{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:41:57Z","timestamp":1790520117580,"version":"4.1.0"},"reference-count":30,"publisher":"Archives of Pathology and Laboratory Medicine","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11]]},"abstract":"\n Context.<\/jats:italic>\n \u2014Molecular tests for clonality performed on atypical lymphoid lesions may yield abnormal results because of the coexistence of monoclonal B lymphocytosis or monoclonal gammopathy of undetermined significance in the sample investigated.\n <\/jats:p>\n \n Objective.<\/jats:italic>\n \u2014To investigate the ability of the BIOMED-2 sets of primers to identify 2 clonal populations in the same formalin-fixed, paraffin-embedded tissue sample.\n <\/jats:p>\n \n Design.<\/jats:italic>\n \u2014Ten cases with 2 B-lymphoproliferative disorders at the same site were analyzed using 5 BIOMED-2 primer sets (IGH FR1, FR2, FR3, IGK VJ, and IGK VKde).\n <\/jats:p>\n \n Results.<\/jats:italic>\n \u2014All 10 cases (100%) showed at least 1 clone; 8 of 10 cases (80%) had 2 clones with at least 1 primer set, and the 2 clones were shown by 4 or 5 primer sets in none of the cases (0%), by 3 sets in 1 of 10 cases (10%), by 2 sets in 4 of 10 cases (40%), and by 1 set in 3 of 10 cases (30%). The most effective set was IGH FR2, detecting 4 of 10 biclonal cases (40%). The IGK VJ and IGK VKde each showed 2 clones in 3 of 10 cases (30% each). The least effective sets were IGH FR1 and FR3, with 2 of 10 cases (20%) each, with IGH FR1 being the least useful.\n <\/jats:p>\n \n Conclusions.<\/jats:italic>\n \u2014The BIOMED-2 primers are effective in the detection of 2 clonal populations in the same sample.\n <\/jats:p>","DOI":"10.5858\/arpa.2012-0666-oa","type":"journal-article","created":{"date-parts":[[2013,10,30]],"date-time":"2013-10-30T08:55:31Z","timestamp":1383123331000},"page":"1654-1659","source":"Crossref","is-referenced-by-count":6,"title":["The Utility of the BIOMED-2 Primers in the Detection of 2 Clonal, B-Lymphoproliferative Disorders Simultaneously Involving the Same Site"],"prefix":"10.5858","volume":"137","author":[{"given":"Brenda","family":"Ly","sequence":"first","affiliation":[{"name":"From the RJ Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudiu V.","family":"Cotta","sequence":"additional","affiliation":[{"name":"From the RJ Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3906","reference":[{"issue":"2","key":"i1543-2165-137-11-1654-b01","series-title":"Leukemia","first-page":"207","article-title":"Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936","volume":"21","author":"Evans\n PA,","year":"2007","unstructured":"Evans\n PA, \n \n Pott\n C, \n \n Groenen\n PJ, \n et al\n . Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2007;21(2):207\u2013214."},{"issue":"12","key":"i1543-2165-137-11-1654-b02","series-title":"Leukemia","first-page":"2257","article-title":"Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936","volume":"17","author":"van Dongen\n JJ,","year":"2003","unstructured":"van Dongen\n JJ, \n \n Langerak\n AW, \n \n Bruggemann\n M, \n et al\n . Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17(12):2257\u20132317."},{"issue":"2","key":"i1543-2165-137-11-1654-b03","series-title":"Leukemia","first-page":"201","article-title":"Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936","volume":"21","author":"van Krieken\n JH,","year":"2007","unstructured":"van Krieken\n JH, \n \n Langerak\n AW, \n \n Macintyre\n EA, \n et al\n . Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2007;21(2):201\u2013206."},{"issue":"2","key":"i1543-2165-137-11-1654-b04","series-title":"Leukemia","first-page":"222","article-title":"Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BMH4-CT98-3936","volume":"21","author":"Langerak\n AW,","year":"2007","unstructured":"Langerak\n AW, \n \n Molina\n TJ, \n \n Lavender\n FL, \n et al\n . Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2007;21(2):222\u2013229."},{"key":"i1543-2165-137-11-1654-b05","series-title":"et al, eds WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed","author":"Swerdlow\n SH,","year":"2008","unstructured":"Swerdlow\n SH, \n \n Campo\n E, \n \n Harris\n NL, \n \n et al, eds WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press;2008. World Health Organization Classification of Tumours; vol 2."},{"issue":"6","key":"i1543-2165-137-11-1654-b06","series-title":"Blood","first-page":"2337","article-title":"Monoclonal CD5+ and CD5\u2212 B-lymphocyte expansions are frequent in the peripheral blood of the elderly","volume":"103","author":"Ghia\n P,","year":"2004","unstructured":"Ghia\n P, \n \n Prato\n G, \n \n Scielzo\n C, \n et al\n . Monoclonal CD5+ and CD5\u2212 B-lymphocyte expansions are frequent in the peripheral blood of the elderly. Blood. 2004;103(6):2337\u20132342."},{"issue":"1","key":"i1543-2165-137-11-1654-b07","series-title":"Blood","first-page":"244","article-title":"Benign monoclonal B cell lymphocytosis\u2014a benign variant of CLL: clinical, immunologic, phenotypic, and cytogenetic studies in 20 patients","volume":"64","author":"Han\n T,","year":"1984","unstructured":"Han\n T, \n \n Ozer\n H, \n \n Gavigan\n M, \n et al\n . Benign monoclonal B cell lymphocytosis\u2014a benign variant of CLL: clinical, immunologic, phenotypic, and cytogenetic studies in 20 patients. Blood. 1984;64(1):244\u2013252."},{"issue":"6","key":"i1543-2165-137-11-1654-b08","series-title":"N Engl J Med","first-page":"575","article-title":"Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia","volume":"359","author":"Rawstron\n AC,","year":"2008","unstructured":"Rawstron\n AC, \n \n Bennett\n FL, \n \n O'Connor\n SJ, \n et al\n . Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med. 2008;359(6):575\u2013583."},{"issue":"3","key":"i1543-2165-137-11-1654-b09","series-title":"Br J Ophthalmol","first-page":"352","article-title":"Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases","volume":"89","author":"Coupland\n SE,","year":"2005","unstructured":"Coupland\n SE, \n \n Hellmich\n M, \n \n Auw-Haedrich\n C, \n \n Lee\n WR, \n \n Anagnostopoulos\n I, \n \n Stein\n H. \n \n Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases. Br J Ophthalmol. 2005;89(3):352\u2013359."},{"issue":"5","key":"i1543-2165-137-11-1654-b10","series-title":"Adv Anat Pathol","first-page":"246","article-title":"Lymphoplasmacytic lymphoma\/Waldenstr\u00f6m macroglobulinemia: an evolving concept","volume":"12","author":"Lin\n P,","year":"2005","unstructured":"Lin\n P, \n \n Medeiros\n LJ. \n \n Lymphoplasmacytic lymphoma\/Waldenstr\u00f6m macroglobulinemia: an evolving concept. Adv Anat Pathol. 2005;12(5):246\u2013255."},{"issue":"9","key":"i1543-2165-137-11-1654-b11","series-title":"Leukemia","first-page":"1651","article-title":"Pathogenesis and progression of monoclonal gammopathy of undetermined significance","volume":"22","author":"Blad\u00e9\n J,","year":"2008","unstructured":"Blad\u00e9\n J, \n \n Rosinol\n L, \n \n Cibeira\n MT, \n \n de Larrea\n CF. \n \n Pathogenesis and progression of monoclonal gammopathy of undetermined significance. Leukemia. 2008;22(9):1651\u20131657."},{"issue":"1\u20132","key":"i1543-2165-137-11-1654-b12","series-title":"J Hematopathol","first-page":"35","article-title":"Multiple clonal Ig\/TCR products: implications for interpretation of clonality findings","volume":"5","author":"Langerak\n AW,","year":"2012","unstructured":"Langerak\n AW, \n \n van Dongen\n JJM. \n \n Multiple clonal Ig\/TCR products: implications for interpretation of clonality findings. J Hematopathol. 2012;5(1\u20132):35\u201343."},{"issue":"10","key":"i1543-2165-137-11-1654-b13","series-title":"Leukemia","first-page":"2159","article-title":"EuroClonality\/BIOMED-2 guidelines for interpretation and reporting of Ig\/TCR clonality testing in suspected lymphoproliferations","volume":"26","author":"Langerak\n AW,","year":"2012","unstructured":"Langerak\n AW, \n \n Groenen\n PJ, \n \n Bruggemann\n M, \n et al\n . EuroClonality\/BIOMED-2 guidelines for interpretation and reporting of Ig\/TCR clonality testing in suspected lymphoproliferations. Leukemia. 2012;26(10):2159\u20132171."},{"issue":"3","key":"i1543-2165-137-11-1654-b14","series-title":"Am J Clin Pathol","first-page":"347","article-title":"Gene rearrangements in the diagnosis of lymphoma\/leukemia: guidelines for use based on a multiinstitutional study","volume":"95","author":"Cossman\n J,","year":"1991","unstructured":"Cossman\n J, \n \n Zehnbauer\n B, \n \n Garrett\n CT, \n et al\n . Gene rearrangements in the diagnosis of lymphoma\/leukemia: guidelines for use based on a multiinstitutional study. Am J Clin Pathol. 1991;95(3):347\u2013354."},{"issue":"4","key":"i1543-2165-137-11-1654-b15","series-title":"Am J Clin Pathol","first-page":"472","article-title":"Comparison of cytogenetic analysis, southern analysis, and polymerase chain reaction for the detection of t(14;18) in follicular lymphoma","volume":"103","author":"Horsman\n DE,","year":"1995","unstructured":"Horsman\n DE, \n \n Gascoyne\n RD, \n \n Coupland\n RW, \n \n Coldman\n AJ, \n \n Adomat\n SA. \n \n Comparison of cytogenetic analysis, southern analysis, and polymerase chain reaction for the detection of t(14;18) in follicular lymphoma. Am J Clin Pathol. 1995;103(4):472\u2013478."},{"issue":"2","key":"i1543-2165-137-11-1654-b01","series-title":"Leukemia","first-page":"207","article-title":"Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936","volume":"21","author":"Evans\n PA,","year":"2007","unstructured":"Evans\n PA, \n \n Pott\n C, \n \n Groenen\n PJ, \n et al\n . Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2007;21(2):207\u2013214."},{"issue":"12","key":"i1543-2165-137-11-1654-b02","series-title":"Leukemia","first-page":"2257","article-title":"Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936","volume":"17","author":"van Dongen\n JJ,","year":"2003","unstructured":"van Dongen\n JJ, \n \n Langerak\n AW, \n \n Bruggemann\n M, \n et al\n . Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17(12):2257\u20132317."},{"issue":"2","key":"i1543-2165-137-11-1654-b03","series-title":"Leukemia","first-page":"201","article-title":"Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936","volume":"21","author":"van Krieken\n JH,","year":"2007","unstructured":"van Krieken\n JH, \n \n Langerak\n AW, \n \n Macintyre\n EA, \n et al\n . Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2007;21(2):201\u2013206."},{"issue":"2","key":"i1543-2165-137-11-1654-b04","series-title":"Leukemia","first-page":"222","article-title":"Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BMH4-CT98-3936","volume":"21","author":"Langerak\n AW,","year":"2007","unstructured":"Langerak\n AW, \n \n Molina\n TJ, \n \n Lavender\n FL, \n et al\n . Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2007;21(2):222\u2013229."},{"key":"i1543-2165-137-11-1654-b05","series-title":"et al, eds WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed","author":"Swerdlow\n SH,","year":"2008","unstructured":"Swerdlow\n SH, \n \n Campo\n E, \n \n Harris\n NL, \n \n et al, eds WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press;2008. World Health Organization Classification of Tumours; vol 2."},{"issue":"6","key":"i1543-2165-137-11-1654-b06","series-title":"Blood","first-page":"2337","article-title":"Monoclonal CD5+ and CD5\u2212 B-lymphocyte expansions are frequent in the peripheral blood of the elderly","volume":"103","author":"Ghia\n P,","year":"2004","unstructured":"Ghia\n P, \n \n Prato\n G, \n \n Scielzo\n C, \n et al\n . Monoclonal CD5+ and CD5\u2212 B-lymphocyte expansions are frequent in the peripheral blood of the elderly. Blood. 2004;103(6):2337\u20132342."},{"issue":"1","key":"i1543-2165-137-11-1654-b07","series-title":"Blood","first-page":"244","article-title":"Benign monoclonal B cell lymphocytosis\u2014a benign variant of CLL: clinical, immunologic, phenotypic, and cytogenetic studies in 20 patients","volume":"64","author":"Han\n T,","year":"1984","unstructured":"Han\n T, \n \n Ozer\n H, \n \n Gavigan\n M, \n et al\n . Benign monoclonal B cell lymphocytosis\u2014a benign variant of CLL: clinical, immunologic, phenotypic, and cytogenetic studies in 20 patients. Blood. 1984;64(1):244\u2013252."},{"issue":"6","key":"i1543-2165-137-11-1654-b08","series-title":"N Engl J Med","first-page":"575","article-title":"Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia","volume":"359","author":"Rawstron\n AC,","year":"2008","unstructured":"Rawstron\n AC, \n \n Bennett\n FL, \n \n O'Connor\n SJ, \n et al\n . Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med. 2008;359(6):575\u2013583."},{"issue":"3","key":"i1543-2165-137-11-1654-b09","series-title":"Br J Ophthalmol","first-page":"352","article-title":"Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases","volume":"89","author":"Coupland\n SE,","year":"2005","unstructured":"Coupland\n SE, \n \n Hellmich\n M, \n \n Auw-Haedrich\n C, \n \n Lee\n WR, \n \n Anagnostopoulos\n I, \n \n Stein\n H. \n \n Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases. Br J Ophthalmol. 2005;89(3):352\u2013359."},{"issue":"5","key":"i1543-2165-137-11-1654-b10","series-title":"Adv Anat Pathol","first-page":"246","article-title":"Lymphoplasmacytic lymphoma\/Waldenstr\u00f6m macroglobulinemia: an evolving concept","volume":"12","author":"Lin\n P,","year":"2005","unstructured":"Lin\n P, \n \n Medeiros\n LJ. \n \n Lymphoplasmacytic lymphoma\/Waldenstr\u00f6m macroglobulinemia: an evolving concept. Adv Anat Pathol. 2005;12(5):246\u2013255."},{"issue":"9","key":"i1543-2165-137-11-1654-b11","series-title":"Leukemia","first-page":"1651","article-title":"Pathogenesis and progression of monoclonal gammopathy of undetermined significance","volume":"22","author":"Blad\u00e9\n J,","year":"2008","unstructured":"Blad\u00e9\n J, \n \n Rosinol\n L, \n \n Cibeira\n MT, \n \n de Larrea\n CF. \n \n Pathogenesis and progression of monoclonal gammopathy of undetermined significance. Leukemia. 2008;22(9):1651\u20131657."},{"issue":"1\u20132","key":"i1543-2165-137-11-1654-b12","series-title":"J Hematopathol","first-page":"35","article-title":"Multiple clonal Ig\/TCR products: implications for interpretation of clonality findings","volume":"5","author":"Langerak\n AW,","year":"2012","unstructured":"Langerak\n AW, \n \n van Dongen\n JJM. \n \n Multiple clonal Ig\/TCR products: implications for interpretation of clonality findings. J Hematopathol. 2012;5(1\u20132):35\u201343."},{"issue":"10","key":"i1543-2165-137-11-1654-b13","series-title":"Leukemia","first-page":"2159","article-title":"EuroClonality\/BIOMED-2 guidelines for interpretation and reporting of Ig\/TCR clonality testing in suspected lymphoproliferations","volume":"26","author":"Langerak\n AW,","year":"2012","unstructured":"Langerak\n AW, \n \n Groenen\n PJ, \n \n Bruggemann\n M, \n et al\n . EuroClonality\/BIOMED-2 guidelines for interpretation and reporting of Ig\/TCR clonality testing in suspected lymphoproliferations. Leukemia. 2012;26(10):2159\u20132171."},{"issue":"3","key":"i1543-2165-137-11-1654-b14","series-title":"Am J Clin Pathol","first-page":"347","article-title":"Gene rearrangements in the diagnosis of lymphoma\/leukemia: guidelines for use based on a multiinstitutional study","volume":"95","author":"Cossman\n J,","year":"1991","unstructured":"Cossman\n J, \n \n Zehnbauer\n B, \n \n Garrett\n CT, \n et al\n . Gene rearrangements in the diagnosis of lymphoma\/leukemia: guidelines for use based on a multiinstitutional study. Am J Clin Pathol. 1991;95(3):347\u2013354."},{"issue":"4","key":"i1543-2165-137-11-1654-b15","series-title":"Am J Clin Pathol","first-page":"472","article-title":"Comparison of cytogenetic analysis, southern analysis, and polymerase chain reaction for the detection of t(14;18) in follicular lymphoma","volume":"103","author":"Horsman\n DE,","year":"1995","unstructured":"Horsman\n DE, \n \n Gascoyne\n RD, \n \n Coupland\n RW, \n \n Coldman\n AJ, \n \n Adomat\n SA. \n \n Comparison of cytogenetic analysis, southern analysis, and polymerase chain reaction for the detection of t(14;18) in follicular lymphoma. Am J Clin Pathol. 1995;103(4):472\u2013478."}],"container-title":["Archives of Pathology and Laboratory Medicine"],"original-title":[],"link":[{"URL":"https:\/\/aplm.kglmeridian.com\/view\/journals\/arpa\/137\/11\/article-p1654.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/meridian.allenpress.com\/aplm\/article-pdf\/137\/11\/1654\/2270659\/arpa_2012-0666-oa.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aplm.kglmeridian.com\/downloadpdf\/journals\/arpa\/137\/11\/article-p1654.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aplm.kglmeridian.com\/downloadpdf\/journals\/arpa\/137\/11\/article-p1654.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:58:23Z","timestamp":1770771503000},"score":1,"resource":{"primary":{"URL":"https:\/\/aplm.kglmeridian.com\/view\/journals\/arpa\/137\/11\/article-p1654.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11]]},"references-count":30,"journal-issue":{"issue":"11"},"URL":"https:\/\/doi.org\/10.5858\/arpa.2012-0666-oa","relation":{},"ISSN":["1543-2165","0003-9985"],"issn-type":[{"value":"1543-2165","type":"electronic"},{"value":"0003-9985","type":"print"}],"subject":[],"published":{"date-parts":[[2013,11]]}}}