Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression.

PURPOSE The treatment of low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphoma with prominent gastric expression is controversial. Total gastrectomy has been proposed, but is associated with significant morbidity. The aim of this monocentric study was to assess the efficacy of continuous oral chemotherapy with a single alkylating agent. PATIENTS AND METHODS Twenty-four consecutive patients, 13 men and 11 women, were studied. Their mean age was 51 years (range, 22 to 79). Low-grade B-cell MALT lymphoma was diagnosed by histologic and immunohistologic examination of endoscopic biopsies. Seventeen patients had stage I disease and seven stage IV disease, with lung and gastric involvement. Two of these seven patients also had bone marrow involvement. The alkylating agent (cyclophosphamide or chlorambucil) was administered orally and daily for periods of 12 to 24 months. RESULTS The median follow-up time was 45 months (range, 14 months to 14 years). Complete remission was obtained in 18 patients (75%) after a median treatment duration of 12 months. Five patients relapsed; two of them were successfully re-treated, and one died of MALT lymphoma that had transformed into large-cell lymphoma. Chemotherapy was stopped after 24 months for six patients who only achieved a partial remission; two of them required further treatment for progressive disease (surgery for a small-bowel localization in one case and cyclophosphamide rechallenge in the other). Nine patients had neutropenia that required a reduced chemotherapy dosage. CONCLUSION In low-grade MALT lymphoma with prominent gastric expression, continuous monochemotherapy may constitute an efficient alternative to gastrectomy, regardless of disease stage.

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Cutaneous lymphomas other than mycosis fungoides: follow-up study of 52 patients.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.11.1994 ◽

1991 ◽

Vol 9 (11) ◽

pp. 1994-2001 ◽

Cited By ~ 41

Author(s):

P Joly ◽

F Charlotte ◽

M Leibowitch ◽

C Haioun ◽

J Wechsler ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Mycosis Fungoides ◽

Stage Iv ◽

Disease Stage ◽

Cell Phenotype ◽

Low Grade ◽

Cutaneous Lymphomas ◽

Radiotherapy Alone

Cutaneous lymphomas other than mycosis fungoides (MF) represent a rare and heterogeneous group of lymphomas. Their clinical behavior remains largely unknown. In this study, the clinical and immunohistologic characteristics and follow-up data of 52 well-documented cases of cutaneous lymphomas other than MF, presenting with initial cutaneous lesions, were reviewed. Twenty-seven patients presented with skin disease alone (stage IE), and 25 patients had concurrent cutaneous and extracutaneous disease (stage IV). The tumors were grouped into high-grade lymphomas (HGLs; 21%), intermediate-grade lymphomas (IGLs; 58%), and low-grade lymphomas (LGLs; 21%). A B-cell phenotype was most often expressed by cutaneous lymphomas (73%), particularly by stage IE lymphomas (85%). Among 13 cases of T-cell lymphomas, loss of one of the pan-T-cell antigens was detected in all cases but one. The clinical course of cutaneous lymphoma was closely dependent on stage and histologic subtype but not on T-cell or B-cell phenotype. Of 20 patients with stage IV HGL or IGL, 13 were treated by polychemotherapy with curative potential. Their median survival was 37 months. Fourteen patients with stage IE HGL or IGL were treated by radiotherapy alone. Nine patients (69%) relapsed within 2 years posttreatment. Seven of them relapsed in the skin outside the initial site involved, suggesting that radiotherapy alone is not an adequate treatment for these patients. Preliminary results concerning seven other patients with stage IE IGL or HGL treated by an initial third-generation polychemotherapy regimen are presented.

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NRG1 fusion-positive lung cancers: Clinicopathologic profile and treatment outcomes from a global multicenter registry.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.9081 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 9081-9081 ◽

Cited By ~ 6

Author(s):

Michaël Duruisseaux ◽

Stephen V. Liu ◽

Ji-Youn Han ◽

Valerie Gounant ◽

Jin-Yuan Shih ◽

...

Keyword(s):

Single Agent ◽

Treatment Strategies ◽

Stage Iv ◽

Large Cell ◽

Disease Stage ◽

Lung Cancers ◽

Best Response ◽

Pathologic Features ◽

Platinum Based Chemotherapy ◽

Stage Iv Disease

9081 Background: NRG1 fusions are potentially actionable driver events enriched in NSCLCs, particularly invasive mucinous adenocarcinomas (IMAs). These fusions activate HER3/HER2, supporting the therapeutic use of HER3 and/or HER2 inhibitors, but optimal treatment strategies remain unclear. Methods: A global, multicenter network of thoracic oncologists (6 countries, 13 institutions) identified patients with pathologically confirmed NRG1 fusion-positive NSCLCs. Anonymized clinical/pathologic features and clinical outcomes were collected retrospectively. Best response to systemic therapy was determined (RECIST v1.1). PFS was calculated (Kaplan-Meier). Results: 80 NRG1 fusion-positive NSCLCs were identified. RNA-based sequencing identified 66% (n = 53/80), DNA-based sequencing 18% (n = 14/80), and FISH 16% (n = 13/80) of cases. The most common upstream partners were CD74 (45%), SLC3A2 (31%), and SDC (9%). Most patients were female (64%) and never smokers (58%). Histology was adenocarcinoma in 95% (IMA, 91%), squamous 4%, large cell neuroendocrine 1%. At diagnosis, most patients had non-metastatic disease (stage: I 33%, II 27%, III 18%, IV 22%). The lifetime frequency of brain metastases was 15%. 12 patients received the HER2 inhibitor afatinib for stage IV disease. PD was the best response in 55% (n = 6/11) of evaluable patients with 18% PR (n = 2/11) and SD 18% (n = 2/11); median PFS was 3.5 months (range 0.6-16.5 months). 19 patients received platinum-based chemotherapy; most patients had SD as their best response (47%, n = 8); PD 41% (n = 7), PR 12% (n = 2). PD-L1 was negative in the majority of tumors (79%, n = 26/33) and none had high PD-L1 expression (range 0-20%). No responses to single-agent anti-PD-1/L1 therapy were observed (PD n = 5/6, SD n = 1/6: nivolumab/atezolizumab). No responses to chemoimmunotherapy (carboplatin, pemetrexed, pembrolizumab) were observed (SD n = 4/5, PD n = 1/5). Conclusions: RNA-based testing is an important component of NRG1 fusion detection. Novel targeted therapeutic approaches are needed as overall outcomes with afatinib are poor. NRG1 fusion-positive NSCLCs do not highly express PD-L1 and outcomes with immunotherapy ± chemotherapy are poor.

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Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue

Blood ◽

10.1182/blood.v85.8.2000.bloodjournal8582000 ◽

1995 ◽

Vol 85 (8) ◽

pp. 2000-2004 ◽

Cited By ~ 210

Author(s):

AC Wotherspoon ◽

TM Finn ◽

PG Isaacson

Keyword(s):

B Cell ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Marginal Zone ◽

B Cell Lymphoma ◽

Low Grade ◽

B Cell Lymphomas ◽

Splenic Lymphoma ◽

Trisomy 3 ◽

Primary Splenic Lymphoma

Characteristic chromosomal aberrations have been associated with subtypes of non-Hodgkin's lymphoma with distinct clinicopathologic features. Low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) form such a group and might be expected to be characterized by a specific cytogenetic abnormality. Metaphase analyses of MALT lymphoma are rare due to problems with fresh tissue collection and poor in vitro proliferation. However, the small number of published series suggests that chromosome trisomies, particularly trisomy 3, might be characteristic of these tumors. The application of interphase cytogenetic techniques to routinely processed material allows the examination of a large series of archival cases and is particularly useful for the demonstration of chromosome trisomies. We have used this technique to analyze 70 cases of low-grade MALT lymphoma from various sites and found trisomy 3 in 60%. This finding compares with 16% in low-grade nodal B-cell lymphoma and 27% in primary splenic lymphoma of marginal zone type (splenic lymphoma with villous lymphocytes). These results provide further evidence that low-grade MALT lymphomas from all sites form a single pathologic entity distinct from nodal B-cell lymphomas. Although MALT lymphoma and primary splenic lymphoma may arise from marginal zone B cells, they are genetically distinct.

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BCL10 gene mutation in lymphoma

Blood ◽

10.1182/blood.v95.12.3885.012k28_3885_3890 ◽

2000 ◽

Vol 95 (12) ◽

pp. 3885-3890 ◽

Cited By ~ 7

Author(s):

Ming-Qing Du ◽

Huaizheng Peng ◽

Hongxiang Liu ◽

Rifat A. Hamoudi ◽

Tim C. Diss ◽

...

Keyword(s):

B Cell ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Eradication Therapy ◽

B Cell Lymphoma ◽

Gastric Malt Lymphoma ◽

Low Grade ◽

Single Strand Conformational Polymorphism ◽

Carboxyl Terminal

BCL10 is directly involved in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma. Wild-type BCL10 promoted apoptosis and suppressed malignant transformation in vitro, whereas truncated mutants lost the pro-apoptotic activity and exhibited gain of function enhancement of transformation. We studied 220 lymphomas for genomic BCL10 mutation by polymerase chain reaction–single-strand conformational polymorphism and DNA sequencing. Nineteen mutations were found in 13 lymphoma specimens, as follows: 8 of 120 (6.7%) mucosa-associated lymphoid tissue (MALT) lymphomas, 4 of 42 (9.5%) follicular lymphomas, and 1 of 23 (4.3%) diffuse large B-cell lymphomas. No mutations were found in 14 mantle cell lymphomas or 21 T-cell lymphomas. High-grade MALT lymphoma tended to show a slightly higher mutation frequency (2 of 25, 8%) than low-grade MALT tumor (6 of 95, 6.3%). Among low-grade gastric MALT lymphoma, mutations were found in 3 of 11 tumors that did not respond to Helicobacter pylori eradication therapy, but none were found in 22 tumors that regressed completely after H pylori eradication. All 14 potentially pathogenic mutations were distributed in the carboxyl terminal domain of BCL10. Deletion accounted for 10 of these mutations; 10 of 14 mutations caused truncated forms of BCL10. Western blot analysis of a mutant case confirmed the presence of truncated BCL10 products of anticipated size. Our results suggest that BCL10 mutation may play a pathogenic role in B-cell lymphoma development, particularly in aggressive and antibiotic unresponsive MALT lymphomas, and may further implicate the biologic importance of the carboxyl terminal of the molecule.

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Mucosa-associated lymphoid tissue lymphoma arising from the kidney

Canadian Urological Association Journal ◽

10.5489/cuaj.1533 ◽

2014 ◽

Vol 8 (1-2) ◽

pp. 86 ◽

Cited By ~ 2

Author(s):

Naoya Niwa ◽

Nobuyuki Tanaka ◽

Minoru Horinaga ◽

Hiroshi Hongo ◽

Yujiro Ito ◽

...

Keyword(s):

B Cell ◽

Malt Lymphoma ◽

Burkitt Lymphoma ◽

Lymphoid Tissue ◽

Cell Lymphoma ◽

Cell Lineage ◽

B Cell Lymphoma ◽

Low Grade ◽

High Grade ◽

Renal Lymphoma

Primary renal lymphoma is rare, and most are intermediate- and high-grade lymphomas of B-cell lineage, such as diffuse large B-cellor Burkitt lymphoma. We report a case of low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) arising from the kidney. Only a few cases of primary renal MALT lymphoma have been published.

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Epstein-Barr Virus–Associated High-Grade B-Cell Lymphoma of Mucosal-Associated Lymphoid Tissue in a 9-Year-Old Boy

Archives of Pathology & Laboratory Medicine ◽

10.5858/2000-124-1520-ebvahg ◽

2000 ◽

Vol 124 (10) ◽

pp. 1520-1524 ◽

Cited By ~ 2

Author(s):

Jianguo Tao ◽

Leonard Kahn

Keyword(s):

B Cell ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Epstein Barr Virus ◽

B Cell Lymphoma ◽

Low Grade ◽

Renal Tubules ◽

High Grade ◽

Barr Virus ◽

Epstein Barr

Abstract We report an unusual case of Epstein-Barr virus (EBV)-associated mucosal-associated lymphoid tissue (MALT) lymphoma involving the lungs, kidneys, and axillary lymph nodes in a child with congenital hypoadrenalism and panhypopituitarism. The patient presented with an aggressive clinical course and histologic evolution. Initial biopsies (1994) of the lung and kidney revealed histologic features of low-grade B-cell MALT lymphoma with lymphoepithelial lesions within the renal tubules and bronchial epithelium. Subsequent biopsies (1996, 1997, and 1999) revealed progressively greater cytologic atypia, polymorphism, and necrosis; an increased mitotic rate; and a preponderance of large cells, indicative of progression from a low-grade to a high-grade MALT lymphoma. Immunophenotyping of the lung and lymph node lesions revealed identical surface marker profiles: cells were CD19+, CD20+, immunoglobulin (Ig) G+, κ+, λ−, CD5−, CD10−, CD23−, and IgM−, and also negative for T-cell markers. Genotypic analysis demonstrated the presence of immunoglobulin heavy chain rearrangement and monoclonality of EBV in the lung lesion by Southern blot hybridization and polymerase chain reaction (PCR). The clinicopathologic features suggest that these lesions might represent an immunosupression-related continuum of low-grade to high-grade MALT lymphomas. Infection with EBV may have contributed to this tumor's aggressive clinical and histologic evolution.

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MicroRNA Profiling in Low-Grade Ocular MALT and Diffuse Large B-Cell Lymphoma: A Role for MYC and NFKB1 Mediated Dysregulation of MicroRNA Expression in Aggressive Disease

Blood ◽

10.1182/blood.v120.21.1600.1600 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1600-1600

Author(s):

Christoffer Hother ◽

Peter Kristian Rasmussen ◽

Tejal Joshi ◽

Ditte Reker ◽

Ulrik Ralfkiaer ◽

...

Keyword(s):

B Cell ◽

Malt Lymphoma ◽

Mirna Expression ◽

Cell Lymphoma ◽

Stage Iv ◽

B Cell Lymphoma ◽

Low Grade ◽

Large B Cell Lymphoma ◽

Expression Cluster ◽

Cluster 2

Abstract Abstract 1600 Introduction: Although rare, ocular adnexal lymphomas (i.e. lymphoma of the orbit, eyelids, conjunctiva, lacrimal gland and lacrimal sac), are among the most common malignant tumors involving the ocular adnexal regions. The main subtypes are low-grade mucosa associated lymphoid tissue (MALT) lymphoma and aggressive diffuse large B cell lymphoma (DLBCL). In rare cases low-grade MALT lymphoma are reported to transform to DLBCL. It is unclear, however, which genetic events distinguish low-grade disease from aggressive, potentially fatal, disease. Material and methods: A total of 18 MALT lymphomas and 25 DLBCLs involving ocular adnexal sites were included in the study. All sections were analyzed immunohistochemically by two independent pathologists (ER, SH) using the following panel of antibodies: bcl-2, bcl-6, CD3, CD5, CD10, CD20, CD23, CD79α, cyclin D1, MUM-1 and Ki-67. Confirmed cases of DLBCL were categorized as either germinal centre B-cell-like (GCB) or non-GCB types according to the algorithm by Hans et al. Using LNA-based arrays from Exiqon, we performed global miRNA expression profiling of RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. The most differentially expressed microRNAs were confirmed by RT-qPCR analyses. Microarray processing was performed using the R environment. Results: Of the18 MALT patients (pts.) 15 pts. (83%) presented with Stage I lymphoma and 3 pts. (17%) had Stage IV. The 5-year overall survival for the entire population was 77%. In the DLBCL group 13 pts. (52%) presented with Stage I lymphoma, 3 pts. (12%) Stage II lymphoma, 1 pt. (4%) Stage III and 8 pts. (32%) presented with Stage IV lymphoma. Nine of the DLBCLs were classified as GCB and 16 as non-GCB type. The 5-year overall survival for the entire group was only 13%. Our miR arrays and confirmatory qPCR analysis revealed 43 miRNAs with significantly altered expression profiles (41 down- and 2 upregulated) in DLBCL compared to MALT lymphoma. Seven of the miRNAs down-regulated in DLBCL relative to MALT lymphoma showed enrichment for a direct transcriptional repression by the oncoprotein MYC. Supervised hieracical clustering analysis identified tree clusters: Cluster 1: MALT (high expression), cluster 2: DLBCL (intermediate expression), cluster 3 DLBCL (low expression). Thus, apparently the DLBCLs in cluster 2 seem to resemble MALT more than DLBCLs in cluster 3. We also report loss of miRNAs involved in the regulation of NFKB1 and DNA methyltransferases in DLBCL vs MALT. Conclusion: We conclude that fundamental differences in miRNA expression exist between ocular adnexal MALT lymphoma and DLBCL. Among the possible consequences of altered miRNA expression are increased NF-kB signaling and DNA hypermethylation. However, in line with the recent observations in gastric MALT/DLBCL transformation1, we suggest the differences may at least in part be caused by MYC transcriptional regulation of miRNAs in aggressive cases. The fraction of DLBCL that is reported to arise from MALT is exceedingly low. However, in the current study we find a group of DLBCLs (cluster 2), whose level of MYC regulated miRNA expression is intermediate between MALT (cluster 1) and DLBCL (cluster 3). Thus it could be speculated whether cluster 2 DLBCLs have developed secondary to a preceding MALT lesion, which, however was not detected by histology. Disclosures: No relevant conflicts of interest to declare.

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BCL10 gene mutation in lymphoma

Blood ◽

10.1182/blood.v95.12.3885 ◽

2000 ◽

Vol 95 (12) ◽

pp. 3885-3890 ◽

Cited By ~ 80

Author(s):

Ming-Qing Du ◽

Huaizheng Peng ◽

Hongxiang Liu ◽

Rifat A. Hamoudi ◽

Tim C. Diss ◽

...

Keyword(s):

B Cell ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Eradication Therapy ◽

B Cell Lymphoma ◽

Gastric Malt Lymphoma ◽

Low Grade ◽

Single Strand Conformational Polymorphism ◽

Carboxyl Terminal

Abstract BCL10 is directly involved in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma. Wild-type BCL10 promoted apoptosis and suppressed malignant transformation in vitro, whereas truncated mutants lost the pro-apoptotic activity and exhibited gain of function enhancement of transformation. We studied 220 lymphomas for genomic BCL10 mutation by polymerase chain reaction–single-strand conformational polymorphism and DNA sequencing. Nineteen mutations were found in 13 lymphoma specimens, as follows: 8 of 120 (6.7%) mucosa-associated lymphoid tissue (MALT) lymphomas, 4 of 42 (9.5%) follicular lymphomas, and 1 of 23 (4.3%) diffuse large B-cell lymphomas. No mutations were found in 14 mantle cell lymphomas or 21 T-cell lymphomas. High-grade MALT lymphoma tended to show a slightly higher mutation frequency (2 of 25, 8%) than low-grade MALT tumor (6 of 95, 6.3%). Among low-grade gastric MALT lymphoma, mutations were found in 3 of 11 tumors that did not respond to Helicobacter pylori eradication therapy, but none were found in 22 tumors that regressed completely after H pylori eradication. All 14 potentially pathogenic mutations were distributed in the carboxyl terminal domain of BCL10. Deletion accounted for 10 of these mutations; 10 of 14 mutations caused truncated forms of BCL10. Western blot analysis of a mutant case confirmed the presence of truncated BCL10 products of anticipated size. Our results suggest that BCL10 mutation may play a pathogenic role in B-cell lymphoma development, particularly in aggressive and antibiotic unresponsive MALT lymphomas, and may further implicate the biologic importance of the carboxyl terminal of the molecule.

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