CD5+ Extranodal Marginal Zone B-Cell (MALT) Lymphoma:A Low Grade Neoplasm With a Propensity for Bone Marrow Involvement and Relapse

1996 ◽  
Vol 105 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Judith A. Ferry ◽  
Woo-Ick Yang ◽  
Lawrence R. Zukerberg ◽  
Andrew C. Wotherspoon ◽  
Andrew Arnold ◽  
...  
Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3993-3993
Author(s):  
Susanna S Gaykazyan ◽  
Nalini Janakiraman ◽  
Philip Kuriakose ◽  
Koichi Maeda ◽  
Tareq Hammour

Abstract SMZL is an indolent B-cell malignancy accounting for 1–2% of chronic lymphoid leukemia found on bone marrow examination and up to 25% of low-grade B-cell neoplasms in splenectomy patients. Aggressive transformation of SMZL rarely occurs. It usually presents as an incidental finding or with symptoms of splenomegaly and anemia. There is still no reliable clinical or biological scoring system for prognostic stratification. We reviewed pathology reports of 41 splenectomized patients at HFHS from 1994 to 2007 and identified 14 patients with splenic marginal zone lymphoma (SMZL). The reasons for splenectomy were symptoms of splenomegaly in all 14 patients, anemia in 13 patients, thrombocytopenia in 12 patients, AIHA in 4 patients, splenic laceration in one patient. We report here the demographics, clinical course and pathology review of these patients. The median age of patients was 77.8 years. There were 7 male and 7 female patients. ECOG performance status was 0–1 in 12(86%), and 2 in 2(14%). Of the 14 patients, 8(57%) were at Ann Arbor stage IV, 1(7%) was at stage III, 4(29%) were at stage II, and 1(7%) at stage I. LDH was above normal in 9(64%) patients B-symptoms were observed in 1(7%). Bone marrow involvement was documented in 8(57%) of the patients. Anemia in 13(93%), thrombocytopenia in 12(86%), AIHA in 4(29%). IPI score was 1–2 in 5(36%), and score 3–4 in 9(64%) of the patients. Median weight of the spleen was 1235 gm. Bone marrow cytogenetics were abnormal in 4(29%) cases. Following splenectomy, cytopenias resolved completely or partially (CR/PR) in 13(93%) patients. Bacterial infections were observed in 4(29%) patients and 2(14%) died of infectious complications. Progressive disease requiring additional systemic therapy was documented in 5(36%) patients. Total of 5(36%) patients died. One secondary to NSLC, 1(7%) of urothelial carcinoma, 1(7%) secondary to hypercalcemia, 2(14%) due to bacterial sepsis. Patients were followed up to 139 months (with median follow-up time of 42 months). The estimated median overall survival (OS) for this group was 116.5 months (9.7 years), the median progression-free survival (PFS) was 91 months (7.6 years). The Kaplan Meier method was used to calculate these estimates. A simple median was calculated for the sample median. In summary, we report the course of 14 patients with SMZL who underwent splenectomy for symptomatic disease. Only 5(36%) required systemic therapy following splenectomy. No death was attributed to progressive SMZL. Overall course was indolent even after splenectomy. Estimated OS was 116.5 months (9.7 years), PFS - 91 month (7.6 years).


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5200-5200
Author(s):  
Hunan Julhakyan ◽  
Aminat Magomedova ◽  
Sergey K Kravchenko ◽  
Tatyana N Obukhova ◽  
Rima Samoylova ◽  
...  

Abstract Abstract 5200 Background: Splenic marginal zone lymphoma (SMZL) is a well recognized B-cell neoplasm which is characterized by splenomegaly, bone marrow involvement, immunologically by typical phenotype of marginal zone cells. The most frequent cytogenetic findings are involvement of chromosomes 1, 3, 7(usually deleted in 7q) and 8. The t(14;19)(q32;q13) is a rare cytogenetic abnormality with bcl-3 rearrangement that has been reported in other B-cell lymphomas. Aims: To describe the clinical, morphological, immunophenotypic findings in SMZL associated with t(14;19)(q32;q13). Methods and results: In Hematological Research Centre, Moscow between January 2001 and May 2011 three cases SMZL with t(14;19)(q32;q13) were identified. All patients were males with age 51, 58, 67 y.o. Lymphoma presented with B-symptoms, high level of lactate dehydrogenase (LDH), hepatosplenomegaly and regional lymphadenopathy (enlarge splenic hilar lymphnodes). The hemoglobin was 92 g/l, 110 g/l, 122 g/l. All patients had normal count of leukocytes with an absolute lymphocytosis (lymphocytes count 72 × 109 g/l, 79 × 109 g/l, 83 × 109/l) and thrombocytopenia. Morphological examination of peripheral blood and bone marrow lymphocytes showed that all lymphocytes are atypical with wide cytoplasm and nuclear indentation. In all cases there was nodular type of bone marrow involvement, composed of majority medium sized cells. Immunophenotypic analysis has shown the expression of mature B-cells antigens (CD19, CD20, CD22, FMC7, sIg) and absence of ÑD10, CD23, CD5, CD43, CyclinD1. Two patients were treated with CHOP-regimen without any response. They progressed with spleen enlargement and decreased of thrombocytes counts. All 3 patients undergo splenectomy. Weight of spleen was 1800 g, 2083 g, 2850 g. Splenic section generally show massive nodular pattern (involvement of the white and red pulp) associated with diffuse invasion of the sinuses. In all cases discovered high Ki-67. All patients demonstrated progression after splenectomy during 3–6 months that was characterized by increase of leukocytes count (range 45,4 – 101,8 × 109 /l), high level of LDH, appearance of peripheral and visceral lymph nodes. Considering the increase leucocytes, presence of lymphadenopathy in all cases CHOP, FMC regimen were used. All patients died of disease progression and infectious complications. Time of observation was 21, 30, 34 months. Conclusions: The t(14;19)(q32;q13)-positive SMZL is distinct variant which is characterized by rapid progression after splenectomy, poor responses to chemotherapy and short survival. So t(14;19)(q32;q13) may be regarded as a poor prognostic factor. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 270-278
Author(s):  
L Baldini ◽  
NS Fracchiolla ◽  
LM Cro ◽  
D Trecca ◽  
L Romitti ◽  
...  

A phenotypic and molecular evaluation was made of 15 patients with mature B-cell leukemia/lymphoma showing exclusive spleen and bone marrow involvement. According to French-American-British criteria, these cases could not be classified as classical B-cell chronic lymphocytic leukemia, hairy cell leukemia and its variant forms, splenic lymphoma with villous lymphocytes, or leukemic phase non- Hodgkin's lymphoma (NHL; follicular or intermediate type). The immunophenotype pattern (high surface Ig and CD25 expression, and little or no reactivity with CD5, CD23, and CD11c) and cytomorphologic features of these neoplasms suggested an origin in the marginal zone of the spleen. Molecular analysis did not show any involvement of the dominantly acting oncogenes generally associated with lymphoid malignancies (c-myc, bcl-2, bcl-1, Ras), but mutations of the p53 tumor suppressor gene involving exons 5, 6, and 8 were found in 6 cases (6 of 15, 40%). In 4 cases, the p53 alterations consisted of a point mutation leading to amino acid substitution. In the remaining 2 cases, an insertion or deletion resulting in a frame-shift of the protein was observed. In all but 1 of the cases, the wild-type sequence at the mutation site was barely visible, implying the loss of the normal p53 allele in leukemic cells. All of the cases showed a clinical course compatible with that of low-grade NHL, regardless of the p53 loss/mutation. Overall, our data suggest the existence of a form of splenic B-cell leukemia/lymphoma of possible marginal zone origin in which p53 inactivation may play an important pathogenetic role.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1775-1775 ◽  
Author(s):  
Silvia Zibellini ◽  
Luca Arcaini ◽  
Francesco Passamonti ◽  
Sara Rattotti ◽  
Marco Lucioni ◽  
...  

Abstract Splenic marginal zone B-cell lymphoma (SMZL) is a rare clinical and pathological entity recognized by the WHO classification. SMZL usually presents with isolated splenomegaly, bone marrow involvement, and leukemic picture. Nodal disease is generally rare at diagnosis. When lymphocytes with villous projections are found in peripheral blood, the disease is termed splenic lymphoma with villous lymphocytes (SLVL). High HCV-seroprevalence is frequently reported in SMZL. The disease commonly pursues an indolent course; however, about a third of pts follow a more aggressive course. SMZL is also heterogeneous with respect to the preferential usage of IgVH genes, as well as the percentage of mutation load. No previous studies correlated IgVH rearrangement features with the clinical characteristics of SMZL. The aim of the present study was to determine the tumor-related IgVH gene rearrangement and compare the gene usage and the mutation status with clinical features of 59 pts. Diagnosis was made according to the WHO classification and to the diagnostic criteria for SMZL (Matutes et al., Leukemia 2008). Paraffin sections from lesional tissues (14 spleens, and 59 bone marrow trephines) were available for all pts. Histology and blood smears were reviewed. Total RNA was extracted from PB (n=13) or BM (n=46) mononuclear cells. IgVH gene rearrangements were amplified using 6 family-specific VH leader primers coupled with a 3′ heavy chain joining (JH) primer or with a constant region of cμ chain primer. The sequence obtained from direct sequencing of the clonal PCR product was compared with germline in the IMGT database. Sixty VDJ rearrangements were amplified and 54 were functional. VH1 family was used in 19 rearrangements (32%), VH3 family in 33 (55%) and VH4 family in 8 (13%). The most frequent VH genes were VH1-02 (n=13), VH3-23 (n=15), VH3-30 (n=7) and VH4-34 (n=5) (67% of all sequences). VH was unmutated in 25%. DH segments were assignable in 56/60 rearrangements (all of the VH unmutated and 41/45 of VH mutated). The most frequent DH families were DH2 (n=9) and DH3 (n=21); the most frequent DH genes were DH3-03 (n=8), DH3-22 (n=6) and DH2-02 (n=6). Most rearrangements used JH4 family (n=21), JH5 (n=8), and JH6 (n=19), accounting for 80% of all rearrangements. JH4b (n=14), JH6b (n=10), and JH6c (n=8) were the most common JH genes. Median length of HCDR3 region was 17 aa (range 11–32). For antigen selection analysis P value was < 0.05 in 41% for CDRs and in 55% for FRs. No correlation was found among VH and DH families (p=0.1), among VH and JH families (p=0.09) and among DH and JH families (p=0.4). Forty-two % of pts were unmutated in VH1 family, 15% in VH3 family and 25% in VH4 family (p=0.09). Unmutated cases were 7% in VH3-23 group, 46% in VH1-02 group and 14% in VH3-30 group (p=0.03). For clinical correlations we considered only the 54 functional rearrangements. Villous lymphocytes >10% were detected in 53% of VH1 pts, in 57% of VH4 pts, and in 17% of VH3 pts (p=0.01). Villous lymphocytes >10% were detected in 21% of VH3-23 pts, in 50% of VH1-02 pts and in no VH3-30 pt (p=0.05). Liver involvement was present in 9% of VH3-23 pts, in no VH1-02 pt and in 50% of VH3-30 pts (p=0.009). HCV serology was positive in 7% of VH3-23 pts, 17% of VH1-02 pts and 50% of VH3-30 pts (p=0.04). Serum MC was detected in 50% of VH3-23 pts, in 9% of VH1-02 pts and in 17% of VH3-30 pts (p=0.06). BM was involved in 86% of VH3-23 pts, in 100% of VH1-02 pts and in 50% of VH3-30 pts (p=0.02). A sinusal localization was detected in 67% of VH3-23 pts, in 20% of VH1-02 and in 100% of VH3-30 (p=0.03). Unmutated status was significantly related to a higher percentage of BM infiltration (p=0.003). The proportion of intermediate and high risk patients according to the SMZL score (Arcaini et al. Blood 2006) was higher in the unmutated respect to the mutated group (69% vs 32%, p=0.05). After a median F-UP of 3 yrs, 10 pts died (7 of lymphoma, 3 of causes non related to lymphoma). The median OS was 12 yrs and the median PFS was 2 yrs. OS did not differ among VH families (p=0.9). Median PFS was 2 yrs for mutated pts and 1 yr for unmutated pts. We performed clustering of pts by applying a 2-means clustering algorithm, using as parameters nodal disease, villous lymphocytes >10%, HCV serology positive, BM involvement: in cluster 1 VH1 family pts accounted for 20%, VH3 family for 71%, VH4 family for 9%; in cluster 2 VH1 family pts accounted for 47%, VH3 family for 29% and VH4 family for 24% (p=0.01). In conclusion, VH rearrangement analysis in SMZL reveals a non-random preference for VH1-02, VH3-23 and VH3-30 genes, whose use differs according to distinctive clinical features at presentation.


2013 ◽  
Vol 137 (4) ◽  
pp. 580-585 ◽  
Author(s):  
Nadia Naderi ◽  
David T. Yang

Lymphoplasmacytic lymphoma (LPL) is a low-grade, B-cell neoplasm composed of small lymphocytes, plasmacytoid lymphocytes, and plasma cells that typically involve the bone marrow, and it is associated with an immunoglobulin M (IgM) gammopathy. The definition of Waldenström macroglobulinemia (WM) and its relationship to LPL has been confusing in the past. In addition, the diagnosis of LPL itself can be challenging because LPL lacks disease-specific morphologic, immunophenotypic, and genetic features to differentiate it from other mature B-cell neoplasms. Accurate diagnosis of LPL/WM rests on recognition of the differential diagnostic features between LPL and other diagnostic possibilities and the use of the recently refined definition of WM and its relationship with LPL: The presence of an IgM monoclonal gammopathy of any level in the setting of bone marrow involvement by LPL. This review summarizes the clinical, laboratory, and histologic features of LPL/WM, with particular emphasis on unique aspects of LPL/WM that may aid in accurate diagnosis.


Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 270-278 ◽  
Author(s):  
L Baldini ◽  
NS Fracchiolla ◽  
LM Cro ◽  
D Trecca ◽  
L Romitti ◽  
...  

Abstract A phenotypic and molecular evaluation was made of 15 patients with mature B-cell leukemia/lymphoma showing exclusive spleen and bone marrow involvement. According to French-American-British criteria, these cases could not be classified as classical B-cell chronic lymphocytic leukemia, hairy cell leukemia and its variant forms, splenic lymphoma with villous lymphocytes, or leukemic phase non- Hodgkin's lymphoma (NHL; follicular or intermediate type). The immunophenotype pattern (high surface Ig and CD25 expression, and little or no reactivity with CD5, CD23, and CD11c) and cytomorphologic features of these neoplasms suggested an origin in the marginal zone of the spleen. Molecular analysis did not show any involvement of the dominantly acting oncogenes generally associated with lymphoid malignancies (c-myc, bcl-2, bcl-1, Ras), but mutations of the p53 tumor suppressor gene involving exons 5, 6, and 8 were found in 6 cases (6 of 15, 40%). In 4 cases, the p53 alterations consisted of a point mutation leading to amino acid substitution. In the remaining 2 cases, an insertion or deletion resulting in a frame-shift of the protein was observed. In all but 1 of the cases, the wild-type sequence at the mutation site was barely visible, implying the loss of the normal p53 allele in leukemic cells. All of the cases showed a clinical course compatible with that of low-grade NHL, regardless of the p53 loss/mutation. Overall, our data suggest the existence of a form of splenic B-cell leukemia/lymphoma of possible marginal zone origin in which p53 inactivation may play an important pathogenetic role.


2008 ◽  
Vol 159 (2) ◽  
pp. 498-500 ◽  
Author(s):  
E. Bathelier ◽  
L. Thomas ◽  
B. Balme ◽  
B. Coiffier ◽  
G. Salles ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4795-4795 ◽  
Author(s):  
F. Morschhauser ◽  
J. Radford ◽  
A. van Hoof ◽  
I. Kuss ◽  
A. Chlistalla ◽  
...  

Abstract Background: [90Y]-Zevalin is a radiolabeled monoclonal antibody approved for the treatment of relapsed or refractory low-grade follicular or transformed B-cell NHL. Myelosuppression following [90Y]-Zevalin is reversible with nadir counts at 7 to 9 wks after administration of Zevalin and grade 4 thrombocytopenia, neutropenia, and anemia occurring in 10%, 30%, and 3% of patients (pts), respectively. Currently, baseline platelet counts and the degree of bone marrow involvement are the most reliable predictors of hematologic toxicity. Recently, plasma FLT3-L levels have been shown to reflect more accurately bone marrow radiosensitivity to iodine I-131 radioimmunotherapy than peripheral blood counts in patients with solid tumors. The purpose of this analysis was to determine if plasma FLT3-L cytokine levels would help to predict the magnitude of hematologic toxicity after [90Y]-Zevalin treatment. Methods/Results: In this prospective, multicenter, phase III clinical trial, [90Y]-Zevalin was studied as consolidation therapy (14.8 MBq/kg [0.4 mCi/kg; maximum 32 mCi]) versus no further treatment in 414 patients with advanced follicular-NHL responding to first-line induction therapy with single-agent chlorambucil, CVP, CHOP/CHOP-like regimens, or regimens containing fludarabine or rituximab. Pts were required to have an absolute neutrophil count (ANC) of at least 1500/μL and a platelet count of >150,000/μL. Hematologic toxicity was determined by collecting hematologic data (platelets, ANC, and hemoglobin [Hb]) before therapy and weekly thereafter for 14 wks. Plasma FLT3-L cytokine levels were evaluated in 71 of 208 patients before treatment with [90Y]-Zevalin. FLT3-L levels (pg/mL) were determined by immunoassay with a reference range from 48.3 to 173.8pg/mL. The mean FLT3-L level of all pts was 140.8 (range 49.5 to 300.4). The incidences of grade 3/4 thrombocytopenia, neutropenia, and anemia were 46.5%/8.5%, 40.8%/33.8%, and 8.5%/4.2%, respectively. Severe hematologic events were transient. The FLT3-L levels were not correlated with the nadir of platelets, ANC and Hb per patient during week 1 to 14. The correlation coefficent between FLT3-L and platelets, ANC and Hb was 0.10, −0.25 and −0.18, respectively for all pts. These results do not indicate a relationship between baseline FLT3-L and any of the 3 hematologic parameters. Conclusions: Baseline FLT3-L levels did not identify pts who are likely to develop a grade 3/4 myelosuppression following [90Y]-Zevalin consolidation therapy. Overall, the incidence and severity of cytopenias were transient, reversible, and comparable to those obtained with [90Y]-Zevalin in relapsed/refractory follicular NHL.


2008 ◽  
Vol 129 (5) ◽  
pp. 714-722 ◽  
Author(s):  
Kedar V. Inamdar ◽  
L. Jeffrey Medeiros ◽  
Jeffrey L. Jorgensen ◽  
Hesham M. Amin ◽  
Ellen J. Schlette

Sign in / Sign up

Export Citation Format

Share Document