Splenic Marginal Zone Cell Lymphoma Research Articles

Expression of LATS mRNA in mantle cell lymphoma and its clinical significance

To investigate the expression level of large tumor suppressor (LATS)1, LATS2 mRNA and its prognostic value in mantle cell lymphoma (MCL). A total of 36 B-NHL cases (including MCL 16 cases, chronic lymphoblastic leukemia (CLL) 11 cases, splenic marginal zone cell lymphoma (SMZL) 9 cases) and 8 healthy donors were enrolled in this study from January 2008 to April 2011 in our Lymphoma Clinic Center. The mRNA level of Yap (effector of Hippo pathway) and LATS1, LATS2 mRNA were detected by using real-time quantitative PCR. Log expression values of real-time quantitative PCR data were used in this analysis. The YAP mRNA expression level in MCL, CLL and SMZL patient were significantly higher than that in health donor (lg: 1.97±0.79, 1.83±0.54, 2.12±0.42 vs 1.21±1.56, all P<0.05). The expression level of LATS1, LATS2 mRNA in MCL was significantly correlated with molecular cytogenetic aberrations, progression free survival (PFS) and overall survival (OS). The LATS1 expression level was statistically lower in the group of MCL with delection P53 than the group of MCL without delection P53 (lg: 0.75±0.27 vs 1.10±0.19, P=0.035). And the LATS1 expression level was statistically lower in the death group than the survival group (lg: 0.76±0.27 vs 1.15±0.17, P=0.026). The PFS and OS were significantly longer in the MCL patients with high level of LATS1 than that of other MCL patients ((70.4±32.7) vs (5.6±2.2) months, P=0.044; (123.8±22.0) vs (7.7±2.2) months, P=0.017). Hippo pathway is dysfunctional in B-NHL, especially in MCL.The reduced expression of LATS1, LATS2 in MCL patients is associated with progressive disease, and might be an important prognostic factor in MCL.

Intrasinusoidal bone marrow infiltration and splenic marginal zone lymphoma: a quantitative study

Intrasinusoidal infiltration (ISI) is a pattern of invasion that is rarely found on bone marrow (BM) biopsies, and is considered as a hallmark of splenic marginal zone cell lymphoma (SMZL). We analysed BM biopsies showing intrasinusoidal infiltration from 54 consecutive patients with different types of lymphoma to verify if ISI quantity was a diagnostic criterion for SMZL. There were 35 primary splenic lymphoma (PSL) and 19 non-PSL; 28 SMZL, three non-splenic MZL, six mantle cell, six small lymphocytic, four follicular, four diffuse large B cell, one peripheral T cell, one lymphoplasmacytic and one anaplastic large-cell lymphoma. The quantity of BM infiltrate was assessed on CD45, CD20 and CD3 stained sections. The mean percentage of total (TI) and intrasinusoidal (ISI) lymphocytes was calculated in 10 areas for each case. TI quantity was 21.57 in PSL and 35.05 in non-PSL (P = 0.04). ISI quantity was 5.23 in PSL and 7.62 in non-PSL (P = 0.08), 5.83 in SMZL and 2.83 in other types of PSL (P = 0.12), 4.46 in non-splenic MZL and 8.21 in other types of non-PSL (P = 0.28). No difference in ISI quantity was found among the lymphoma subtypes, either in PSL (P = 0.74) or non-PSL (P = 0.3). The data demonstrate that ISI quantity in BM biopsies is not a reliable diagnostic parameter for SMZL.

A unique case of splenic marginal zone-cell lymphoma with synchronous clonal T-cell large granular lymphocyte proliferation: an immunologic, immunohistochemical and genotypic study

We describe a case of synchronous splenic marginal zone-cell lymphoma (SMZL) and T-cell large granular lymphocyte leukemia involving the spleen, liver, bone marrow and peripheral blood. The synchronous occurrence of these two processes was documented by morphological, immunophenotypical and molecular (PCR) analyses of all affected tissues. The pathogenetic mechanisms which may be responsible for the concomitant appearance of these two rather infrequent entities in the same anatomic sites are discussed.

Splenectomy influences bone marrow infiltration in patients with splenic marginal zone cell lymphoma with or without villous lymphocytes.

Splenic marginal zone cell lymphoma (SMZL) is a low grade B-cell lymphoma in which patients can have circulating villous lymphocytes and can show a peculiar intrasinusoidal bone marrow (BM) infiltration. Splenectomy is the reported treatment of choice for these patients. The objective of this study was to evaluate the effects of splenectomy on patients with BM lymphomatous infiltration. BM biopsies of 16 patients with SMZL were studied morphologically and immunohistochemically. In 12 patients, BM biopsies were taken before and after splenectomy. Four patients did not undergo splenectomy, and their BM biopsies were performed with an approximately 1 year interval. BM infiltration ranged from 10% to 40% of overall cellularity and was mostly of the intrasinusoidal type. After splenectomy, BM infiltration tended to become frankly nodular and showed an increase in tumor burden. Nonsplenectomized patients showed an unmodified picture. Splenectomy seems to induce important changes in patients with BM infiltration, probably through the lack of microenvironmental factors on circulating cells. These effects suggest reconsidering the role of splenectomy in the treatment of patients with SMZL.

The product of the t(ll;18), an API2-MLT fusion, is an almost exclusive finding in marginal zone cell lymphoma of extranodal MALT-type

BackgroundExtranodal marginal zone cell lymphoma (MZCL) of MALT-type share similar features with nodal and splenic MZCL regarding morphology and immunopheno-type. At the genetic level, recent cytogenetic studies have shown that t(ll;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(ll;18) in a large series of nodal, splenic and extranodal MALT-type MZCL, using a sensitive real-time RT-PCR method. Materials and methodsNinety-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(l1;18) was performed on RNA extracted from frozen tissue sections. ResultsThe 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. ConclusionsWhile 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(ll;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.

Poor prognosis in non-villous splenic marginal zone cell lymphoma is associated with p53 mutations.

We have recently reported a series of 15 non-villous splenic marginal zone lymphoma patients, six of whom showed p53 mutations (40%). This molecular alteration did not correlate with any particular clinico-pathologic feature at diagnosis. After a median follow-up of 56 months, four cases evolved into aggressive fatal non-Hodgkin's lymphoma (NHL) and two had refractory progressive disease; interestingly, p53 mutations were demonstrated in five of these patients at diagnosis. As the patients with wild-type p53 presented responsive or indolent disease, this genetic alteration may be an early marker of aggressive transformation or refractoriness. p53 evaluation at diagnosis could be advisable in this particular subset of NHL.

Marginal Zone B-Cell Lymphomas Including Mucosa-Associated Lymphoid Tissue Type Lymphoma (MALT), Monocytoid B-Cell Lymphoma and Splenic Marginal Zone Cell Lymphoma and Their Relation to the Reactive Marginal Zone

The marginal zone of the B follicle represents a well-defined compartment of the B area. Its cellular composition is distinct from that of the follicle centre, from which it also differs in its functional role in the immune response. Several newly identified lymphoma entities, e.g. extranodal MALT type lymphoma, nodal monocytoid B-cell lymphoma and splenic marginal zone B-cell lymphoma, display in common a very peculiar organoid growth pattern reminiscent of the marginal zone. Moreover, their neoplastic components share morphologic and phe-notypic similarities to the cellular components of the marginal zone. The clinical characteristics of these various marginal zone cell lymphomas may differ depending of the organ which is involved. Nevertheless, they all share common cytogenetic abnormalities suggesting a common pathogenesis.

Follicular lymphoma with involvement of the splenic marginal zone: A pitfall in the differential diagnosis of splenic marginal zone cell lymphoma

Follicular lymphomas (FL) involving the spleen arise in and expand the germinal centers of the white pulp, whereas mantle cell lymphomas arise in the mantle zone and surround the benign germinal center. The recently described marginal zone cell lymphoma (MZCL) is a B-cell neoplasm characterized by concentric expansion of cells around the follicle, with or without infiltration of the mantle zone or germinal center. In addition, the immunoglobulin heavy chain gene is rearranged although none of the MZCL reported have been shown to be positive for the bcl-2 gene translocation by molecular studies. We report a patient with FL showing preferential involvement of the marginal zone of spleen morphologically mimicking a primary splenic MZCL. The patient reported here had a well-documented previous lymph node diagnosis of FL. The immunoglobulin heavy chain gene and bcl-2 gene rearrangement analysis confirmed the clonal origin of both the original FL, as well as the lymphoma, with a marginal zone pattern in the spleen.

Splenic Marginal Zone Cell Lymphoma:An Immunophenotypic and Molecular Study of Five Cases

Splenic marginal zone cell lymphoma (SMZCL) is a recently described clinicopathologic entity, that is reported to overlap with splenic B-cell lymphoma with villous lymphocytes. The authors describe the clinicopathologic, immunophenotypic, and molecular findings in five cases of SMZCL. There were two males and three females, with a mean age of 68.4 years, who presented with peripheral blood cytopenias and splenomegaly. One patient had an absolute lymphocytosis with many villous lymphocytes. With clinical follow-up of 9 to 37 months, two patients are alive and three patients died of unrelated causes. Splenectomy was done in each patient and the spleens were large, 970-2,400 g. Histologically, the SMZCLs preferentially replaced the marginal and mantle zones with partial or complete replacement of germinal centers in the white pump. The neoplastic cells were predominantly small to medium in size with oval or slightly irregular nuclei and relatively abundant pale or eosinophilic cytoplasm. Immunophenotypic studies demonstrated that the neoplastic cells expressed monotypic immunoglobulin, IgD in four tumors, pan-B-cell antigens, and bcl-2. The tumor cells were negative for the CD2, CD3, CD5, CD10, CD11c, CD25, CD35, CD38, CD45RO, and CD68 antigens, and tartrate-resistant acid phosphatase. Southern blot hybridization revealed immunoglobulin gene rearrangements in all tumors. The major breakpoint region of the bcl-2 gene and the T-cell receptor beta chain gene were in the germline configuration. Polymerase chain reaction studies did not identify the t(14;18) or t(11;14). All cases were negative for p53 protein and single-stranded conformational polymorphism analysis for p53 gene mutations was negative. Our results support the concept that SMZCL is a clinically indolent, low grade B-cell lymphoma that probably arises from splenic marginal zone lymphocytes.

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

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.