Skip to main content

Bone Marrow at Initial Diagnosis: Clinical Associations and Approach to Diagnosis

  • Chapter
  • First Online:
Practical Lymph Node and Bone Marrow Pathology

Part of the book series: Practical Anatomic Pathology ((PAP))

Abstract

Bone marrow examinations are done for a variety of benign and malignant conditions and are often triggered by abnormalities in the complete blood count and peripheral blood smear. In this chapter, a diagnostic approach to evaluating bone marrows in both adults and children will be reviewed. Optimal use of different aspects of the examination will be discussed as well as the use of ancillary testing. Finally, the organization of bone marrow reports and determination of when one can render a definitive versus a descriptive diagnosis will be reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Parapia LA. Trepanning or trephines: a history of bone marrow biopsy. Br J Haematol. 2007;139(1):14–9.

    Article  Google Scholar 

  2. Ellis LD, Jensen WN, Westerman MP. Needle biopsy of bone and marrow; an experience with 1,445 biopsies. Arch Intern Med. 1964;114:213–21.

    Article  CAS  Google Scholar 

  3. Arbor DA, Orazi A, Hasserjian RP, Brunning RD, Beau MML, Porwit A, et al. Introduction and overview of the classification of myeloid neoplasms. In: Swerdlow SH, et al., editors. WHO Classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer; 2017. p. 16–27.

    Google Scholar 

  4. Wazir SM, Ghobrial I. Copper deficiency, a new triad: anemia, leucopenia, and myeloneuropathy. J Community Hosp Intern Med Perspect. 2017;7(4):265–8.

    Google Scholar 

  5. Gabreyes AA, Abbasi HN, Forbes KP, McQuaker G, Duncan A, Morrison I. et al. Hypocupremia associated cytopenia and myelopathy: a national retrospective review. Eur J Haematol. 2013;90(1):1–9.

    Google Scholar 

  6. Papageorgiou A, Ziakas PD, Tzioufas AG, Voulgarelis M. Indications for bone marrow examination in autoimmune disorders with concurrent haematologic alterations. Clin Exp Rheumatol. 2013;31(1):76–83.

    Google Scholar 

  7. Hunt KE, Salama ME, Sever CE, Foucar K. Bone marrow examination for unexplained cytopenias reveals nonspecific findings in patients with collagen vascular disease. Arch Pathol Lab Med. 2013;137(7):948–54.

    Google Scholar 

  8. Pullarkat V, Bass RD, Gong JZ, Feinstein DI, Brynes RK. Primary autoimmune myelofibrosis: definition of a distinct clinicopathologic syndrome. Am J Hematol. 2003;72(1):8–12.

    Google Scholar 

  9. Mahabir VK, Ross C, Popovic S, Sur ML, Bourgeois J, Lim W, et al. A blinded study of bone marrow examinations in patients with primary immune thrombocytopenia. Eur J Haematol. 2013;90(2):121–6.

    Google Scholar 

  10. Leguit RJ, van den Tweel JG. The pathology of bone marrow failure. Histopathology. 2010;57(5):655–70.

    Google Scholar 

  11. Weinzierl EP, Arber DA. The differential diagnosis and bone marrow evaluation of new-onset pancytopenia. Am J Clin Pathol. 2013;139(1):9–29.

    Google Scholar 

  12. Delsol G, Guiu-Godfrin B, Guiu M, Pris J, Corberand J, Fabre J. Leukoerythroblastosis and cancer frequency, prognosis, and physiopathologic significance. Cancer. 1979;44(3):1009–13.

    Google Scholar 

  13. Kakkar N, Mittal D, Das S, John JM, Rajamanickam T. Bone marrow involvement in systemic oxalosis: a rare cause of leukoerythroblastic anemia. Indian J Pathol Microbiol. 2011;54(3):659–60.

    Google Scholar 

  14. Simon D, Galambos JT. Leukoerythroblastosis with blasts in a patient with alcoholic hepatitis. J Clin Gastroenterol. 1987;9(2):217–8.

    Google Scholar 

  15. Tapia G, Navarro JT, Navarro M. Leukoerythroblastic anemia due to oxalosis with extensive bone marrow involvement. Am J Hematol. 2008;83(6):515–6.

    Google Scholar 

  16. Phillips L, Opie J. The utility of bone marrow sampling in the diagnosis and staging of lymphoma in South Africa. Int J Lab Hematol. 2018;40:276.

    Google Scholar 

  17. Xiao L, Luxi S, Ying T, Yizhi L, Lingyun W, Quan P. Diagnosis of unknown nonhematological tumors by bone marrow biopsy: a retrospective analysis of 10,112 samples. J Cancer Res Clin Oncol. 2009;135(5):687–93.

    Google Scholar 

  18. Ozkalemkas F, Ali R, Ozkocaman V, Ozcelik T, Ozan U, Ozturk H, et al. The bone marrow aspirate and biopsy in the diagnosis of unsuspected nonhematologic malignancy: a clinical study of 19 cases. BMC Cancer. 2005;5:144.

    Google Scholar 

  19. Garewal G, Ahluwalia J, Kumar V, Shukla R, Das R, Varma N, et al. The utility of bone marrow examination in renal transplantation: nine years of experience from north India. Transplantation. 2006;81(9):1354–6.

    Google Scholar 

  20. Mirzai AZ, Hosseini N, Sadeghipour A. Indications and diagnostic utility of bone marrow examination in different bone marrow disorders in Iran. Lab Hematol. 2009;15(4):38–44.

    Google Scholar 

  21. Borcek P, Ozdemir BH, Sercan C, Yilmaz Akcay E, Karakus S, Haberal M. Histologic changes in bone marrow biopsies from liver transplant patients. Exp Clin Transplant. 2016;14(Suppl 3):109–11.

    Google Scholar 

  22. Kilby JM, Marques MB, Jaye DL, Tabereaux PB, Reddy VB, Waites KB. The yield of bone marrow biopsy and culture compared with blood culture in the evaluation of HIV-infected patients for mycobacterial and fungal infections. Am J Med. 1998;104(2):123–8.

    Google Scholar 

  23. Hot A, Jaisson I, Girard C, French M, Durand DV, Rousset H, et al. Yield of bone marrow examination in diagnosing the source of fever of unknown origin. Arch Intern Med. 2009;169(21):2018–23.

    Google Scholar 

  24. Wang HY, Yang CF, Chiou TJ, Yang SH, Gau JP, Yu YB, et al. A “bone marrow score” for predicting hematological disease in immunocompetent patients with fevers of unknown origin. Medicine (Baltimore). 2014;93(27):e243.

    Google Scholar 

  25. Rosado FG, Kim AS. Hemophagocytic lymphohistiocytosis: an update on diagnosis and pathogenesis. Am J Clin Pathol. 2013;139(6):713–27.

    Google Scholar 

  26. Goel S, Polski JM, Imran H. Sensitivity and specificity of bone marrow hemophagocytosis in hemophagocytic lymphohistiocytosis. Ann Clin Lab Sci. 2012;42(1):21–5.

    Google Scholar 

  27. Gupta A, Tyrrell P, Valani R, Benseler S, Weitzman S, Abdelhaleem M. The role of the initial bone marrow aspirate in the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008;51(3):402–4.

    Google Scholar 

  28. Wang HY, Yang CF, Chiou TJ, Yang SH, Gau JP, Yu YB, et al. Risk of hemophagocytic lymphohistiocytosis in adults with fevers of unknown origin: the clinical utility of a new scoring system on early detection. Hematol Oncol. 2017;35(4):835–44.

    Google Scholar 

  29. Sreedharanunni S, Sachdeva MU, Kumar N, Sharma P, Naseem S, Ahluwalia J, et al. Spectrum of diseases diagnosed on bone marrow examination of 285 infants in a single tertiary care center. Hematology. 2015;20(3):175–81.

    Google Scholar 

  30. Naseem S, Varma N, Das R, Ahluwalia J, Sachdeva MU, Marwaha RK. Pediatric patients with bicytopenia/pancytopenia: review of etiologies and clinico-hematological profile at a tertiary center. Indian J Pathol Microbiol. 2011;54(1):75–80.

    Google Scholar 

  31. Elmadhoun WM, Noor SK, Bushara SO, Almobarak AO, Husain NE, Ahmed MH. Bone marrow aspiration in north Sudan: the procedure, indications and the diagnostic value. Int J Health Sci (Qassim). 2015;9(4):434–9.

    Google Scholar 

  32. Abla O, Friedman J, Doyle J. Performing bone marrow aspiration and biopsy in children: recommended guidelines. Paediatr Child Health. 2008;13(6):499–501.

    Google Scholar 

  33. Afkhami M, Vergara-Lluri M, Brynes RK, Siddiqi IN. Peripheral blood smears, bone marrow aspiration, trephine and clot biopsies: methods and protocols. Methods Mol Biol. 2014;1180:257–69.

    Google Scholar 

  34. Friedlis MF, Centeno CJ. Performing a better bone marrow aspiration. Phys Med Rehabil Clin N Am. 2016;27(4):919–39.

    Google Scholar 

  35. Yang RK, Nazeef M, Patel SS, Mattison R, Yang DT, Ranheim EA, et al. Improving bone marrow biopsy quality through peer discussion and data comparisons: a single institution experience. Int J Lab Hematol. 2018;40:419.

    Google Scholar 

  36. Lee SH, Erber WN, Porwit A, Tomonaga M, Peterson LC. ICSH guidelines for the standardization of bone marrow specimens and reports. Int J Lab Hematol. 2008;30(5):349–64.

    Google Scholar 

  37. Gong X, Lu X, Wu X, Xu R, Tang Q, Xu G, et al. Role of bone marrow imprints in haematological diagnosis: a detailed study of 3781 cases. Cytopathology. 2012;23(2):86–95.

    Google Scholar 

  38. Gilotra M, Gupta M, Singh S, Sen R. Comparison of bone marrow aspiration cytology with bone marrow trephine biopsy histopathology: an observational study. J Lab Physicians. 2017;9(3):182–9.

    Google Scholar 

  39. Naresh KN, Lampert I, Hasserjian R, Lykidis D, Elderfield K, Horncastle D, et al. Optimal processing of bone marrow trephine biopsy: the Hammersmith Protocol. J Clin Pathol. 2006;59(9):903–11.

    Google Scholar 

  40. Douglas DD, Risdall RJ. Bone marrow biopsy technic. Artifact induced by aspiration. Am J Clin Pathol. 1984;82(1):92–4.

    Google Scholar 

  41. Kremer M, Quintanilla-Martinez L, Nahrig J, von Schilling C, Fend F. Immunohistochemistry in bone marrow pathology: a useful adjunct for morphologic diagnosis. Virchows Arch. 2005;447(6):920–37.

    Google Scholar 

  42. Grant RC, Shaikh F, Abdelhaleem M, Alexander SW, Cada M. Risk factors for inadequate bone marrow biopsies in children. Am J Hematol. 2015;90(9):E187–9.

    Google Scholar 

  43. Reid MM, Roald B. Adequacy of bone marrow trephine biopsy specimens in children. J Clin Pathol. 1996;49(3):226–9.

    Google Scholar 

  44. van der Bruggen W, Glaudemans A, Vellenga E, Slart R. PET in benign bone marrow disorders. Semin Nucl Med. 2017;47(4):397–407.

    Google Scholar 

  45. El Karak F, Bou-Orm IR, Ghosn M, Kattan J, Farhat F, Ibrahim T, et al. PET/CT scanner and bone marrow biopsy in detection of bone marrow involvement in diffuse large B-cell lymphoma. PLoS One. 2017;12(1):e0170299.

    Google Scholar 

  46. Agbay R, Loghavi S, Zuo Z, Fayad L, Dabaja B, Medeiros LJ, et al. Bone marrow involvement in patients with nodular lymphocyte predominant Hodgkin lymphoma. Am J Surg Pathol. 2018;42(4):492–9.

    Google Scholar 

  47. Puccini B, Nassi L, Minoia C, Volpetti S, Ciancia R, Riccomagno PC, et al. Role of bone marrow biopsy in staging of patients with classical Hodgkin’s lymphoma undergoing positron emission tomography/computed tomography. Ann Hematol. 2017;96(7):1147–53.

    Google Scholar 

  48. Friebert SE, Shepardson LB, Shurin SB, Rosenthal GE, Rosenthal NS. Pediatric bone marrow cellularity: are we expecting too much? J Pediatr Hematol Oncol. 1998;20(5):439–43.

    Google Scholar 

  49. Onciu M. Pediatric bone marrow interpretation. Surg Pathol Clin. 2010;3(4):1091–125.

    Google Scholar 

  50. Sutton L, Vusirikala M, Chen W. Hematogone hyperplasia in copper deficiency. Am J Clin Pathol. 2009;132(2):191–9; quiz 307.

    Google Scholar 

  51. Liang J, Malherbe JAJ, Fuller KA, Mirzai B, George C, Carter TL, et al. Automated enumeration of lymphoid and plasma cells in bone marrow to establish normal reference ranges. J Clin Pathol. 2018;71:916.

    Google Scholar 

  52. Ganser A, Heuser M. Therapy-related myeloid neoplasms. Curr Opin Hematol. 2017;24(2):152–8.

    Google Scholar 

  53. Fadini GP, Ciciliot S, Albiero M. Concise review: perspectives and clinical implications of bone marrow and circulating stem cell defects in diabetes. Stem Cells. 2017;35(1):106–16.

    Google Scholar 

  54. Soliman AT, De Sanctis V, Yassin M, Wagdy M, Soliman N. Chronic anemia and thyroid function. Acta Biomed. 2017;88(1):119–27.

    Google Scholar 

  55. Azevedo P, Cardoso PSR, Farah KP, de Melo FHC, Rezende SM. Complete reversal of bone marrow fibrosis after parathyroidectomy for secondary hyperparathyroidism. Br J Haematol. 2017;178(4):500.

    Google Scholar 

  56. Thiele J, Zirbes TK, Bertsch HP, Titius BR, Lorenzen J, Fischer R. AIDS-related bone marrow lesions--myelodysplastic features or predominant inflammatory-reactive changes (HIV-myelopathy)? A comparative morphometric study by immunohistochemistry with special emphasis on apoptosis and PCNA-labeling. Anal Cell Pathol. 1996;11(3):141–57.

    Google Scholar 

  57. Piatek CI, Vergara-Lluri ME, Pullarkat V, Siddiqi IN, O’Connell C, Brynes RK, et al. Autoimmune myelofibrosis: clinical features, course, and outcome. Acta Haematol. 2017;138(3):129–37.

    Google Scholar 

  58. Abaza Y, Yin CC, Bueso-Ramos CE, Wang SA, Verstovsek S. Primary autoimmune myelofibrosis: a case report and review of the literature. Int J Hematol. 2017;105(4):536–9.

    Google Scholar 

  59. Vergara-Lluri ME, Piatek CI, Pullarkat V, Siddiqi IN, O’Connell C, Feinstein DI, et al. Autoimmune myelofibrosis: an update on morphologic features in 29 cases and review of the literature. Hum Pathol. 2014;45(11):2183–91.

    Google Scholar 

  60. Ungprasert P, Chowdhary VR, Davis MD, Makol A. Autoimmune myelofibrosis with pancytopenia as a presenting manifestation of systemic lupus erythematosus responsive to mycophenolate mofetil. Lupus. 2016;25(4):427–30.

    Google Scholar 

  61. Tang VK, Huh YO, Tayar JH, Rojas Hernandez CM. Primary autoimmune myelofibrosis as etiology of pancytopenia mimicking myelodysplastic syndrome. Leuk Lymphoma. 2016;57(3):731–4.

    Google Scholar 

  62. Lewandowski K, Complak A, Hellmann A. Microscopic examination of bone marrow aspirates in malignant disorders of haematopoiesis--a comparison of two slide preparation techniques. Ann Hematol. 2012;91(4):497–505.

    Google Scholar 

  63. Sharma P, Sachdeva MU, Varma N. Bone marrow aspirate smear preparation: morphological superiority of the timely wedge smear and the importance of imprints. Ann Hematol. 2014;93(6):1063–4.

    Google Scholar 

  64. Aleem A, Alsaleh K, Aljabry M, Aziz S, Iqbal Z, Almomen A. A comparison of two techniques of preparing bone marrow aspirate slides. J Pak Med Assoc. 2016;66(5):528–7.

    Google Scholar 

  65. Oo TH, Hu S. Copper deficiency-related bone marrow changes secondary to long-term total parenteral nutrition. Clin Case Rep. 2017;5(2):195–6.

    Google Scholar 

  66. Dalal N, Hooberman A, Mariani R, Sirota R, Lestingi T. Copper deficiency mimicking myelodysplastic syndrome. Clin Case Rep. 2015;3(5):325–7.

    Google Scholar 

  67. Beutler E. Clinical evaluation of iron stores. N Engl J Med. 1957;256(15):692–7.

    Google Scholar 

  68. Wallerstein RO. Marrow iron. JAMA. 1977;238(15):1661–2.

    Google Scholar 

  69. Das S, Mishra P, Kar R, Basu D. Gelatinous marrow transformation: a series of 11 cases from a tertiary care centre in South India. Turk J Haematol. 2014;31(2):175–9.

    Google Scholar 

  70. Bohm J. Gelatinous transformation of the bone marrow: the spectrum of underlying diseases. Am J Surg Pathol. 2000;24(1):56–65.

    Google Scholar 

  71. Tadmor T, Shvidel L, Aviv A, Ruchlemer R, Bairey O, Yuklea M, et al. Significance of bone marrow reticulin fibrosis in chronic lymphocytic leukemia at diagnosis: a study of 176 patients with prognostic implications. Cancer. 2013;119(10):1853–9.

    Google Scholar 

  72. Brackers de Hugo L, Ffrench M, Broussolle C, Seve P. Granulomatous lesions in bone marrow: clinicopathologic findings and significance in a study of 48 cases. Eur J Intern Med. 2013;24(5):468–73.

    Google Scholar 

  73. Wool GD, Deucher A. Bone marrow necrosis: ten-year retrospective review of bone marrow biopsy specimens. Am J Clin Pathol. 2015;143(2):201–13; quiz 306.

    Google Scholar 

  74. Himchak E, Marks E, Shi Y, Wang Y. Did I miss it? discovering hidden coexisting hematological neoplasms: a single institutional review of 100 collision tumors. Int J Surg Pathol. 2018;26(4):296–305.

    Google Scholar 

  75. Alley CL, Wang ED, Dunphy CH, Gong JZ, Lu CYM, Boswell EL, et al. Diagnostic and clinical considerations in concomitant bone marrow involvement by plasma cell myeloma and chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis. Arch Pathol Lab Med. 2013;137(4):503–17.

    Google Scholar 

  76. Seegmiller AC, Kim AS, Mosse CA, Levy MA, Thompson MA, Kressin MK, et al. Optimizing personalized bone marrow testing using an evidence-based, interdisciplinary team approach. Am J Clin Pathol. 2013;140(5):643–50.

    Google Scholar 

  77. Seegmiller AC, Kim AS, Mosse CA, Shaver AC, Thompson MA, Li S, et al. Data-driven iterative refinement of bone marrow testing protocols leads to progressive improvement in cytogenetic and molecular test utilization. Am J Clin Pathol. 2016;146(5):585–93.

    Google Scholar 

  78. Arroz M, Came N, Lin P, Chen W, Yuan C, Lagoo A, et al. Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting. Cytometry B Clin Cytom. 2016;90(1):31–9.

    Google Scholar 

  79. Sever C, Abbott CL, de Baca ME, Khoury JD, Perkins SL, Reichard KK, et al. Bone marrow synoptic reporting for hematologic neoplasms: guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2016;140(9):932–49.

    Google Scholar 

  80. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. In: Sosman FT, et al., editors. World Health Organization classification of tumours. Revised 4 ed. Lyon: International Agency for Research on Cancer; 2017. p. 585.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anand Shreeram Lagoo .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lagoo, A.S., Rosenthal, N.S. (2020). Bone Marrow at Initial Diagnosis: Clinical Associations and Approach to Diagnosis. In: Wang, E., Lagoo, A.S. (eds) Practical Lymph Node and Bone Marrow Pathology. Practical Anatomic Pathology. Springer, Cham. https://doi.org/10.1007/978-3-030-32189-5_20

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-32189-5_20

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-32188-8

  • Online ISBN: 978-3-030-32189-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics