{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:43:01Z","timestamp":1784331781819,"version":"3.55.0"},"reference-count":82,"publisher":"Archives of Pathology and Laboratory Medicine","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,4]]},"abstract":"Lymphoplasmacytic lymphoma (LPL) is a low-grade, B-cell neoplasm composed of small lymphocytes, plasmacytoid lymphocytes, and plasma cells that typically involve the bone marrow, and it is associated with an immunoglobulin M (IgM) gammopathy. The definition of Waldenstr\u00f6m macroglobulinemia (WM) and its relationship to LPL has been confusing in the past. In addition, the diagnosis of LPL itself can be challenging because LPL lacks disease-specific morphologic, immunophenotypic, and genetic features to differentiate it from other mature B-cell neoplasms. Accurate diagnosis of LPL\/WM rests on recognition of the differential diagnostic features between LPL and other diagnostic possibilities and the use of the recently refined definition of WM and its relationship with LPL: The presence of an IgM monoclonal gammopathy of any level in the setting of bone marrow involvement by LPL. This review summarizes the clinical, laboratory, and histologic features of LPL\/WM, with particular emphasis on unique aspects of LPL\/WM that may aid in accurate diagnosis.<\/jats:p>","DOI":"10.5858\/arpa.2012-0034-rs","type":"journal-article","created":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T16:29:13Z","timestamp":1364833753000},"page":"580-585","source":"Crossref","is-referenced-by-count":48,"title":["Lymphoplasmacytic Lymphoma and Waldenstr\u00f6m Macroglobulinemia"],"prefix":"10.5858","volume":"137","author":[{"given":"Nadia","family":"Naderi","sequence":"first","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Yang","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3906","reference":[{"issue":"2","key":"i1543-2165-137-4-580-b01","series-title":"Semin Oncol","first-page":"110","article-title":"Clinicopathological definition of Waldenstr\u00f6m's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstr\u00f6m's macroglobulinemia","volume":"30","author":"Owen\n RG,","year":"2003;","unstructured":"Owen\n RG, \n \n Treon\n SP, \n \n Al-Katib\n A, \n et al\n . 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Clin Lymphoma. 2005;5(4):246\u2013249."},{"issue":"6","key":"i1543-2165-137-4-580-b17","series-title":"Mod Pathol","first-page":"807","article-title":"Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenstr\u00f6m's macroglobulinemia","volume":"22","author":"Morice\n WG,","year":"2009;","unstructured":"Morice\n WG, \n \n Chen\n D, \n \n Kurtin\n PJ, \n \n Hanson\n CA, \n \n McPhail\n ED. \n \n Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenstr\u00f6m's macroglobulinemia. 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Arch Intern Med. 2008;168(17):1903\u20131909."},{"issue":"1","key":"i1543-2165-137-4-580-b23","series-title":"Am J Hematol","first-page":"83","article-title":"Hepatitis C viral infection is not associated with Waldenstr\u00f6m's macroglobulinemia","volume":"82","author":"Leleu\n X,","year":"2007;","unstructured":"Leleu\n X, \n \n O'Connor\n K, \n \n Ho\n AW, \n et al\n . Hepatitis C viral infection is not associated with Waldenstr\u00f6m's macroglobulinemia. Am J Hematol. 2007;82(1):83\u201384."},{"issue":"5","key":"i1543-2165-137-4-580-b24","series-title":"Haematologica","first-page":"635","article-title":"Molecular characterization of heavy chain immunoglobulin gene rearrangements in Waldenstr\u00f6m's macroglobulinemia and IgM monoclonal gammopathy of undetermined significance","volume":"92","author":"Martin-Jim\u00e9nez\n P,","year":"2007;","unstructured":"Martin-Jim\u00e9nez\n P, \n \n Garcia-Sanz\n R, \n \n Balanzategui\n A, \n et al\n . 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Blood. 2011;118:261."},{"key":"i1543-2165-137-4-580-b31","series-title":"Proceedings of the 53rd Annual American Society of Hematology Meeting and Exposition","article-title":"Whole genome sequencing reveals a widely expressed mutation (MYD88 L265P) with oncogenic activity in Waldenstr\u00f6m's macroglobulinemia","author":"Treon\n SP,","year":"2011;","unstructured":"Treon\n SP, \n \n Xu\n L, \n \n Zhou\n Y, \n et al\n . Whole genome sequencing reveals a widely expressed mutation (MYD88 L265P) with oncogenic activity in Waldenstr\u00f6m's macroglobulinemia. In: Proceedings of the 53rd Annual American Society of Hematology Meeting and Exposition; December 12, 2011;Atlanta, GA. Blood 118. Abstract 300."},{"key":"i1543-2165-137-4-580-b32","series-title":"Proceedings of the 53rd Annual American Society of Hematology Meeting and Exposition","article-title":"Disruption of MYD88 pathway signaling leads to loss of constitutive IRAK1, NF-\u03baB and JAK\/STAT signaling and induces apoptosis of cells expressing the MYD88 L265P mutation in Waldenstr\u00f6m's macroglobulinemia","author":"Yang\n G,","year":"2011;","unstructured":"Yang\n G, \n \n Zhou\n Y, \n \n Liu\n X, \n \n Cao\n Y, \n \n Hunter\n Z, \n \n Treon\n SP. \n \n Disruption of MYD88 pathway signaling leads to loss of constitutive IRAK1, NF-\u03baB and JAK\/STAT signaling and induces apoptosis of cells expressing the MYD88 L265P mutation in Waldenstr\u00f6m's macroglobulinemia. In: Proceedings of the 53rd Annual American Society of Hematology Meeting and Exposition; December 12, 2011;Atlanta, GA. Blood 118. Abstract 597."},{"issue":"9","key":"i1543-2165-137-4-580-b33","series-title":"Leukemia","first-page":"1634","article-title":"Trisomy 4, a new chromosomal abnormality in Waldenstr\u00f6m's macroglobulinemia: a study of 39 cases","volume":"20","author":"Terr\u00e9\n C,","year":"2006;","unstructured":"Terr\u00e9\n C, \n \n Nguyen-Khac\n F, \n \n Barin\n C, \n et al\n . Trisomy 4, a new chromosomal abnormality in Waldenstr\u00f6m's macroglobulinemia: a study of 39 cases. Leukemia. 2006;20(9):1634\u20131636."},{"issue":"1","key":"i1543-2165-137-4-580-b34","series-title":"Clin Lymphoma Myeloma","first-page":"17","article-title":"IgM monoclonal gammopathy of undetermined significance and smoldering Waldenstr\u00f6m's macroglobulinemia","volume":"9","author":"Kyle\n RA,","year":"2009;","unstructured":"Kyle\n RA, \n \n Benson\n J, \n \n Larson\n D, \n et al\n . IgM monoclonal gammopathy of undetermined significance and smoldering Waldenstr\u00f6m's macroglobulinemia. 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Cancer Genet Cytogenet. 2005;163(1):77\u201380."},{"issue":"2","key":"i1543-2165-137-4-580-b37","series-title":"Am J Clin Pathol","first-page":"195","article-title":"Lymphoplasmacytic lymphoma and other non-marginal zone lymphomas with plasmacytic differentiation","volume":"136","author":"Lin\n P,","year":"2011;","unstructured":"Lin\n P, \n \n Molina\n TJ, \n \n Cook\n JR, \n \n Swerdlow\n SH. \n \n Lymphoplasmacytic lymphoma and other non-marginal zone lymphomas with plasmacytic differentiation. Am J Clin Pathol. 2011;136(2):195\u2013210."},{"issue":"2","key":"i1543-2165-137-4-580-b38","series-title":"Br J Haematol","first-page":"158","article-title":"Prognostic model for disease-specific and overall mortality in newly diagnosed symptomatic patients with Waldenstr\u00f6m macroglobulinaemia","volume":"133","author":"Ghobrial\n IM,","year":"2006;","unstructured":"Ghobrial\n IM, \n \n Fonseca\n R, \n \n Gertz\n MA, \n et al\n . Prognostic model for disease-specific and overall mortality in newly diagnosed symptomatic patients with Waldenstr\u00f6m macroglobulinaemia. Br J Haematol. 2006;133(2):158\u2013164."},{"issue":"5","key":"i1543-2165-137-4-580-b39","series-title":"Expert Rev Hematol","first-page":"473","article-title":"Individualizing treatment for Waldenstr\u00f6m's macroglobulinemia","volume":"2","author":"Stedman\n J,","year":"2009;","unstructured":"Stedman\n J, \n \n Roccaro\n A, \n \n Ghobrial\n IM. \n \n Individualizing treatment for Waldenstr\u00f6m's macroglobulinemia. Expert Rev Hematol. 2009;2(5):473\u2013476."},{"issue":"2","key":"i1543-2165-137-4-580-b40","series-title":"Crit Rev Oncol Hematol","first-page":"172","article-title":"Lymphoplasmacytic lymphoma-Waldenstr\u00f6m's macroglobulinemia","volume":"67","author":"Vitolo\n U,","year":"2008;","unstructured":"Vitolo\n U, \n \n Ferreri\n AJ, \n \n Montoto\n S. \n \n Lymphoplasmacytic lymphoma-Waldenstr\u00f6m's macroglobulinemia. 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Clin Lymphoma. 2005;5(4):246\u2013249."},{"issue":"6","key":"i1543-2165-137-4-580-b17","series-title":"Mod Pathol","first-page":"807","article-title":"Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenstr\u00f6m's macroglobulinemia","volume":"22","author":"Morice\n WG,","year":"2009;","unstructured":"Morice\n WG, \n \n Chen\n D, \n \n Kurtin\n PJ, \n \n Hanson\n CA, \n \n McPhail\n ED. \n \n Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenstr\u00f6m's macroglobulinemia. 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Clin Cancer Res. 2007;13(7):2005\u20132013."},{"issue":"7","key":"i1543-2165-137-4-580-b19","series-title":"Blood","first-page":"1913","article-title":"Frequent somatic mutations in D and\/or JH segments of ig gene in Waldenstr\u00f6m's macroglobulinemia and chronic lymphocytic leukemia (CLL) with Richter's syndrome but not in common CLL","volume":"85","author":"Aoki\n H,","year":"1995;","unstructured":"Aoki\n H, \n \n Takishita\n M, \n \n Kosaka\n M, \n \n Saito\n S. \n \n Frequent somatic mutations in D and\/or JH segments of ig gene in Waldenstr\u00f6m's macroglobulinemia and chronic lymphocytic leukemia (CLL) with Richter's syndrome but not in common CLL. Blood. 1995;85(7):1913\u20131919."},{"issue":"12","key":"i1543-2165-137-4-580-b20","series-title":"Blood","first-page":"3647","article-title":"Similar patterns of V\u03ba gene usage but different degrees of somatic mutation in hairy cell leukemia, prolymphocytic leukemia, Waldenstr\u00f6m's macroglobulinemia, and myeloma","volume":"83","author":"Wagner\n SD,","year":"1994;","unstructured":"Wagner\n SD, \n \n Martinelli\n V, \n \n Luzzatto\n L. \n \n Similar patterns of V\u03ba gene usage but different degrees of somatic mutation in hairy cell leukemia, prolymphocytic leukemia, Waldenstr\u00f6m's macroglobulinemia, and myeloma. Blood. 1994;83(12):3647\u20133653."},{"issue":"18","key":"i1543-2165-137-4-580-b21","series-title":"JAMA","first-page":"2010","article-title":"Risk of non-hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus","volume":"297","author":"Giordano\n TP,","year":"2007;","unstructured":"Giordano\n TP, \n \n Henderson\n L, \n \n Landgren\n O, \n et al\n . Risk of non-hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus. JAMA. 2007;297(18):2010\u20132017."},{"issue":"17","key":"i1543-2165-137-4-580-b22","series-title":"Arch Intern Med","first-page":"1903","article-title":"Chronic immune stimulation and subsequent Waldenstr\u00f6m macroglobulinemia","volume":"168","author":"Koshiol\n J,","year":"2008;","unstructured":"Koshiol\n J, \n \n Gridley\n G, \n \n Engels\n EA, \n \n McMaster\n ML, \n \n Landgren\n O. \n \n Chronic immune stimulation and subsequent Waldenstr\u00f6m macroglobulinemia. Arch Intern Med. 2008;168(17):1903\u20131909."},{"issue":"1","key":"i1543-2165-137-4-580-b23","series-title":"Am J Hematol","first-page":"83","article-title":"Hepatitis C viral infection is not associated with Waldenstr\u00f6m's macroglobulinemia","volume":"82","author":"Leleu\n X,","year":"2007;","unstructured":"Leleu\n X, \n \n O'Connor\n K, \n \n Ho\n AW, \n et al\n . Hepatitis C viral infection is not associated with Waldenstr\u00f6m's macroglobulinemia. Am J Hematol. 2007;82(1):83\u201384."},{"issue":"5","key":"i1543-2165-137-4-580-b24","series-title":"Haematologica","first-page":"635","article-title":"Molecular characterization of heavy chain immunoglobulin gene rearrangements in Waldenstr\u00f6m's macroglobulinemia and IgM monoclonal gammopathy of undetermined significance","volume":"92","author":"Martin-Jim\u00e9nez\n P,","year":"2007;","unstructured":"Martin-Jim\u00e9nez\n P, \n \n Garcia-Sanz\n R, \n \n Balanzategui\n A, \n et al\n . Molecular characterization of heavy chain immunoglobulin gene rearrangements in Waldenstr\u00f6m's macroglobulinemia and IgM monoclonal gammopathy of undetermined significance. Haematologica. 2007;92(5):635\u2013642."},{"issue":"3","key":"i1543-2165-137-4-580-b25","series-title":"Leukemia","first-page":"541","article-title":"Gene expression profiling of B lymphocytes and plasma cells from Waldenstr\u00f6m's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals","volume":"21","author":"Guti\u00e9rrez\n NC,","year":"2007;","unstructured":"Guti\u00e9rrez\n NC, \n \n Ocio\n EM, \n \n de Las Rivas\n J, \n et al\n . Gene expression profiling of B lymphocytes and plasma cells from Waldenstr\u00f6m's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals. Leukemia. 2007;21(3):541\u2013549."},{"issue":"8","key":"i1543-2165-137-4-580-b26","series-title":"Blood","first-page":"2996","article-title":"Waldenstr\u00f6m macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions","volume":"100","author":"Schop\n RF,","year":"2002;","unstructured":"Schop\n RF, \n \n Kuehl\n WM, \n \n Van Wier\n SA, \n et al\n . Waldenstr\u00f6m macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions. Blood. 2002;100(8):2996\u20133001."},{"issue":"4","key":"i1543-2165-137-4-580-b27","series-title":"Am J Clin Pathol","first-page":"543","article-title":"Cytogenetic findings in lymphoplasmacytic lymphoma\/Waldenstr\u00f6m macroglobulinemia: chromosomal abnormalities are associated with the polymorphous subtype and an aggressive clinical course","volume":"116","author":"Mansoor\n A,","year":"2001;","unstructured":"Mansoor\n A, \n \n Medeiros\n LJ, \n \n Weber\n DM, \n et al\n . Cytogenetic findings in lymphoplasmacytic lymphoma\/Waldenstr\u00f6m macroglobulinemia: chromosomal abnormalities are associated with the polymorphous subtype and an aggressive clinical course. Am J Clin Pathol. 2001;116(4):543\u2013549."},{"issue":"3","key":"i1543-2165-137-4-580-b28","series-title":"Eur J Haematol","first-page":"244","article-title":"Analysis of 6q deletion in Waldenstr\u00f6m macroglobulinemia","volume":"79","author":"Chang\n H,","year":"2007;","unstructured":"Chang\n H, \n \n Qi\n X, \n \n Xu\n W, \n \n Reader\n JC, \n \n Ning\n Y. \n \n Analysis of 6q deletion in Waldenstr\u00f6m macroglobulinemia. Eur J Haematol. 2007;79(3):244\u2013247."},{"issue":"8","key":"i1543-2165-137-4-580-b29","series-title":"Cancer Res","first-page":"3579","article-title":"Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-\u03baB signaling pathways in Waldenstr\u00f6m's macroglobulinemia","volume":"69","author":"Braggio\n E,","year":"2009;","unstructured":"Braggio\n E, \n \n Keats\n JJ, \n \n Leleu\n X, \n et al\n . Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-\u03baB signaling pathways in Waldenstr\u00f6m's macroglobulinemia. Cancer Res. 2009;69(8):3579\u20133588."},{"key":"i1543-2165-137-4-580-b30","series-title":"Blood","first-page":"261","article-title":"A somatic variant in MYD88 (L265P) revealed by whole genome sequencing differentiates lymphoplasmacytic lymphoma from marginal zone lymphomas","volume":"118","author":"Xu\n L,","year":"2011;","unstructured":"Xu\n L, \n \n Sohani\n AR, \n \n Arcaini\n L, \n et al\n . A somatic variant in MYD88 (L265P) revealed by whole genome sequencing differentiates lymphoplasmacytic lymphoma from marginal zone lymphomas. Blood. 2011;118:261."},{"key":"i1543-2165-137-4-580-b31","series-title":"Proceedings of the 53rd Annual American Society of Hematology Meeting and Exposition","article-title":"Whole genome sequencing reveals a widely expressed mutation (MYD88 L265P) with oncogenic activity in Waldenstr\u00f6m's macroglobulinemia","author":"Treon\n SP,","year":"2011;","unstructured":"Treon\n SP, \n \n Xu\n L, \n \n Zhou\n Y, \n et al\n . Whole genome sequencing reveals a widely expressed mutation (MYD88 L265P) with oncogenic activity in Waldenstr\u00f6m's macroglobulinemia. In: Proceedings of the 53rd Annual American Society of Hematology Meeting and Exposition; December 12, 2011;Atlanta, GA. Blood 118. Abstract 300."},{"key":"i1543-2165-137-4-580-b32","series-title":"Proceedings of the 53rd Annual American Society of Hematology Meeting and Exposition","article-title":"Disruption of MYD88 pathway signaling leads to loss of constitutive IRAK1, NF-\u03baB and JAK\/STAT signaling and induces apoptosis of cells expressing the MYD88 L265P mutation in Waldenstr\u00f6m's macroglobulinemia","author":"Yang\n G,","year":"2011;","unstructured":"Yang\n G, \n \n Zhou\n Y, \n \n Liu\n X, \n \n Cao\n Y, \n \n Hunter\n Z, \n \n Treon\n SP. \n \n Disruption of MYD88 pathway signaling leads to loss of constitutive IRAK1, NF-\u03baB and JAK\/STAT signaling and induces apoptosis of cells expressing the MYD88 L265P mutation in Waldenstr\u00f6m's macroglobulinemia. In: Proceedings of the 53rd Annual American Society of Hematology Meeting and Exposition; December 12, 2011;Atlanta, GA. Blood 118. Abstract 597."},{"issue":"9","key":"i1543-2165-137-4-580-b33","series-title":"Leukemia","first-page":"1634","article-title":"Trisomy 4, a new chromosomal abnormality in Waldenstr\u00f6m's macroglobulinemia: a study of 39 cases","volume":"20","author":"Terr\u00e9\n C,","year":"2006;","unstructured":"Terr\u00e9\n C, \n \n Nguyen-Khac\n F, \n \n Barin\n C, \n et al\n . Trisomy 4, a new chromosomal abnormality in Waldenstr\u00f6m's macroglobulinemia: a study of 39 cases. Leukemia. 2006;20(9):1634\u20131636."},{"issue":"1","key":"i1543-2165-137-4-580-b34","series-title":"Clin Lymphoma Myeloma","first-page":"17","article-title":"IgM monoclonal gammopathy of undetermined significance and smoldering Waldenstr\u00f6m's macroglobulinemia","volume":"9","author":"Kyle\n RA,","year":"2009;","unstructured":"Kyle\n RA, \n \n Benson\n J, \n \n Larson\n D, \n et al\n . IgM monoclonal gammopathy of undetermined significance and smoldering Waldenstr\u00f6m's macroglobulinemia. Clin Lymphoma Myeloma. 2009;9(1):17\u201318."},{"issue":"2","key":"i1543-2165-137-4-580-b35","series-title":"Am J Clin Pathol","first-page":"211","article-title":"Marginal zone lymphomas with plasmacytic differentiation and related disorders","volume":"136","author":"Molina\n TJ,","year":"2011;","unstructured":"Molina\n TJ, \n \n Lin\n P, \n \n Swerdlow\n SH, \n \n Cook\n JR. \n \n Marginal zone lymphomas with plasmacytic differentiation and related disorders. Am J Clin Pathol. 2011;136(2):211\u2013225."},{"issue":"1","key":"i1543-2165-137-4-580-b36","series-title":"Cancer Genet Cytogenet","first-page":"77","article-title":"Rarity of IgH translocations in Waldenstr\u00f6m macroglobulinemia","volume":"163","author":"Ackroyd\n S,","year":"2005;","unstructured":"Ackroyd\n S, \n \n O'Connor\n SJ, \n \n Owen\n RG. \n \n Rarity of IgH translocations in Waldenstr\u00f6m macroglobulinemia. 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Prognostic model for disease-specific and overall mortality in newly diagnosed symptomatic patients with Waldenstr\u00f6m macroglobulinaemia. Br J Haematol. 2006;133(2):158\u2013164."},{"issue":"5","key":"i1543-2165-137-4-580-b39","series-title":"Expert Rev Hematol","first-page":"473","article-title":"Individualizing treatment for Waldenstr\u00f6m's macroglobulinemia","volume":"2","author":"Stedman\n J,","year":"2009;","unstructured":"Stedman\n J, \n \n Roccaro\n A, \n \n Ghobrial\n IM. \n \n Individualizing treatment for Waldenstr\u00f6m's macroglobulinemia. Expert Rev Hematol. 2009;2(5):473\u2013476."},{"issue":"2","key":"i1543-2165-137-4-580-b40","series-title":"Crit Rev Oncol Hematol","first-page":"172","article-title":"Lymphoplasmacytic lymphoma-Waldenstr\u00f6m's macroglobulinemia","volume":"67","author":"Vitolo\n U,","year":"2008;","unstructured":"Vitolo\n U, \n \n Ferreri\n AJ, \n \n Montoto\n S. \n \n Lymphoplasmacytic lymphoma-Waldenstr\u00f6m's macroglobulinemia. 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