Increased Immunohistochemical CD138 Expression in Waldenström's Macroglobulinemia (WM) in Comparison with Splenic Marginal Zone Lymphoma (SMZL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5008-5008
Author(s):  
Tatiana K Tzenou ◽  
G.A. Pangalis ◽  
Georgia Levidou ◽  
Christina Kalpadakis ◽  
Spyros Siakavellas ◽  
...  

Abstract Abstract 5008 Introduction Differentiating Waldenström's Macroglobulinemia (WM) from other lymphomas and especially Splenic Marginal Zone lymphoma (SMZL), which presents common features with WM, consists a challenge. There is no characteristic molecular abnormality neither for WM nor for SMZL, while in addition, serum IgM cut off is no longer used for the diagnosis of WM. Moreover, while paratrabecular and intrasinusoidal pattern of bone marrow infiltration are described as typical of WM and SMZL respectively, there is often overlap between them. B-lymphocytes' immunophenotype is usually CD5 and CD23 negative in both entities, although deviations from this pattern may be observed; CD38, a marker of lymphocyte activation, theoretically related to lymphoplasmacytic differentiation and adverse prognosis in Chronic Lymphocytic Leukemia, may be expressed. Both WM and SMZL are included among the least reproducible diagnoses of the WHO classification when the diagnosis is based only on clinical grounds, routine laboratory tests and bone marrow biopsy (absence of lymph node or spleen biopsy or typical leukemic picture). CD138 (Syndecan) is expressed in immature as well as in terminally differentiated B-lymphocytes, especially in plasma cells. A strong CD138 expression is observed in myeloma plasma cells. Aim To evaluate firstly whether CD138 is expressed in WM and SMZL and secondly if its expression may help in the differential diagnosis of these entities. Patients and methods 61 patients were studied at presentation, 40 with WM and 21 with SMZL. Among WM patients, 16 were females and 24 males with a median age of 64 years. 57% presented anemia with hemoglobin<12gr/lt, 12% lymphathenopathy and 5% splenomegaly. Among SMZL patients, there were 8 females and 13 males (median age 61 years). 70% presented anemia and 9% lymphathenopathy. In all 61 patients bone marrow was infiltrated by neoplastic cells. By definition, all WM patients had a monoclonal serum IgM paraprotein while 19% of SMZL patients secreted a serum monoclonal paraprotein, either IgM or IgG. Paraffin embedded sections of bone marrow biopsies performed at diagnosis, were stained with anti-CD138 monoclonal antibody, CD138 expression was evaluated in the bone marrow of all patients and comparison between the two patient groups was made. 10% CD 138 expression in bone marrow neoplastic cells was used as cut-off for the evaluation of positivity or negativity. Results 62% of WM patients presented CD138 expression in contrast with 14% of SMZL patients. Median percentage of total CD138 expression in neoplastic cells in WM was 26.5% (range 2-100%) while in SMZL it was 8% (range 0-30%). These differences were statistically significant (p<0.01). It is interesting to note that, 3 out of 4 SMZL patients who secreted IgM at low levels did not express CD138. Otherwise in WM patients CD138 expression correlated only with serum IgM levels. In addition it was observed that 68% of WM patients expressed CD38 by bone marrow lymphocyte flow cytometry compared to 5% of SMZL (p<0.01); however this finding was not related to CD138 immunohistochemical expression. Conclusions Patients with WM presented increased CD138 expression when compared to SMZL patients. If confirmed in larger series, CD138 expression could help differentiating the two entities. Disclosures No relevant conflicts of interest to declare.

2018 ◽  
Vol 53 (4) ◽  
pp. 267
Author(s):  
João Tadeu Damian Souto Filho ◽  
Rodrigo Aires de Morais ◽  
Ana Laura Oliveira Silveira ◽  
Arthur Pires Lacerda ◽  
Isabela Peçanha Bogado Fassbender ◽  
...  

2006 ◽  
Vol 76 (5) ◽  
pp. 392-398 ◽  
Author(s):  
Achille Pich ◽  
Flavio Fraire ◽  
Alessandro Fornari ◽  
Laura Davico Bonino ◽  
Laura Godio ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4654-4654
Author(s):  
Elizabeth A. Stephens ◽  
Imelda Bates ◽  
George Bedu-Addo ◽  
Ivy Ekem ◽  
Yvonne Dei ◽  
...  

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 (&gt;98% homology) and 7/16 (44%) were mutated (&lt;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.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5086-5086
Author(s):  
Luz Martínez-Avilés ◽  
Marta Salido ◽  
Beatriz Bellosillo ◽  
Vera Adema ◽  
Ana Ferrer ◽  
...  

Abstract Abstract 5086 Background Splenic marginal zone lymphoma (SMZL) is a rare low-grade B-cell lymphoproliferative disorder with characteristic clinical, cytological, histological and immunophenotypical features. The most common cytogenetic abnormality, present in 30–40% of the patients is the 7q deletion, that extends from 7q21 to 7q36. This aberration may represent a primary pathogenic event in SMZL. Recently, mutations in the EZH2 gene, located at 7q36.1, have been described in different hematological malignancies including B-cell lymphomas. However, the role of the EZH2 gene in SMZL has to be elucidated. Aim To determine the prevalence of EZH2 mutations in a cohort of SMZL patients. Patients and Methods Twenty-nine patients with SMZL were screened for mutations in the EZH2 gene. From the whole cohort, 11 patients presented 7q deletion (three of them as a single anomaly), 11 had a normal karyotype and 7 had other cytogenetic aberrations. The mutational analysis of the EZH2 gene was performed by direct sequencing using primers covering the whole exome of the gene. DNA was extracted from CD19 isolated B-cells from peripheral blood or from total lymphocytes if the percentage of pathologic B-cell was higher than 50%. Results From the whole cohort of 29 SMZL patients, no pathogenic mutations (frameshift or nonsense mutations) were detected in the EZH2 gene in any of the patients analyzed. Five patients harboured the missense mutation D185H in exon 6, that has been previously described as a single nucleotide polymorphism (SNP). Conclusions In conclusion, the EZH2 gene is not mutated in our series of SMZL patients suggesting that this gene is not involved in the pathogeny of this entity. Acknowledgments: Fellowship FI2008 (AGAUR) to LMA, This work was supported (in part) by grants from Instituto de Salud Carlos III FEDER; Red Temática de Investigación Cooperativa en Cáncer (RTICC, FEDER): RD06/0020/0031 and RD07/0020/2004; Ministerio de Sanidad y Consumo (Spain): PI07/0586. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5129-5129
Author(s):  
Alessandro Pulsoni ◽  
Pasqualina D'Urso ◽  
Gianna Maria D'Elia ◽  
Giorgia Annechini ◽  
Caterina Stefanizzi ◽  
...  

Abstract Introduction Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoma characterized by splenomegaly, frequent moderate lymphocytosis with or without villous morphology and possible involvement of various organs, especially the bone marrow (BM). Diagnosis is classically based on the spleen histology, but it can be made on the BM biopsy, based on the typical intrasinusoidal cell infiltration pattern and immunohistochemistry. Different therapeutic options are available, but to date there are no conclusive comparative data. Patients and methods We retrospectively analyzed 83 consecutive patients with a diagnosis of SMZL observed at our Institution between 1999 and 2013. The diagnosis was based on the BM biopsy in 79 patients; the BM was negative in 4 patients. Diagnosis was histologically confirmed on the spleen in 27 patients who underwent splenectomy. Patients presented a median age of 72.5 years (range 38-84); 43 were males. The median spleen size at diagnosis was 145 mm, ranging from 100 to 300 mm. The majority of patients were stage IV at diagnosis for BM infiltration (95%); B symptoms were present in 4 of them (4.8%). Forty-two patients (50.6%) had a lymphocytosis at diagnosis and 13 (15.6%) presented an IPI score higher than 3. Thirty-five of them (42%) had a MZL BM infiltration superior to 30% of the total bone cellularity. Forty-two patients (50.6%) underwent a watch and wait policy (WW), while 41 (49.4%) were treated within 6 months from diagnosis, mainly because of symptomatic splenomegaly; in these patients, treatment consisted of splenectomy, chemotherapy or chemotherapy plus immunotherapy with Rituximab. The features of patients submitted to WW with respect to patients treated at diagnosis were comparable for the various parameters mentioned above, except for spleen size (higher in patients treated at presentation) and lymphocyte count (higher in patients who were observed). After a median follow-up of 64 months, the overall median survival was 96%. Among the 42 WW patients, 18 (42.8%) are still untreated after a median follow-up of 57.5 months, while 24 (57.2%) have required therapy; the median treatment-free interval in these patients was 25.5 months. Concerning the 41 patients who underwent treatment at diagnosis, after a median follow-up of 50 months, 13 (31.7%) have required a subsequent second-line treatment. The interval between first-line approach and re-treatment in patients treated at diagnosis was 30 months. Overall, 27 patients were treated with splenectomy only (either at diagnosis or after a WW period): only 6 of them (22%) had a subsequent progression after a median latency of 42 months; 26 were treated with chemotherapy alone (alkylating agents in the majority of them, combination therapy in a minority): 15 of them (60%) had a subsequent relapse or progression after a median of 9 months; 12 patients received a Rituximab-containing regimen: of these, only 2 (16%) have so far required a second-line therapy after 10 and 26 months respectively. Conclusions The WW policy is a valid option for asymptomatic patients: in these patients, after 4.5 years from diagnosis more than 40% is still untreated. In patients requiring treatment, splenectomy alone is followed in the majority of patients by a long period of good disease control: only 22% required a second-line therapy after 3.5 years. The addiction of Rituximab to chemotherapy seems to reduce the probability of relapse and to prolong the response duration. However, these preliminary data need to be confirmed by larger studies. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5399-5399
Author(s):  
Assia Bassarova ◽  
Gunhild Trøen ◽  
Signe Spetalen ◽  
Francesca Micci ◽  
Anne Tierens ◽  
...  

Abstract Lymphoplasmacytic lymphoma and marginal zone lymphoma in the bone marrow: paratrabecular involvement as an important distinguishing feature Assia Bassarova, Gunhild Tr¿en, Signe Spetalen, Francesca Micci, Anne Tierens, Delabie Abstract Lymphoplasmacytic lymphoma (LPL) is a neoplasm of small B-lymphocytes, lymphoplasmacytoid and plasma cells involving bone marrow and sometimes lymph nodes and spleen. Lymphoplasmacytic lymphoma is often accompanied by Waldenström macroglobulinemia. Since the original description, Waldenström macroglobulinemia has become recognized as a distinct clinicopathological entity defined by serum IgM paraprotein and bone marrow involvement by lymphoplasmacytic lymphoma. Since serum IgM paraprotein in itself is not specific and can be seen in a variety of small B-cell lymphoproliferative disorders, notable chronic lymphatic leukemia and marginal zone lymphoma, as well as in rare cases of myeloma, the diagnosis of Waldenström macroglobulinemia rests largely upon the proper diagnosis of LPL in the bone marrow. The differential diagnosis between bone marrow involvement by lymphoplasmacytic lymphoma (LPL) and marginal zone lymphoma (MZL) is challenging because histology and immunophenotype of both diseases overlap. The diagnosis may be helped by demonstrating the MYD88 L265P mutation, seen in most LPL. However, the mutation is also present in MZL, although at a lower frequency. To better define the distinguishing features of LPL we studied a series of bone marrow trephine biopsies of 59 patients with Waldenström's macroglobulinemia (WM) without extramedullary involvement and compared the findings with bone marrow biopsies from 23 patients with well-characterized MZL who also had bone marrow involvement. H&E and immunoperoxidase-stained sections of bone marrow trephine biopsies as well as flow cytometry and classical cytogenetics performed on aspirations were reviewed. The study was complemented with MYD88L265P mutation analysis on the bone marrow trephine biopsies of all patients. The features are summarized in Table 1. The most distinguishing features of LPL with respect to MZL were focal paratrabecular involvement (p<0.001), the presence of lymphoplasmacytoid cells (p<0.001), Dutcher bodies (p<0.001), increased numbers of mast cells (p<0.001) and the MYD88L265P mutation (p<0.001). Other features such as sinusoidal infiltration and immunophenotype were not distinguishing. Table 1. Summary of the pathology features of lymphoplasmacytic and marginal zone lymphoma in bone marrow trephine biopsies Lymphoplasmacytic lymphoma Marginal zone lymphoma p Infiltration pattern* Paratrabecular Nodular non-paratrabecular Paratrabecular and non-paratrabecular Intrasinusoidal Diffuse 37% (10/27) 0% (0/27) 56% (15/27) 37% (10/27) 0% (0/27) 0% (0/16) 75% (12/16) 0% (0/16) 37% (6/16) 25% (4/16) <0,001 <0,001 <0,001 1 0,015 Cytology Small lymphoid cells Plasmacytoid cells Plasma cells Dutcher nuclear inclusions Mast cells 100% (59/59) 100% (59/59) 93% (55/59) 90% (53/59) 87% (49/56) 100% (23/23) 0% (0/23) 78% (18/23) 0% (0/23) 9% (2/23) - <0,001 0,108 <0,001 <0,001 Immunophenotype of the lymphoma CD20 CD138 (plasma cells) CD5 CD23 IgK IgL IgM IgG Focal CD21+ or CD23+ follicular dendritic cell network in the stroma 100% (59/59) 88% (50/57) 21% (12/52) 29% (15/51) 81% (48/59) 19% (11/59) 97% (57/59) 3% (2/59) 20% (10/51) 100% (23/23) 80% (12/15) 0% (0/23) 13% (5/23) 26% (5/19) 10% (2/19) 64% (7/11) 0% (0/11) 48% (11/23) - - 0,014 0,580 - - - - 0,024 MYD88 L265P mutation 96% (45/47) 20% (3/15) 0,001 *the analysis was only performed on bone marrow trephine biopsies showing less than 66% lymphoma infiltration In conclusion, LPL can reliably be distinguished from MZL in the bone marrow by using a combination of pathology characteristics. In contrast to other studies, our findings stress the diagnostic importance of paratrabecular infiltration in LPL. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 37 (2) ◽  
pp. 219-222 ◽  
Author(s):  
Maria K. Angelopoulou ◽  
Theodoros P. Vassilakopoulos ◽  
Eliana Konstantinou ◽  
George Boutsikas ◽  
John V. Asimakopoulos ◽  
...  

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