Journal List > Lab Med Online > v.9(4) > 1142042

Shin, Bang, Kim, Park, Shin, and Choi: A Case of Lymphoplasmacytic Lymphoma/Waldenström's Macroglobulinemia with IgM-κ and IgA-λ Biclonal Gammopathy

Abstract

Lymphoplasmacytic lymphoma (LPL) is a low-grade B-cell neoplasm, composed of small B lymphocytes, plasmacytoid lymphocytes, and plasma cells, usually involving bone marrow and sometimes lymph nodes or spleen. LPL with bone marrow involvement and an IgM monoclonal gammopathy of any concentration is designated as Waldenström macroglobulinemia (WM). LPL associated with non-IgM monoclonal gammopathy or biclonal gammopathy is rarely observed. LPL diagnosis was based on clinical, morphological, and immunophenotypic findings. Recently, the test for L265P mutation of the myeloid differentiation factor 88 (MYD88) gene has been helpful in the diagnosis of LPL. Here, we reported the first case of LPL/WM with IgM-κ/IgA-λ biclonal gammopathy in Korea.

Figures and Tables

Fig. 1

Immunofixation electrophoresis (serum). Two monoclonal peaks, IgA-λ and IgM-κ types, are observed in gamma-region. IgA-λ type monoclonal peak is dominant. M protein was 3.04 g/dL.

lmo-9-263-g001
Fig. 2

Bone marrow observations. (A) Microscopic observation of bone marrow (×1,000). Hypercellular marrow with markedly increased lymphocytes. Mixture of small lymphocytes, plasma cells, and plasmacytic lymphocytes formed clusters. Mast cells increased in number. (B) Bone marrow biopsy shows interstitial infiltration of plasmacytic lymphocytes (×400). (C) Immunophenotypic investigation revealed that neoplastic cells express CD19+ and CD56− and exhibit cytoplasmic lambda restriction. The Neoplastic cell population shows cells with a range of CD138 expression, from CD138 dim plasmacytic lymphocytes to CD138 bright mature plasma cells. (D) Next-generation sequencing (NGS) revealed MYD88 L265P mutation in 4.36% of bone marrow cells (depth: 436).

lmo-9-263-g002

References

1. The Korean Society of Hematology. Hematology. 3rd ed. Seoul: Panmun Education;2018. p. 367.
2. Swerdlow SH, Campo E, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon, France: IARC;2017. p. 236.
3. Kang J, Hong JY, Suh C. Clinical features and survival outcomes of patients with lymphoplasmacytic lymphoma, including non-IgM type, in Korea: a single-center experience. Blood Res. 2018; 53:189–197.
crossref
4. King RL, Gonsalves WI, Ansell SM, Greipp PT, Frederick LA, Viswanatha DS, et al. Lymphoplasmacytic lymphoma with a non-IgM paraprotein shows clinical and pathologic heterogeneity and may harbor MYD88 L265P mutations. Am J Clin Pathol. 2016; 145:843–851.
crossref
5. Cao X, Medeiros LJ, Xia Y, Wang X, Thomas SK, Loghavi S, et al. Clinicopathologic features and outcomes of lymphoplasmacytic lymphoma patients with monoclonal IgG or IgA paraprotein expression. Leuk Lymphoma. 2016; 57:1104–1113.
crossref
6. Shin SY, Lee ST, Kim HY, Park CH, Kim HJ, Kim JW, et al. Detection of MYD88 L265P in patients with lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia and other B-cell non-Hodgkin lymphomas. Blood res. 2016; 51:181–186.
crossref
7. Wadhwa J, Karyampudi A, Balaguru S, Hamide A. Lymphoplasmacytic lymphoma. JIPMER Journal of Cancer. 2014; 4:52–54.
8. García-García P, Enciso-Alvarez K, Diaz-Espada F, Vargas-Nuñez JA, Moraru M, Yebra-Bango M. Biclonal gammopathies: retrospective study of 47 patients. Rev Clin Esp. 2015; 215:18–24.
crossref
9. Naderi N, Yang DT. Lymphoplasmacytic lymphoma and Waldenström macroglobulinemia. Arch Pathol Lab Med. 2013; 137:580–585.
crossref
10. Kumar SK, Callander NS, Alsina M, Atanackovic D, Biermann JS, Chandler JC, et al. Multiple myeloma, version 3.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2017; 15:230–269.
crossref
11. Kapoor P, Ansell SM, Fonseca R, Chanan-Khan A, Kyle RA, Kumar SK, et al. Diagnosis and management of Waldenström macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines 2016. JAMA Oncol. 2017; 3:1257–1265.
crossref
12. Schuster SR, Rajkumar SV, Dispenzieri A, Morice W, Aspitia AM, Ansell S, et al. IgM multiple myeloma: disease definition, prognosis, and differentiation from Waldenstrom's macroglobulinemia. Am J Hematol. 2010; 85:853–855.
crossref
13. Wang E, Kulbacki E, Stoecker M. Concomitant Waldenstrom macroglobulinemia and IgA plasmablastic myeloma in a patient with untreated IgM paraproteinemia: sequential development of biclonal B-cell neoplasms over a 10-year period in a single individual. Hum Pathol. 2012; 43:1135–1141.
crossref
14. Rossi D. Role of MYD88 in lymphoplasmacytic lymphoma diagnosis and pathogenesis. Hematology Am Soc Hematol Educ Program. 2014; 2014:113–118.
15. Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018; 378:241–249.
crossref
16. McMaster ML, Kristinsson SY, Turesson I, Björkholm M, Landgren O. Novel aspects pertaining to the relationship of Waldenström's macroglobulinemia, IgM monoclonal gammopathy of undetermined significance, polyclonal gammopathy, and hypoglobulinemia. Clin Lymphoma Myeloma. 2009; 9:19–22.
crossref
17. Murphy K, Travers P, editors. Janeway's Immunobiology. 7th ed. US: Garland Science, Taylor & Francis Group, LLC;2009. p. 167.
18. Treon SP, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. N Engl J Med. 2012; 367:826–833.
crossref
19. Willenbacher W, Willenbacher E, Brunner A, Manzl C. Improved accuracy of discrimination between IgM multiple myeloma and Waldenström macroglobulinemia by testing for MYD88 L265P mutations. Brit J Haematol. 2013; 161:902–904.
crossref
20. Xu L, Hunter ZR, Yang G, Zhou Y, Cao Y, Liu X, et al. MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood. 2013; 121:2051–2058.
crossref
21. Jiménez C, Sebastián E, Chillón MC, Giraldo P, Mariano Hernández J, Escalante F, et al. MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenström's macroglobulinemia. Leukemia. 2013; 27:1722–1728.
crossref
22. Ondrejka SL, Lin JJ, Warden DW, Durkin L, Cook JR, Hsi ED. MYD88 L265P somatic mutation: its usefulness in the differential diagnosis of bone marrow involvement by B-cell lymphoproliferative disorders. Am J Clin Pathol. 2013; 140:387–394.
23. Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008; 26:1135–1145.
crossref
24. Schuster SC. Next-generation sequencing transforms today's biology. Nat Methods. 2008; 5:16–18.
crossref
TOOLS
ORCID iDs

Hae In Bang
https://orcid.org/0000-0001-7854-3011

Similar articles