Ann Lab Med.  2012 Jan;32(1):95-98. 10.3343/alm.2012.32.1.95.

CD5-negative Blastoid Variant Mantle Cell Lymphoma with Complex CCND1/IGH and MYC Aberrations

• Seok Y
• Kim J
• Choi JR
• Kim YR
• Park SJ
• Kim SJ
• Song J
• Lee KA

• KMID: 1781446
• DOI: http://doi.org/10.3343/alm.2012.32.1.95

Abstract

The coexistence of CCND1/IGH and MYC rearrangements in mantle cell lymphoma (MCL) is a rare finding associated with a very poor prognosis. In this study, a patient with blastoid variant (MCL) is reported. The disease was clinically aggressive and refractory to chemotherapy, and the patient only survived for 1 month following diagnosis. Conventional cytogenetic study, FISH, and multicolor FISH (mFISH) demonstrated the involvement of the BCL1/CCND1 locus in a complex translocation, t(3;11)(q25;p15)t(11;14)(q13;q32). In addition, subclonal abnormalities in the 8q24 region, manifested as a t(8;14)(q24;q32)/MYC rearrangement, were identified. To the best of our knowledge, this is the first MCL case in Korea bearing these complex genomic aberrations.

Keyword

Mantle cell lymphoma; CCND1; MYC

MeSH Terms

Aged, 80 and over
Antigens, CD5/*metabolism
Bone Marrow/immunology/metabolism
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 3
Gene Rearrangement
Humans
Immunophenotyping
In Situ Hybridization, Fluorescence
Lymphoma, Mantle-Cell/*diagnosis/genetics/immunology
Male
Oncogene Proteins, Fusion/*genetics
Proto-Oncogene Proteins c-myc/*genetics
Translocation, Genetic

Figure

• 

  Fig. 1 The peripheral blood smear shows an increased number of medium- to large-sized blastoid cells with polymorphous nuclei and basophilic cytoplasm (Wright-Giemsa stain, ×1,000).

• 

  Fig. 2 (A) Giemsa-banding karyogram of bone marrow cells: 45-47,XY,-9,-11,der(14)t(11;14)(q13;q32),-22,+2~3mar. M1 and M2 indicate marker chromosome 1 and 2, respectively. (B) Single color galleries of mFISH analysis showing der(14)t(11;14)(q13;q32), der(11) t(3;11)(q25;p15)t(11;14)(q13;q32), der(14)t(8;14)(q24.1;q32), and der(17)t(8;17)(q?;q?) respectively. (C) Diagrammatic representation of der(11)t(3;11)(q25;p15)t(11;14)(q13;q32). The arrows indicate breakpoints in chromosomes 3, 11, and 14. (D) FISH analysis using a dual-color dual-fusion BCL1(green)/IGH(orange) probe, a subclone harboring 2 fusion (F), 1 BCL1(G) and 2 IGH (R) signals. The corresponding chromosomes are marked as F, G, and R on the karyogram (A).

Reference

1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 2008. IARC: Lyon.

2. Jares P, Campo E. Advances in the understanding of mantle cell lymphoma. Br J Haematol. 2008. 142:149–165.

3. Bertoni F, Zucca E, Cotter FE. Molecular basis of mantle cell lymphoma. Br J Haematol. 2004. 124:130–140.

4. Salaverria I, Espinet B, Carrio A, Costa D, Astier L, Slotta-Huspenina J, et al. Multiple recurrent chromosomal breakpoints in mantle cell lymphoma revealed by a combination of molecular cytogenetic techniques. Genes Chromosomes Cancer. 2008. 47:1086–1097.

5. Sathanoori M, Shekhter-Levin S, Marks SM, Swerdlow SH. Derivative (14)t(11;14)(q13;q32)t(11;14)(p11.2;p11.2): a novel unbalanced variant of the t(11;14)(q13;q32) translocation in mantle cell lymphoma. Cancer Genet Cytogenet. 2007. 172:158–164.

6. Aamot HV, Tjonnfjord GE, Delabie J, Heim S. Molecular cytogenetic analysis of leukemic mantle cell lymphoma with a cryptic t(11;14). Cancer Genet Cytogenet. 2006. 165:172–175.

7. Salaverria I, Zettl A, Bea S, Moreno V, Valls J, Hartmann E, et al. Specific secondary genetic alterations in mantle cell lymphoma provide prognostic information independent of the gene expression-based proliferation signature. J Clin Oncol. 2007. 25:1216–1222.

8. Sander S, Bullinger L, Leupolt E, Benner A, Kienle D, Katzenberger T, et al. Genomic aberrations in mantle cell lymphoma detected by interphase fluorescence in situ hybridization. Incidence and clinicopathological correlations. Haematologica. 2008. 93:680–687.

9. Smith SM, Anastasi J, Cohen KS, Godley LA. The impact of MYC expression in lymphoma biology: beyond Burkitt lymphoma. Blood Cells Mol Dis. 2010. 45:317–323.

10. Reddy K, Ansari-Lari M, Dipasquale B. Blastic mantle cell lymphoma with a Burkitt translocation. Leuk Lymphoma. 2008. 49:740–750.

11. Maravelaki S, Burford A, Wotherspoon A, Joshi R, Matutes E, Catovsky D, et al. Molecular cytogenetic study of a mantle cell lymphoma with a complex translocation involving the CCND1 (11q13) region. Cancer Genet Cytogenet. 2004. 154:67–71.

12. Au WY, Gascoyne RD, Viswanatha DS, Connors JM, Klasa RJ, Horsman DE. Cytogenetic analysis in mantle cell lymphoma: a review of 214 cases. Leuk Lymphoma. 2002. 43:783–791.

13. Michaux L, Wlodarska I, Theate I, Stul M, Scheiff JM, Deneys V, et al. Coexistence of BCL1/CCND1 and CMYC aberrations in blastoid mantle cell lymphoma: a rare finding associated with very poor outcome. Ann Hematol. 2004. 83:578–583.

14. M'Kacher R, Farace F, Bennaceur-Griscelli A, Violot D, Clausse B, Dossou J, et al. Blastoid mantle cell lymphoma: evidence for nonrandom cytogenetic abnormalities additional to t(11;14) and generation of a mouse model. Cancer Genet Cytogenet. 2003. 143:32–38.

15. Au WY, Horsman DE, Viswanatha DS, Connors JM, Klasa RJ, Gascoyne RD. 8q24 translocations in blastic transformation of mantle cell lymphoma. Haematologica. 2000. 85:1225–1227.

16. Korz C, Pscherer A, Benner A, Mertens D, Schaffner C, Leupolt E, et al. Evidence for distinct pathomechanisms in B-cell chronic lymphocytic leukemia and mantle cell lymphoma by quantitative expression analysis of cell cycle and apoptosis-associated genes. Blood. 2002. 99:4554–4561.

17. Dreyling M, Hoster E, Bea S, Hartmann E, Horn H, Hutter G, et al. Update on the molecular pathogenesis and clinical treatment of Mantle Cell Lymphoma (MCL): minutes of the 9th European MCL Network conference. Leuk Lymphoma. 2010. 51:1612–1622.

18. Sawyer JR, Lukacs JL, Munshi N, Desikan KR, Singhal S, Mehta J, et al. Identification of new nonrandom translocations in multiple myeloma with multicolor spectral karyotyping. Blood. 1998. 92:4269–4278.

19. Morice WG, Hodnefield JM, Kurtin PJ, Hanson CA. An unusual case of leukemic mantle cell lymphoma with a blastoid component showing loss of CD5 and aberrant expression of CD10. Am J Clin Pathol. 2004. 122:122–127.

20. Schlette E, Fu K, Medeiros LJ. CD23 expression in mantle cell lymphoma: clinicopathologic features of 18 cases. Am J Clin Pathol. 2003. 120:760–766.