Advertisement

Virchows Archiv A

, Volume 415, Issue 3, pp 191–202 | Cite as

Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/-sclerosis (agnogenic myeloid metaplasia) - correlations between clinical and morphological features

  • Juergen Thiele
  • Bert Hoeppner
  • Rudolf Zankovich
  • Robert Fischer
Article

Summary

Histomorphometry was performed on representative trephine biopsies of the bone marrow on admission of 50 patients (21 male, 29 female-age 67 years) with so-called primary osteomyelofibrosis/-sclerosis (OMF) not preceded by any other subtype of chronic myeloproliferative disorders. This study was firstly aimed at testing correlations between histological features (amount of haematopoiesis, cytological aspects of mega-karyocytes, density of reticulin and collagen fibres and degree of osteosclerosis) and laboratory data, as well as spleen size and duration of relevant prediagnostic symptoms. Secondly, we concentrated on a discrimination of OMF patients into two sub-groups according to bone marrow morphology and clinical variables. Statistical evaluation of histomorphometric variables and haematological findings disclosed that there was a progressive fibro-osteosclerotic process in the evolution of disease features. Increase in medullary fibrosis was significantly paralleled by an abnormal or pleomorphic megakaryopoiesis in the bone marrow: there was an increase in irregularity of perimeters for megakaryocytes and naked nuclei combined with smaller sizes of these elements including the nuclei. Additionally, there was a greater number of pycnotic bare nuclei. A number of morphometric features (density of fibres, degree of osteosclerosis, amount of haematopoiesis) were associated with corresponding clinical data (spleen size, length of preclinical history). By consideration of a set of basic histomorphometric variables our co-hort of 50 patients could be divided into an early hyperplastic subtype with no or minimal medullary reticulin and another group with conspicuous fibrotic and osteosclerotic alterations of the bone marrow. It was noticeable that we found no significant correlation between amount of haematopoiesis or marrow cellularity with splenomegaly. This result suggests that splenic haematopoiesis (myeloid metaplasia) may represent an autonomous or neoplastic process and not only compensation for a failing fibro-osteosclerotic bone marrow.

Key words

Primary osteomyelofibrosis/-sclerosis Agnogenic myeloid metaplasia Amount of haematopoiesis Content of fibres Degree of osteosclerosis Spleen size Duration of preclinical symptoms Histomorphometry Clinical findings 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arlet Ph, Nicodeme R, Adoue D, Larregain-Fournier D, Delsol G, Le Tallec Y (1984) Clinical evidence for 1,25-hydroxy-cholecalciferol action in myelofibrosis. Lancet I:1013–1014Google Scholar
  2. Bentley SA, Herman CJ (1979) Bone marrow fibre production in myelofibrosis: a quantitative study. Br J Haematol 42:51–59Google Scholar
  3. Burkhardt R, Bartl R, Jäger K, Frisch B, Kettner B, Mahl G, Sund M (1984) Chronic myeloproliferative disorders (CMPD). Pathol Res Pract 1:131–1868Google Scholar
  4. Burkhardt R, Bart R, Jöger K, Frisch B, Kettner B, Mahl G, Sund M (1986) Working classification of chronic myeloproliferative disorders based on histological, haematological and clinical findings. J Clin Pathol 39:237–252Google Scholar
  5. Burstein SA, Malpass TW, Yee E, Kadin M, Bridgen M, Adamson JW, Harker LA (1984) Platelet factor 4-excretion in myeloproliferative disease: implications for the aetiology of myelofibrosis. Br J Haematol 57:383–392Google Scholar
  6. Caligaris Cappio F, Vigliani R, Novarino A, Camussi G, Campagna G, Gavosto F (1981) Idiopathic myelofibrosis: a possible role for immune-complexes in the pathogenesis of bone marrow fibrosis. Br J Haematol 49:17–21Google Scholar
  7. Castro-Malaspina H (1984) Pathogenesis of myelofibrosis: role of ineffective megakaryopoioesis and megakaryocytic components. In: Berk P, Castro-Malaspina H, Wasserman L (eds) Myelofibrosis and the biology of connective tissue. AR Liss, New York, pp 427–454Google Scholar
  8. Castro-Malaspina H, Rabellino M, Yen A, Nachman RL, Moore MAS (1981) Human megakaryocyte stimulation of proliferation of bone marrow fibroblasts. Blood 57:781–787Google Scholar
  9. Clough V, Geary CG, Hashmi K, Davson J, Knowlson T (1979) Myelofibrosis in chronic granulocytic leukaemia. Br J Haematol 42:515–526Google Scholar
  10. Dameshek W (1951) Some speculations on the myeloproliferative syndromes. Blood 6:372–375Google Scholar
  11. Devred C, Diebold J (1974) La myelofibrose au cours des hematopathies. Valeur diagnostique et prognostique. A propos de 402 observations. Sem Hop Paris 50:1625–1634Google Scholar
  12. Duhamel G, Najman, Andre R (1970) L'histologie de la moelle osseuse dans la maladie de Vaquez et le probleme de la myelosclerose a propos de 70 biopsies. Nouv Rev Franc Hematol 10:209–222Google Scholar
  13. Duncombe AS, Pearson TC, Nunan TO, Miller A, McCarthy DM (1987) 1,25 dihydroxyvitamin D3 (1,25 vit (OH)2, D3) in the treatment of idiopathic myelofibrosis. Br J Hematol 66:579–580Google Scholar
  14. Ellis JT, Perterson P, Geller SA, Rappaport H (1986) Studies of the bone marrow in polycythemia vera and the evolution of myelofibrosis and second hematologic malignancies. Semin Hematol 23:144–155Google Scholar
  15. Fisher RA (1972) Statistical methods for research workers. Oliver & Boyd, EdinburghGoogle Scholar
  16. Frisch B, Bartl R (1985) Histology of myelofibrosis and osteomyelosclerosis. In: Lewis SM (ed) Myelofibrosis. Pathophysiology and clinical management. Marcel Dekker, New York, pp 51–86Google Scholar
  17. Frisch B, Bartl R, Burkhardt R, Jäger K, Mahl G, Kettner G (1984) Classification of myeloproliferative disorders by bone marrow histology. Bibl Haematol (Basel) 50:57–80Google Scholar
  18. Fruchtman SM (1984) Therapeutic implications of the collagen metabolism in myelofibrosis. Prog Clin Biol Res 154:467–474Google Scholar
  19. Geary CG (1985) Clinical and hematological aspects of chronic myelofibrosis. In: Lewis SM (ed) Myelofibrosis. Pathophysiology and clinical management. Marcel Dekker, New York, pp 15–49Google Scholar
  20. Georgii A, Vykoupil KF, Thiele J (1984a) Classification of chronic myeloproliferative diseases by bone marrow biopsies. Hematological and cytogenetic findings and clinical course. Bibl Haematol (Basel) 50:41–56Google Scholar
  21. Georgii A, Vykoupil KF, Thiele J (1984b) Histopathology of bone marrow and clinical findings in chronic myeloproliferative disorders. In: Lennert K and Hübner K (eds) Pathology of the bone marrow. Gustav Fischer Verlag, Stuttgart New York, pp 147–169Google Scholar
  22. Gilbert HS (1973) The spectrum of myeloproliferative disorders. Med Clin North Am 57:355–393Google Scholar
  23. Gordon BR, Coleman M, Kohen P, Day NK (1981) Immunologic abnormalities in myelofibrosis with activation of the complement system. Blood 58:904–910Google Scholar
  24. Greenberg BR, Woo L, Veomett IC, Payne CM, Ahmann FR (1987) Cytogenetics of bone marrow fibroblastic cells in idiopathic chronic myelofibrosis. Br J Haematol 66:487–490Google Scholar
  25. Jacobson RJ, Salo A, Fialkow PJ (1978) Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis. Blood 51:189–194Google Scholar
  26. Jamshidi K, Swaim WR (1971) Bone marrow biopsy with unaltered architecture: a new biopsy device. J Lab Clin Med 77:335–342Google Scholar
  27. Kaplan KL, Chao FC, Stiles CD, Antoniades HN, Scher CD (1979) Platelet alpha-granules contain a growth factor for fibroblasts. Blood 53:1043–1052Google Scholar
  28. Laszlo J (1975) Myeloproliferative disorders (MPD): myelofibrosis, myelosclerosis, extramedullary hematopoiesis, undifferentiated MPD, and hemorrhagic thrombocythemia. Semin Hematol 12:409–432Google Scholar
  29. Lazzarino M, Morra E, Castello A, Inveradi D, Coci A, Pagnucco G, Magrini U, Zei G, Bernasconi C (1986) Myelofibrosis in chronic granulocytic leukemia: clinicopathologic correlations and prognostic significance. Br J Hematol 64:227–240Google Scholar
  30. Lennert K, Nagai K, Schwarze E-W (1975) Patho-anatomical features of the bone marrow. Clin Hematol 4:331–351Google Scholar
  31. Lewis CM, Pegrum GD (1978) Immune complexes in myelofibrosis: a possible guide to management. Br J Haematol 39:233–239Google Scholar
  32. Lewis SM (1985) Myelofibrosis: Historical perspective. In: Lewis SM (ed) Myelofibrosis. Pathophysiology and clinical management. Marcel Dekker, New York, pp 1–13Google Scholar
  33. Linman JW, Bethell FH (1957) Agnogenic myeloid metaplasia. Am J Med 22:107–122Google Scholar
  34. Lohman TP, Beckman EN (1983) Progressive myelofibrosis in agnogenic myeloid metaplasia. Arch Pathol Lab Med 107:593–594Google Scholar
  35. MacCarthy DM (1985) Fibrosis of the bone marrow: content and causes. Br J Haematol 59:1–7Google Scholar
  36. Monoharan A (1988) Myelofibrosis: prognostic factors and treatment. Br J Hematol 69:295–298Google Scholar
  37. Mc Kinley R, Kwan YL, Ford D, Lam-Po-Tang PRI, Mason RS, Manoharan A (1987) Clinical and laboratory studies of 1,25 dihydroxycholecalciferol in myelofibrosis. Br J Hematol 64:252–254Google Scholar
  38. Petrini M, Cecconi N, Azzara A, Ambrogi F, Grassi B (1986) 1,25-dihydroxyvitamin D3 (1,25 (OH)2 vit D3) in the treatment of idiopathic myelofibrosis. Br J Hematol 64:624–625Google Scholar
  39. Pitcock JA, Reinard EH, Justus BW, Mendelsohn RS (1982) A clinical and pathological study of seventy cases of myelofibrosis. Ann Intern Med 57:73–84Google Scholar
  40. Richard C, Mazorra F, Iriondo A, Mazo E, Bello C, Zubizarete A (1986) The usefulness of 1,25-dihydroxyvitamin D 3 (1,25 (OH)2 vit D 3) in the treatment of idiopathic myelofibrosis. Br J Hematol 62:399–400Google Scholar
  41. Rondeau E, Solal-Celigny P, Dhermy D, Vroclans M, Brousse N, Bernard JF, Boivin P (1983) Immune disorders in agnogenic myeloid metaplasia: relations to myelofibrosis. Br J Haematol 53:467–475Google Scholar
  42. Ross R, Vogel A (1978) The platelet-derived growth factor. Cell 14:203–210Google Scholar
  43. Rozman C, Vives-Corrons JL, Hernandez-Nieto L, Feliu E, Ester A (1982) Idiopathic myelofibrosis: a possible role of immunological phenomena. Br J Haematol 50:375–376Google Scholar
  44. Schaefer HE (1984) How to fix, decalcify and stain paraffin embedded bone marrow biopsies. In: Lennert K, Hübner K (eds) Pathology of the bone marrow. Gustav Fischer Verlag, Stuttgart New York, pp 6–9Google Scholar
  45. Schaefer HE Hellriegel KP, Fischer R (1977) Vorkommen von tartratresistenter saurer Phosphatase in verschiedenen Zelltypen des lymphoreticulären und hämatopoetischen Zellsystems. Blut 34:393–397Google Scholar
  46. Silverstein MN (1974) Postpolycythemia myeloid metaplasia. Arch Intern Med 134:113–115Google Scholar
  47. Silverstein MN (1975) Agnogenic myeloid metaplasia. Publishing Science Group, Acton, MassGoogle Scholar
  48. Thiele J, Thienel C, Zankovich R, Fischer R (1988) Prognostic features at diagnosis of chronic myeloid leukemia with special emphasis on histological parameters. Med Oncol Tumor Pharmacother 5:49–60Google Scholar
  49. Thiele J, Simon K-G, Fischer R, Zankovich R (1988) Follow-up studies with sequential bone marrow biopsies in chronic myeloid leukemia and so-called primary (idiopathic) osteomyelofibrosis. Evolution of histopathological lesions and clinical courses in 40 patients. Pathol Res Pract 183:434–445Google Scholar
  50. Ward HP, Block MH (1971) The natural history of agnogenic myeloid metaplasia. Medicine 50:357–420Google Scholar
  51. Wasserman LR, Balcerak SP, Berk PD (1981) Influence of therapy on causes of death in polycythemia vera. Trans Assoc Am Physiol 54:30–38Google Scholar
  52. Wolf BC, Neiman RS (1985) Myelofibrosis with myeloid metaplasia: pathophysiologic implications of the correlation between bone marrow changes and progression of splenomegaly. Blood 65:803–809Google Scholar
  53. Wolf BC, Neiman RS (1987) Hypothesis: splenic filtration and the pathogenesis of extramedullary hematopoiesis in agnogenic myeloid metaplasia. Hem Pathol 1:77–80Google Scholar
  54. Wolf BC, Luevano E, Neiman RS (1983) Evidence that the human fetal spleen is not a hematopoietic organ. Am J Clin Pathol 80:140–144Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Juergen Thiele
    • 1
  • Bert Hoeppner
    • 1
  • Rudolf Zankovich
    • 2
  • Robert Fischer
    • 1
  1. 1.Institute of PathologyKöln 41Federal Republic of Germany
  2. 2.First Clinic of MedicineUniversity of CologneFederal Republic of Germany

Personalised recommendations