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1

Shaye, Omid S., and Alexandra M. Levine. "Marginal Zone Lymphoma." Journal of the National Comprehensive Cancer Network 4, no. 3 (March 2006): 311–18. http://dx.doi.org/10.6004/jnccn.2006.0026.

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Marginal zone lymphomas (MZLs) comprise 3 distinct entities: extranodal MZL of mucosa-associated lymphoid tissue (MALT), splenic MZL, and nodal MZL. Gastric MALT lymphoma is the most common extranodal MZL and often develops as a result of chronic Helicobacter pylori gastritis. Such cases frequently respond to antibiotics directed against H. pylori. Antigen-driven lymphomatous disease can also be seen in the association of Borrelia burgdorferi with MALT lymphoma of the skin, Chlamydia psittaci with MALT lymphoma of the ocular adnexa, Campylobacter jejuni with immunoproliferative disease of the small intestine, and hepatitis C with splenic MZL. This article discusses the pathogenesis and clinical features of MZL and the treatment options available to patients.
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2

Rossi, Davide, Francesco Bertoni, and Emanuele Zucca. "Marginal-Zone Lymphomas." New England Journal of Medicine 386, no. 6 (February 10, 2022): 568–81. http://dx.doi.org/10.1056/nejmra2102568.

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3

Kimby, Eva. "Marginal zone lymphoma." HemaSphere 2 (June 2018): 96. http://dx.doi.org/10.1097/hs9.0000000000000110.

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4

Bron, Dominique, and Nathalie Meuleman. "Marginal zone lymphomas." Current Opinion in Oncology 31, no. 5 (September 2019): 386–93. http://dx.doi.org/10.1097/cco.0000000000000554.

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5

Ferreri, Andrés J. M., and Emanuele Zucca. "Marginal-zone lymphoma." Critical Reviews in Oncology/Hematology 63, no. 3 (September 2007): 245–56. http://dx.doi.org/10.1016/j.critrevonc.2007.04.009.

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6

Zucca, Emanuele. "Marginal Zone Lymphomas." Clinical Lymphoma Myeloma and Leukemia 18 (September 2018): S93—S94. http://dx.doi.org/10.1016/j.clml.2018.06.068.

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7

Zucca, Emanuele. "Marginal Zone Lymphomas." Clinical Lymphoma Myeloma and Leukemia 19 (September 2019): S97—S99. http://dx.doi.org/10.1016/j.clml.2019.07.434.

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8

Kadin, M. "Marginal Zone Lymphoma." ASH Image Bank 2004, no. 1119 (November 19, 2004): 101238. http://dx.doi.org/10.1182/ashimagebank-2004-101238.

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9

Mueller-Hermelink, MD, H. K. "Marginal Zone Lymphoma." ASH Image Bank 2004, no. 1120 (November 20, 2004): 101242. http://dx.doi.org/10.1182/ashimagebank-2004-101242.

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10

Bertoni, Francesco, Davide Rossi, Markus Raderer, and Emanuele Zucca. "Marginal Zone Lymphomas." Cancer Journal 26, no. 4 (July 2020): 336–47. http://dx.doi.org/10.1097/ppo.0000000000000463.

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11

Piris, Miguel A., Alberto Arribas, and Manuela Mollejo. "Marginal zone lymphoma." Seminars in Diagnostic Pathology 28, no. 2 (May 2011): 135–45. http://dx.doi.org/10.1053/j.semdp.2011.03.001.

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12

Mazloom, Ali, L. Jeffrey Medeiros, Peter W. McLaughlin, Valerie Reed, Fernando F. Cabanillas, Luis E. Fayad, Barbara Pro, et al. "Marginal zone lymphomas." Cancer 116, no. 18 (August 19, 2010): 4291–98. http://dx.doi.org/10.1002/cncr.25325.

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13

Zucca, Emanuele, Francesco Bertoni, Anastasios Stathis, and Franco Cavalli. "Marginal Zone Lymphomas." Hematology/Oncology Clinics of North America 22, no. 5 (October 2008): 883–901. http://dx.doi.org/10.1016/j.hoc.2008.07.011.

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14

Swerdlow, Steven H. "Pediatric Follicular Lymphomas, Marginal Zone Lymphomas, and Marginal Zone Hyperplasia." Pathology Patterns Reviews 122, suppl_1 (December 1, 2004): S98—S109. http://dx.doi.org/10.1309/4bknake4d7ct3c1b.

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15

You, Yuying, Riley C. Myers, Larry Freeberg, Jeremy Foote, John F. Kearney, Louis B. Justement, and Robert H. Carter. "Marginal Zone B Cells Regulate Antigen Capture by Marginal Zone Macrophages." Journal of Immunology 186, no. 4 (January 21, 2011): 2172–81. http://dx.doi.org/10.4049/jimmunol.1002106.

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16

Depowski, Peter L., Harry Dunn, Sheila Purdy, Jeffrey S. Ross, and Tipu Nazeer. "Splenic Marginal Zone Lymphoma." Archives of Pathology & Laboratory Medicine 126, no. 2 (February 1, 2002): 214–16. http://dx.doi.org/10.5858/2002-126-0214-smzl.

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Abstract Splenic marginal zone lymphoma is a recently described primary splenic lymphoproliferative disorder that mainly affects older individuals. We report the case of a 22-year-old woman with morphologic and immunophenotypic findings consistent with splenic marginal zone lymphoma. This woman is one of the youngest patients ever described with this disease. The patient presented with complaints of left-sided abdominal fullness and was noted to have splenomegaly on physical examination. Laboratory evaluation revealed pancytopenia and a serum M component. The spleen was removed and weighed 1550 g. Histology showed prominent white pulp with an expanded marginal zone. The neoplastic cells were marginal zone–type cells with small to intermediate-sized nuclei with occasional conspicuous nucleoli and moderate amounts of pale to amphophilic cytoplasm. Immunophenotypic analysis revealed a B-cell population (CD20 positive) with κ-light-chain restriction. The patient was treated with adjuvant therapy, but developed progressive disease less than 2 years after initial diagnosis.
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17

Hammer, Richard D., Alan D. Glick, John P. Greer, Robert D. Collins, and John B. Cousar. "Splenic Marginal Zone Lymphoma." American Journal of Surgical Pathology 20, no. 5 (May 1996): 613–26. http://dx.doi.org/10.1097/00000478-199605000-00008.

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18

Weisenburger, Dennis D. "Nodal Marginal Zone Lymphoma." American Journal of Surgical Pathology 24, no. 2 (February 2000): 315. http://dx.doi.org/10.1097/00000478-200002000-00034.

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19

Campo, Elias, and Elaine S. Jaffe. "Nodal Marginal Zone Lymphoma." American Journal of Surgical Pathology 24, no. 2 (February 2000): 315. http://dx.doi.org/10.1097/00000478-200002000-00035.

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20

Angelopoulou, Maria K., Christina Kalpadakis, Gerassimos A. Pangalis, Marie-Christine Kyrtsonis, and Theodoros P. Vassilakopoulos. "Nodal marginal zone lymphoma." Leukemia & Lymphoma 55, no. 6 (November 12, 2013): 1240–50. http://dx.doi.org/10.3109/10428194.2013.840888.

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21

Dogan, Ahmet, and Peter G. Isaacson. "Splenic marginal zone lymphoma." Seminars in Diagnostic Pathology 20, no. 2 (May 2003): 121–27. http://dx.doi.org/10.1016/s0740-2570(03)00012-1.

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22

Zucca, E. "IN12 Marginal zone lymphomas." Critical Reviews in Oncology/Hematology 82 (April 2012): S9. http://dx.doi.org/10.1016/s1040-8428(12)70026-4.

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23

Magro, Cynthia M., Amy Yang, and Garth Fraga. "Blastic Marginal Zone Lymphoma." American Journal of Dermatopathology 35, no. 3 (May 2013): 319–26. http://dx.doi.org/10.1097/dad.0b013e318267495f.

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24

Pillai, Shiv, Annaiah Cariappa, and Stewart T. Moran. "MARGINAL ZONE B CELLS." Annual Review of Immunology 23, no. 1 (April 2005): 161–96. http://dx.doi.org/10.1146/annurev.immunol.23.021704.115728.

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25

Franco, Vito, Ada Maria Florena, and Emilio Iannitto. "Splenic marginal zone lymphoma." Blood 101, no. 7 (April 1, 2003): 2464–72. http://dx.doi.org/10.1182/blood-2002-07-2216.

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Splenic marginal zone lymphoma (SMZL) is a specific low-grade small B-cell lymphoma that is incorporated in the World Health Organization classification. Characteristic features are splenomegaly, moderate lymphocytosis with villous morphology, intrasinusoidal pattern of involvement of various organs, especially bone marrow, and relative indolent course. Tumor progression with increase of blastic forms and aggressive behavior are observed in a minority of patients. Molecular and cytogenetic studies have shown heterogeneous results probably because of the lack of standardized diagnostic criteria. To date, no definitive therapy has been established. Therapeutic options include treatment abstention, splenectomy, splenic irradiation, and chemotherapy.
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26

Yazbeck, Victor, Ian McConnell, Emily Harris, Joseph Lownik, Ariel Sindel, Roy Sabo, Alden Chesney, et al. "Modeling Marginal Zone Lymphomagenesis." Blood 136, Supplement 1 (November 5, 2020): 31. http://dx.doi.org/10.1182/blood-2020-142768.

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Introduction: Indolent B-Cell Non-Hodgkin's Lymphomas (NHL) represent a heterogeneous group of lymphoproliferative malignancies, that remain largely incurable. Marginal zone lymphomas (MZL) are the second most common subtype of indolent NHL, and lack a unique cytogenetic identifying abnormality. The B-cell receptor signaling pathway is activated in B-cell malignancy and mediates its activity mainly through the Phosphoinositide 3-kinase (PI3K) pathway. Furthermore, novel PI3K inhibitors, such as copanlisib and parsaclisib, have shown impressive clinical activity in several indolent lymphomas including MZL. This further supports the important role of the PI3K pathway in the pathogenesis of this tumor. Therefore, we hypothesized that the PI3K-mTOR pathway is sufficient for driving the pathogenesis of MZL. Methods: In order to test our hypothesis, we generated a genetically engineered mouse model carrying heterozygous global knockout alleles of both the tumor suppressor genes Phosphatase and Tensin Homolog (PTEN) and Liver Kinase B1 (LKB1). This led to over-activation of the PI3K-mTOR pathway in all mouse tissues. We closely monitored these mice for tumor formation via weekly physical examinations for several months. Upon tumor detection, the mouse was sacrificed, and tumors were sectioned for histological characterization. In order to generate a more specific model of B cells, and more accurately mimic the underlying human disease, we used the Cre-LoxP system to create the CD19-Cre-PTENfl/fl-LKB1fl/fl. Results: Thirty mice of global KO PTEN+/- LKB1 +/- died or were sacrificed due to disease progression, defined as either lymph node enlargement and/or splenomegaly. All mice showed either abnormal lymphadenopathy or splenomegaly. By Kaplan-Meier analysis, we saw a steady decrease in both tumor-free and overall survival after 3 months of age. Utilizing the product limit method, the median survival time was 6 months (95% CI: 6, 8). A total of 51 lymph nodes were sent for immunohistochemistry and pathological characterization. Of the 51 nodes, 61.5% (N=32) showed indolent Non-Hodgkin's Lymphoma, 25% (N=13) were atypical, and 11.5% (N=6) were reactive. All lymph nodes with indolent NHL were of MZL subtype. Compared to wild type (n=3), the new CD19-Cre-PTENfl/fl -LKB1fl/fl (n=3) showed an overall increase in spleen mass (120 vs 196 mg, p=0.0564), % B1 cells (4% vs 59%, p= 0.0075), % MZ cells (5% vs 30%, p=0.0547), % plasma cells (1% vs 12%, p=0.0729), and decrease in % FO cells (80% vs 12%, p=0.0003) by flowcytometry. Further characterization of the new model is currently underway. Conclusion: Marginal zone lymphoma remains an incurable lymphoma that lacks reliable preclinical models. Our data provides, for the first time, a proof of concept on the role of the PI3K-mTOR pathway in the pathogenesis of marginal zone lymphoma and paves the way for future studies understanding the biology of this disease, and developing rational therapies for this incurable malignancy. Disclosures Yazbeck: Celgene: Consultancy; AstraZeneca: Consultancy; Gilead: Research Funding; Seattle Genetics: Consultancy; Verastem: Speakers Bureau.
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27

Martin, Flavius, and John F. Kearney. "Marginal-zone B cells." Nature Reviews Immunology 2, no. 5 (May 2002): 323–35. http://dx.doi.org/10.1038/nri799.

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28

Isaacson, Peter G., and Miguel A. Piris. "Splenic Marginal Zone Lymphoma." Advances in Anatomic Pathology 4, no. 3 (May 1997): 191–201. http://dx.doi.org/10.1097/00125480-199705000-00051.

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29

Swerdlow, Steven H. "Cutaneous marginal zone lymphomas." Seminars in Diagnostic Pathology 34, no. 1 (January 2017): 76–84. http://dx.doi.org/10.1053/j.semdp.2016.11.007.

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30

Piris, Miguel A., Arantza Onaindía, and Manuela Mollejo. "Splenic marginal zone lymphoma." Best Practice & Research Clinical Haematology 30, no. 1-2 (March 2017): 56–64. http://dx.doi.org/10.1016/j.beha.2016.09.005.

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31

Oscier, David, Roger Owen, and Stephen Johnson. "Splenic marginal zone lymphoma." Blood Reviews 19, no. 1 (January 2005): 39–51. http://dx.doi.org/10.1016/j.blre.2004.03.002.

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32

Birjandi, Shirin Z., Jill A. Ippolito, Anand K. Ramadorai, and Pamela L. Witte. "Alterations in Marginal Zone Macrophages and Marginal Zone B Cells in Old Mice." Journal of Immunology 186, no. 6 (February 9, 2011): 3441–51. http://dx.doi.org/10.4049/jimmunol.1001271.

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33

Cerhan, James R., and Thomas M. Habermann. "Epidemiology of marginal zone lymphoma." Annals of Lymphoma 5 (March 2021): 1. http://dx.doi.org/10.21037/aol-20-28.

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34

Gorgu, Metin, Ali Gokkaya, Ertugrul Karanfil, and Jehat Kizilkan. "Primary cutaneous marginal zone lymphoma." Turkish Journal of Plastic Surgery 29, no. 4 (2021): 225. http://dx.doi.org/10.4103/tjps.tjps_15_21.

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35

Yazdanbakhsh, Karina. "“Allo” from the (marginal) zone." Blood 138, no. 8 (May 4, 2021): 595–96. http://dx.doi.org/10.1182/blood.2021011973.

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36

Slater, David N. "Marginal Zone Lymphoma of Skin." American Journal of Surgical Pathology 21, no. 6 (June 1997): 739. http://dx.doi.org/10.1097/00000478-199706000-00019.

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37

Bailey, Elizabeth M., Judith A. Ferry, Nancy L. Harris, and Lyn M. Duncan. "Marginal Zone Lymphoma of Skin." American Journal of Surgical Pathology 21, no. 6 (June 1997): 739–40. http://dx.doi.org/10.1097/00000478-199706000-00020.

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38

Deinbeck, Kristin, Hans Geinitz, Bernhard Haller, and Khashayar Fakhrian. "Radiotherapy in marginal zone lymphoma." Radiation Oncology 8, no. 1 (2013): 2. http://dx.doi.org/10.1186/1748-717x-8-2.

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39

Ahmadi, Sebastian A., Stephan Frank, Daniel Hänggi, and Sven O. Eicker. "Primary Spinal Marginal Zone Lymphoma." Neurosurgery 71, no. 2 (February 6, 2012): E495—E508. http://dx.doi.org/10.1227/neu.0b013e31824e50fb.

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Abstract BACKGROUND AND IMPORTANCE: Marginal zone lymphoma (MZL) describes a heterogeneous group of indolent B-cell lymphomas. The World Health Organization recognizes 3 types of MZLs: splenic MZL, nodal MZL, and extranodal MZL of mucosa-associated lymphoid tissue. There is no consensus on the optimal adjuvant treatment modalities for intracranial primary MZLs. To date, no case of spinal primary MZL has been reported. CLINICAL PRESENTATION: We present the first case of spinal MZL diagnosed in a 65-year-old man with progressive paraparesis. He underwent surgical removal of the main spinal tumor mass, which extended epidurally from vertebral body T3 to T7. Surgery was followed by 10 sessions of local irradiation for a total dose of 31 Gy. On long-term follow-up in 2010, the patient was in good health without any signs of residual or recurrent disease. Twenty-seven publications reporting on 61 cases of intracranial primary MZL were identified and reviewed. In the majority of cases of marginal zone B-cell lymphoma, adjuvant radiotherapy was used, with some combining radiotherapy and chemotherapy after surgical removal of the bulk of the main tumor. Long-term follow-up in most patients showed no evidence of disease and clinical well-being years after the initial diagnosis. CONCLUSION: Chemotherapy and/or radiation have been used in larger case series. Although there is no defined treatment guideline for this rare disease entity, our review of the literature suggests a favorable prognosis when combining surgical and adjuvant radiotherapy approaches.
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40

Schmid, C., N. Kirkham, T. Diss, and P. G. Isaacson. "Splenic Marginal Zone Cell Lymphoma." American Journal of Surgical Pathology 16, no. 5 (May 1992): 455–66. http://dx.doi.org/10.1097/00000478-199205000-00004.

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41

Thieblemont, Catherine, Frederic Davi, Maria-Elena Noguera, and Josette Brière. "Non-MALT marginal zone lymphoma." Current Opinion in Hematology 18, no. 4 (July 2011): 273–79. http://dx.doi.org/10.1097/moh.0b013e3283477815.

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42

Spencer, Jo, Marta E. Perry, and Deborah K. Dunn-Walters. "Human marginal-zone B cells." Immunology Today 19, no. 9 (September 1998): 421–26. http://dx.doi.org/10.1016/s0167-5699(98)01308-5.

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43

Dalle, Stéphane, Luc Thomas, Brigitte Balme, Charles Dumontet, and Catherine Thieblemont. "Primary cutaneous marginal zone lymphoma." Critical Reviews in Oncology/Hematology 74, no. 3 (June 2010): 156–62. http://dx.doi.org/10.1016/j.critrevonc.2009.09.003.

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44

Noy, Ariela. "Treatment of Marginal Zone Lymphoma." Clinical Lymphoma Myeloma and Leukemia 17 (September 2017): S166—S167. http://dx.doi.org/10.1016/j.clml.2017.08.076.

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45

Weill, Jean-Claude, Sandra Weller, and Claude-Agnès Reynaud. "Human Marginal Zone B Cells." Annual Review of Immunology 27, no. 1 (April 2009): 267–85. http://dx.doi.org/10.1146/annurev.immunol.021908.132607.

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46

Thieblemont, C. "Non-MALT marginal zone lymphomas." Annals of Oncology 19 (June 2008): iv70—iv73. http://dx.doi.org/10.1093/annonc/mdn202.

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47

Boxer, Michael, and Rashad Aboul Nasr. "Treatments for Marginal Zone Lymphoma." Blood 106, no. 11 (November 16, 2005): 4767. http://dx.doi.org/10.1182/blood.v106.11.4767.4767.

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Abstract Marginal Zone Lymphoma (MZL) is a low grade malignant B cell lymphoproliferative disorder that comprises 2% of all lymphomas. Often an enlarged spleen and villous lymphocytes are present. Many patients however may appear to have chronic lymphocytic leukemia or other lymphoproliferative disorders. Immunophenotyping can differentiate these low grade lymphoproliferative disorders. MZL frequently is CD 20 + but CD5, CD 10, and CD23−. Treatment regimens include observation, chemotherapy, splenectomy, and immunotherapy with or without chemotherapy. 20 patients over the past six have been identified with MZL based on pathologic and immunophenotypic characteristics. 6 patients have had no treatment and have had stable disease from 9 months to over 4 years. 2 patients underwent splenectomy from 3 months to 2 years from diagnosis and have stable disease. 1 patient was diagnosed at splenectomy and relapsed 5 1/2 years later and remitted with rituxin. 1 patient received weekly rituxin for 4 weeks and has been in remission for 40 months.1 patient received weekly rituxin for 4 weeks, relapsed 9 months later, and remitted with rituxin and then maintenance rituxin. 1 patient responded to weekly rituxin for 4 weeks and is receiving maintenance rituxin. 1 patient responded to weekly rituxin for 4 weeks and then had residual disease irradiated. 1 patient remains in remission after 50 months after a cervical node was irradiated. 1 patient with blastic MZL remitted with CHOP-rituxin. 2 patients progressed after rituxin and required chemotherapy. A 92 yo patient has had a partial response to rituxin. An 82 yo patient died from complications from MZL. 15/20 patients have so far avoided chemotherapy. Rituxin may be an appropriate treatment for MZL, but clinical trials will be necessary to confirm this approach.
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48

Piris, Miguel A. "Nodal marginal zone mutational signature." Blood 128, no. 10 (September 8, 2016): 1315–16. http://dx.doi.org/10.1182/blood-2016-07-724963.

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49

Segal, Glenn H. "Marginal Zone B Cell Lymphoma." Advances in Anatomic Pathology 4, no. 1 (January 1997): 44–50. http://dx.doi.org/10.1097/00125480-199701000-00006.

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50

Thieblemont, Catherine, and Bertrand Coiffier. "Management of marginal zone lymphomas." Current Treatment Options in Oncology 7, no. 3 (May 2006): 213–22. http://dx.doi.org/10.1007/s11864-006-0014-9.

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