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Normales Knochenmark und häufige reaktive Veränderungen

Normal bone marrow and common reactive alterations

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Zusammenfassung

Die histologische Knochenmarkuntersuchung spielt, wegen ihrer großen Aussagekraft bei relativ geringem Aufwand eine bedeutende Rolle in der Diagnostik von hämatologischen und nichthämatologischen Erkrankungen. Dafür ist die Kenntnis des normalen Knochenmarks mit seiner individuellen, insbesondere altersabhängigen, Variabilität, unentbehrlich. Neben entnahmebedingten Artefakten, die falsch interpretiert werden können, oder suboptimal fixierten bzw. verarbeiteten Biopsien, die diagnostisch überbewertet werden, gibt es eine Vielfalt von reaktiven Knochenmarkveränderungen, die einen neoplastischen Prozess vortäuschen und zu schwerwiegenden diagnostischen Fehlern führen können. Bei derartigen nichtneoplastischen Veränderungen können ein oder auch mehrere Kompartimente der Hämatopoiese qualitativ und quantitativ betroffen sein. Es kann zu Verteilungs- bzw. Architekturstörungen und/oder zu Veränderungen des Knochenmarkstromas kommen. Eine optimale Knochenmarkdiagnostik erfordert, neben Spezialfärbungen, zusätzlich oftmals immunhistochemische Untersuchungen und manchmal molekularpathologische Analysen. Mehr als bei anderen Organbiopsien ist die Kenntnis klinischer Befunde, insbesondere vorangegangener Therapien, relevant, um eine korrekte Diagnose zu stellen. In diesem Beitrag sind neben dem normalen Knochenmark die häufigsten reaktiven Veränderungen dargestellt.

Abstract

Histological examination of bone marrow biopsies is an important and powerful diagnostic tool to assess various hematological and non-hematological disorders. Morphological examination of such biopsies requires knowledge of the composition of normal bone marrow and its variations, such as age-related changes. Diagnostic problems may arise due to poor specimen quality, insufficient sections or stainings and insufficient experience with reactive bone marrow changes which occasionally resemble neoplastic disorders. Reactive bone marrow processes can affect one or more hematopoietic cell lines, lead to disruption of the normal architecture and specifically affect the bone marrow stroma. Optimal bone marrow diagnosis requires adequately stained slides and, when needed, immunophenotyping and molecular examinations. Furthermore, rather than biopsy interpretation of other organs, pathologists routinely need clinical history information for correct interpretation and diagnosis of bone marrow changes. In this article, the normal features of bone marrow as well as the most frequent reactive bone marrow alterations are described.

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Literatur

  1. Bain BJ (2001) Bone marrow trephine biopsy. J Clin Pathol 54:737–742

    Article  PubMed  CAS  Google Scholar 

  2. Bartakke S, Abdelhaleem M, Carcao M (2008) Valproate-induced pure red cell aplasia and megakaryocyte dysplasia. Br J Haematol 141:133

    Article  PubMed  Google Scholar 

  3. Bataille R, Jégo G, Robillard N et al (2006) The phenotype of normal, reactive and malignant plasma cells. Identification of „many and multiple myelomas“ and of new targets for myeloma therapy. Haematologica 91:1234–1240

    PubMed  CAS  Google Scholar 

  4. Böhm J (2000) Gelatinous transformation of the bone marrow: the spectrum of underlying diseases. Am J Surg Pathol 24:56–65

    Article  PubMed  Google Scholar 

  5. Brown DC, Gatter KC (1993) The bone marrow trephine biopsy: a review of normal histology. Histopathology 22:411–422

    Article  PubMed  CAS  Google Scholar 

  6. Bruin M, Dassen A, Pajkrt D et al (2005) Primary autoimmune neutropenia in children: a study of neutrophil antibodies and clinical course. Vox Sang 88:52–59

    Article  PubMed  CAS  Google Scholar 

  7. Brunner A, Kantner J, Tzankov A (2005) Granulomatous reactions cause symptoms or clinically imitate treatment resistance in small lymphocytic lymphoma/chronic lymphocytic leukaemia more frequently than in other non-Hodgkin lymphomas. J Clin Pathol 58:815–819

    Article  PubMed  CAS  Google Scholar 

  8. Colvin BT, Revell PA, Ibbotson RM, Turnbull AL (1980) Necrosis of bone marrow and bone in malignant disease. Clin Oncol 6:265–672

    PubMed  CAS  Google Scholar 

  9. Dokal I, Vulliamy T (2008) Inherited aplastic anaemias/bone marrow failure syndromes. Blood Rev 22:141–153

    Article  PubMed  CAS  Google Scholar 

  10. Engels K, Oeschger S, Hansmann ML et al (2007) Bone marrow trephines containing lymphoid aggregates from patients with rheumatoid and other autoimmune disorders frequently show clonal B-cell infiltrates. Hum Pathol 38:1402–1411

    Article  PubMed  CAS  Google Scholar 

  11. Felderbauer P, Ritter PR, Mattern D et al (2004) Acquired pure megakaryocytic aplasia: a separate haematological disease entity or a syndrome with multiple causes? Eur J Haematol 72:451–454

    Article  PubMed  CAS  Google Scholar 

  12. Foucar K, Reichard K, Czuchlewski D (2010) Bone marrow pathology. 3. Aufl. ASCP Press, Chicago

  13. Gale E, Torrance J, Bothwell T (1963) The quantitative estimation of total iron stores in human bone marrow. J Clin Invest 42:1076–1082

    Article  PubMed  CAS  Google Scholar 

  14. Girodon F, Favre B, Carli PM et al (2001) Minor dysplastic changes are frequently observed in the bone marrow aspirate in elderly patients without haematological disease. Clin Lab Haematol 23:297–300

    Article  PubMed  CAS  Google Scholar 

  15. Gruppo RA, Lampkin BC, Granger S (1977) Bone marrow cellularity determination: comparison of the biopsy, aspirate, and buffy coat. Blood 49:29–31

    PubMed  CAS  Google Scholar 

  16. Harris AC, Todd WM, Hackney MH, Ben-Ezra J (1994) Bone marrow changes associated with recombinant granulocyte-macrophage and granulocyte colony-stimulating factors. Discrimination of granulocytic regeneration. Arch Pathol Lab Med 118:624–629

    PubMed  CAS  Google Scholar 

  17. Hassanein NM, Alcancia F, Perkinson KR et al (2009) Distinct expression patterns of CD123 and CD34 on normal bone marrow B-cell precursors („hematogones“) and B lymphoblastic leukemia blasts. Am J Clin Pathol 132:573–580

    Article  PubMed  Google Scholar 

  18. Ibáñez L, Vidal X, Ballarín E, Laporte JR (2005) Population-based drug-induced agranulocytosis. Arch Intern Med 165:869–874

    Article  PubMed  Google Scholar 

  19. Janka GE (2007) Hemophagocytic syndromes. Blood Rev 21:245–253

    Article  PubMed  CAS  Google Scholar 

  20. Kirby MA, Weitzman S, Freedman MH (1990) Juvenile chronic myelogenous leukemia: differentiation from infantile cytomegalovirus infection. Am J Pediatr Hematol Oncol 12:292–296

    Article  PubMed  CAS  Google Scholar 

  21. Krause JR, Penchansky L, Knisely AS (1992) Morphological diagnosis of parvovirus B19 infection. A cytopathic effect easily recognized in air-dried, formalin-fixed bone marrow smears stained with hematoxylin-eosin or Wright-Giemsa. Arch Pathol Lab Med 116:178–180

    PubMed  CAS  Google Scholar 

  22. Kuter DJ, Bain B, Mufti G et al (2007) Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol 139:351–362

    Article  PubMed  CAS  Google Scholar 

  23. Lu W, Uetrecht JP (2008) Peroxidase-mediated bioactivation of hydroxylated metabolites of carbamazepine and phenytoin. Drug Metab Dispos 36:1624–1636

    Article  PubMed  CAS  Google Scholar 

  24. Marsh JC, Ball SE, Cavenagh J et al and British Committee for Standards in Haematology (2009) Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 147:43–70

    Article  PubMed  CAS  Google Scholar 

  25. McMillan R (2007) The pathogenesis of chronic immune thrombocytopenic purpura. Semin Hematol 44(4 Suppl 5):3–11

    Article  Google Scholar 

  26. Medinger M, Buser A, Stern M et al (2012) Aplastic anemia in association with a lymphoproliferative neoplasm: coincidence or causality? Leuk Res 36:250–251

    Article  PubMed  Google Scholar 

  27. Medinger M, Fischer N, Tzankov A (2010) Vascular endothelial growth factor-related pathways in hemato-lymphoid malignancies. J Oncol 729725

  28. Naeim F (1995) Topobiology in hematopoiesis. Hematol Pathol 9:107–119

    PubMed  CAS  Google Scholar 

  29. Poje EJ, Soori GS, Weisenburger DD (1992) Systemic polyclonal B-immunoblastic proliferation with marked peripheral blood and bone marrow plasmacytosis. Am J Clin Pathol 98:222–226

    PubMed  CAS  Google Scholar 

  30. Qubaja M, Marmey B, Le Tourneau A et al (2009) The detection of CD14 and CD16 in paraffin-embedded bone marrow biopsies is useful for the diagnosis of chronic myelomonocytic leukemia. Virchows Arch 454:411–419

    Article  PubMed  CAS  Google Scholar 

  31. Rimsza LM, Larson RS, Winter S (2000) Benign hematogone-rich lymphoid proliferations can be distinguished from B-lineage acute lymphoblastic leukemia by integration of morphology, immunophenotype, adhesion molecule expression, and architectural features. Am J Clin Pathol 114:66–75

    Article  PubMed  CAS  Google Scholar 

  32. Rosenthal NS, Farhi DC (1989) Bone marrow findings in connective tissue disease. Am J Clin Pathol 92:650–654

    PubMed  CAS  Google Scholar 

  33. Sawada K, Hirokawa M, Fujishima N (2009) Diagnosis and management of acquired pure red cell aplasia. Hematol Oncol Clin North Am 23:249–259

    Article  PubMed  Google Scholar 

  34. Thiele J, Kvasnicka HM, Facchetti F et al (2005) European Consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 90:1128–1132

    PubMed  Google Scholar 

  35. Thiele J, Ammers E von, Wagner S et al (1991) Megakaryocytopoiesis in idiopathic thrombocytopenic purpura: a morphometric and immunohistochemical study on bone marrow biopsies with special emphasis on precursor cells. Hematol Pathol 5:75–82

    PubMed  CAS  Google Scholar 

  36. Thiele J, Zirbes TK, Kvasnicka HM, Fischer R (1999) Focal lymphoid aggregates (nodules) in bone marrow biopsies: differentiation between benign hyperplasia and malignant lymphoma—a practical guideline. J Clin Pathol 52:294–300

    Article  PubMed  CAS  Google Scholar 

  37. Valent P (1995) Mast cell differentiation antigens: expression in normal and malignant cells and use for diagnostic purposes. Eur J Clin Invest 25:715–720

    Article  PubMed  CAS  Google Scholar 

  38. Wang EC, Borysiewicz LK (1995) The role of CD8+, CD57+ cells in human cytomegalovirus and other viral infections. Scand J Infect Dis Suppl 99:69–77

    PubMed  CAS  Google Scholar 

  39. Wickramsinghe SN (2007) Bone marrow. In: Mills SE (Hrsg) Histology for pathologists. Lippincott Williams & Wilkins, Philadelphia, S 799–836

  40. Wilkins BS (2011) Pitfalls in bone marrow pathology: avoiding errors in bone marrow trephine biopsy diagnosis. Review. J Clin Pathol 64:380–386

    Article  PubMed  Google Scholar 

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Danksagung

Die Autoren möchten sich bei Dr. Bertha Frisch für ihre Pionierarbeit bei der histologischen Knochenmarkuntersuchung bedanken.

Interessenkonflikt

Der korrespondierende Autor gibt für sich und seine Koautoren an, dass kein Interessenkonflikt besteht.

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Authors and Affiliations

  1. Institut für Pathologie, Universitätsspital Basel, Schoenbeinstr. 40, 4031, Basel, Schweiz

    A. Tzankov, S. Dirnhofer & C. Beham-Schmid

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  1. A. Tzankov
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  2. S. Dirnhofer
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  3. C. Beham-Schmid
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Correspondence to A. Tzankov.

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Tzankov, A., Dirnhofer, S. & Beham-Schmid, C. Normales Knochenmark und häufige reaktive Veränderungen. Pathologe 33, 496–507 (2012). https://doi.org/10.1007/s00292-012-1649-x

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