Principles of Pathomorphological Differential Diagnosis of Myelodysplastic Syndromes

AM Kovrigina1, SA Glinkina1, VV Baikov2

1 Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

For correspondence: Alla Mikhailovna Kovrigina, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-61-12; e-mail: kovrigina.alla@gmail.com

For citation: Kovrigina AM, Glinkina SA, Baikov VV. Principles of Pathomorphological Differential Diagnosis of Myelodysplastic Syndromes. Clinical oncohematology. 2015;8(1):62–8 (In Russ).


ABSTRACT

The article dwells on the diagnosis of myelodysplastic syndromes (MDS) in bone marrow trephine biopsies. The paper describes problems of a complex approach to differential diagnostics of MDS and non-clonal/reactive changes in hematopoiesis. It is emphasized that clinical and laboratory data, as well as data on patient’s medical history should be submitted to a pathologist. The authors substantiate the algorithm for the morphological investigation of a bone marrow trephine bioptate, including evaluation of cellularity, stromal patterns, and morphological signs of dysplasia. The diagnostic value of histochemistry and immunohistochemistry is discussed.


Keywords: myelodysplastic syndrome, bone marrow trephine biopsy, pathomorphology, differential diagnostics.

Received: October 22, 2014

Accepted: November 10, 2014

Read in PDF (RUS)pdficon


REFERENCES

  1. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008.
  2. Boultwood J, Wainscoat JS. Gene silencing by DNA methylation in haematological malignancies. Br J Haematol. 2007;138(1):3–11. doi: 10.1111/j.1365-2141.2007.06604.x.
  3. Cazzola M, Porta MG, Malcovati L. The genetic basis of myelodysplasia and its clinical relevance. Blood. 2013;122(25):4021–34. doi: 10.1182/blood-2013-09-381665.
  4. Lindsley RC, Elbert BL. Molecular pathophysiology of myelodysplastic syndromes. Annu Rev Pathol. 2013;8(1):21–47. doi: 10.1146/annurev-pathol-011811-132436.
  5. Maciejewski JP, Mufti GJ. Whole genome scanning as a cytogenetic tool in hematologic malignancies. Blood. 2008;112(4):965–74. doi: 10.1182/blood-2008-02-130435.
  6. Mohamedali A, Gаken J, Twine NA, et al. Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. Blood. 2007;110(9):3365–73. doi: 10.1182/blood-2007-03-079673.
  7. Raza A, Galili N. The genetic basis of phenotypic heterogeneity in myelodysplastic syndromes. Cancer. 2012;12(12):849–59. doi: 10.1038/nrc3321.
  8. Smith AE, Mohamedali AM, Kulasekararaj A, et al. Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value. Blood. 2010;116(19):3923–32. doi: 10.1182/blood-2010-03-274704.
  9. Thol F, Friesen I, Damm F, et al. Prognostic significance of ASXL1 mutations in patients with myelodysplastic syndromes. J Clin Oncol. 2011;29(18):2499–506. doi: 10.1200/jco.2010.33.4938.
  10. Thol F, Kade S, Schlarmann C, et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood. 2012;119(15):3578–84. doi: 10.1182/blood-2011-12-399337.
  11. Yoshida K, Sanada M, Shiraishi Y, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011;478(7367):64–9. doi: 10.1038/nature10496.
  12. Koca E, Buyukasik Y, Cetiner D, et al. Copper deficiency with increased hematogones mimicking refractory anemia with excess blasts. Leuk Res. 2008;32(3):495–9. doi: 10.1016/j.leukres.2007.06.023.
  13. Steensma DP. Dysplasia has a differential diagnosis: distinguishing genuine myelodysplastic syndromes (MDS) from mimics, imitators, copycats and impostors. Curr Hematol Malig Rep. 2012;7(4):310–20. doi: 10.1016/j.leukres.2007.06.023.
  14. Tanaka N, Kim JS, Newell JD, et al. Rheumatoid arthritis-related lung diseases: CT findings. Radiology. 2004;232(1):81–91. doi: 10.1148/radiol.2321030174.
  15. Song Y, Du X, Hao F, et al. Immunosuppressive therapy of cyclosporin A for severe benzene-induced haematopoetic disorders and a 6-month follow-up. Chem Biol Interact. 2010;186(1):96–102. doi: 10.1016/j.cbi.2010.03.049.
  16. Komrokji RS, Moffitt HL, Padron E. Deletion 5q MDS: Molecular and therapeutic implications. Best Pract Res Clin Haematol. 2013;26(4):365–75. doi: 10.1016/j.beha.2013.10.013.
  17. Ковригина А.М., Байков В.В. Принципы патоморфологической дифференциальной диагностики первичного миелофиброза. Москва, Санкт-Петербург, 2014. 63 с. [Kovrigina AM, Baikov VV. Printsipy patomorfologicheskoi differentsial’noi diagnostiki pervichnogo mielofibroza. (Principles of pathomorphological differential diagnosis of primary myelofibrosis.) Moscow, Saint Petersburg; 2014. 63 p. (In Russ)]
  18. Foucar K. Myelodysplastic/Myeloproliferative Neoplasms. Am J Clin Pathol. 2009;132(2):281–9. doi: 10.1309/AJCPJ71PTVIKGEVT.
  19. Wang SA. Diagnosis of myelodysplastic syndromes in cytopenic patients. Hematol Oncol Clin North Am. 2011;25(5):1085–110. doi: 10.1016/j.hoc.2011.09.009.
  20. Thiele J, Kvasnicka H-M, Facchetti F, et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90(8):1128–32.
  21. Baur AS, Meuge-Moraw C, Schmidt PM, et al. CD34/QBEND10 immunostaining in bone marrow biopsies: an additional parameter for the diagnosis and classification of myelodysplastic syndromes. Eur J Haematol. 2000;64(2):71–9.
  22. Horny HP, Sotlar K, Valent P. Diagnostic value of histology and immunohistochemistry in myelodysplastic syndromes. Leuk Res. 2007;31(12):1609–16. doi: 10.1016/j.leukres.2007.05.010.
  23. Valent P, Horny HP. Minimal diagnostic criteria for myelodysplastic syndromes and separation from ICUS and IDUS: update and open questions. Eur J Clin Invest. 2009;39(7):548–53. doi: 10.1111/j.1365-2362.2009.02151.x.
  24. Valent P, Jager E, Mitterbauer-Hohendanner G, et al. Idiopathic bone marrow dysplasia of unknown significance (IDUS): definition, pathogenesis, follow up, and prognosis. Am J Cancer Res. 2011;1:531–41.
  25. Wimazal F, Fonatsch C, Thalhammer R. Idiopathic cytopenia of undetermined significance (ICUS) versus low risk MDS: The diagnostic interface. Leuk Res. 2007;31(11):1461–8. doi: 10.1016/j.leukres.2007.03.015.