the latter group appears to correspond to the cases that express IgM but lack IgD and it has been suggested that these cases could have been derived from true marginal zone cells.10

Cytogenetic, comparative genomic hybridization and loss of heterozygosity studies of SMZL have shown diverse abnormalities in chromosomes 1, 3, 5, 7, 8, and 17.29, 30, 31 Amongst these 7q31-32 allelic loss is seen in 40% of these cases and appears to be specific for SMZL.32 This abnormality is seen more frequently in cases with germline, unmutated VH sequences. Chromosomal translocation characteristic of other lymphomas including t(11;14), t(14;18) or t(11;18) have not been reported in histologically defined cases of SMZL.33, 34, 35 Abnormalities of p53 is seen on approximately 10% of the cases and may be associated with high-grade transformation.36, 37

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Normal cell counterpart of SMZL and its relationship to other marginal zone lymphomas 

The normal cell counterpart of splenic marginal zone lymphoma is not currently known. The term “SMZL” was coined by Schmid et al3 who observed the morphological and immunophenotypic similarity between the outer marginal zone of the SMZL and normal splenic marginal zone. It later became apparent the tumor was biphasic and had an inner center of smaller cells.1, 8, 23 These smaller cells, unlike other marginal zone lymphomas, were not separated from the germinal center by a polytypic mantle zone and preferentially occupied the mantle zone and colonised the follicles. It was also realised that splenic follicular lymphomas or mantle zone lymphomas can show marginal zone differentiation, which is morphologically indistinguishable from the marginal zone component of the SMZL.22 This indicates that marginal zone phenotype, in isolation, can not be used to assign cell lineage. Furthermore most cases co-expressed IgD and IgM suggesting a naı̈ve (mantle zone?) B-cell origin. Analysis VH sequences, as described above, indicates that this entity may be originating 2 different B-cell subsets, one with memory B-cell features, the other with naive B-cell features.

The Revised European American Lymphoma (REAL) classification9 and the current WHO classification1 recognize 3 distinct entities as marginal zone lymphomas (MZL), nodal marginal zone lymphomas, extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) (MALT lymphoma), and SMZL. This is rather unfortunate and has lead to inclusion of these tumors as a single disease entity to several biological and clinical studies.30, 38 The clinical, morphological, immunophenotypic, and genetic features of these 3 entities strongly indicate these are 3 unique, biologically unrelated diseases and cannot be considered under 1 umbrella despite their shared terminology.

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Differential diagnosis 

The histological differential diagnosis of SMZL include a number of reactive and neoplastic conditions. The most important of these are reactive marginal zone hyperplasia, follicular lymphoma, mantle cell lymphoma, B-CLL, hairy cell leukemia, and MALT lymphoma. The differential diagnosis often requires examination of peripheral blood findings, histological features and immunophenotyping. The differential diagnosis of more common entities that cause difficulty in a clinical setting are summarized in Table 1, Table 2, others are discussed below.

Table 1. Histological Features Helpful in Differential Diagnosis of SMZL
SMZLFLMCLB-CLL
Peripheral blood involvementCommonInfrequentInfrequentCommon
Bone marrow involvementNodular, intrasinusoidalParatrabecularNodular, interstitialNodular, interstitial
Splenic involvementNodularNodularNodularDiffuse
Marginal zone differentiationAlwaysOccasionallyOccasionallyAbsent
Follicular colonisationFrequentAbsentFrequentAbsent
Red pulp infiltrationAlwaysFrequentFrequentAlways
Reactive folliclesFrequentAbsentOccasionallyRare
CytologyPolymorphic, biphasicFollicle centre cellsMonomorphousSmall lymphocytes, paraimmunoblasts

Abbreviations: SMZL, splenic marginal zone lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; B-CLL, B-cell lymphocytic lymphoma/chronic lymphocytic leukemia.

Table 2. Immunophenotypic Features Helpful in Differential Diagnosis of SMZL
SMZLFLMCLB-CLL
CD20++++
CD5−−++
CD43−−++
CD10−+−−
CD23−−/+−−
Bcl-6−+−−
Bcl-2++++
IgH expressionM+D, MG, M, M+D, AM+DM+D
Cyclin D1−−+−
Ki67Low, Target patternLow, FollicularLow-medium, Follicular and interstitialLow Proliferation, centers
CD21FDC++FDC+++FDC++FDC−/+

Abbreviations: SMZL, splenic marginal zone lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; B-CLL, B-cell lymphocytic lymphoma/chronic lymphocytic leukaemia; IgH, immunoglobulin heavy chain; FDC, follicular dendritic cells.

The differential diagnosis from reactive marginal zone hyperplasia is not usually difficult. In hyperplasia, the marginal zones are expanded and there could be significant mitotic activity within the marginal zone. However, the normal architecture is preserved, there is no red pulp involvement and the marginal zones are separated from the hyperplasic reactive follicle with a well-defined mantle zone. If necessary, immunohistochemistry can be used to confirm the reactive nature of the proliferation.

One of the most important differential diagnoses remains the hairy cell leukaemia, which may clinically, cytologically, and phenotypically mimic SMZL. However, on histological sections, the diagnosis is straightforward. There is a distinctive bone marrow infiltration pattern and splenic involvement is diffuse with extensive infiltration of the red pulp with formation of characteristic blood sinuses and effacement of normal white pulp.

Gastric MALT lymphoma often shows cryptic infiltration of the marginal zone yet microscopically identifiable tumor involvement is a relatively rare event and is not a problem in daily practice.39 In most cases, there is appropriate clinical history of MALT lymphoma elsewhere and, histologically, the tumor cells occupy the true marginal zone outside the polytypic mantle zone. The characteristic biphasic morphology of SMZL is not seen and red pulp infiltration is not apparent.

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References 

  1. Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organisation Classification of Tumors. Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissue. Lyon: IARC Press; 2001;
  2. Kraus MD, Fleming MD, Vonderheid RH. The spleen as a diagnostic specimen (A review of 10 years’ experience at two tertiary care institutions). Cancer. 2001;91:2001–2009
  3. Schmid C, Kirkham N, Diss T, et al.  Splenic marginal zone cell lymphoma. Am J Surg Pathol. 1992;16:455–466
  4. Spriano P, Barosi G, Invernizzi R, et al.  Splenomegalic immunocytoma with circulating hairy cells (Report of eight cases and revision of the literature). Haematologica. 1986;71:25–33
  5. Melo JV, Robinson DS, Gregory C, et al.  Splenic B cell lymphoma with “villous” lymphocytes in the peripheral blood (A disorder distinct from hairy cell leukemia). Leukemia. 1987;1:294–298
  6. Melo JV, Hegde U, Parreira A, et al.  Splenic B cell lymphoma with circulating villous lymphocytes (Differential diagnosis of B cell leukemias with large spleens). J Clin Pathol. 1987;40:642–651
  7. Mulligan SP, Matutes E, Dearden C, et al.  Splenic lymphoma with villous lymphocytes (Natural history and response to therapy in 50 cases). Br J Haematol. 1991;78:206–209
  8. Isaacson PG, Matutes E, Burke M, et al.  The histopathology of splenic lymphoma with villous lymphocytes. Blood. 1994;84:3828–3834
  9. Harris NL, Jaffe ES, Stein H, et al.  A revised European-American classification of lymphoid neoplasms (A proposal from the International Lymphoma Study Group). Blood. 1994;84:1361–1392
  10. Bahler DW, Pindzola JA, Swerdlow SH. Splenic marginal zone lymphomas appear to originate from different B cell types. Am J Pathol. 2002;161:81–88
  11. Chacon JI, Mollejo M, Munoz E, et al.  Splenic marginal zone lymphoma (Clinical characteristics and prognostic factors in a series of 60 patients). Blood. 2002;100:1648–1654
  12. Gruszka-Westwood AM, Hamoudi RA, Matutes E, et al.  p53 abnormalities in splenic lymphoma with villous lymphocytes. Blood. 2001;97:3552–3558
  13. Hammer RD, Glick AD, Greer JP, et al.  Splenic marginal zone lymphoma (A distinct B-cell neoplasm). Am J Surg Pathol. 1996;20:613–626
  14. Jadayel D, Matutes E, Dyer MJ, et al.  Splenic lymphoma with villous lymphocytes (Analysis of BCL-1 rearrangements and expression of the cyclin D1 gene). Blood. 1994;83:3664–3671
  15. Oscier DG, Matutes E, Gardiner A, et al.  Cytogenetic studies in splenic lymphoma with villous lymphocytes. Br J Haematol. 1993;85:487–491
  16. Van Huyen JP, Molina T, Delmer A, et al.  Splenic marginal zone lymphoma with or without plasmacytic differentiation. Am J Surg Pathol. 2000;24:1581–1592
  17. Dogan A, Du MQ, Aiello A, et al.  Follicular lymphomas contain a clonally linked but phenotypically distinct neoplastic B-cell population in the interfollicular zone. Blood. 1998;91:4708–4714
  18. Mollejo M, Lloret E, Menarguez J, et al.  Lymph node involvement by splenic marginal zone lymphoma (Morphological and immunohistochemical features). Am J Surg Pathol. 1997;21:772–780
  19. Labouyrie E, Marit G, Vial JP, et al.  Intrasinusoidal bone marrow involvement by splenic lymphoma with villous lymphocytes (A helpful immunohistologic feature). Mod Pathol. 1997;10:1015–1020
  20. Lloret E, Mollejo M, Mateo MS, et al.  Splenic marginal zone lymphoma with increased number of blasts (An aggressive variant?). Hum Pathol. 1991;30:1153–1160
  21. Dogan A, Bagdi E, Munson P, et al.  CD10 and BCL-6 expression in paraffin sections of normal lymphoid tissue and B-cell lymphomas. Am J Surg Pathol. 2000;24:846–852
  22. Piris MA, Mollejo M, Campo E, et al.  A marginal zone pattern may be found in different varieties of non-Hodgkin’s lymphoma (The morphology and immunohistology of splenic involvement by B-cell lymphomas simulating splenic marginal zone lymphoma). Histopathology. 1998;33:230–239
  23. Mollejo M, Menarguez J, Lloret E, et al.  Splenic marginal zone lymphoma: A distinctive type of low-grade B-cell lymphoma. A clinicopathological study of 13 cases. Am J Surg Pathol. 1995;19:1146–1157
  24. Matutes E, Morilla R, Owusu-Ankomah K, et al.  The immunophenotype of splenic lymphoma with villous lymphocytes and its relevance to the differential diagnosis with other B-cell disorders. Blood. 1994;83:1558–1562
  25. Wu CD, Jackson CL, Medeiros LJ. Splenic marginal zone cell lymphoma (An immunophenotypic and molecular study of five cases). Am J Clin Pathol. 1996;105:277–285
  26. Dunn-Walters DK, Boursier L, Spencer J, et al.  Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation. Hum Pathol. 1998;29:585–593
  27. Zhu D, Oscier DG, Stevenson FK. Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes. Blood. 1995;85:1603–1607
  28. Algara P, Mateo MS, Sanchez-Beato M, et al.  Analysis of the IgV(H) somatic mutations in splenic marginal zone lymphoma defines a group of unmutated cases with frequent 7q deletion and adverse clinical course. Blood. 2002;99:1299–1304
  29. Sole F, Woessner S, Florensa L, et al.  Frequent involvement of chromosomes 1, 3, 7 and 8 in splenic marginal zone B-cell lymphoma. Br J Haematol. 1997;98:446–449
  30. Dierlamm J, Pittaluga S, Wlodarska I, et al.  Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features. Blood. 1996;87:299–307
  31. Hernandez JM, Garcia JL, Gutierrez NC, et al.  Novel genomic imbalances in B-cell splenic marginal zone lymphomas revealed by comparative genomic hybridization and cytogenetics. Am J Pathol. 2001;158:1843–1850
  32. Mateo M, Mollejo M, Villuendas R, et al.  7q31-32 allelic loss is a frequent finding in splenic marginal zone lymphoma. Am J Pathol. 1999;154:1583–1589
  33. Dyer MJ, Zani VJ, Lu WZ, et al.  BCL2 translocations in leukemias of mature B cells. Blood. 1994;83:3682–3688
  34. Remstein ED, James CD, Kurtin PJ. Incidence and subtype specificity of API2-MALT1 fusion translocations in extranodal, nodal, and splenic marginal zone lymphomas. Am J Pathol. 2000;156:1183–1188
  35. Maes B, Baens M, Marynen P, et al.  The product of the t(11;18), an API2-MLT fusion, is an almost exclusive finding in marginal zone cell lymphoma of extranodal MALT-type. Ann Oncol. 2000;11:521–526
  36. Sol MM, Mollejo M, Villuendas R, et al.  Analysis of the frequency of microsatellite instability and p53 gene mutation in splenic marginal zone and MALT lymphomas. Mol Pathol. 1998;51:262–267
  37. Camacho FI, Mollejo M, Mateo MS, et al.  Progression to large B-cell lymphoma in splenic marginal zone lymphoma (A description of a series of 12 cases). Am J Surg Pathol. 2001;25:1268–1276
  38. Berger F, Felman P, Thieblemont C, et al.  Non-MALT marginal zone B-cell lymphomas (A description of clinical presentation and outcome in 124 patients). Blood. 2000;95:1950–1956
  39. Du MQ, Peng HZ, Dogan A, et al.  Preferential dissemination of B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma to the splenic marginal zone. Blood. 1997;90:4071–4077

PII: S0740-2570(03)00012-1

doi:10.1016/S0740-2570(03)00012-1

Seminars in Diagnostic Pathology
Volume 20, Issue 2 , Pages 121-127, May 2003

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