Case Report

Hyperdiploid Multiple Myeloma with Novel Complex Structural Chromosome Abnormalities Associated with Poor Prognosis : A Rare Case Report


Hyperdiploid multiple myeloma (MM) is associated with better prognosis and non-hyperdiploid subtype is associated with variable to adverse prognosis based on the nature of karyotype abnormality.  Rarely exceptions to this hyperdiploid and non-hyperdiploid divisions do exist in a minority. We report an adult male MM patient who showed hyperdiploid karyotype with few novel complex abnormalities and who showed poor clinical outcome. Conventional cytogenetic analysis carried out in 22 GTG banded metaphases showed 53,Y,der(X)t(X;22)(q27;q11.2),+3,+5,+6,+9,+11,+15,der(17)ins(17;1;3)(q11.2;?;?),der(17)ins(17;1;3)(q11.2;?;?),+19,-22 karyotype pattern in 15 metaphases whereas 7 metaphases showed 46,XY karyotype  pattern.  Interphase FISH revealed biallelic del(13q14) and del(17p13) but no translocations involving the 14q32 region. Through Spectral karyotyping FISH, the origin of complex abnormalities involving der(17) chromosome,  translocation t(X;22), and marker chromosome could be clearly delineated. Although the present case showed hyperdiploid karyotype, he showed an adverse prognosis probably due to the co-existence of complex abnormalities and expired 5 months after initial diagnosis despite standard treatment given.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
2. Sawyer JR. The prognostic significance of cytogenetics and molecular profiling in multiple myeloma. Cancer Genet. 2011;204(1):3-12.
3. Moreau P, Cavo M, Sonneveld P, , et al. Combination of international scoring system 3, high lactate dehydrogenase, and t(4;14) and/or del(17p) identifies patients with multiple myeloma (MM) treated with front-line autologous stem-cell transplantation at high risk of early MM progression-related death. J Clin Oncol. 2014;32(20):2173-80.
4. Landgren O, Weiss BM. Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia. 2009;23(10):1691-7.
5. Rajshekhar C, Shaji K. Risk Stratification in Multiple Myeloma. . Ann Hematol Oncol. 2015;2(6):1046.
6. Chng WJ, Dispenzieri A, Chim CS, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014;28(2):269-77.
7. Prideaux SM, Conway O'Brien E, Chevassut TJ. The genetic architecture of multiple myeloma. Adv Hematol. 2014;2014:864058.
8. de Mel S, Lim SH, Tung ML, et al. Implications of heterogeneity in multiple myeloma. Biomed Res Int. 2014;2014:232546.
9. Bergsagel PL, Mateos M-V, Gutierrez NC, et al. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma. Blood. 2013;121(6):884-92.
10. Rajan AM, Rajkumar SV. Interpretation of cytogenetic results in multiple myeloma for clinical practice. Blood Cancer J. 2015;5(10):e365.
11. Fonseca R, Barlogie B, Bataille R, et al. Genetics and Cytogenetics of Multiple Myeloma: A Workshop Report. Cancer Res. 2004;64(4):1546-58.
12. Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007;109(8):3489-95.
13. Durie BGM, Salmon SE. A clinical staging system for multiple myeloma correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975;36(3):842-54.
14. Greipp PR, Miguel JS, Durie BGM, et al. International Staging System for Multiple Myeloma. J Clin Oncol. 2005;23(15):3412-20.
15. McGowan-Jordan J, Simons A, Schmid M. ISCN: an International System for Human Cytogenomic Nomenclature (2016). Basel(Switzerland): S. Karger; 2016.
16. Faiman B. Myeloma genetics and genomics: Practice implications and future directions. Clin Lymphoma Myeloma Leuk. 2014;14(6):436-40.
17. Rajkumar SV. Multiple myeloma: 2014 Update on diagnosis, risk-stratification, and management. Am J Hematol. 2014;89(10):998-1009.
18. Rajkumar SV. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91(7):719-34.
19. Barwick BG, Gupta VA, Vertino PM, et al. Cell of Origin and Genetic Alterations in the Pathogenesis of Multiple Myeloma. Front Immunol. 2019;10:1121.
20. Chavan SS, He J, Tytarenko R, et al. Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker. Blood Cancer J. 2017;7(2):e535.
21. Weinhold N, Ashby C, Rasche L, et al. Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma. Blood. 2016;128(13):1735-44.
22. Nemec P, Zemanova Z, Kuglik P, et al. Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial. Leuk Lymphoma. 2012;53(5):920-7.
23. Carballo-Zarate AA, Medeiros LJ, Fang L, et al. Additional–structural–chromosomal aberrations are associated with inferior clinical outcome in patients with hyperdiploid multiple myeloma: a single-institution experience. Mod Pathol. 2017;30(6):843-53.
24. Mileshkin L, Prince HM. The adverse prognostic impact of advanced age in multiple myeloma. Leuk Lymphoma. 2005;46(7):951-66.
25. Fonseca R, San Miguel J. Prognostic Factors and Staging in Multiple Myeloma. Oncol Clin North Am. 2007;21(6):1115-40.
26. Ludwig H, Bolejack V, Crowley J, et al. Survival and Years of Life Lost in Different Age Cohorts of Patients With Multiple Myeloma. J Clin Oncol. 2010;28(9):1599-605.
27. Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for Multiple Myeloma: A
IssueVol 15 No 3 (2021) QRcode
SectionCase Report(s)
Multiple myeloma; Conventional cytogenetics; Interphase fluorescence in situ hybridization (iFISH); Spectral karyotyping ; Novel complex cytogenetic abnormalities

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Ankathil R, Foong E, Siti-Mariam I, Norhidayah R, Nazihah MY, Sangeetha V, Hariharan S, Azlan H. Hyperdiploid Multiple Myeloma with Novel Complex Structural Chromosome Abnormalities Associated with Poor Prognosis : A Rare Case Report. Int J Hematol Oncol Stem Cell Res. 2021;15(3):199-205.