Splenic marginal zone lymphoma presenting as myelofibrosis associated with bone marrow involvement of lymphoma cells which secrete a large amount of TGF-�

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).

Download Full-text

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.

Download Full-text

Immunophenotypic profile and role of adhesion molecules in splenic marginal zone lymphoma with bone marrow involvement

Leukemia & Lymphoma ◽

10.1080/10428190500272556 ◽

2006 ◽

Vol 47 (1) ◽

pp. 49-57 ◽

Cited By ~ 11

Author(s):

A. M. Florena ◽

C. Tripodo ◽

R. Porcasi ◽

S. Ingrao ◽

M. R. Fadda ◽

...

Keyword(s):

Bone Marrow ◽

Adhesion Molecules ◽

Marginal Zone ◽

Bone Marrow Involvement ◽

Marginal Zone Lymphoma ◽

Splenic Marginal Zone Lymphoma

Download Full-text

Patterns of bone marrow involvement in 58 patients presenting primary splenic marginal zone lymphoma with or without circulating villous lymphocytes

British Journal of Haematology ◽

10.1046/j.1365-2141.2003.04449.x ◽

2003 ◽

Vol 122 (3) ◽

pp. 404-412 ◽

Cited By ~ 52

Author(s):

Josée Audouin ◽

Agnès Le Tourneau ◽

Thierry Molina ◽

Sophie Camilleri-Broët ◽

Colette Adida ◽

...

Keyword(s):

Bone Marrow ◽

Marginal Zone ◽

Bone Marrow Involvement ◽

Marginal Zone Lymphoma ◽

Splenic Marginal Zone Lymphoma

Download Full-text

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

European Journal Of Haematology ◽

10.1111/j.1600-0609.2005.00624.x ◽

2006 ◽

Vol 76 (5) ◽

pp. 392-398 ◽

Cited By ~ 12

Author(s):

Achille Pich ◽

Flavio Fraire ◽

Alessandro Fornari ◽

Laura Davico Bonino ◽

Laura Godio ◽

...

Keyword(s):

Bone Marrow ◽

Quantitative Study ◽

Marginal Zone ◽

Marginal Zone Lymphoma ◽

Bone Marrow Infiltration ◽

Splenic Marginal Zone Lymphoma

Download Full-text

Authors response to Tripodo et al.'Reply to Pich et al.: Intrasinusoidal bone marrow infiltration and splenic marginal zone lymphoma: a quantitative study'

European Journal Of Haematology ◽

10.1111/j.1600-0609.2006.00750.x ◽

2006 ◽

Vol 77 (4) ◽

pp. 361-361

Author(s):

A. Pich ◽

F. Fraire ◽

A. Fornari ◽

L. Davico-Bonino ◽

L. Godio ◽

...

Keyword(s):

Bone Marrow ◽

Quantitative Study ◽

Marginal Zone ◽

Marginal Zone Lymphoma ◽

Bone Marrow Infiltration ◽

Splenic Marginal Zone Lymphoma

Download Full-text

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

Blood ◽

10.1182/blood.v108.11.4654.4654 ◽

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.

Download Full-text

Lymphoplasmacytic Lymphoma and Marginal Zone Lymphoma in the Bone Marrow: Paratrabecular Involvement As an Important Distinguishing Feature

Blood ◽

10.1182/blood.v124.21.5399.5399 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5399-5399

Author(s):

Assia Bassarova ◽

Gunhild Trøen ◽

Signe Spetalen ◽

Francesca Micci ◽

Anne Tierens ◽

...

Keyword(s):

Bone Marrow ◽

Marginal Zone ◽

Plasma Cells ◽

Bone Marrow Involvement ◽

Marginal Zone Lymphoma ◽

Lymphoplasmacytic Lymphoma ◽

Waldenström Macroglobulinemia ◽

Bone Marrow Trephine ◽

Waldenstrom Macroglobulinemia ◽

Myd88 L265p Mutation

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.

Download Full-text