Top

Published in:

01-09-2020 | Lymphoma | Case Report

Transformation of de novo high-grade B cell lymphoma with MYC and BCL2 rearrangements to double-hit B lymphoblastic leukemia/lymphoma: a case report and review of literature

Authors: Afshin Shameli, Fariborz Rashid-Kolvear, Xiu Yan Jiang

Published in: Journal of Hematopathology | Issue 3/2020

Abstract

High-grade B cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (“double-hit” lymphoma (DHL)/“triple-hit” lymphoma (THL)) are mature B cell neoplasms with highly aggressive clinical behavior and poor response to therapy. Lymphoblastic transformation of mature B cell neoplasms is an uncommon event that is best recognized for follicular lymphoma (FL). To our knowledge, only one case of “B lymphoblastic” transformation of de novo DHL has been reported in the literature. Here, we describe another case of such transformation. The patient was a 57-year-old man who presented with hypercalcemia, high lactate dehydrogenase (LDH), and multiple lytic bone lesions and was diagnosed with high-grade B cell lymphoma with MYC and BCL2 rearrangements. The neoplastic cells were positive for CD45, CD19, CD20, CD79a, PAX5, CD10, BCL6, and BCL2 and negative for CD34, CD99, and terminal deoxynucleotidyl transferase (TdT). The patient received chemotherapy followed by autologous stem cell transplant and achieved complete remission. Nine months after the initial presentation, he developed general weakness and found to have cytopenias and circulating blasts. Bone marrow examination revealed extensive involvement by a high-grade B cell neoplasm co-expressing PAX5, CD10, and BCL2, in addition to precursor markers TdT and CD99. There was loss of CD20, CD79a, and BCL6 expression, and CD34 remained negative. A diagnosis of B lymphoblastic leukemia/lymphoma (B-LBL) was established. Similar MYC and BCL2 rearrangements were identified. IGH gene rearrangement studies confirmed clonal relatedness. The patient passed away 3 days after bone marrow examination. This case represents an extremely rare case of DHL transformation to B-LBL.

Swerdlow, S.H., et al., WHO classification of tumours of haematopoietic and lymphoid tissues. 2017: International Agency for Research on Cancer.

Snuderl M, Kolman OK, Chen YB, Hsu JJ, Ackerman AM, Cin PD, Ferry JA, Harris NL, Hasserjian RP, Zukerberg LR, Abramson JS, Hochberg EP, Lee H, Lee AI, Toomey CE, Sohani AR (2010) B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma. Am J Surg Pathol 34(3):327–340PubMedPubMedCentralCrossRef

Sesques P, Johnson NA (2017) Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Blood 129(3):280–288PubMedCrossRef

Loghavi S, Kutok JL, Jorgensen JL (2015) B-acute lymphoblastic leukemia/lymphoblastic lymphoma. Am J Clin Pathol 144(3):393–410PubMedCrossRef

De Jong D et al (1988) Activation of the c-myc oncogene in a precursor-B-cell blast crisis of follicular lymphoma, presenting as composite lymphoma. N Engl J Med 318(21):1373–1378PubMedCrossRef

Geyer JT, Subramaniyam S, Jiang Y, Elemento O, Ferry JA, de Leval L, Nakashima MO, Liu YC, Martin P, Mathew S, Orazi A, Tam W (2015) Lymphoblastic transformation of follicular lymphoma: a clinicopathologic and molecular analysis of 7 patients. Hum Pathol 46(2):260–271PubMedCrossRef

Kelemen K, Holden J, Johnson LJ, Davion S, Robetorye RS (2017) Immunophenotypic and cytogenetic findings of B-lymphoblastic leukemia/lymphoma associated with combined IGH/BCL2 and MYC rearrangement. Cytometry B Clin Cytom 92(4):310–314PubMedCrossRef

Kishimoto W, Shirase T, Chihara D, Maeda T, Arimoto-Miyamoto K, Takeoka T, Tsuji M, Ohno T, Kita K (2012) Double-hit lymphoma with a feature of follicular lymphoma concurrent with clonally related B lymphoblastic leukemia : a preference of transformation for the bone marrow. J Clin Exp Hematop 52(2):113–119PubMedCrossRef

Kroft SH, Domiati-Saad R, Finn WG, Dawson DB, Schnitzer B, Singleton TP, Ross CW (2000) Precursor B-lymphoblastic transformation of grade I follicle center lymphoma. Am J Clin Pathol 113(3):411–418PubMedCrossRef

10.

Slot LM, Hoogeboom R, Smit LA, Wormhoudt TAM, Biemond BJ, Oud MECM, Schilder-Tol EJM, Mulder AB, Jongejan A, van Kampen AHC, Kluin PM, Guikema JEJ, Bende RJ, van Noesel CJM (2016) B-Lymphoblastic lymphomas evolving from follicular lymphomas co-express surrogate light chains and mutated gamma heavy chains. Am J Pathol 186(12):3273–3284PubMedCrossRef

11.

Young KH, Xie Q, Zhou G, Eickhoff JC, Sanger WG, Aoun P, Chan WC (2008) Transformation of follicular lymphoma to precursor B-cell lymphoblastic lymphoma with c-myc gene rearrangement as a critical event. Am J Clin Pathol 129(1):157–166PubMedCrossRef

12.

Glazyrin A, Douglas-Nikitin V, Huang J, Micale M (2011) Transformation of double-hit large B-cell lymphoma into B-lymphoblastic lymphoma: a case report. Journal of Hematopathology 4(4):199–205CrossRef

13.

Moore EM, Aggarwal N, Surti U, Swerdlow SH (2017) Further exploration of the complexities of large B-cell lymphomas with MYC abnormalities and the importance of a blastoid morphology. Am J Surg Pathol 41(9):1155–1166PubMedCrossRef

14.

Kanagal-Shamanna R, Medeiros LJ, Lu G, Wang SA, Manning JT, Lin P, Penn GM, Young KH, You MJ, Vega F, Bassett R, Miranda RN (2012) High-grade B cell lymphoma, unclassifiable, with blastoid features: an unusual morphological subgroup associated frequently with BCL2 and/or MYC gene rearrangements and a poor prognosis. Histopathology 61(5):945–954PubMedCrossRef

15.

Ok CY, Medeiros LJ, Thakral B, Tang G, Jain N, Jabbour E, Pierce SA, Konoplev S (2019) High-grade B-cell lymphomas with TdT expression: a diagnostic and classification dilemma. Mod Pathol 32(1):48–58PubMedCrossRef

16.

Soliman DS et al (2017) High-grade B-cell neoplasm with surface light chain restriction and Tdt coexpression evolved in a MYC-rearranged diffuse large B-cell lymphoma: a dilemma in classification. Case Rep Hematol 2017:6891957PubMedPubMedCentral

17.

Kallen ME, Rao NP, Kulkarni SK, Pullarkat ST, Said J, Tirado CA, Ahmed RS, Miller JM, Chung PY, Kahn DG, Song SX (2015) B-lymphoblastic transformation of mantle cell lymphoma/leukemia with “double hit” changes. Journal of Hematopathology 8(1):31–36CrossRef

18.

Pasqualucci L, Khiabanian H, Fangazio M, Vasishtha M, Messina M, Holmes AB, Ouillette P, Trifonov V, Rossi D, Tabbò F, Ponzoni M, Chadburn A, Murty VV, Bhagat G, Gaidano G, Inghirami G, Malek SN, Rabadan R, Dalla-Favera R (2014) Genetics of follicular lymphoma transformation. Cell Rep 6(1):130–140PubMedPubMedCentralCrossRef

19.

Yano T, Jaffe ES, Longo DL, Raffeld M (1992) MYC rearrangements in histologically progressed follicular lymphomas. Blood 80(3):758–767PubMedCrossRef

20.

Wu D, Wood BL, Dorer R, Fromm JR (2010) "Double-Hit" mature B-cell lymphomas show a common immunophenotype by flow cytometry that includes decreased CD20 expression. Am J Clin Pathol 134(2):258–265PubMedCrossRef

21.

Harrington AM, Olteanu H, Kroft SH, Eshoa C (2011) The unique immunophenotype of double-hit lymphomas. Am J Clin Pathol 135(4):649–650PubMedCrossRef

22.

Platt MY et al (2013) Flow cytometry is of limited utility in the early identification of "double-hit" B-cell lymphomas. Cytometry B Clin Cytom 84(3):143–148PubMedCrossRef

23.

Alsuwaidan A, Pirruccello E, Jaso J, Koduru P, Garcia R, Krueger JE, Doucet M, Chaudhry R, Fuda F, Chen W (2019) Bright CD38 expression by flow cytometric analysis is a biomarker for double/triple hit lymphomas with a moderate sensitivity and high specificity. Cytometry B Clin Cytom 96:368–374PubMedCrossRef

24.

Lee SP, Park S, Park J, Hong J, Ko YH (2011) Clinicopathologic characteristics of CD99-positive diffuse large B-cell lymphoma. Acta Haematol 125(3):167–174PubMedCrossRef

25.

Kunkel TA, Gopinathan KP, Dube DK, Snow ET, Loeb LA (1986) Rearrangements of DNA mediated by terminal transferase. Proc Natl Acad Sci U S A 83(6):1867–1871PubMedPubMedCentralCrossRef

26.

Onciu M, Lorsbach RB, Henry EC, Behm FG (2002) Terminal deoxynucleotidyl transferase-positive lymphoid cells in reactive lymph nodes from children with malignant tumors: incidence, distribution pattern, and immunophenotype in 26 patients. Am J Clin Pathol 118(2):248–254PubMedCrossRef

27.

Orazi A, Cattoretti G, John K, Neiman RS (1994) Terminal deoxynucleotidyl transferase staining of malignant lymphomas in paraffin sections. Mod Pathol 7(5):582–586PubMed

28.

Orazi A, Cotton J, Giorgio C, Patricia KK, John K, John T. M, Neiman RS (1994) Terminal deoxynucleotidyl transferase staining in acute leukemia and normal bone marrow in routinely processed paraffin sections. Am J Clin Pathol 102(5):640–645

29.

Drexler HG, Sperling C, Ludwig WD (1993) Terminal deoxynucleotidyl transferase (TdT) expression in acute myeloid leukemia. Leukemia 7(8):1142–1150PubMed

30.

Sangle NA, Schmidt RL, Patel JL, Jeffrey Medeiros L, Agarwal AM, Perkins SL, Salama ME (2014) Optimized immunohistochemical panel to differentiate myeloid sarcoma from blastic plasmacytoid dendritic cell neoplasm. Mod Pathol 27(8):1137–1143PubMedCrossRef

31.

Sidiropoulos M, Hanna W, Raphael SJ, Ghorab Z (2011) Expression of TdT in Merkel cell carcinoma and small cell lung carcinoma. Am J Clin Pathol 135(6):831–838PubMedCrossRef

32.

Mathewson RC, Kjeldsberg CR, Perkins SL (1997) Detection of terminal deoxynucleotidyl transferase (TdT) in nonhematopoietic small round cell tumors of children. Pediatr Pathol Lab Med 17(6):835–844PubMedCrossRef

33.

Moench L, Sachs Z, Aasen G, Dolan M, Dayton V, Courville EL (2016) Double- and triple-hit lymphomas can present with features suggestive of immaturity, including TdT expression, and create diagnostic challenges. Leuk Lymphoma 57(11):2626–2635PubMedPubMedCentralCrossRef

34.

Soliman, D.S., et al., De novo precursor B-lymphoblastic leukemia/lymphoma with double-hit gene rearrangements ( MYC/BCL-2 ) presented with spinal cord compression and acquired factor XIII deficiency. 2017. 2017.

35.

Liu W, Hu S, Konopleva M, Khoury JD, Kalhor N, Tang G, Bueso-Ramos CE, Jorgensen JL, Lin P, Medeiros LJ, Lu X (2015) De novo MYC and BCL2 double-hit B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in pediatric and young adult patients associated with poor prognosis. Pediatr Hematol Oncol 32(8):535–547PubMedCrossRef

36.

Subramaniyam S, Fraser CR, Rao PH, Feldman E, Ely S, Mathew S (2011) De novo B lymphoblastic leukemia/lymphoma in an adult with t(14;18)(q32;q21) and c-MYC gene rearrangement involving 10p13. Leuk Lymphoma 52(11):2195–2199PubMedCrossRef

37.

D'Achille P, Seymour JF, Campbell LJ (2006) Translocation (14;18)(q32;q21) in acute lymphoblastic leukemia: a study of 12 cases and review of the literature. Cancer Genet Cytogenet 171(1):52–56PubMedCrossRef

Title: Transformation of de novo high-grade B cell lymphoma with MYC and BCL2 rearrangements to double-hit B lymphoblastic leukemia/lymphoma: a case report and review of literature
Authors: Afshin Shameli
Fariborz Rashid-Kolvear
Xiu Yan Jiang
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Keywords: Lymphoma
Leukemia
Published in: Journal of Hematopathology / Issue 3/2020
Print ISSN: 1868-9256
Electronic ISSN: 1865-5785
DOI: https://doi.org/10.1007/s12308-020-00400-0

At a glance: The STEP trials

Springer Medicine

Transformation of de novo high-grade B cell lymphoma with MYC and BCL2 rearrangements to double-hit B lymphoblastic leukemia/lymphoma: a case report and review of literature

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2020

Osteopetrosis in a six-month-old infant

Mantle cell lymphoma: pathologic and immunophenotyping study of 50 cases and correlation with survival—a single institute experience

Mucosal intralymphatic spread in a relapsed diffuse large B cell lymphoma

A practical approach to FISH testing for MYC rearrangements and brief review of MYC in aggressive B-cell lymphomas

The molecular analysis of four coexistent mutations in additional sex combs like 1 (ASXL1) gene in a patient with acute myeloid leukemia

Prevalence of β-haemoglobinopathies in Eastern India and development of a novel formula for carrier detection