Bone marrow origin of a B-cell lymphoma

To search for precursors of the neoplastic B cells in a patient with a nodular lymphoma, we produced a monoclonal antibody to a variable region idiotope on the lymphoma IgM heavy chain. Clonal ancestors of the lymphoma cells were identified by this marker among bone marrow pre- B cells (5% to 26%). A second antiidiotype (anti-Id) antibody specific for the complete lymphoma IgM kappa recognized 10% of B cells in bone marrow and blood and greater than 95% of B cells in lymphomatous lymph nodes, including one obtained after tumor conversion to a diffuse large cell lymphoma. Immunoglobulin gene analysis surprisingly revealed expansion of multiple clones of early B lineage cells in bone marrow, including members of the neoplastic clone. The data suggest that this lymphoma arose through a progression of transformational events beginning in bone marrow: first, creation of an oligoclonal pre- neoplastic pool of pre-B cells, subsequent conversion of a single subclone into low grade neoplastic B cells that homed to the lymph node follicles, and later progression to a more invasive form of the B-cell lymphoma.

Download Full-text

Bone marrow origin of a B-cell lymphoma

Blood ◽

10.1182/blood.v72.1.94.94 ◽

1988 ◽

Vol 72 (1) ◽

pp. 94-101 ◽

Cited By ~ 25

Author(s):

LF Bertoli ◽

H Kubagawa ◽

GV Borzillo ◽

PD Burrows ◽

MT Schreeder ◽

...

Keyword(s):

Bone Marrow ◽

B Cells ◽

B Cell ◽

Cell Lymphoma ◽

Variable Region ◽

B Cell Lymphoma ◽

Large Cell ◽

Low Grade ◽

Immunoglobulin Gene ◽

B Lineage

Abstract To search for precursors of the neoplastic B cells in a patient with a nodular lymphoma, we produced a monoclonal antibody to a variable region idiotope on the lymphoma IgM heavy chain. Clonal ancestors of the lymphoma cells were identified by this marker among bone marrow pre- B cells (5% to 26%). A second antiidiotype (anti-Id) antibody specific for the complete lymphoma IgM kappa recognized 10% of B cells in bone marrow and blood and greater than 95% of B cells in lymphomatous lymph nodes, including one obtained after tumor conversion to a diffuse large cell lymphoma. Immunoglobulin gene analysis surprisingly revealed expansion of multiple clones of early B lineage cells in bone marrow, including members of the neoplastic clone. The data suggest that this lymphoma arose through a progression of transformational events beginning in bone marrow: first, creation of an oligoclonal pre- neoplastic pool of pre-B cells, subsequent conversion of a single subclone into low grade neoplastic B cells that homed to the lymph node follicles, and later progression to a more invasive form of the B-cell lymphoma.

Download Full-text

Primary cutaneous B-cell lymphoma (low-grade, non large cell)

Dermatology Online Journal ◽

10.5070/d33tn0b9k4 ◽

2007 ◽

Vol 13 (1) ◽

Author(s):

Megan M Moore ◽

Olympia I Kovich ◽

Lance H Brown

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large Cell ◽

Low Grade ◽

Cutaneous B Cell Lymphoma

Download Full-text

Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.4.1654 ◽

1997 ◽

Vol 15 (4) ◽

pp. 1654-1663 ◽

Cited By ~ 48

Author(s):

D Wendum ◽

C Sebban ◽

P Gaulard ◽

B Coiffier ◽

H Tilly ◽

...

Keyword(s):

Bone Marrow ◽

Prognostic Factors ◽

B Cell ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

B Cell Lymphoma ◽

Large Cell ◽

Intensive Chemotherapy ◽

Large B Cell Lymphoma ◽

Beta 2 Microglobulin

PURPOSE The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial. PATIENTS AND METHODS Eighty-nine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol. RESULTS After intensive induction treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvement (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%). CONCLUSION FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 microglobulin) have been identified to define a subset of patients who require other therapeutic approach.

Download Full-text

CD5-Negative, CD10-Negative Low-Grade B-Cell Lymphoproliferative Disorders of the Spleen

Current Oncology ◽

10.3390/curroncol28060430 ◽

2021 ◽

Vol 28 (6) ◽

pp. 5124-5147

Author(s):

John J. Schmieg ◽

Jeannie M. Muir ◽

Nadine S. Aguilera ◽

Aaron Auerbach

Keyword(s):

Bone Marrow ◽

B Cell ◽

Hairy Cell Leukemia ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoproliferative Disorders ◽

Low Grade ◽

Hairy Cell ◽

Cell Leukemia ◽

Red Pulp

CD5-negative, CD10-negative low-grade B-cell lymphoproliferative disorders (CD5-CD10-LPD) of the spleen comprise a fascinating group of indolent, neoplastic, mature B-cell proliferations that are essential to accurately identify but can be difficult to diagnose. They comprise the majority of B-cell LPDs primary to the spleen, commonly presenting with splenomegaly and co-involvement of peripheral blood and bone marrow, but with little to no involvement of lymph nodes. Splenic marginal zone lymphoma is one of the prototypical, best studied, and most frequently encountered CD5-CD10-LPD of the spleen and typically involves white pulp. In contrast, hairy cell leukemia, another well-studied CD5-CD10-LPD of the spleen, involves red pulp, as do the two less common entities comprising so-called splenic B-cell lymphoma/leukemia unclassifiable: splenic diffuse red pulp small B-cell lymphoma and hairy cell leukemia variant. Although not always encountered in the spleen, lymphoplasmacytic lymphoma, a B-cell lymphoproliferative disorder consisting of a dual population of both clonal B-cells and plasma cells and the frequent presence of the MYD88 L265P mutation, is another CD5-CD10-LPD that can be seen in the spleen. Distinction of these different entities is possible through careful evaluation of morphologic, immunophenotypic, cytogenetic, and molecular features, as well as peripheral blood and bone marrow specimens. A firm understanding of this group of low-grade B-cell lymphoproliferative disorders is necessary for accurate diagnosis leading to optimal patient management.

Download Full-text

Large Cell Variants of CD5+, CD23− B-Cell Lymphoma/Leukemia

Archives of Pathology & Laboratory Medicine ◽

10.5858/2001-125-0513-lcvocc ◽

2001 ◽

Vol 125 (4) ◽

pp. 513-518

Author(s):

Cherie H. Dunphy ◽

Sherrie L. Perkins

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

B Cell ◽

Cyclin D1 ◽

Clinical Data ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large Cell ◽

Cell Leukemia ◽

Mantle Cell

Abstract Context.—Mantle cell lymphoma (MCL), and its leukemic phase, constitute a well-studied hematologic malignancy with known overall survival, prognostic indicators, morphologic findings at diagnosis and in bone marrow, and known incidence of the bcl-1 immunoglobulin gene rearrangement. Large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype (CD5+, CD23−), including but not limited to blastic MCL, prolymphocytoid MCL, blastic mantle cell leukemia, and prolymphocytic mantle cell leukemia, are not as well characterized. Although blastic MCL is known to be associated with a shorter overall survival than conventional MCL, the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype have not been described as fully as conventional MCL. Objective.—The purpose of the present study was to describe the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype. Design.—Nineteen cases of large cell variants of CD5+, CD23− B-cell lymphoma/leukemia are reviewed and described in regard to morphology, bone marrow morphological findings, Cyclin D1 immunostaining, and bcl-1 analysis. Clinical data were not available owing to the varied clinical sources of the specimens. Setting.—Tertiary-care academic institution. Results.—Lymph node involvement in blastic CD5+, CD23− B-cell lymphoma was diffuse (100%) with a nodular component (33%) or focal mantle zone pattern (10%). Bone marrow involvement in blastic CD5+, CD23− B-cell lymphoma was seen in only 27% of cases and was composed predominantly of small, slightly irregular lymphocytes. Cyclin D1 was demonstrated in 60% of the 15 cases analyzed and more sensitive in B5–fixed tissue. Bcl-1 (performed in 5 cases) was not detected in the 4 cases of blastic CD5+, CD23− B-cell lymphoma analyzed and was detected in the case of the prolymphocytoid MCL. Cyclin D1 was demonstrated in all 4 bcl-1 negative cases and was negative in the bcl-1 positive prolymphocytoid MCL. Conclusion.—Careful analysis of clinical data, morphology, immunophenotype, Cyclin D1 expression, and molecular analysis are required to differentiate the unusual large cell variants of MCL from other processes.

Download Full-text

Bone Marow (BM) Involvement in Diffuse Large B Cell Lymphoma (DLBCL): Clinical Impact of Discordant Disease.

Blood ◽

10.1182/blood.v108.11.2031.2031 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2031-2031

Author(s):

Mukesh Chhanabhai ◽

Joseph Connors ◽

Wayne Seville ◽

Dan Matso ◽

Randy Gascoyne

Keyword(s):

Bone Marrow ◽

B Cell ◽

De Novo ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Clinical Impact ◽

Low Grade ◽

Large B Cell Lymphoma ◽

Clinical Records ◽

Large B Cell

Abstract Background and Methods: Most published studies have suggested that survival of de novo DLBCL with discordant BM involvement by small B cell lymphoma is indistinguishable from patients having a negative staging BM. The aim of the study was to investigate the incidence and clinical impact of BM involvement by concordant and discordant B cell lymphoma in patients with DLBCL seen in a single institution over a 5 year period (1\1\2000 – 31\12\2004). The cases were identified from pathology records and BCCA Lymphoid Cancer Database. Results: The group of interest for this study comprised 652 patients with de novo DLBCL with staging marrow available for review. 60 of 652 (9.2%) of patients with DLBCL had concordant large B-cell lymphoma in their bone marrow. 523 (80.2%) were negative, 16 patients showed what we considered to be atypical lymphoid (ALH) infiltrates lacking definitive features of malignancy. In 50 patients (7.7%) the bone marrow showed discordant histology with predominantly small B-cells, some showing paratrabecular localization. In total there were five cases of TCRBCL in the study, three with marrow involvement. Furthermore, all 54 cases of primary mediastinal B-cell lymphoma (PMBCL) had a negative BM. Of the 652 cases with DLBCL with staging bone marrows available, merging the pathology and clinical databases resulted in 599 patients with complete clinical records. Of these, bone marrows were either not done or deemed inadequate in 101 cases. Therefore, there were 488 patients with DLBCL with an interpretable marrow of which 344 had advanced stage disease. Staging marrows in these patients were negative = 264, positive 41, discordant 28, and ALH 11. The overall survival and progression free survival were strongly affected by the IPI score for these 344 cases (P<0.00001) (see figure). Compared to those without BM involvement patients with concordant large B-cell lymphoma in their BM (n=41) had the worst outcome and those with discordant small B-cell lymphoma in the bone marrow (n=28) had an inferior but intermediate outcome (median survivals (months) = not reached;12 and 20, respectively). Conclusion: Diffuse large B-cell lymphoma is a heterogenous group of lymphomas as demonstrated by gene expression profiling. Our data suggests that discordant low grade B-cell lymphoma in patients who have coincident DLBCL has a poorer prognosis and the presence or absence of BM disease has clinical significance. Though we had very few cases, TCRBCL show a higher incidence of BM involvement in keeping with the reported literature. The absence of marrow disease in PMBCL is consistent with recent data indicating it is a biologically distinct form of DLBCL. Figure Figure

Download Full-text

Non-Hodgkin lymphoma across the pediatric and adolescent and young adult age spectrum

Hematology ◽

10.1182/asheducation-2016.1.589 ◽

2016 ◽

Vol 2016 (1) ◽

pp. 589-597 ◽

Cited By ~ 18

Author(s):

John T. Sandlund ◽

Mike G. Martin

Keyword(s):

B Cell ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Tumor Biology ◽

B Cell Lymphoma ◽

Large Cell ◽

Low Grade ◽

Large B Cell Lymphoma ◽

Large Cell Lymphoma ◽

Large B Cell

Abstract The non-Hodgkin lymphomas (NHLs) occurring in children and adolescents and young adults (AYA) are characterized by various age-related differences in tumor biology and survival. Children generally present with high-grade lymphomas, such as Burkitt lymphoma, diffuse large B-cell lymphoma, lymphoblastic lymphoma, and anaplastic large cell lymphoma, whereas low-grade histologic subtypes, such as follicular lymphoma, occur more frequently with increasing age. Treatment outcome for children with NHL is generally superior to that observed in adults. Factors contributing to this discrepancy include psychosocial factors, patient factors, and differences in tumor biology and therapy. These factors will be reviewed, with particular attention to the biological features of diffuse large B-cell lymphoma and anaplastic large cell lymphoma and corresponding therapeutic challenges. Novel targeting agents have been developed, which have been shown to be active in some patients. There is clearly a need for treatment protocols with eligibility criteria that cover the full span of the pediatric and AYA age range and that incorporate detailed molecular characterization of the tumors.

Download Full-text

Ongoing Monoclonal B-Cell Proliferation Is Not Common in Gastric B-Cell Lymphoma After Combined Radiochemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2004.08.177 ◽

2004 ◽

Vol 22 (15) ◽

pp. 3039-3045 ◽

Cited By ~ 8

Author(s):

Birgit Alpen ◽

Rolf Kuse ◽

Radzak Parwaresch ◽

Hans Konrad Müller-Hermelink ◽

Manfred Stolte ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Variable Region ◽

B Cell Lymphoma ◽

Large Cell ◽

Before And After ◽

Ann Arbor ◽

Combined Radiochemotherapy ◽

H Pylori

Purpose Gastric marginal-zone B-cell lymphoma (MZBCL) of the mucosa-associated lymphoid tissue (MALT) is associated with chronic Helicobacter pylori gastritis. Stable complete remission (CR) can be induced by H pylori eradication. Whether this is paralleled by cure of the lymphoma remains unclear. Persisting monoclonal bands for immunoglobulin heavy chain variable region (VH) representing the lymphoma clone have been described in up to 50% of patients in CR. This retrospective study investigated whether this phenomenon also occurs after radiochemotherapy. Patients and Methods Biopsy samples of 20 patients receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone and irradiation were analyzed before and after therapy. Study patients had Ann Arbor stage I/II primary gastric cancer, including four cases of MZBCL of MALT type, 12 cases of diffuse large-cell lymphomas (DLCL), and four cases of mixed MALT type/DLCL. Polymerase chain reaction (PCR) for VH rearrangement was performed. Monoclonal PCR products were cloned and sequenced. Results Fourteen of 20 patients had a monoclonal or oligoclonal band distribution at diagnosis converted into polyclonal pattern after radiochemotherapy. Of the remaining six patients, two were lost to follow-up. One patient did not respond and died of progressive disease. PCR in this patient showed persistent B-cell clonality. In three patients, the initial PCR showed a polyclonal pattern and thus could not be evaluated during follow-up. Conclusion In contrast with H pylori eradication alone, radiochemotherapy results in clearing of monoclonal cells during follow-up. This may result in better elimination of residual lymphoma cells. Further study is needed to determine whether this translates into lower risk of relapse.

Download Full-text

An unusual case of primary hepatic lymphoma with dramatic but unsustained response to bendamustine plus rituximab and literature review

SAGE Open Medical Case Reports ◽

10.1177/2050313x17709190 ◽

2017 ◽

Vol 5 ◽

pp. 2050313X1770919 ◽

Cited By ~ 1

Author(s):

Sih-Han Liao ◽

Yin-Kai Chen ◽

Shan-Chi Yu ◽

Ming-Shiang Wu ◽

Hsiu-Po Wang ◽

...

Keyword(s):

Computed Tomography ◽

Bone Marrow ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Low Grade ◽

Hepatic Tumors ◽

Primary Hepatic Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Objectives: Primary hepatic lymphoma is an uncommon cause of hepatic space-occupying lesions. Methods: We describe the case of a 73-year-old man with primary hepatic lymphoma, who presented with a low-grade fever and lower limb weakness which had progressed in the past 2 months. Results: Abdominal ultrasound and computed tomography showed multiple small hepatic tumors. Echo-guided biopsy of the hepatic tumor demonstrated primary hepatic diffuse large B cell lymphoma. Moreover, bone marrow was uninvolved, but the bone marrow smear disclosed hemophagocytosis, which is uncommon in diffuse large B cell lymphoma. Chemotherapy with bendamustine and rituximab treatment was initiated with a dramatic response: hepatic tumors markedly shrank in size shown by follow-up computed tomography and the patient returned to his normal life. Nevertheless, the response was sustained for only 8 months. Finally, the disease resisted further chemotherapy and this patient died of a severe Klebsiella pneumoniae infection. Conclusion: Chemotherapy with bendamustine and rituximab has shown a dramatic, but not durable, response in the present case with old age and multiple comorbidities.

Download Full-text