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Quantification of Dendritic Cells and Osteoclasts in the Bone Marrow of Patients with Monoclonal Gammopathy

  • Original Paper
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Pathology & Oncology Research

Abstract

The purpose of this study was to find histological clues for reliable differentiation between monoclonal gammopathy of undetermined significance (MGUS) and myeloma when clinical parameters are controversial. Differential appearance of dendritic cells and osteoclasts, two cell types developing from the monocytic lineage upon distinct cytokine activation profile, might be a useful approach. Bone and bone-marrow biopsies performed in 105 patients were studied using histomorphometry after identification of osteoclasts (by histochemical identification of tartrate resistant acid phosphatase) and dendritic cells (by immunohistochemical detection of the S-100 protein). Patients were classified by the World Health Organization criteria but histopathological criteria were more adapted to identify MGUS (53 cases), myeloma (46), B-cell lymphoma (six) since six myeloma were not correctly classified. Histomorphometry was compared to 15 control cases. The number of marrow dendritic cell was significantly increased with B-cell lymphoma >MGUS >myeloma > controls. Dendritic cell were often mixed with lymphoma cells. Myeloma had increased bone resorption with a high osteoclast number and moderate increase in dendritic cells. B-cell lymphomas had a considerable increase in dendritic cell but presented mononucleated osteoclasts. These findings can help in the classification of MGUS in the early stages of the disease and could help to propose preventive treatments.

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Abbreviations

BL:

B lymphoma

BV/TV:

trabecular bone volume

CFU-M:

colony forming unit (monocytic)

DC:

dendritic cell

ES/BS:

Eroded surfaces

IL-6:

interleukin 6

M-CSF:

mononuclear phagocyte colony-stimulating factor

MGUS:

monoclonal gammopathy of undetermined significance

MM:

multiple myeloma

NOc/B.Ar:

number of osteoclasts (bone referent)

NOc/T.Ar:

number of osteoclasts (tissue referent)

Oc:

osteoclast

OPG:

osteoprotegerin

OS/BS:

osteoid surfaces

OV/BV:

osteoid volume

RANK:

receptor activator of nuclear factor-κ B

RANKL:

receptor activator of nuclear factor-κ B ligand

TRAcP:

tartrate-resistant acid phosphatase

References

  1. Kyle RA, Therneau TM, Rajkumar SV et al (2004) Long-term follow-up of 241 patients with monoclonal gammopathy of undetermined significance: the original Mayo Clinic series 25 years later. Mayo Clin Proc 79:859–866

    Article  PubMed  Google Scholar 

  2. Blouin S, Baslé MF, Chappard D (2008) Interactions between microenvironment and cancer cells in two animal models of bone metastasis. Br J Cancer 98:809–815

    Article  PubMed  CAS  Google Scholar 

  3. Bataille R, Chappard D, Baslé M (1995) Excessive bone resorption in human plasmacytomas: direct induction by tumour cells in vivo. Br J Haematol 90:721–724

    Article  PubMed  CAS  Google Scholar 

  4. Colla S, Zhan F, Xiong W et al (2007) The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Blood 109:4470–4477

    Article  PubMed  CAS  Google Scholar 

  5. Tian E, Zhan F, Walker R et al (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494

    Article  PubMed  CAS  Google Scholar 

  6. Aubin JE, Bonnelye E (2000) Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption. Osteoporos Int 11:905–913

    Article  PubMed  CAS  Google Scholar 

  7. Banchereau J, Briere F, Caux C et al (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811

    Article  PubMed  CAS  Google Scholar 

  8. Dubois B, Massacrier C, Vanbervliet B et al (1998) Critical role of IL-12 in dendritic cell-induced differentiation of naive B lymphocytes. J Immunol 161:2223–2231

    PubMed  CAS  Google Scholar 

  9. Dubois B, Bridon JM, Fayette J et al (1999) Dendritic cells directly modulate B cell growth and differentiation. J Leukoc Biol 66:224–230

    PubMed  CAS  Google Scholar 

  10. Rettig MB, Ma HJ, Vescio RA et al (1997) Kaposi’s sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients. Science 276:1851–1854

    Article  PubMed  CAS  Google Scholar 

  11. Olsen SJ, Tarte K, Sherman W et al (1998) Evidence against KSHV infection in the pathogenesis of multiple myeloma. Virus Res 57:197–202

    Article  PubMed  CAS  Google Scholar 

  12. Miyamoto T, Ohneda O, Arai F et al (2001) Bifurcation of osteoclasts and dendritic cells from common progenitors. Blood 98:2544–2554

    Article  PubMed  CAS  Google Scholar 

  13. Hsu HC, Lee YM, Yang CF et al (2001) Detection of Kaposi sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma. Cancer 91:1409–1413

    Article  PubMed  CAS  Google Scholar 

  14. Brown RD, Pope B, Murray A et al (2001) Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7–1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta1 and interleukin-10. Blood 98:2992–2998

    Article  PubMed  CAS  Google Scholar 

  15. Ratta M, Fagnoni F, Curti A et al (2002) Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood 100:230–237

    Article  PubMed  CAS  Google Scholar 

  16. Bataille R, Chappard D, Baslé M (1996) Quantifiable excess of bone resorption in monoclonal gammopathy is an early symptom of malignancy: a prospective study of 87 bone biopsies. Blood 87:4762–4769

    PubMed  CAS  Google Scholar 

  17. Rossi JF, Chappard D, Marcelli C et al (1990) Microosteoclast resorption as a characteristic feature of B-cell malignancies other than multiple myeloma. Brit J Haematol 76:469–475

    Article  CAS  Google Scholar 

  18. Coindre JM, Reiffers J, Goussot JF et al (1984) Histomorphometric analysis of sclerotic bone from idiopathic myeloid metaplasia (nine cases). J Pathol 144:163–169

    Article  PubMed  CAS  Google Scholar 

  19. Schmidt A, Blanchet O, Dib M et al (2007) Bone changes in myelofibrosis with myeloid metaplasia: A histomorphometric and microcomputed tomographic study. Eur J Haematol 78:500–509

    Article  PubMed  Google Scholar 

  20. Beebe K (2000) Alcohol/xylene: the unlikely fixative /dehydrant/clearant. J Histotechnol 23:45–50

    Google Scholar 

  21. Chappard D, Palle S, Alexandre C et al (1986) Simultaneous identification of calcified cartilage bone and osteoid tissue on plastic sections. New polychrome procedures specially adapted to image analysor systems. J Histotechnol 9:95–97

    Google Scholar 

  22. Parfitt AM, Drezner MK, Glorieux FG et al (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res 2:595–610, Report of the ASBMR Histomorphometry Nomenclature Committee

    Article  PubMed  CAS  Google Scholar 

  23. Chappard D, Alexandre C, Riffat G (1983) Histochemical identification of osteoclasts. Review of current methods and reappraisal of a simple procedure for routine diagnosis on undecalcified human iliac bone biopsies. Basic Appl Histochem 27:75–85

    PubMed  CAS  Google Scholar 

  24. Chappard D (1990) Osteoclast count on human bone biopsies: Why and How? In: Takahashi HE (ed) Bone morphometry. Nishimura-Smith–Gordon, Niigata, pp 248–255

    Google Scholar 

  25. van Hensbergen Y, Luykx-de Bakker SA, Heideman DA et al (2001) Rapid stereology based quantitative immunohistochemistry of dendritic cells in lymph nodes: a methodological study. Anal Cell Pathol 22:143–149

    PubMed  Google Scholar 

  26. Hsieh HL, Schafer BW, Sasaki N et al (2003) Expression analysis of S100 proteins and RAGE in human tumors using tissue microarrays. Biochem Biophys Res Commun 307:375–381

    Article  PubMed  CAS  Google Scholar 

  27. Grogan TM, van Kamp B, Kyle RA et al (2001) Mature B-cell neoplasms. In: Jaffe ES, Harris NL, Stein H, JW V (eds) World Health Organization Classification of Tumours Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. IARC, Lyon, pp 142–148

    Google Scholar 

  28. Meunier P, Courpron P (1976) Iliac trabecular bone volume in 236 controls—representativeness of iliac samples. In: Jaworski ZFG, klosevych S (eds) Proceeding of the first worhshop on bone histomorphometry. Univ. of Ottawa, Ottawa, pp 100–105

    Google Scholar 

  29. Bataille R, Chappard D, Klein B (1992) Mechanisms of bone lesions in multiple myeloma. Hematol Oncol Clin North Am 6:285–295

    PubMed  CAS  Google Scholar 

  30. Chappard D, Rossi JF, Bataille R et al (1991) Osteoclast cytomorphometry demonstrates an abnormal population in B-cell malignancies but not in multiple myeloma. Calcif Tissue Int 48:13–17

    Article  PubMed  CAS  Google Scholar 

  31. Chappard D, Bataille R, Alexandre C et al (1986) Monoclonal gammopathy of undetermined significance or multiple myeloma? Histomorphometric analysis of bone changes in 46 patients. J Exp Clin Cancer Res 5:239–248

    Google Scholar 

  32. Barretina J, Junca J, Llano A et al (2003) CXCR4 and SDF-1 expression in B-cell chronic lymphocytic leukemia and stage of the disease. Ann Hematol 82:500–505

    Article  PubMed  CAS  Google Scholar 

  33. Marcelli C, Chappard D, Rossi JF et al (1988) Histologic evidence of an abnormal bone remodeling in B cell malignancies other than multiple myeloma. Cancer 62:1163–1170

    Article  PubMed  CAS  Google Scholar 

  34. Tsuge K, Takeda H, Kawada S et al (2005) Characterization of dendritic cells in differentiated thyroid cancer. J Pathol 205:565–576

    Article  PubMed  CAS  Google Scholar 

  35. Okuyama T, Maehara Y, Kakeji Y et al (1998) Interrelation between tumor-associated cell surface glycoprotein and host immune response in gastric carcinoma patients. Cancer 82:1468–1475

    Article  PubMed  CAS  Google Scholar 

  36. Ocqueteau M, Orfao A, Almeida J et al (1998) Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma. Am J Pathol 152:1655–1665

    PubMed  CAS  Google Scholar 

  37. Goldman SA, Baker E, Weyant RJ et al (1998) Peritumoral CD1a-positive dendritic cells are associated with improved survival in patients with tongue carcinoma. Arch Otolaryngol Head Neck Surg 124:641–646

    PubMed  CAS  Google Scholar 

  38. Bethwaite PB, Holloway LJ, Thornton A et al (1996) Infiltration by immunocompetent cells in early stage invasive carcinoma of the uterine cervix: a prognostic study. Pathology 28:321–327

    Article  PubMed  CAS  Google Scholar 

  39. Eisenthal A, Polyvkin N, Bramante-Schreiber L et al (2001) Expression of dendritic cells in ovarian tumors correlates with clinical outcome in patients with ovarian cancer. Hum Pathol 32:803–807

    Article  PubMed  CAS  Google Scholar 

  40. Frassanito MA, Cusmai A, Dammacco F (2001) Deregulated cytokine network and defective Th1 immune response in multiple myeloma. Clin Exp Immunol 125:190–197

    Article  PubMed  CAS  Google Scholar 

  41. Wu L Dakic A (2004) Development of dendritic cell system. Cell Mol Immunol 1:112–118

    Google Scholar 

Download references

Acknowledgments

This work was supported in part by financial help of INSERM. Authors have no conflict of interest.

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Correspondence to Daniel Chappard.

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Josselin, N., Libouban, H., Dib, M. et al. Quantification of Dendritic Cells and Osteoclasts in the Bone Marrow of Patients with Monoclonal Gammopathy. Pathol. Oncol. Res. 15, 65–72 (2009). https://doi.org/10.1007/s12253-008-9092-2

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  • DOI: https://doi.org/10.1007/s12253-008-9092-2

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