Histogenesis and Pathogenesis of Primary Breast Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1371-1371 ◽  
Author(s):  
Davide Rossi ◽  
Eva Berra ◽  
Mirella Marino ◽  
Daniela Capello ◽  
Michaela Cerri ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Base Pair ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Missense Mutations ◽  
Primary Breast Lymphoma ◽  
Single Base ◽  
Breast Lymphoma ◽  
Single Base Pair

Abstract Primary lymphoma of the breast accounts for <2% of extranodal non-Hodgkin’s lymphoma and generally displays morphology consistent with diffuse large B-cell lymphoma (DLBCL). The pathogenesis and histogenesis of primary breast lymphoma are currently unknown and represented the aim of this study. Thirteen cases of primary breast lymphoma (all DLBCL) were analyzed for physiological somatic hypermutation (SHM) of IgV and BCL-6 genes, as well as for aberrant SHM of PAX-5, PIM-1, RhoH/TTF and c-MYC genes. A functional IgVH rearrangement was identified in 8/13 (61.5%) primary breast lymphomas. All IgVH genes displayed SHM, with a mutation frequency ranging from 4.0% to 25.9%, suggesing that primary breast lymphomas derive from GC-related B-cells. The IgVH gene families utilized included VH4 (4/8 cases), VH3 (3/8 cases) and VH2 (1/8 case). Three cases utilized the same VH 4.30.1/4-31 gene. Mutations of BCL-6 were detected in 7/13 (53.8%) cases, further confirming the finding that primary lymphomas of the breast derive from GC-experienced B cells. Analysis of aberrant SHM of proto-oncogenes was performed on selected regions known to contain >90% of mutations found in lymphoma. Overall, mutations in at least one of the four proto-oncogenes targeted by aberrant SHM were found in 9/13 (69%) primary breast lymphomas, whereas mutations in more than one gene were found in 4/9 (44%) cases. Each of the four proto-oncogenes was altered in a significant fraction of primary breast lymphomas (PAX-5 in 4/9 cases; RhoH/TTF in 5/9 cases; PIM-1 in 5/9 cases and c-MYC in 2/9 cases). The overwhelming majority of mutations was represented by single base-pair substitutions (n=36), whereas in only one instance a deletion of a short DNA stretch was observed. Among the 36 single base-pair substitutions detected in primary breast lymphoma, the transition/transversion ratio was 1.76 (expected 0.5; p<0.01; Chi square test), reflecting the mutational profile seen in nodal DLBCL of immunocompetent hosts. In PIM-1, a fraction of mutations led to amino acid substitution, with potential functional consequences. In particular, three primary breast lymphomas displayed four missense mutations localized within the serine-threonine kinase domain of PIM-1. The association of primary breast lymphoma with aberrant SHM of proto-oncogenes expands the types of aggressive lymphomas marked by this molecular abnormality and provides clues for understanding breast lymphoma pathogenesis. In particular, missense mutations in the PIM-1 coding region can deregulate its function, whereas mutations of the 5′ regulatory regions of PAX-5, RhoH/TTF and c-MYC are expected to influence the expression and regulation of these genes in a fashion similar to that reported for the BCL-6 gene in B-cell lymphoma. Consistent with the role of PAX-5 in B-cell differentiation, of RhoH/TTF in signal transduction, and of c-MYC in B-cell growth and fate, deregulation of these genes by aberrant hypermutation may contribute to breast lymphoma pathogenesis by multiple pathways.

Aberrant Somatic Hypermutation in Primary Mediastinal Large B-Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2268-2268 ◽  
Author(s):  
Davide Rossi ◽  
Michaela Cerri ◽  
Daniela Capello ◽  
Clara Deambrogi ◽  
Eva Berra ◽  
...  
Keyword(s):  
B Cell ◽  
Base Pair ◽  
Mutation Frequency ◽  
Cell Lymphoma ◽  
Somatic Hypermutation ◽  
B Cell Lymphoma ◽  
Single Base ◽  
Large B Cell Lymphoma ◽  
Single Base Pair ◽  
Large B Cell

Abstract Primary mediastinal large B-cell lymphoma (PMLBCL) is recognised as a subtype of diffuse large B-cell lymphoma (DLBCL) arising in the mediastinum. With respect to DLBCL, PMLBCL displays specific clinical, molecular and morphological features suggesting that PMLBCL may represent a distinct clinico-pathologic entity. Aberrant somatic hypermutation (SHM) of PIM-1, PAX-5, RhoH/TTF and c-MYC has been advocated as a molecular feature distinctive of DLBCL. To investigate wether the same mechanism is associated with PMLBCL, we performed mutational analysis of PIM-1, PAX-5, RhoH/TTF and c-MYC in a panel of 19 PMLBCL. For comparison, 19 DLBCL were also analysed. For each gene, a region previously shown to contain >90% of mutations was analysed by PCR amplification and DNA direct sequencing. Overall, the prevalence of mutated cases was similar among DLBCL and PMLBCL. Mutations targeting at least one of the 4 genes were found in 14/19 (73.6%) PMLBCL and 13/19 (68.4%) DLBCL, while mutations in more than one gene were found in 7/19 (36.8%) PMLBCL and 9/19 (47.3%) DLBCL. Among the four genes, the prevalence of mutation and the mutation frequency was superimposable between PMLBCL and DLBCL. In fact, PAX-5 was mutated in 9/19 (47.3%) PMLBCL with a mean mutation frequency of 0.20 x 10−2/bp and in 7/19 (36.8%) DLBCL with a mean mutation frequency of 0.18 x 10−2/bp; RhoH/TTF was mutated in 6/19 (31.5%) PMLBCL with a mean mutation frequency of 0.08 x 10−2/bp and in 8/19 (42.1%) DLBCL with a mean mutation frequency of 0.27 x 10−2/bp; PIM-1 was mutated in 3/19 (15.7%) PMLBCL with a mean mutation frequency of 0.09 x 10−2/bp and in 7/19 (36.8%) DLBCL with a mean mutation frequency of 0.11 x 10−2/bp; c-MYC was mutated in 6/19 (31.5%) PMLBCL with a mean mutation frequency of 0.23 x 10−2/bp and in 5/19 (26.3%) DLBCL with a mean mutation frequency of 0.11 x 10−2. The mutation pattern was also similar between PMLBCL and DLBCL and was consistent with the SHM process. A total of 74 mutational events were detected in PMLBCL. The majority of mutations were represented by single base-pair substitution (n=66), whereas only 8 deletions of a short DNA stretch were observed. Of the 66 single base-pair substitutions, 41 were transitions and 25 were transversions, with a transition/transversion ratio of 1.64 and a G+C/A+T ratio of 3.6. Eleven out of 66 (16.6%) single base-pair substitutions felt within RGYW/WRCY motifs. Among DLBCL a total of 87 mutational events were detected. Mutations were preferentially represented by single base-pair substitutions (n=81), whereas only 4 deletions and 2 insertions of a short DNA stretch were observed. Of the 81 single base-pair substitutions, 42 were transitions and 39 were transversions, with a transition/transversion ratio of 1.07 and a G+C/A+T ratio of 1.89. Twenty six out of 81 (32.1%) single base-pair substitutions felt within RGYW/WRCY motifs. The implication of our results are twofold. First, aberrant SHM is involved in the pathogenesis of PMLBCL. Second, our results indicate that aberrant SHM targets both PMLBCL and DLBCL with similar prevalence, distribution and mutation pattern. Since aberrant SHM has been advocated as a molecular marker of DLBCL, our results corroborate the notion that PMLBCL represent a subtype of DLBCL rather than a distinct clinico-pathologic entity.

scholarly journals 170 Primary Breast Lymphoma-Mimicking Inflammatory Breast Disease: A Case Report

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
R Alam ◽  
B Basak ◽  
A Ahsan ◽  
A S Gupta ◽  
S Islam ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Primary Breast Lymphoma ◽  
Palpable Mass ◽  
Large B Cell Lymphoma ◽  
Breast Lymphoma ◽  
History Of ◽  
Large B Cell

Abstract Primary breast lymphoma (PBL) is an unusual clinical entity accounting for 0.4–0.5% of all breast neoplasms. The usual presentation includes a painless palpable mass similar to that of breast carcinoma. Diffuse large B-cell lymphoma (DLBCL) is the most common identifiable type of PBL based on the histopathological examination. We report an unusual case of 22 years old Bangladeshi woman presented with a 6-month history of a lump on left breast. Although the lump was initially small, it began a rapid growth after 4 months. The swelling was localized and did not show any skin involvement or discharge and as she didn’t have any positive familial history of breast carcinoma her primary attending physician diagnosed it as a case of breast abscess. When local incision and drainage proved ineffective, she was referred to us. After doing an immunohistochemistry from incisional biopsy the diagnosis was confirmed as Diffuse Large B-cell Lymphoma. The patient was treated initially by chemotherapy with CHOP therapy followed by wide local excision. Early and accurate diagnosis of PBL is crucial for selecting the appropriate MDT treatment strategies to avert potentially harmful surgical interventions.

scholarly journals Primary breast lymphoma of childhood: a case report and review of literature

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Giulia A. Restivo ◽  
Marta Pillon ◽  
Lara Mussolin ◽  
Clara Mosa ◽  
Angela Guarina ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Local Treatment ◽  
B Cell Lymphoma ◽  
Left Breast ◽  
Primary Breast Lymphoma ◽  
Therapeutic Approaches ◽  
Case Presentation ◽  
Breast Lymphoma ◽  
The Right

Abstract Background Primary breast lymphoma (PBL) is an extremely rare neoplasm in children; by definition, it manifests in the breast without evidence of lymphoma elsewhere, except ipsilateral axillary nodes. Case presentation We report a case of a 15-year-old girl diagnosed with diffuse large B-cell lymphoma (DLBCL) of the right breast: the patient received chemotherapy and rituximab, achieving complete remission. A literature review revealed other 11 cases of pediatric PBL; it mainly affects female adolescents and can involve right and left breast equally. Different histologic subtypes have been described, arising from both B-cell and T-cell. Therapeutic approaches were very different, from chemotherapy to local treatment with surgery and/or radiotherapy. Conclusions Our case is the first in which rituximab was administered, suggesting to be a promising therapy in B-cell PBL, as already demonstrated in pediatric B-cell lymphoma from other sites. Further investigations are needed to identify prognostic factors and establish the most effective treatment.

scholarly journals Primary diffuse large B-cell lymphoma of the breast

2009 ◽  
Vol 17 (3-4) ◽  
pp. 80-82
Author(s):  
Lazar Popovic ◽  
Darjana Jovanovic ◽  
Gorana Matovina-Brko ◽  
Dragana Petrovic ◽  
Zoran Nikin ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Histological Subtype ◽  
Primary Breast Lymphoma ◽  
Large B Cell Lymphoma ◽  
Breast Lymphoma ◽  
Rare Location ◽  
Large B Cell

Primary breast lymphoma is rare location of this disease. Diffuse large B-cell lymphoma is the most common histological subtype. We presented two cases of primary diffuse large B-cell lymphoma of the breast and reviewed a literature about this topic.

scholarly journals Long-Term Survival and Gradual Recovery of B Cells in Patients (Pts) with Refractory Large B Cell Lymphoma (LBCL) Treated with Axicabtagene Ciloleucel (Axi-Cel)

2021 ◽  
Vol 27 (3) ◽  
pp. S404-S405
Author(s):  
Caron A. Jacobson ◽  
Frederick L. Locke ◽  
Armin Ghobadi ◽  
David B. Miklos ◽  
Lazaros J. Lekakis ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Term Survival ◽  
Long Term Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Primary Type3 (Non-ABC, Non-GCB) Subtype of Extranodal Diffuse Large B-Cell Lymphoma of the Thyroid Bearing No MYD88 Mutation by Padlock Probe Hybridization

2017 ◽  
Vol 10 (2) ◽  
pp. 508-514 ◽  
Author(s):  
Yukiko Nishi ◽  
Riko Kitazawa ◽  
Ryuma Haraguchi ◽  
Ayaka Ouchi ◽  
Yasuo Ueda ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Malignant Lymphoma ◽  
Cell Lymphoma ◽  
Clinical Phenotype ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Japanese Female ◽  
Old Japanese ◽  
Large B Cell

Primary extranodal malignant lymphoma of the thyroid is a rare entity composed of mostly neoplastic transformation of germinal center-like B cells (GCB) or memory B cells. Other B-cell-type malignancies arising primarily in the thyroid have rarely been described. Immunohistochemical examination of autopsied primary malignant lymphoma of the thyroid in an 83-year-old Japanese female revealed the presence of a non-GCB subtype of diffuse large B-cell lymphoma (DLBCL) without the typical codon 206 or 265 missense mutation of MYD88. The lack of the highly oncogenic MYD88 gene mutation, frequently observed in DLBCL of the activated B-cell (ABC) subtype, and the detection of an extremely aggressive yet local clinical phenotype demonstrated that the present case was an exceptional entity of the type3 (non-GCB and non-ABC) subtype.

Inactivating SOCS1 mutations are caused by aberrant somatic hypermutation and restricted to a subset of B-cell lymphoma entities

Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4503-4506 ◽  
Author(s):  
Anja Mottok ◽  
Christoph Renné ◽  
Marc Seifert ◽  
Elsie Oppermann ◽  
Wolf Bechstein ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
Somatic Hypermutation ◽  
B Cell Lymphoma ◽  
Rare Mutations ◽  
Large B Cell Lymphoma ◽  
Mantle Cell ◽  
Follicular Lymphomas ◽  
Large B Cell

Abstract STATs are constitutively activated in several malignancies. In primary mediastinal large B-cell lymphoma and Hodgkin lymphoma (HL), inactivating mutations in SOCS1, an inhibitor of JAK/STAT signaling, contribute to deregulated STAT activity. Based on indications that the SOCS1 mutations are caused by the B cell–specific somatic hypermutation (SHM) process, we analyzed B-cell non-HL and normal B cells for mutations in SOCS1. One-fourth of diffuse large B-cell lymphoma and follicular lymphomas carried SOCS1 mutations, which were preferentially targeted to SHM hotspot motifs and frequently obviously inactivating. Rare mutations were observed in Burkitt lymphoma, plasmacytoma, and mantle cell lymphoma but not in tumors of a non–B-cell origin. Mutations in single-sorted germinal center B cells were infrequent relative to other genes mutated as byproducts of normal SHM, indicating that SOCS1 inactivation in primary mediastinal large B-cell lymphoma, HL, diffuse large B-cell lymphoma, and follicular lymphoma is frequently the result of aberrant SHM.

BCL2 protein expression parallels its mRNA level in normal and malignant B cells

Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2936-2939 ◽  
Author(s):  
Yulei Shen ◽  
Javeed Iqbal ◽  
James Z. Huang ◽  
Guimei Zhou ◽  
Wing C. Chan
Keyword(s):  
B Cells ◽  
Protein Expression ◽  
B Cell ◽  
Posttranscriptional Regulation ◽  
Cell Lymphoma ◽  
Dominant Role ◽  
Mrna Level ◽  
B Cell Lymphoma ◽  
Transcriptional Level ◽  
Bcl2 Protein

Abstract The regulation of B-cell lymphoma 2 (BCL2) protein expression in germinal center (GC) B cells has been controversial. Previous reports have indicated posttranscriptional regulation plays a dominant role. However, a number of recent studies contradicted these reports. Using real-time polymerase chain reaction (PCR) and Standardized Reverse Transcriptase-PCR (StaRT-PCR), we measured the level of mRNA expression in GC, mantle zone (MNZ), and marginal zone (MGZ) cells from laser capture microdissection. Both quantitative RT-PCR measurements of microdissected GC cells from tonsils showed that GC cells had low expression of BCL2 transcripts commensurate with the low protein expression level. These results are in agreement with microarray studies on fluorescence-activated cell sorter (FACS)-sorted cells and microdissected GC cells. We also examined BCL2 mRNA and protein expression on a series of 30 cases of diffuse large B-cell lymphoma (DLBCL) and found, in general, a good correlation. The results suggested that BCL2 protein expression is regulated at the transcriptional level in normal B cells and in the neoplastic cells in most B-cell lymphoproliferative disorders.

Distinct roles for PARP-1 and PARP-2 in c-Myc-driven B-cell lymphoma in mice

Blood ◽  
2021 ◽  
Author(s):  
Miguel A Galindo-Campos ◽  
Nura Lutfi ◽  
Sarah Bonnin ◽  
Carlos Martínez ◽  
Talia Velasco-Hernandez ◽  
...  
Keyword(s):  
Dna Damage ◽  
B Cells ◽  
B Cell ◽  
Immune Escape ◽  
Cell Lymphoma ◽  
Tumour Progression ◽  
Cancer Therapeutics ◽  
B Cell Lymphoma ◽  
B Cell Lymphomas ◽  
Parp 1

Dysregulation of the c-Myc oncogene occurs in a wide variety of haematologic malignancies and its overexpression has been linked with aggressive tumour progression. Here, we show that Poly (ADP-ribose) polymerase (PARP)-1 and PARP-2 exert opposing influences on progression of c-Myc-driven B-cell lymphomas. PARP-1 and PARP-2 catalyse the synthesis and transfer of ADP-ribose units onto amino acid residues of acceptor proteins in response to DNA-strand breaks, playing a central role in the response to DNA damage. Accordingly, PARP inhibitors have emerged as promising new cancer therapeutics. However, the inhibitors currently available for clinical use are not able to discriminate between individual PARP proteins. We found that genetic deletion of PARP-2 prevents c-Myc-driven B-cell lymphomas, while PARP-1-deficiency accelerates lymphomagenesis in the Em-Myc mouse model of aggressive B-cell lymphoma. Loss of PARP-2 aggravates replication stress in pre-leukemic Em-Myc B cells resulting in accumulation of DNA damage and concomitant cell death that restricts the c-Myc-driven expansion of B cells, thereby providing protection against B-cell lymphoma. In contrast, PARP-1-deficiency induces a proinflammatory response, and an increase in regulatory T cells likely contributing to immune escape of B-cell lymphomas, resulting in an acceleration of lymphomagenesis. These findings pinpoint specific functions for PARP-1 and PARP-2 in c-Myc-driven lymphomagenesis with antagonistic consequences that may help inform the design of new PARP-centred therapeutic strategies with selective PARP-2 inhibition potentially representing a new therapeutic approach for the treatment of c-Myc-driven tumours.

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