Monoclonal gammopathy in extranodal marginal zone lymphoma (ENMZL) correlates with advanced disease and bone marrow involvement

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.

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Splenic Marginal Zone Lymphoma (SMZL): Clinical Course after Splenectomy. A Single Institution Experience

Blood ◽

10.1182/blood.v112.11.3993.3993 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3993-3993

Author(s):

Susanna S Gaykazyan ◽

Nalini Janakiraman ◽

Philip Kuriakose ◽

Koichi Maeda ◽

Tareq Hammour

Keyword(s):

Bone Marrow ◽

B Cell ◽

Systemic Therapy ◽

Marginal Zone ◽

Clinical Course ◽

Bone Marrow Involvement ◽

Marginal Zone Lymphoma ◽

Low Grade ◽

Splenic Marginal Zone Lymphoma ◽

Symptomatic Disease

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).

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DISTINCT CLINICOLABORATORY CHARACTERISTICS of the t(14;19)(q32;q13)-POSITIVE SPLENIC MARGINAL ZONE LYMPHOMA

Blood ◽

10.1182/blood.v118.21.5200.5200 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5200-5200

Author(s):

Hunan Julhakyan ◽

Aminat Magomedova ◽

Sergey K Kravchenko ◽

Tatyana N Obukhova ◽

Rima Samoylova ◽

...

Keyword(s):

Bone Marrow ◽

B Cell ◽

Marginal Zone ◽

Bone Marrow Involvement ◽

Marginal Zone Lymphoma ◽

Research Centre ◽

Rapid Progression ◽

Splenic Marginal Zone Lymphoma ◽

Poor Prognostic Factor ◽

High Level

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.

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Efficacy of 90yttrium-Ibritumomab Tiuxetan in Extranodal Marginal-Zone Lymphoma,

Blood ◽

10.1182/blood.v118.21.3713.3713 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3713-3713

Author(s):

Anna Vanazzi ◽

Chiara Grana ◽

Cristiano Crosta ◽

Giancarlo Pruneri ◽

Stefania Rizzo ◽

...

Keyword(s):

Marginal Zone ◽

Conflicts Of Interest ◽

Bone Marrow Involvement ◽

Complete Response ◽

Marginal Zone Lymphoma ◽

Disease Stage ◽

Clinical Activity ◽

Single Shot ◽

Ibritumomab Tiuxetan ◽

Extranodal Marginal Zone Lymphoma

Abstract Abstract 3713 BACKGROUND: To evaluate clinical activity of 90Y-Ibritumomab Tiuxetan in Extranodal Marginal-Zone Lymphoma. PATIENTS AND METHODS: From May 2004 to April 2011 thirty patients affected by relapsed/refractory Marginal-Zone Lymphoma - arisen at any extranodal site - were enrolled to receive 90Y-Ibritumomab Tiuxetan at the activity of 0,4 mCi/kg. Median age was 57 years (range 36–83 ys); 16 female and 14 male. Thirtheen patients had Helicobacter Pylori-negative gastric Mucosa-Associated Lymphoid tissue Non Hodgkin Lymphoma, while 17 patients had extra-gastric Marginal-Zone Lymphoma. At time of treatment 13 out of 30 patients had disseminated disease (stage III/IV; Ann-Arbor Staging System); 4 patients bone marrow involvement. All patients had received a previous treatment with a maximum of 7. The median number of previous treatments administered - including antibiotics, CT, RT or surgery - was 1 with a maximum of 7; 14/30 had received at least 2 previous treatments, 5 of them more than 3. RESULTS: Toxicities were primarily hematological, as expected, and reversible; infection or febrile neutropenia was observed in 3 patients. Up to now no myelodisplastic syndrome occurred. Overall Response Rate was 90%: twenty-three patients achieved a complete response (77%); partial response occurred in 4 patients (13%), stable disease in 2 patients (7%) and 1 progression (3%). With a median follow-up of 47 months, 2 patients relapsed after complete response; 8 out of 20 complete responses are still responder after > 3 years and 5 patients after > 5 years. CONCLUSIONS: 90Y-Ibritumomab Tiuxetan seems to be active in patients with Extranodal Marginal-Zone Lymphoma resistant or refractory to conventional systemic treatment. These results suggest as a single shot of radioimmunotherapy could represent a possible option for the treatment of relapsed Marginal Zone Lymphoma. Disclosures: No relevant conflicts of interest to declare.

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A rare case of marginal zone lymphoma in a 15-year old ataxia telangiectasia patient with massive bone marrow involvement and a challenging nodal diagnosis

Human Pathology Case Reports ◽

10.1016/j.ehpc.2018.10.007 ◽

2019 ◽

Vol 15 ◽

pp. 44-49

Author(s):

Feryal A. Hilmi ◽

Dina S. Soliman ◽

Ahmad Al Sabbagh ◽

Einas Alkuwari ◽

Ruba Y. Taha ◽

...

Keyword(s):

Bone Marrow ◽

Ataxia Telangiectasia ◽

Rare Case ◽

Marginal Zone ◽

Bone Marrow Involvement ◽

Marginal Zone Lymphoma ◽

Massive Bone

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Marginal Zone Lymphoma: Factors That Affect the Final Outcome, a Study of 275 Patients

Blood ◽

10.1182/blood.v112.11.3764.3764 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3764-3764

Author(s):

Ali Mazloom ◽

Valerie K Reed ◽

Fernando Cabanillas ◽

Luis Fayad ◽

Barbara Pro ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Multivariate Analysis ◽

Marginal Zone ◽

Bone Marrow Involvement ◽

Stage Iv ◽

Marginal Zone Lymphoma ◽

P Value ◽

Beta 2 ◽

Beta 2 Microglobulin

Abstract Purpose: Retrospective review and analysis of 275 patients with marginal zone lymphoma (MZL) to determine the prognostic factors that affect outcome in an effort to find a specific prognostic score. Materials and Methods: Two hundred and seventy five patients with pathologically confirmed MZL were studied. Their median age was 60 years (range 18–89). Male sex was found in 123 patients (45%). Ann Arbor stage I was present in 104 patients (38%), stage II in 27 (10%), stage III in 16 (6%), stage IV in 124 (45%), and unknown in 4 (1%). Most patients were asymptomatic at presentation (90%), with 96% presenting with Zubrod score of 0 or 1. Patients were divided into three groups according to sites of involvement: extranodal (211), nodal (27), and splenic (37). Treatment strategy consisted of: observation in 75 (27%), chemotherapy in 103 (37%), combined chemotherapy and radiation in 24 (9%), and definitive radiation in 71 (26%). Results: Both univariate and multivariate analysis showed that splenic presentation had a better outcome with a hazard ratio (HR) of 0.14 and p value=0.006, while extranodal presentation with bone marrow involvement had an inferior outcome with HR of 2.27 and p value =0.045. Two factors were found to be associated with decreased overall survival (OS) in the multivariate analysis: Older age (p=0.007) and beta 2 microglobulin >1.8 mg/L (p <0.0001). On the other hand splenic presentation and being asymptomatic at presentation were associated with an improved OS with a p value of 0.002 and 0.017, respectively. Stage at presentation had no impact on the overall survival or disease free survival, and although all patients with splenic MZL were stage IV, these patients had the best outcome. Nodal presentation had a similar survival to extranodal presentation. Conclusion: Splenic presentation even at advanced stage is associated with a better outcome. Bone marrow involvement in patients with extranodal presentation had a lower OS. Older age, high beta 2 microglobulin, and symptoms at presentation adversely affected the overall survival of patients with MZL.

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