scholarly journals The histopathology of splenic lymphoma with villous lymphocytes

Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3828-3834 ◽  
Author(s):  
PG Isaacson ◽  
E Matutes ◽  
M Burke ◽  
D Catovsky
Keyword(s):  
Lymph Nodes ◽  
Marginal Zone ◽  
Molecular Characteristics ◽  
White Pulp ◽  
Splenic Marginal Zone Lymphoma ◽  
Mantle Zone ◽  
Marginal Zone B Cells ◽  
Splenic Lymphoma ◽  
Spleen And Lymph Nodes ◽  
Red Pulp

Whereas the hematologic, immunophenotypic, and molecular characteristics of splenic lymphoma with villous lymphocytes (SLVL) have been well documented, the histologic features of the spleen and lymph nodes remain uncharacterized. We have reviewed the histopathology of the spleen in 37 cases of SLVL and of involved splenic hilar lymph nodes in 6 cases. Tissue immunophenotyping was performed in 24 cases, 6 of which had frozen tissue available, and the results were compared with the membrane immunophenotype of the circulating villous lymphocytes and cells extracted from spleen and lymph nodes. In the spleen, SLVL is characterized by involvement of the white pulp follicles, which may be surrounded or replaced by the lymphoma cells. In the red pulp, the cells form small nodules and infiltrate diffusely with sinusoidal invasion. The cytologic appearance of the neoplastic cells varies from a resemblance to small mantle-zone--like lymphocytes to that of marginal-zone cells and there are scattered blast forms. In involved lymph nodes, the infiltrate again centers on the follicles that are usually replaced, but occasionally show preservation of follicle centers; sinuses are often preserved. The tissue immunophenotype is similar to that of marginal-zone B cells. Membrane immunophenotyping may give different results in some cases and may vary depending on the compartment from which the cells are obtained. SLVL in the peripheral blood is a histologically homogeneous entity identical to the condition previously characterised by histopathologists as splenic marginal-zone lymphoma.

scholarly journals Acetylcholinesterase (AChE) – Positive Innervation of the Guinea-Pig Spleen

2004 ◽  
Vol 47 (3) ◽  
pp. 205-208 ◽  
Author(s):  
Katarína Schmidtová ◽  
Mária Siroťáková ◽  
Monika Kočišová ◽  
Eva Mechírová
Keyword(s):  
Guinea Pig ◽  
Splenic Artery ◽  
Marginal Zone ◽  
Nerve Cells ◽  
Nerve Plexus ◽  
White Pulp ◽  
Nerve Fibres ◽  
Mantle Zone ◽  
Central Artery ◽  
Red Pulp

The presence and intraorgan distribution of the acetylcholinesterase (AChE)- positive nerve structures in the guinea-pig spleen were studied by means of the direct thiocholine method. Visualized AChE-positive nerve fibres entered the guinea-pig spleen at its hilum in the vicinity of the splenic artery branches and intra parenchyma were gradually distributed to form thicker periarterial nerves and also fine adventitial nerve plexus. In described topography the AChE-positive nerve fibres were identified in association with the central artery running through the white pulp. Some of the perivascular nerve fibres associated with the central artery extended away and passed into the periarterial lymphatic sheath (PALS) to reach the marginal zone and in continuation entered into the mantle zone of lymphatic follicles. Several AChE-positive nerve fibres were seen in the red pulp but less in the splenic capsule. We did not find any AChE – positive nerve cells in the guinea-pig spleen.

scholarly journals The role of spleen macrophages in malaria: an ultrastructural study

1984 ◽  
Vol 17 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Carlos Eduardo Tosta ◽  
Greta Ruiz ◽  
Nina Wedderburn
Keyword(s):  
Ultrastructural Study ◽  
Plasmodium Berghei ◽  
Marginal Zone ◽  
White Pulp ◽  
Limited Extent ◽  
Phagocytic Cells ◽  
Mantle Zone ◽  
Red Pulp

An electronmicroscopy study of the spleen from mice infected with Plasmodium berghei was carried out to investigate the types ofcells in volved in the removal of parasites from the blood, and the mechanisms by which this occurs. Macrophages, particularly from the red pulp and the marginal zone of the spleen, constituted the most important population of phagocytic cells in the spleen. At the height ofparasitaemia, macrophages in the periphery of the white pulp, especially in the mantle zone of secondary follicles, were also found to participate in phagocytosis, although to a limited extent. Our fingings suggest that phagocytosis of free parasites or parasitized erythrocytes in the spleen is an important mechanism of clearance of parasites from the circulation. Parasites removed from the erythrocytes when these cells cross the interendothelial slits are further phagocytosed by neighbouring macrophages. Evidence is presented suggesting that spleen macrophages may act against the parasite through a process of cytotoxicity.

scholarly journals Hyperplasia of Mantle/Marginal Zone B Cells With Clear Cytoplasm in Peripheral Lymph Nodes

2001 ◽  
Vol 116 (4) ◽  
pp. 550-559 ◽  
Author(s):  
John P. Hunt ◽  
Joel A. Chan ◽  
Michael Samoszuk ◽  
Russell K. Brynes ◽  
Antonio M. Hernandez ◽  
...  
Keyword(s):  
B Cells ◽  
Lymph Nodes ◽  
Marginal Zone ◽  
Marginal Zone B Cells ◽  
Peripheral Lymph ◽  
Clear Cytoplasm

Role of Rituximab in the Treatment of Splenic Marginal Zone Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4694-4694
Author(s):  
Saaib Al Shehadat ◽  
Martin A. Bast ◽  
Gene Sehi ◽  
Greory R. Bociek ◽  
Anne Kessinger ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Complete Remission ◽  
Lymph Nodes ◽  
Marginal Zone ◽  
Objective Response ◽  
B Cell Lymphoma ◽  
Marginal Zone Lymphoma ◽  
Cytotoxic Agents ◽  
Aggressive Lymphoma ◽  
Splenic Marginal Zone Lymphoma

Abstract Background: Splenic marginal zone lymphoma (SMZL) is a rare malignancy accounting for less than 1% of all lymphomas. The tumor involves the spleen, splenic hilar lymph nodes, bone marrow, and often the peripheral blood. The peripheral lymph nodes are not typically enlarged. Patients typically have circulating neoplastic cells characterized by cytoplasmic projections, round or oval nuclei and clumped chromatin. The lymphoma cells express CD19, CD20, and CD22 but not usually CD5, CD10, CD23, CD25, CD43, CD103 or cyclin D1. The tumor may be surprisingly resistant to chemotherapy that would ordinarily be effective for chronic lymphocytic leukemia. For patients needing treatment, splenectomy is the usual first treatment, which may be followed by prolonged remission. The best approach for patients following splenectomy is not clear. Methods: The characteristics of seven patients with SMZL who progressed after splenectomy are shown in the table. Six of the seven patients received rituximab therapy alone or in combination with other cytotoxic agents. One patient was ineligible for rituximab therapy due to hepatitis C. Results: One patient who relapsed 16 months after splenectomy to diffuse large B cell lymphoma (DLBCL) achieved a complete remission after 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and then electively underwent autologous peripheral stem cell transplantation. His remission persisted 72+ months later. The two patients who received rituximab in combination with other cytotoxic agents 2 months after splenectomy (one had CNOP/cyclophosphamide, mitoxantrone, vincristine, and prednisone; and one had CVP/cyclophosphamide, vincristine, prednisone) remained in remission 52+ months. One patient with anemia refractory to splenectomy responded to 4 cycles of rituximab. One patient who developed anemia and monoclonal gammopathy post splenectomy received 8 weekly cycles of rituximab. Although anemia improved there was no objective response. One patient’s disease transformed to DLBCL 18 months post splenectomy, and did not respond to 8 cycles of rituximab. Conclusion: These results suggest that SMZL in patients who relapsed after splenectomy transforms to aggressive lymphoma more commonly than several thought. Most patients respond to rituximab containing regimens and may achieve a prolonged remission. More studies are warranted to investigate whether rituximab therapy shortly after splenectomy provides better progression free survival than treatment after relapse. Patients’ Characteristics 1 2 3 4 5 6* 7 F: female, CR: complete remission, M: male, P: progression, PR: partial remission, * Hepatitis C. Age 62 33 53 53 67 55 67 Sex M M F F F M F Year 1997 1998 2000 2001 2001 2001 2002 CD20 + + + + + + + DLBCL Transformation + - - - - - + Rituximab # of Cycles 6 8 4 4 6 0 8 Concurrent Chemotherapy CHOP CNOP - Fludarabine CVP CHOP - Response CR CR CR PR CR CR P Follow up (Months) 72+ 61+ 49+ 50+ 50+ 52+ 0

Tropical Splenic Lymphoma: Splenic Marginal Zone Lymphoma or Distinct Entity?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4654-4654
Author(s):  
Elizabeth A. Stephens ◽  
Imelda Bates ◽  
George Bedu-Addo ◽  
Ivy Ekem ◽  
Yvonne Dei ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Diagnosis ◽  
Malaria Infection ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Laboratory Assessment ◽  
Distinct Entity ◽  
Collaborative Project ◽  
Splenic Lymphoma

Abstract In the early 1990’s we described a series of patients from Kumasi, Ghana, West Africa who appeared to have a distinctive lymphoproliferative disorder (LPD) characterised by massive splenomegaly and lymphocytosis with characteristic morphology. At the time this was termed tropical splenic lymphoma (TSL). These patients, in contrast to most patients with LPD’s, tended to be female and relatively young and were frequently diagnosed as having hyper-reactive malarial splenomegaly. An aetiological role for chronic malaria infection has been postulated but remains as yet unproven. Only limited phenotypic and genotypic characterisation of such patients has been possible previously. Given the clinical features and potential aetiological role for malaria infection we wanted to determine whether TSL represented a distinct entity or may be more appropriately considered as splenic marginal zone lymphoma (SMZL). We have therefore evaluated the clinical, immunophentypic and genotypic features of 19 pts (median age 63 years, range 40–78) with a clinical diagnosis of TSL. Peripheral blood, bone marrow aspirate and trephine biopsies were obtained in all patients and the laboratory assessment were performed in the HMDS laboratory, Leeds, UK as part of an on-going collaborative project investigating lymphomas in Ghana. 14 of the 19 patients (73%) were female and all had significant splenomegaly (median length below the costophrenic margin of 17cm, range 6–30 cm). 5/19 patients (26%) had lymphadenopathy and 17/19 patients (89%) had a lymphocytosis - median 30.1×09/l (range 5.4×09/l - unrecordable). Bone marrow infiltration was evident in the trephine biopsies of all patients and was extensive in the majority. Immunophenotyping was performed primarily by immunohistochemistry on the trephine sections although flow cytometry was possible in a proportion of patients. The majority of cases were characterised by a CD5− CD10− CD20+ CD23− CD79+ BCL2+ BCL6− MUM1/IRF4- cyclin D1- immunophenotype. The rate of cell proliferation was low in all cases. FISH studies were performed and these demonstrated del7q31 in 4/18 cases and del6q21 in 1/19 cases. There was no evidence of the t(11;14), t(9;14) or MALT1 rearrangements. IgH sequence analysis was also performed in 16 cases and this demonstrated that 9/16 cases (56%) were germline (>98% homology) and 7/16 (44%) were mutated (<98% homology). Within the mutated group the overall mutation load appeared to be relatively low - median 3.3% (range 3–6%) with most utilising the VH3 family genes. This is the first detailed clinicopathological assessment of patients with a clinical diagnosis of TSL. These patients clearly have some pathological features seen in patients with SMZL such as a CD5− CD10− CD23− immunophenotype, 7q31 deletions and cases with both germline and mutated Ig genes. Definitive phenotypic and genotypic features are unfortunately lacking in SMZL and it remains uncertain whether patients with a clinical diagnosis of TSL should be considered as having SMZL.

Expression of a Dysfunctional Activation Induced Cytidine Deaminase Is Correlated with Disease Progression in Splenic Marginal Zone Lymphoma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2397-2397
Author(s):  
Gabriel Brisou ◽  
Laurent Jallades ◽  
Alexandra Traverse-Glehen ◽  
Francoise Berger ◽  
Aurélie Verney ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Marginal Zone ◽  
Cytidine Deaminase ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Marginal Zone B Cells ◽  
Activation Induced Cytidine Deaminase ◽  
Splicing Variants

Abstract Abstract 2397 B cells can undergo at least two differentiation pathways, dependent of T cells or not, starting from follicular or marginal zone B cells respectively. The T-independent response, less understood than the germinal center reaction, is triggered by specific antigens and arises from marginal zone B cells. During this development, some B cells undergo somatic hypermutation (SHM) and class switch recombination (CSR), triggered by the same DNA editing enzyme called Activation Induced Cytidine Deaminase (AID). The splenic marginal zone lymphoma (SMZL) is a rare lymphoproliferative disorder characterized by a clonal expansion of B cells in the marginal zone of the spleen. These B-cells underwent SHM in roughly 60% of the cases but nearly none underwent CSR. These observations suggest that tumor clones originate from a particular activated B cell subset not transiting through the germinal center. In order to confirm this hypothesis, we focused our work on the status and impact of AID in this disease and worked on purified B cells extracted from spleen of well-characterized SMZL cases. We determined AID status by quantitative RT-PCR analysis on 27 SMZL samples and compared it with 5 controls. In the SMZL group the relative level of expression of AID is heterogeneous but two subgroups could be distinguished: one considered as expressing AID (14 cases out of the 27 analyzed), the remaining considered as not expressing AID. When we compared AID expression rate with occurrence of SHM and CSR, no clear correlation between AID expression and presence of SHM or CSR could be observed suggesting that AID, when expressed, is dysfunctional. To address this hypothesis, we first analyzed AID protein by immunohistochemistry and a good correlation between IHC signal and AID mRNA expression level has been observed. As AID gene was not mutated, we next focused our work on AID mRNA splicing variants as these variants exhibit different functions according to the domain of the protein they contain in a murine model. We found that SMZL B cells express various splicing variants of AID mRNA, some of those variants corresponding to the full length isoform (n = 6/17), and other variants corresponding to AID-ΔE4a (n = 2/17) or AID-ΔE4 (n = 7/17) isoforms known to be expressed in normal germinal center B cells as well as in Chronic Lymphocytic and Acute Lymphoblastic Leukemia. These findings indicate that although expressed at the mRNA and protein levels, AID may not be fully functional in SMZL cases. Finally we addressed the potential clinical significance of AID expression. We identified for that purpose a group of “progressive SMZL” patients that had received immuno-chemotherapy after splenectomy because of a significant risk of progression or transformation into aggressive large B cell lymphoma (n = 8/27) pre-empting outcome differences. We found a higher proportion of AID expressing patients in the defined “progressive SMZL” group (n = 7/8) as compared to the proportion found in the “indolent SMZL” group (n = 5/14, p = 0,03). Altogether, this data suggest that the B cell clone leading to SMZL originate from the marginal zone and support the hypothesis of a lymphoproliferative disorder affecting the T-independent response. AID expression in SMZL may reflect an advanced stage of the disease and could be correlated with the evolution of the lymphoma into a more clinically or pathologically aggressive form. Disclosures: No relevant conflicts of interest to declare.

Splenic marginal zone lymphoma with VH1-02 gene rearrangement expresses poly- and self-reactive antibodies with similar reactivity

Blood ◽  
2011 ◽  
Vol 118 (12) ◽  
pp. 3331-3339 ◽  
Author(s):  
Abdirashid A. Warsame ◽  
Hans-Christian Aasheim ◽  
Kjell Nustad ◽  
Gunhild Trøen ◽  
Anne Tierens ◽  
...  
Keyword(s):  
B Cells ◽  
Gene Rearrangement ◽  
Marginal Zone ◽  
Recombinant Antibodies ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Hepatitis C Virus Infection ◽  
Marginal Zone B Cells ◽  
Lymphatic Leukemia ◽  
Complementarity Determining Regions

Abstract One-third of all splenic marginal zone lymphomas (SMZL) use the IgH VH1-02 gene. These cases are usually not associated with hepatitis C virus infection. Of interest, the rearranged VH1-02 genes display similar complementarity determining regions 3, a finding confirmed by our study. The latter suggests that these SMZL may produce antibodies with similar reactivity. We produced recombinant antibodies from 5 SMZL cases with VH1-02 gene rearrangement to study the binding reactivity of these antibodies. Surprisingly, the recombinant antibodies demonstrated poly- and self-reactivity as demonstrated by their reactivity with nuclear, cytoplasmic, as well as membranous antigens expressed by human cells and by reactivity with human serum. This polyreactivity was specific as demonstrated by ELISA. The antibodies did not react with proteins on the cell surface that are induced by apoptosis as shown for antibodies produced by chronic lymphatic leukemia with VH1-02 gene rearrangement. The results indicate that a common subset of SMZL arises from polyreactive B cells, a subset of marginal zone B cells that are important in the immunologic defense against infection.

scholarly journals Fc chimeric protein containing the cysteine-rich domain of the murine mannose receptor binds to macrophages from splenic marginal zone and lymph node subcapsular sinus and to germinal centers.

1996 ◽  
Vol 184 (5) ◽  
pp. 1927-1937 ◽  
Author(s):  
L Martínez-Pomares ◽  
M Kosco-Vilbois ◽  
E Darley ◽  
P Tree ◽  
S Herren ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
B Cell ◽  
Marginal Zone ◽  
Chimeric Protein ◽  
Mannose Receptor ◽  
Germinal Centers ◽  
White Pulp ◽  
Subcapsular Sinus ◽  
Splenic White Pulp

Ligands for the cysteine-rich (CR) domain of the mannose receptor (MR) were detected by incubating murine tissues with a chimeric protein containing CR fused to the Fc region of human IgG1 (CR-Fc). In naive mice, CR-Fc bound to sialoadhesin+, F4/80low/-, macrosialin+ macrophages (M phi) in spleen marginal zone (metallophilic M phi) and lymph node subcapsular sinus. Labeling was also observed in B cell areas of splenic white pulp. Western blotting analysis of spleen and lymph nodes lysates revealed a restricted number of molecules that interacted specifically with CR-Fc. In immunized mice, labeling was upregulated on germinal centers in splenic white pulp and follicular areas of lymph nodes. Kinetic analysis of the pattern of CR-Fc labeling in lymph nodes during a secondary immune response to ovalbumin showed that CR ligand expression migrated towards B cell areas, associated with cells displaying distinctive dendritic morphology, and accumulated in developing germinal centers. These studies suggest that MR+ cells or MR-carbohydrate-containing antigen complexes could be directed towards areas where humoral immune responses take place, through the interaction of the MR CR domain with molecules expressed in specialized macrophage populations and antigen transporting cells.

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