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The splenic marginal zone lymphoma is a special type of lymphoma that has undergone several classification changes within the past years. Currently, the International Lymphoma Study Group (ILSG) classifies this lymphoma with lymphomas of the extranodal MALT type and nodal lymphomas of the monocytoid B-cell type.

The spleen has a marginal zone which is easily visualized in normal conditions, unlike the lymph node and other extranodal organs. These patients typically present with splenomegaly with frequent involvement of the peripheral blood, liver, and bone marrow.


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INCIDENCE Probably the most common small B-cell lymphoma of the spleen
AGE Usually >50 years


Autoimmune hemolytic anemia  
Splenic Marginal Zone Lymphoma With Micronodular T-Cell Rich B-Cell Lymphoma.

Wang SA, Olson N, Zukerberg L, Harris NL.

From the *Department of Pathology, Massachusetts General Hospital, Boston, MA; and daggerDepartment of Pathology, Kaiser Permanente Health System, Portland, OR.

Am J Surg Pathol. 2006 Jan;30(1):128-132. Abstract quote  

The types of B-cell lymphoma commonly involving the spleen include splenic marginal zone lymphoma and T-cell/histiocyte-rich large B-cell lymphoma. We describe a unique case of splenic marginal zone lymphoma associated with micronodular T cell/histiocyte-rich large B-cell lymphoma in the red pulp, a combination that has not previously reported in the literature.


Marginal zone cell These lymphocytes are post-follicular memory B-cells, derived from recirculating cells after specific stimulation by T-cell dependent antigen

Splenic marginal zone lymphomas presenting with splenomegaly and typical immunophenotype are characterized by allelic loss in 7q31-32.

Boonstra R, Bosga-Bouwer A, van Imhoff GW, Krause V, Palmer M, Coupland RW, Dabbagh L, van den Berg E, van den Berg A, Poppema S.

Departments of Pathology and Laboratory Medicine, University Medical Center Groningen, The Netherlands.
Mod Pathol. 2003 Dec;16(12):1210-7. Related Articles, Links

Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin's lymphoma that recently has been recognized as an entity.

The first goal of this study was to identify potential chromosomal aberrations in this entity by cytogenetic analysis and comparative genomic hybridization (CGH). The second goal was to assess the frequency of 7q31-32 allelic imbalances in SMZL with primary involvement of the spleen and the typical immunophenotype (IgM+; IgD(dim); and CD5-, CD10-, and CD23-). We applied CGH and cytogenetics to 13 cases of SMZL with primary splenic involvement. By CGH, we found DNA copy number changes in 11 of 13 cases. Overall chromosomal gains were more frequent than chromosomal losses. Gains were most frequently detected for chromosome X, chromosome 3, and chromosome 18. Losses commonly involved chromosome 7 and chromosome 6.CGH and cytogenetic analysis showed a deletion in chromosome 7q31 in 4 cases. Loss of heterozygosity (LOH) analysis using three microsatellite markers located at 7q31 revealed LOH in 9 cases. Remarkably, 2 of the 4 cases that lacked a 7q31 deletion had an atypical immunophenotype because they were partially CD23 positive. The other 2 cases were not informative.

The findings indicate that SMZL with primary splenic presentation and the typical IgM+, IgDdim, CD5-, CD10-, CD23- immunophenotype is characterized by the presence of deletions in chromosome 7q31-32.

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.

Maes B, Baens M, Marynen P, De Wolf-Peeters C.

Department of Pathology, University of Leuven, Belgium.

Ann Oncol 2000 May;11(5):521-6 Abstract quote

BACKGROUND: Extranodal marginal zone cell lymphoma (MZCL) of MALT-type share similar features with nodal and splenic MZCL regarding morphology and immunophenotype. At the genetic level, recent cytogenetic studies have shown that t(11;18) is a recurring abnormality in extranodal MALT-type MZCL but has hitherto never been reported in nodal or splenic MZCL. The aim of the present study was to determine the prevalence of t(11;18) in a large series of nodal, splenic and extranodal MALT-type MZCL, using a sensitive real-time RT-PCR method.

MATERIALS AND METHODS: Ninety-three MZCL cases were divided on clinical grounds into 61 extranodal MALT-type, 19 splenic and 12 nodal MZCL. One case that presented with a massive splenomegaly but for which also gastro-intestinal localisations were found, was left unclassified. A real-time RT-PCR method for the detection of the API2-MLT fusion resulting from t(11;18) was performed on RNA extracted from frozen tissue sections.

RESULTS: The API2-MLT fusion was detected in 12 cases, which were all extranodal MALT-type lymphomas of the stomach, except for one case. The remaining positive case was the unclassified case, for which the translocation was detected in the spleen and in hilar lymph node tissue.

CONCLUSIONS: While similarities between MZCL from different anatomic sites have lend us to propose that all MZCL have a common normal counterpart, the almost exclusive detection of t(11;18) in gastric MALT-type lymphoma favours its recognition as a separate lymphoma entity. The absence of the translocation in nodal and splenic MZCL challenges the idea of these lymphomas being secondary to MALT-type lymphomas of the gut. The unclassified case illustrates the inadequate approaches available at present to identify and define the various MZCL.

A novel recurrent translocation t(11;14)(p11;q32) in splenic marginal zone B cell lymphoma.

Cuneo A, Bardi A, Wlodarska I, Selleslag D, Roberti MG, Bigoni R, Cavazzini F, De Angeli C, Tammiso E, del Senno L, Cavazzini P, Hagemeijer A, Castoldi G.

Dipartimento di Scienze Biomediche e Terapie Avanzate, University of Ferrara, Italy.

Leukemia 2001 Aug;15(8):1262-7 Abstract quote

A novel recurrent translocation t(11;14)(p11;q32) was found in three patients with splenic marginal zone B cell lymphoma (MZBCL).

Fluorescence in situ hybridization (FISH) studies with IgH probes revealed in all cases involvement of the IgH locus, with breakpoint downstream of the IGVH sequences. Partner genes at 11p11 were not identified. The translocation defined the stem line in two patients, who carried additional cytogenetic aberrations, including a 17p deletion, present in both cases. In one patient a 7q- chromosome was the primary cytogenetic defect, the t(11;14) having been found in four out of 11 abnormal metaphase cells at the time of transformation into high-grade MZBCL. Hematological features in all cases included splenomegaly with peripheral blood (PB) involvement by a monoclonal B cell population consisting of lymphocytes with villous projections and several blast-like cells. The immunophenotype was CD19+; CD22bright+; CD23-, CD10-, CD5-, surface Igbright+. A bone biopsy in one patient revealed an interstitial infiltration with an intrasinusoidal pattern of growth. Histological studies on spleen specimens in two patients showed an expanded marginal zone, with small lymphocytes and several blast-like cells. One patient had a therapy-demanding disease, with partial, short-term responses to cytotoxic treatment; one patient transformed into a high-grade MZBCL involving the gut, the PB and the bone marrow 2 years after diagnosis; one patient was unresponsive to cytotoxic treatment and underwent splenectomy.

The t(11;14)(p11;q32) may define a subset of splenic MZBCL with a high-grade component and a relatively aggressive clinical behavior.


GENERAL Micronodular appearance
Splenic Marginal-zone Lymphoma: One or More Entities? A Histologic, Immunohistochemical, and Molecular Study of 42 Cases.

*Hemopathology Department, Evangelismos Hospital, Athens daggerHematology Department and Hematopoietic Cell Transplantation Unit, G. Papanicolaou Hospital, Thessaloniki double daggerHematology Department section signPathology Department, Nikea General Hospital, Piraeus, Greece.


Am J Surg Pathol. 2007 Mar;31(3):438-446. Abstract quote

We analyzed 42 splenic marginal-zone lymphoma (SMZL) cases diagnosed on splenectomy specimens after established World Health Organization criteria. A predominantly nodular growth pattern was observed in 24 cases; the remainder showed predominantly (11/42) or exclusively (7/42) diffuse infiltration.

Twenty-one cases showed the "classic" biphasic appearance; 13 cases exhibited marginal-zone morphology; finally, 8 cases were composed predominantly of small cells. CD21 and CD35 were expressed by 12/42 and 17/38 cases, respectively. DBA.44 was detected in 24/42 cases. Seventeen of 37 cases were surface IgD (SIgD)-positive. Twenty-one of 22 analyzed cases were SIgM-positive (12/21 coexpressed SIgD). Five of 37 cases were SIgG-positive. CD27 staining was observed in 21/35 cases; 7/18 CD27-positive cases coexpressed SIgD; 7/14 CD27-negative cases were SIgD-positive. Forty IGHV-D-J rearrangements were amplified in 34/42 cases: the IGHV4-34 gene predominated, followed by IGHV1-2. Using the 98% homology cut-off, 25/40 (62.5%) IGHV sequences were considered as "mutated": 10/11 cases with monomorphous, marginal-zone morphology were IGHV-mutated; in contrast, 4/6 cases with monomorphous, small-cell morphology were IGHV-unmutated. Five of 7 cases expressing IGHV1 subgroup genes had biphasic morphology, whereas 6/9 IGHV3-expressing cases had monomorphous, marginal-zone morphology. Most IGHV-mutated cases (14/20; 70%) were SIgD-negative; in contrast, 8/11 IGHV-unmutated cases expressed SIgD. CD27 was detected in 10/17 IGHV-mutated and 6/10 IGHV-unmutated cases. Seven of 11 CD27-negative cases were IGHV-mutated; 5/7 CD27-negative/IGHV-mutated cases expressed DBA.44.

These results confirm the considerable histologic, immunohistochemical, and molecular heterogeneity of SMZL and indicate an origin from the diverse resident B-cell populations of the normal SMZ.

Splenic Marginal Zone Lymphoma
A Case Report and Review of the Literature

Peter L. Depowski, MD, Harry Dunn, MD, Sheila Purdy, MD, Jeffrey S. Ross, MD, and Tipu Nazeer, MD

From the Departments of Pathology and Laboratory Medicine (Drs Depowski, Purdy, Ross, and Nazeer) and Hematology and Oncology (Dr Dunn), Albany Medical College, Albany, NY

Arch Pathol Lab Med 2002;Vol. 126, No. 2, pp. 214–216. Abstract quote

Splenic marginal zone lymphoma is a recently described primary splenic lymphoproliferative disorder that mainly affects older individuals.

We report the case of a 22-year-old woman with morphologic and immunophenotypic findings consistent with splenic marginal zone lymphoma. This woman is one of the youngest patients ever described with this disease. The patient presented with complaints of left-sided abdominal fullness and was noted to have splenomegaly on physical examination. Laboratory evaluation revealed pancytopenia and a serum M component. The spleen was removed and weighed 1550 g.

Histology showed prominent white pulp with an expanded marginal zone. The neoplastic cells were marginal zone–type cells with small to intermediate-sized nuclei with occasional conspicuous nucleoli and moderate amounts of pale to amphophilic cytoplasm. Immunophenotypic analysis revealed a B-cell population (CD20 positive) with -light-chain restriction.

The patient was treated with adjuvant therapy, but developed progressive disease less than 2 years after initial diagnosis.



Marginal zone is an area of lighter staining zone that surrounds the follicles of the sleen

Neoplastic lymphocytes may have a variety of morphology including:

Extension to bone marrow and liver is frequent

Term marginal zone may be a misnomer:

Lack of preserved mantle zone in the involved lymphoid nodules in the spleen, not in the marginal zone compartment
Neoplastic cells not confined to marginal zone
Biphasic cytology with significant population of small neoplastic cells lacking splenic marginal zone morphology
Histologic, immunophenotypic and cytogenetic features dissimilar from other marginal zone B-cell lymphomas

Comparative Study of Marginal Zone Lymphoma Involving Bone Marrow

Sara A. Kent, MD, Daina Variakojis, MD, and LoAnn C. Peterson, MD

Am J Clin Pathol 2002;117:698-708 Abstract quote

Few studies have characterized or compared the pathologic features of bone marrow involvement by extranodal (EMZL), splenic (SMZL), and nodal marginal zone lymphoma (NMZL).

We evaluated 45 bone marrow biopsy specimens from 39 patients with marginal zone lymphomas. As previously reported, bone marrow involvement was frequent (100%) in patients with SMZL. We also identified lymphoma involving bone marrow in 11 (44%) of 25 patients with EMZL and 1 of 2 patients with NMZL. The patterns of infiltration were mixed in all groups; however, the extent of involvement was greater in SMZL than in EMZL. In addition, germinal centers were present in bone marrow biopsy specimens involved by lymphoma in 4 patients with SMZL. Intrasinusoidal infiltration was common (10/12 [83%]) and prominent in patients with bone marrow involvement by SMZL, but was not invariably present.

Intrasinusoidal infiltration of the bone marrow also was not specific for SMZL since similar infiltrates, although subtle, also were found in patients with other small B-cell lymphoproliferative disorders, including 6 (55%) of 11 patients whose bone marrow samples were infiltrated by EMZL.

PERIPHERAL BLOOD Villous lymphocytes may be present

Splenic marginal zone cell lymphoma.

Schmid C, Kirkham N, Diss T, Isaacson PG.

Department of Histopathology, University College & Middlesex School of Medicine, London, England.

Am J Surg Pathol 1992 May;16(5):455-66 Abstract quote

We describe four female patients with primary splenic low-grade non-Hodgkin's B-cell lymphomas with the morphology and immunophenotype of splenic marginal zone lymphocytes.

The patients presented with splenomegaly, anemia, and weight loss. The bone marrow was involved in all four cases. Liver involvement was found in one patient; and in another, a CT scan revealed lymphadenopathy in the chest and abdomen.

The histology of the spleen was characterized by broad concentric strands of monomorphic medium-sized lymphocytes around lymphoid follicles in one case and infiltrating follicles in two cases. Selective replacement of follicles was seen in one case. Tumor in splenic hilar lymph nodes (four cases) and liver (one case) was similar. Three patients remain well 4, 9, and 12 months, respectively, after splenectomy without further treatment. One patient who received chemotherapy died 1 year after splenectomy.

Splenic marginal zone lymphoma: a distinctive type of low-grade B-cell lymphoma. A clinicopathological study of 13 cases.

Mollejo M, Menarguez J, Lloret E, Sanchez A, Campo E, Algara P, Cristobal E, Sanchez E, Piris MA.

Department of Pathology, Hospital Virgen de la Salud, Toledo, Spain.

Am J Surg Pathol 1995 Oct;19(10):1146-57 Abstract quote

The recognition and classification of the different varieties of splenic low-grade B-cell lymphomas have been hampered by the rarity of histological studies of surgical splenectomy specimens of B-cell lymphoma.

In an effort to characterize the recently described splenic marginal zone lymphoma (SMZL), we conducted a survey of 13 patients with this type of tumor using the criteria defined by Schmid for its recognition (Schmid et al., Am J Surg Pathol 1992;16:455-66). Primary splenic high-grade lymphomas, T-cell lymphomas, and secondary infiltration by other recognized low-grade B-cell lymphomas, with the exception of splenic lymphoma with villous lymphocytes, were excluded. This selection gave rise to a homogeneous group of tumors with similar clinical, histological, immunohistochemical, and molecular features. Our study showed the critical parameters for their recognition to be morphological, including macroscopic micronodularity and the constant presence of white- and red-pulp infiltration, marginal zone pattern, and plasmacytic differentiation. No t(14;18) or PRAD-1/cyclin D1 overexpression was detect able in any case.

Clinically, the tumors were widespread with a protracted evolution. Nodal infiltration by SMZL in our cases was morphologically similar to monocytoid B-cell lymphoma. SMZL could constitute the largest group of primary splenic malignant lymphomas, partially overlapping with splenic lymphoma with villous lymphocytes. Specific molecular markers for SMZL have yet to be defined.

Because of the limited number of cases, the question of therapy for this group of lymphomas must remain open for the future.

Splenic marginal zone lymphoma. A distinct B-cell neoplasm.

Hammer RD, Glick AD, Greer JP, Collins RD, Cousar JB.

Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Am J Surg Pathol 1996 May;20(5):613-26 Abstract quote

The splenic marginal zone is a morphologically and perhaps immunologically distinct B-cell compartment. Lymphomas arising from cells of the splenic marginal zone are rare.

Here we describe the morphologic, immunologic, and clinical features of 14 cases. Patient age ranged from 35 to 79 years (median, 68 years) with a male-to-female ratio of 1:1.8. The spleen was uniformly enlarged (median, 1,540 g; range, 388-3,845 g) in all patients, the neoplastic infiltrate had a nodular pattern in three cases, nodular and diffuse in seven cases, and diffuse in four cases. The neoplastic cells had small to medium-sized nuclei with round, oval, or slightly indented contours, small eosinophilic nucleoli, and a moderate amount of pale cytoplasm. Extrasplenic involvement was present in 12 patients. Lymph nodes often had a vaguely nodular pattern and preservation of sinuses; bone marrow was infiltrated focally (seven cases) or diffusely (one case). Five patients had hepatic involvement. Ultrastructurally, neoplastic cells differed from other small B cells and resembled normal marginal zone cells by having long, serpentine rough endoplasmic reticulum profiles. All lymphomas marked as B cells and light chain restriction was demonstrated in 12 cases. Bcl-2 protein expression was present in all cases. Most cases (70%) were negative for DBA.44 (CD72). Plasmacytic differentiation was present in three cases.

In conclusion, splenic marginal zone lymphoma is a B-cell neoplasm with distinctive clinical, morphologic, immunologic, and ultrastructural characteristics.


Splenic marginal zone cell lymphoma: report of an indolent variant without massive splenomegaly presumably representing an early phase of the disease.

Rosso R, Neiman RS, Paulli M, Boveri E, Kindl S, Magrini U, Barosi G.

Department of Pathology, University of Pavia, Italy.

Hum Pathol 1995 Jan;26(1):39-46 Abstract quote

Splenic marginal zone (MRZ) cell lymphoma is a recently described neoplasm arising in a unique compartment of splenic white pulp, producing massive splenomegaly and spreading to bone marrow and distant lymph nodes.

We report three cases of splenic lymphoma that morphologically and immunohistochemically appear to originate from MRZ cells that presented as indolent neoplasms involving the spleen but with no or only moderate enlargement of the organ, presumably representing an early clinical stage of this disorder. Despite the evidence of involvement of the liver in one case, lymph nodes and bone marrow proved to be uninvolved.

Histologically, the three spleens showed similar features, being characterized by the involvement of white pulp follicles and periarteriolar lymphoid sheaths by medium-sized lymphoid cells with slightly irregular nuclei and ample cytoplasm. Immunohistochemically, all the specimens expressed a series of B-lineage markers that, in contrast to specimens of monocytoid B cell lymphoma (MBCL) and hairy cell leukemia (HCL) studied for comparison, did not react with KiB3, LN1, and DBA.44 monoclonal antibodies.

Splenic Marginal Zone Lymphoma With or Without Plasmacytic Differentiation

Jean-Paul Duong Van Huyen, M.D.; Thierry Molina, M.D., Ph.D.; Alain Delmer, M.D.; Josée Audouin, M.D.; Agnés Le Tourneau, M.D.; Robert Zittoun, M.D.; Alain Bernadou, M.D.; Jacques Diebold, M.D.

From the Departments of Pathology (J.-P.D.V.H., T.M., J.A., A.L.T., J.D.), Hematology (A.D., R.Z.), and Oncology (A.B.), Hôtel Dieu, AP-HP, Paris, France.

Am J Surg Pathol 2000;24:1581-1592 Abstract quote

We report a series of 31 cases of splenic marginal zone lymphomas with an enlarged spleen and a multimicronodular macroscopic pattern.

Two groups, A and B, were distinguished based on the presence (A) or absence (B) of a lymphoplasmacytic component with monoclonal immunoglobulin expression in the cytoplasm.

There were no differences between the groups as far as age, sex, spleen weight, and progression. The only difference was the presence in group A of a monoclonal serum component and autoimmune disorders, particularly autoimmune hemolytic anemia. In most cases in which a liver and/or bone marrow biopsy was performed, lymphomatous infiltration was detected. Seven cases had a seric monoclonal IgM of 5 g/L or more and liver or bone marrow infiltration, corresponding to the definition of Waldenström's macroglobulinemia. Lymphoma cells had a monocytoid, centrocytoid and, in group A, lymphoplasmacytic morphology. The lymphomatous cells were positive for CD20, CD45 RA, and bcl-2. They expressed IgD in 9 cases, partially in 6, and were negative for IgD in 9 of the 24 cases studied. Progression seems to be slow, with a long survival. Three patients presented with transformation into a large B-cell lymphoma, which was responsible for death in two patients.


Special stains  

Positive for:

IgD frequently positive


Hairy Cell Leukemia Variant
Fact or Fiction

Melissa H. Cessna, MD, etal.
Am J Clin Pathol 2005;123:132-138 Abstract quote

Hairy cell leukemia variant (HCL-V) is a poorly described, rare B-cell lymphoproliferative disorder typically positive for CD103 and CD11c, while lacking CD25. Splenic marginal zone lymphomas (SMZL) also have this unusual phenotype in 15% to 25% of cases, have other overlapping clinical or morphologic features, and are more common than HCL-V.

The purpose of our study was to better characterize HCL-V and determine whether most cases could be distinguished from SMZL. Cases with an HCL-V phenotype were identified from our flow cytometry service, and 10 were selected for further study based on bone marrow or splenic tissue availability. All cases had cytologic features consistent with HCL-V, and 9 of 10 patients had lymphocytosis. Bone marrow involvement was mostly interstitial and/or sinusoidal without lymphoid nodules. Coexpression of preswitched with postswitched heavy chain isotypes, an unusual feature of HCL, was seen in 2 of 4 cases.

This study better defines HCL-V and establishes that most cases do not represent SMZL.
Lymphoplasmacytoid immunocytoma This is a lymphoplasmacytoid variant of B-CLL expressing CD5
Marginal zone B-cell lymphomas Splenic tumors will:
Lack true marginal zone growth pattern
Frequent expression of IgD
Absence of t(11;18)
Histopathologic Features of Splenic Small B-Cell Lymphomas A Study of 42 Cases With a Definitive Diagnosis by the World Health Organization Classification

Rina Kansal, MD, Charles W. Ross, MD, Timothy P. Singleton, MD, William G. Finn, MD, and Bertram Schnitzer, MD
Am J Clin Pathol 2003;120:335-347 Abstract quote

We studied 42 cases of splenic small B-cell lymphoma (SBL) (21 women, 21 men; aged 32-82 years; median, 65 years) with a definitive diagnosis by the World Health Organization classification: chronic lymphocytic leukemia (CLL), 8; mantle cell lymphoma (MCL), 9; follicular lymphoma (FL), 12; marginal zone lymphoma, 13 (splenic [SMZL], 12; extranodal [EMZL], 1). Splenectomy was performed for diagnosis or therapy; splenic weights were 0.2 to 3.8 kg (median, 1.4 kg).

In general, splenic SBLs showed white pulp (WP) expansion; morphologic features of the nodules recapitulated the corresponding lymph node histopathologic features. "Marginal zones" were observed commonly in SMZL and FL, may be present in MCL involving the spleen, and may be seen in hilar lymph nodes (HLNs) in SBLs other than SMZL. FL may simulate SMZL and can be distinguished by the presence of neoplastic follicles and HLN morphologic features. Extracellular hyaline deposits (EH) are common in FL and SMZL.

MCL typically shows WP expansion by a monotonous small lymphocytic infiltrate, without diffuse red pulp (RP) infiltration or EH; leukemic MCL may show RP infiltration. Splenic morphologic features in CLL vary in WP or RP dominance; marginal zones usually are not observed in CLL.

Micronodular T-cell/Histiocyte-Rich Large B-cell Lymphoma of the Spleen: Histology, Immunophenotype, and Differential Diagnosis.

Dogan A, Burke JS, Goteri G, Stitson RN, Wotherspoon AC, Isaacson PG.

Am J Surg Pathol. 2003 Jul;27(7):903-11. Abstract quote

Occasionally, primary large B-cell lymphomas (LBLs) arising in the spleen present with a micronodular pattern involving the splenic white pulp but sparing the red pulp. Histologically, the nodules contain scattered large B cells in a background of numerous T cells and histiocytes. They can cause substantial difficulty in histologic diagnosis as the morphology can mimic reactive and inflammatory lesions as well as other lymphoid neoplasms.

In this study, we examined the histology and immunophenotype of the micronodular T-cell/histiocyte-rich LBL (MTLBL) of the spleen with a view to establish the characteristics that may be helpful in diagnosis. Paraffin-embedded material from 17 cases of MTLBL was studied. Clinical features and histology were reviewed and immunohistochemistry was performed for immunoglobulins, CD20, CD79a, CD3, CD68, CD10, BCL6, BCL2, OCT-2, epithelial membrane antigen, CD30, CD138, and EBV markers. The median age of presentation was 56 years, and the most frequent presenting features were anemia and B symptoms.

All cases showed a micronodular pattern of involvement. The tumor nodules comprised a mixture of numerous CD3+ T cells and CD68+ histiocytes and scattered large CD20+ B cells with immunoglobulin light chain restriction. They were positive for BCL6 and OCT2 but negative for CD10, CD138, and EBV markers. There was variable expression of epithelial membrane antigen, Bcl-2, and CD30. No follicle dendritic cell meshwork infrastructure underlying the nodules could be demonstrated by staining for CD21 or CD35 antigens. The prognosis was poor; seven of the 12 cases with follow-up were dead within 2 years. MTLBL is unique variant of T-cell/histiocyte-rich diffuse LBL, characterized by primary splenic presentation and a micronodular architecture. T

he main differential diagnoses include granulomatous inflammation, Hodgkin's lymphoma, follicular lymphoma, and peripheral T-cell lymphomas.



Indolent course with 10 year survival about 70%

May be occasional development of a large cell lymphoma

Splenic marginal zone lymphoma with increased number of blasts: an aggressive variant?

Lloret E, Mollejo M, Mateo MS, Villuendas R, Algara P, Martinez P, Piris MA.

Department of Pathology and Genetics, Hospital Virgen de la Salud, Toledo, Spain.

Hum Pathol 1999 Oct;30(10):1153-60 Abstract quote

Splenic marginal zone lymphoma (SMZL) is a recently described and distinctive type of splenic lymphoma and is characterized by an indolent clinical course.

By analyzing a large series of SMZL cases, we recognized the existence of a subset of 6 cases characterized by an aggressive clinical course that led to death caused by the tumor in 5 of 6 cases, whereas the remaining patient showed signs of tumor progression. The morphological, immunohistological, and molecular study of these cases has allowed us to detect precise distinctive features of this SMZL variant. The cases included here were characterized by massive splenomegaly and a morphological picture showing a micronodular pattern of splenic involvement with follicle replacement, biphasic cytology, and marginal zone differentiation. Unlike classical SMZL cases, a conspicuous component of larger lymphocytes was distributed in the marginal zone ring, occasionally overrunning it, with isolated presence of the same cells within the central small cell component and also in the red pulp. The bone marrow and peripheral lymph nodes showed similar histological findings to those described for SMZL in these locations. The genetic and molecular study of these cases showed no alterations specific to other lymphoma types, such as t14;18 and t11;14. Instead of this, it showed 7q loss in 3 of 5 cases, p53 inactivation in 2 of 6 cases, cyclinD1 overexpression in 2 of 6 cases, and the presence of translocations involving the 1q32 region in 2 of 4 cases.

The recognition of this aggressive variant, besides offering a prognostic indication, could lead to a more suitable form of clinical management of these patients. Further molecular studies would clarify the role of the different genetic alterations found.

Blastic transformation of splenic marginal zone B-cell lymphoma.

Cualing H, Steele P, Zellner D.

Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0529, USA.

Arch Pathol Lab Med 2000 May;124(5):748-52 Abstract quote

To our knowledge, blastic transformation of splenic marginal zone lymphoma, a recently characterized low-grade lymphoproliferative disorder, has not been reported previously.

In this regard, we report the unique case of a 70-year-old woman whose untreated splenic marginal zone lymphoma underwent blastic transformation 3 years after diagnosis. Her hematologic medical history started in 1988 as thrombocytopenia refractory to steroids associated with atypical lymphoid infiltrate in the bone marrow. She underwent splenectomy in 1989, which revealed splenic marginal zone lymphoma. One year later, the patient developed lymphadenopathy noted in the chest, axillary, abdominal, and retroperitoneal lymph nodes. Because she was asymptomatic, treatment was limited to a conservative supportive regimen. The nodal lymphoma cells had features associated with marginal zone lymphoma and expressed B-cell monotypic kappa light chain. She was readmitted for the last time 2 years later with findings of 16% blasts in the peripheral blood and massive infiltration of the bone marrow by large blastoid cells. The blasts showed dispersed chromatin and prominent nucleoli, and possessed a moderate amount of clear cytoplasm. The blasts, like the previous nodal and splenic lymphomas, had a CD20-, CD19-, IgM-positive phenotype, but lacked reactivity for CD5, CD10, and CD23. The patient displayed clinical remission after treatment with vincristine and prednisone, but died of aspiration pneumonia 1 month later.

These observations suggest that, similar to the other low-grade lymphoproliferative disorders, an untreated splenic marginal zone lymphoma may undergo high-grade blastic transformation.

Progression to Large B-Cell Lymphoma in Splenic Marginal Zone Lymphoma A Description of a Series of 12 Cases

Francisca I. Camacho, M.D.; Manuela Mollejo, M.D.; María-Sol Mateo, Ph.D.; Patrocinio Algara, Ph.D.; Concepción Navas, Ph.D.; Jesús-María Hernández, M.D.; Carlos Santoja, M.D.; Francesc Solé, M.D.; Margarita Sánchez-Beato, Ph.D.; Miguel A. Piris, M.D.

From the Molecular Pathology Program, Fundación Centro Nacional de Investigaciones Oncológicas Carlos III-CNIO (F.I.C., M.S.-B., M.A.P.), Madrid; Department of Pathology and Genetics, Hospital Virgen de la Salud (M.M., M.-S.M., P.A., C.N.), Toledo; Department of Hematology, Hospital Clínico (J.-M.H.), Salamanca; Department of Pathology, Hospital Universitario de Getafe (C.S.), Madrid; and Department of Cytology and Hematology (F.S.), Hospital del Mar, Barcelona, Spain.

Am J Surg Pathol 2001;25:1268-1276 Abstract quote

Splenic marginal zone lymphoma (SMZL) is considered to be an indolent extranodal B-cell lymphoma. Despite its low aggressivity, histologic progression has been described in sporadic reports, although the frequency, characteristics, and underlying molecular abnormalities of this phenomenon are largely unknown.

We review here the clinical, morphologic, immunohistochemical, and molecular features of a series of 12 SMZL cases that showed progression to large B-cell lymphoma (LBCL). The most frequent location of secondary LBCL was in peripheral lymph node. This occurred between 12 and 85 months after diagnosis of SMZL. However, in two cases LBCL was diagnosed at the initial stage of the disease (one spleen tumoral nodule and one hilar lymph node). The histologic and immunophenotypic features of these cases were similar to those of transformed LBCL at other sites. In four cases the immunoglobulin heavy chain gene polymerase chain study revealed the same rearrangement pattern in both primary and secondary tumors, thereby confirming their identity and excluding the possibility of a second malignancy. As is the case with other low-grade lymphoproliferative disorders, SMZL may undergo high-grade transformation. These 12 cases represent 13% of our series of SMZL with adequate follow-up. The incidence of large cell transformation in SMZL seems to be lower than in follicular lymphoma (25–60%) and mantle cell lymphoma (11–39%), although it is similar to the frequency of transformation in B-chronic lymphocytic lymphoma/small lymphocytic lymphoma (1–10%). The mean proliferative index (MIB1 staining) in initial SMZL specimens of cases with LBCL transformation was 28.6%, higher than that of MIB1 staining in the overall SMZL series (21.8%), although not statistically significantly so. p53 or p16 INK4a inactivation in this series was observed in only one case, in contrast with the situation observed in chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma.

It seems that progression in SMZL is mainly independent of p53 or p16 INK4a inactivation. The frequency of the 7q deletion in this series was 3 of 7 (42%). 7q loss may play an alternative role in the inactivation of the p53 and p16 INK4a pathway, thereby favoring tumoral progression.

Survival Slow progression of disease usually with long survival

Splenic marginal zone cell lymphoma involving liver and bone marrow. Report of a case with protracted follow-up, showing progressive disappearance of the lymphoma after splenectomy.

Rosso R, Castello A, Colosini G, Astori C, Lazzarino M, Magrini U.

Department of Pathology, University of Pavia, Italy.

Haematologica 1996 Jan-Feb;81(1):44-6 Abstract quote

We report the case of a 42-year-old man who presented with B-symptoms, moderate splenomegaly and multiple nodules in the liver.

Histologically, lymphocytic infiltrates were seen in the portal spaces and sinusoids of the liver and in the paratrabecular areas of the bone marrow. After excision, the spleen showed minimal disturbance of architecture with an expansion of the follicular marginal zones. These findings were considered inconclusive for lymphoma and the patient was treated only with non-steroidal anti-inflammatory drugs for persisting fever. Five months after splenectomy, a bone marrow biopsy still showed diffuse lymphoid infiltrates. From then on, the patient's condition improved with no further evidence of disease. Ten years after splenectomy the case was reconsidered as a splenic marginal cell lymphoma, indolent variant. Immunohistochemical and gene rearrangement studies demonstrated the monoclonality of the splenic proliferation, supporting the diagnosis. A further bone marrow biopsy did not detect residual lymphoid infiltrates.

This case confirms that splenic marginal zone cell lymphoma may have a deceptively favorable course, even when presenting at an advanced stage. Moreover, it indicates that extrasplenic localizations of the lymphoma may persist for a long while after splenectomy but may vanish over time without therapy.

TREATMENT Treatment of choice is splenectomy
Poor response to chemotherapy

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