Rare cases of laboratory tests discrepancies in diagnostics of pediatric Burkitt lymphoma/leukemia

Introduction. The main features of bone marrow blasts cells in Burkitt lymphoma/leukemia (BL) are L3 morphology, mature immunophenotype of blasts with surface IgM expression, and presence of typical MYC gene rearrangements.

The aim of the study was to show discrepancy examples in laboratory signs of BL.

Patients and methods. 10 patients (8 boys and 2 girls) aged 1 to 18 years were included in the present study. The inclusion criterion was the identification of discrepancies between flow cytometric, morphological and cytogenetic data.

Results. In 2 cases there were no rearrangements of the MYC gene. In 2 patients, the L2 morphological variant went against the presence of typical MYC gene rearrangements. In one case, undifferentiated blasts cells were described by morphology together with presence of surface IgM, and atypical genetics. In 8 patients, there was no expression of surface IgM. Of these, patients with absence of cytomorphological data cytometric and genetic data were controversial.

Сonclusion. The cases presented in this study and the cases described in the literature demonstrate the importance of an attentive and comprehensive approach in evaluating the results of laboratory tests in the diagnosis of BL.

1. Burkitt D. A sarcoma involving the jaws in African children. Br J Surg 1958;46(197):218–23. PMID: 13628987.

2. Lenze D., Leoncini L., Hummel M. et al. The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma. Leukemia 2011;25(12):1869–76. DOI: 10.1038/leu.2011.156. PMID: 21701491.

3. Piccaluga P.P., De Falco G., Kustagi M. et al. Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes. Blood 2011;117(13):3596–608. DOI: 10.1182/blood-2010-08-301556. PMID: 21245480.

4. Leoncini L., Raphael M., Stein H. et al. Burkitt lymphoma. In: Swerdlow S.H., Campo E., Harris N.L. et al. (eds). WHO classification of tumours of haematopoietic and lymphoid tissues. IARC press, 2008. P. 262–264.

5. Swerdlow S., Campo E., Harris N.L. et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC, 2008;262–4.

6. Bene M., Castoldi G., Knapp W. et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995;9(10):1783–6. PMID: 7564526.

7. Angi M., Kamath V., Yuvarani S. et al. The t(8;14)(q24.1;q32) and its variant translocations: A study of 34 cases. Hematol Oncol Stem Cell Ther 2017;10(3):126–34. DOI: 10.1016/j.hemonc.2017.03.002. PMID: 28390216.

8. Demina I.A., Verzhbitskaya T.Yu., Kashpor S.A. et al. Heterogeneity of childhood B-cell acute lymphoblastic leukemia (EGIL subtype BIV). Onkogematologiya = Oncohematology 2017;12(4):34–40 (In Russ.). DOI: 10.17650/1818-8346-2017-12-4-34-40.

9. Creutzig U., van den Heuvel-Eibrink M.M., Gibson B. et al. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood 2012;120(16):3187–205. DOI: 10.1182/blood-2012-03-362608. PMID: 22879540.

10. ISCN 2016: An International System for Human Cytogenomic Nomenclature (2016). Eds.: McGovan-Jordan J., Simons A., Schmid M. (Reprint of: Cytogenetic and Genome Research 2016;149:1–2).

11. Karachunskiy A.I., Rumyantseva Yu.V., Rumyantsev A.G. Evolution of therapy for acute lymphoblastic leukemia in children: Critical use of experience, gained in the World, in Russia. Voprosy gematologii/onkologii i immunopatologii v pediatrii = Pediatric Hematology/Oncology and Immunopathology 2011;10(2):15–31 (In Russ.).

12. Samochatova E.V., Shelikhova L.N., Myakova N.V. et al. Opportunities and problems of modern non-Hodgkin’s lymphomas therapy in children and adolescents. Pediatria = Pediatrics 2011;90(4):37–43 (In Russ.).

13. Demina I.A., Verzhbitskaya T.Yu., Kashpor S.A. et al. Immunophenotypic features of bone marrow tumor cell in Burkitt lymphoma/leukemia: B-lineage acute lymphoblastic leukemia diagnostic opportunities. Onkogematologiya = Oncohematology 2017;12(1):55 (In Russ.). DOI: 10.17650/1818-8346-2017-12-1-55-61.

14. Dave S.S., Fu K., Wright G.W. et al. Lymphoma/leukemia molecular profiling project: molecular diagnosis of Burkitt’s lymphoma. N Engl J Med 2006;354(23):2431–42. DOI: 10.1056/NEJMoa055759. PMID: 16760443.

15. Hummel M., Bentink S., Berger H. et al. Molecular mechanisms in malignant lymphomas network project of the Deutsche Krebshilfe: a biologic definition of Burkitt’s lymphoma from transcriptional and genomic profiling. N Engl J Med 2006;354(23):2419–30. DOI: 10.1056/NEJMoa055351. PMID: 16760442.

16. Dunleavy K., Little R.F., Wilson W.H. Update on Burkitt Lymphoma. Hematol Oncol Clin N Am 2016;30(6):1333–43. DOI: 10.1016/j.hoc.2016.07.009. PMID: 27888884.

17. Kansal R., Deeb G., Barcos M. et al. Precursor B lymphoblastic leukemia with surface light chain immunoglobulin restriction: a report of 15 patients. Am J Clin Pathol 2004;121(4):512–25. DOI: 10.1309/WTXC-Q5NR-ACVXTYBY. PMID: 15080303.

18. Kelemen K., Braziel R.M., Gatter K. et al. Immunophenotypic variations of Burkitt lymphoma. Am J Clin Pathol 2010;134(1):127–38. DOI: 10.1309/AJCP93LJPTRQPDKR. PMID: 20551277.

19. Kim B., Lee S.-T., Kim H.-J. et al. Acute Lymphoblastic Leukemia with Mature B-Cell Phenotype and t(9;11;11)(p22;q23;p11.2): A Case Study and Literature Review. Ann Lab Med 2014;34(2):166–9. DOI: 10.3343/alm.2014.34.2.166. PMID: 24624357.

20. Blin N., Méchinaud F., Talmant P. et al. Mature B-cell lymphoblastic leukemia with MLL rearrangement: an uncommon and distinct subset of childhood acute leukemia. Leukemia 2008;22(5):1056–9. DOI: 10.1038/sj.leu.2404992. PMID: 18007578.

21. Smith M.C., Kressin M.K., Crawford E., et al. B Lymphoblastic Leukemia With a Novel t(11;15)(q23;q15) and Unique Burkittoid Morphologic and Immunophenotypic Findings in a 9-Year-Old Boy. Lab Med Fall 2015;46(4):320–6. DOI: 10.1309/LM0BOC84GSQGHYKD. PMID: 26489677.

22. Sato Y., Kurosawa H., Fukushima K. et al. Burkitt-Type Acute Lymphoblastic Leukemia With Precursor B-Cell Immunophenotype and Partial Tetrasomy of 1q: A Case Report. Medicine (Baltimore) 2016;95(10):e2904. DOI: 10.1097/MD.0000000000002904. PMID: 26962787.

23. Swerdlow S.H., Campo E., Harris N.L. et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th edition. International Agency for Research on Cancer. Lyon, 2017.