DOI 10.1515/cclm-2014-0182 Clin Chem Lab Med 2014; 52(8): e183–e185
Letter to the Editor Anna Caldini*, Fiamma Balboni, Paola Parronchi, Silvia Scoccianti, Tiziana Biagioli, Alessandro Terreni, Beatrice Morrocchi, Marco Brogi, Margherita Berardi and Maristella Graziani
A rare condition: IgE type monoclonal gammopathy of undetermined significance Keywords: IgE; immunofixation; monoclonal gammo pathy of undetermined significance (MGUS); myeloma. *Corresponding author: Dr. Anna Caldini, Laboratorio Generale, Dipartimento Diagnostica di Laboratorio, Azienda OspedalieroUniversitaria Careggi, Largo Brambilla, 3, 50134 Florence, Italy, Phone: +39 55 7949452, Fax: +39 55 7949416, E-mail: [email protected] Tiziana Biagioli, Alessandro Terreni, Marco Brogi and Margherita Berardi: General Laboratory, Laboratory Diagnostics Department, Careggi University Hospital, Florence, Italy Fiamma Balboni and Beatrice Morrocchi: Clinical Chemistry Laboratory, IFCA, Florence, Italy Paola Parronchi: Center of High Excellence, Transfer and Education DENOTHE, University of Florence, Florence, Italy Silvia Scoccianti: Radiation Oncology Unit, Careggi University Hospital, Florence, Italy Maristella Graziani: Azienda Ospedaliero Universitaria Integrata, Verona, Italy
To the Editor, The frequency of the monoclonal gammopathies (MG) isotype roughly reflects their serum concentrations [1]; accordingly, IgE MG are the less frequent, and IgE mul tiple myeloma (MM) is also very rare. The first case was reported in 1967 [2] and up to now 90 1.73 m2 Hb, g/dL 12.9
7–16 0.7–4.0 0.4–2.3 60 14–18
eGFR, estimated glomerular filtration rate (by MDRD); FLC, serum free light chains.
The diagnostic criteria for plasma cell dyscrasias (PCDs) include the size of MC, the presence of organ damage (anemia, renal failure, hypercalcemia, bone lesions) and the number of bone marrow plasma cells [5]. The classification of this patient does not fulfill these cri teria since bone marrow examination and bone scan to detect any bone lesions were not performed. Furthermore, since the studies used to establish the diagnostic criteria do not include subjects or patients with IgD or IgE mono clonal gammopathies [5, 6], these criteria cannot be fully applicable to IgE MG. All these considerations made us confident that the present patient could be classified as IgE MGUS even if not all the indicated criteria were fulfilled. The main criterion used was the clinical one since there had not been any progression towards MM for 18 years. To the best of our knowledge, only one case of IgE MGUS has been published so far [7]. In 1977, an IgE mono clonal component was indeed typed in a 77-year-old woman. Proof of a monoclonal λ chain dated back 11 years before, but the MC was not characterized as IgE at that time as IgE isotype was only discovered in that very year (1966). In 1977, it was considered that a switch from mono clonal λ-free light chain to IgE λ was rather unlikely. The condition was defined “benign” for its stability since the MGUS term was not so commonly in use in those years and was suggested by R.A. Kyle for the first time in 1978 [8]. So the definition of “benign” MC was based on the absence of clinical signs and evolution, as it is for the present case. Plasma cell dyscrasias of IgE type are quite uncommon. The exact number is difficult to establish because quite often the same case is presented more than once in the literature to illustrate different characteristics. Clinical and pathologi cal features of IgE MGs are thus difficult to analyze due to the limited number of patients involved. Further, case reports rather than systematic reviews are mostly reported in the lit erature making it difficult to apply general criteria to single observed cases. IgE (and IgD) PCDs often pose diagnostic and monitoring problems because the monoclonal protein can be small or hidden in the β or α regions on electrophore sis and difficult to measure and to type [9, 10]. In conclusion, this is the second case of IgE MGUS reported in the litera ture, and confirms that IgE MGs do not necessarily imply a malignant proliferation. We feel that the presentation of this case is an important reminder to clinical biochemists that anti-ε and anti-δ antisera should be used when the immu nological typing of a monoclonal protein is negative for γ, α and μ heavy chains but positive for κ or λ light chains. As these cases are uncommon, it is probably not necessary that these specialty tests are performed in every general clinical laboratory but rather, that they should be sent to reference laboratories for full immunofixation.
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Caldini et al.: IgE MGUS case report e185
However, the problem should be recognized, since it is important that every patient receives a correct diagnosis and the plasma cell disorder is appropriately treated.
Research funding: None declared. Employment or leadership: None declared. Honorarium: None declared.
Conflict of interest statement Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.
Received February 19, 2014; accepted April 6, 2014; previously published online May 1, 2014
References 1. Kyle RA, Therneau TM, Rajkumar VS, Larson DR, Plevak MF, Offord JR, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 2006;354:1362–9. 2. Johanson SG, Bennich H. Immunological studies of an atypical (myeloma) immunoglobulin. Immunology 1967; 13:381–94. 3. Macro M, André E, Comby S, Cheze F, Chapon JJ, Ballet O, et al. IgE multiple myeloma. Leukem Lymph 1999;32:597–603. 4. Takemura Y, Ikeda M, Kobayashi K, Nakazawa Y, Mori Y, Mitsuishi T, et al. Plasma cell leukemia producing monoclonal immunoglobulin E. Int J Hematol 2009;90:402–6. 5. Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009;23:3–9.
6. The International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749–57. 7. Ludwig H, Vormittag W. “Benign” monoclonal IgE gammopathy. Br Med J 1980;281:539–40. 8. Kyle RA. Monoclonal gammopathy of undetermined significance. Am J Med 1978;64:814–26. 9. Pandey S, Kyle RA. Unusual myelomas: a review of IgD and IgE variants. Oncology (Williston Park) 2013;27:798–803. 10. Altinier S, Barberio G, Varagnolo M, Zaninotto M, Furlan A, Caberlotto L, et al. An IgE multiple myeloma: contradictory f indings in clinical laboratory testing. Clin Chim Acta 2013;425:114–6.
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Letter to the Editor Anna Caldini*, Fiamma Balboni, Paola Parronchi, Silvia Scoccianti, Tiziana Biagioli, Alessandro Terreni, Beatrice Morrocchi, Marco Brogi, Margherita Berardi and Maristella Graziani
A rare condition: IgE type monoclonal gammopathy of undetermined significance Keywords: IgE; immunofixation; monoclonal gammo pathy of undetermined significance (MGUS); myeloma. *Corresponding author: Dr. Anna Caldini, Laboratorio Generale, Dipartimento Diagnostica di Laboratorio, Azienda OspedalieroUniversitaria Careggi, Largo Brambilla, 3, 50134 Florence, Italy, Phone: +39 55 7949452, Fax: +39 55 7949416, E-mail: [email protected] Tiziana Biagioli, Alessandro Terreni, Marco Brogi and Margherita Berardi: General Laboratory, Laboratory Diagnostics Department, Careggi University Hospital, Florence, Italy Fiamma Balboni and Beatrice Morrocchi: Clinical Chemistry Laboratory, IFCA, Florence, Italy Paola Parronchi: Center of High Excellence, Transfer and Education DENOTHE, University of Florence, Florence, Italy Silvia Scoccianti: Radiation Oncology Unit, Careggi University Hospital, Florence, Italy Maristella Graziani: Azienda Ospedaliero Universitaria Integrata, Verona, Italy
To the Editor, The frequency of the monoclonal gammopathies (MG) isotype roughly reflects their serum concentrations [1]; accordingly, IgE MG are the less frequent, and IgE mul tiple myeloma (MM) is also very rare. The first case was reported in 1967 [2] and up to now 90 1.73 m2 Hb, g/dL 12.9
7–16 0.7–4.0 0.4–2.3 60 14–18
eGFR, estimated glomerular filtration rate (by MDRD); FLC, serum free light chains.
The diagnostic criteria for plasma cell dyscrasias (PCDs) include the size of MC, the presence of organ damage (anemia, renal failure, hypercalcemia, bone lesions) and the number of bone marrow plasma cells [5]. The classification of this patient does not fulfill these cri teria since bone marrow examination and bone scan to detect any bone lesions were not performed. Furthermore, since the studies used to establish the diagnostic criteria do not include subjects or patients with IgD or IgE mono clonal gammopathies [5, 6], these criteria cannot be fully applicable to IgE MG. All these considerations made us confident that the present patient could be classified as IgE MGUS even if not all the indicated criteria were fulfilled. The main criterion used was the clinical one since there had not been any progression towards MM for 18 years. To the best of our knowledge, only one case of IgE MGUS has been published so far [7]. In 1977, an IgE mono clonal component was indeed typed in a 77-year-old woman. Proof of a monoclonal λ chain dated back 11 years before, but the MC was not characterized as IgE at that time as IgE isotype was only discovered in that very year (1966). In 1977, it was considered that a switch from mono clonal λ-free light chain to IgE λ was rather unlikely. The condition was defined “benign” for its stability since the MGUS term was not so commonly in use in those years and was suggested by R.A. Kyle for the first time in 1978 [8]. So the definition of “benign” MC was based on the absence of clinical signs and evolution, as it is for the present case. Plasma cell dyscrasias of IgE type are quite uncommon. The exact number is difficult to establish because quite often the same case is presented more than once in the literature to illustrate different characteristics. Clinical and pathologi cal features of IgE MGs are thus difficult to analyze due to the limited number of patients involved. Further, case reports rather than systematic reviews are mostly reported in the lit erature making it difficult to apply general criteria to single observed cases. IgE (and IgD) PCDs often pose diagnostic and monitoring problems because the monoclonal protein can be small or hidden in the β or α regions on electrophore sis and difficult to measure and to type [9, 10]. In conclusion, this is the second case of IgE MGUS reported in the litera ture, and confirms that IgE MGs do not necessarily imply a malignant proliferation. We feel that the presentation of this case is an important reminder to clinical biochemists that anti-ε and anti-δ antisera should be used when the immu nological typing of a monoclonal protein is negative for γ, α and μ heavy chains but positive for κ or λ light chains. As these cases are uncommon, it is probably not necessary that these specialty tests are performed in every general clinical laboratory but rather, that they should be sent to reference laboratories for full immunofixation.
Brought to you by | Purdue University Libraries Authenticated Download Date | 5/23/15 1:32 AM
Caldini et al.: IgE MGUS case report e185
However, the problem should be recognized, since it is important that every patient receives a correct diagnosis and the plasma cell disorder is appropriately treated.
Research funding: None declared. Employment or leadership: None declared. Honorarium: None declared.
Conflict of interest statement Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.
Received February 19, 2014; accepted April 6, 2014; previously published online May 1, 2014
References 1. Kyle RA, Therneau TM, Rajkumar VS, Larson DR, Plevak MF, Offord JR, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 2006;354:1362–9. 2. Johanson SG, Bennich H. Immunological studies of an atypical (myeloma) immunoglobulin. Immunology 1967; 13:381–94. 3. Macro M, André E, Comby S, Cheze F, Chapon JJ, Ballet O, et al. IgE multiple myeloma. Leukem Lymph 1999;32:597–603. 4. Takemura Y, Ikeda M, Kobayashi K, Nakazawa Y, Mori Y, Mitsuishi T, et al. Plasma cell leukemia producing monoclonal immunoglobulin E. Int J Hematol 2009;90:402–6. 5. Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009;23:3–9.
6. The International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749–57. 7. Ludwig H, Vormittag W. “Benign” monoclonal IgE gammopathy. Br Med J 1980;281:539–40. 8. Kyle RA. Monoclonal gammopathy of undetermined significance. Am J Med 1978;64:814–26. 9. Pandey S, Kyle RA. Unusual myelomas: a review of IgD and IgE variants. Oncology (Williston Park) 2013;27:798–803. 10. Altinier S, Barberio G, Varagnolo M, Zaninotto M, Furlan A, Caberlotto L, et al. An IgE multiple myeloma: contradictory f indings in clinical laboratory testing. Clin Chim Acta 2013;425:114–6.
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