A 42-year-old woman was diagnosed with myelodysplastic syndrome with fibrosis that developed bilaterally, cervical lymphadenopathy and cutaneous infiltration by trilineage extramedullary hematopoiesis after granulocyte colony-stimulating factor therapy because of severe neutropenia. Hepatosplenomegaly was not observed during her follow-up. Extramedullary hematopoiesis disappeared after growth factor therapy was stopped. Although the neutropenia was alleviated by growth factor administration, the appearance of an unusual involvement of extramedullary hematopoiesis should be kept in mind.

Keywords:
Extramedullary hematopoiesis, Granulocyte colony-stimulating factor, Myelodysplastic syndrome with fibrosis
1.
Lawrence LW: Refractory anemia and myelodysplastic syndromes. Clin Lab Sci 2004;17:178–186.
2.
Steensma DP, Hanson CA, Letendre L, Tefferi A: Myelodysplasia with fibrosis: a distinct entity? Leuk Res 2001;25:829–838.
3.
Lambertenghi-Deliliers G, Orazi A, Luksch R, Annaloro C, Soligo D: Myelodysplastic syndrome with increased marrow fibrosis: a distinct clinico-pathological entity. Br J Haematol 1991;78:161–166.
4.
Maschek H, Georgii A, Kaloutsi V, Werner M, Bandecar K, Kressel MG, Choritz H, Freund M, Hufnagl D: Myelofibrosis in primary myelodysplastic syndromes: a retrospective study of 352 patients. Eur J Haematol 1992;48:208–214.
5.
Verhoef GE, DeVolf-Peeters C, Ferrant A, Deprez S, Meeus P, Stul M, Zachee P, Cassman JJ, Berghe H, Boogaerts MA: Myelodysplastic syndromes with bone marrow fibrosis: a myelodysplastic disorder with proliferative features. Ann Hematol 1991;63:235–241.
6.
Pagliuca A, Layton DM, Manoharan A, Gordon S, Green PJ, Mufti GJ: Myelofibrosis in primary myelodysplastic syndromes: a clinico-morphological study of 10 cases. Br J Haematol 1989;71:499–504.
7.
Cunningham I, MacCallum SJ, Nicholls MD, Byth K, Hawson JW, Arnold B, Motum PI, Mulligan SP, Crane GG: The myelodysplastic syndromes: an analysis of prognostic factors in 226 cases from a single institution. Br J Haematol 1995;90:602.
8.
Cassano E, Giordano M, Riccardi A, Coci A, Cazzola M: Myelodysplastic syndromes: a multiparametric study of prognostic factors and a proposed scoring system. Haematologica 1990;75:141–145
9.
Appelbaum FR, Storb R, Ramberg RE, Shulman HM, Buckner CD, Clift RA, Deeg HJ, Fefer A, Sanders J, Self S, Singer J, Stewart P, Sullivan K, Witherspoon R, Thomas ED: Treatment of preleukemic syndromes with marrow transplantation. Blood 1987;69:92–96.
10.
Soll E, Massumoto C, Clift RA, Buckner CD, Appelbaum FR, Storb R, Sale G, Hackman R, Martin P: Relevance of marrow fibrosis in bone marrow transplantation: a retrospective analysis of engraftment. Blood 1995;86:4667–4673.
11.
Fenaux P: Myelodysplastic syndromes: from pathogenesis and treatment. Semin Hematol 2004;41(2 suppl 4):6–12.
12.
Rigolin GM, Porta MD, Ciccone M, Bugli AM, Bragotti LZ, Mauro E, Fraulini C, Rossi AR, Bardi A, Cuneo A, Castoldi G: In patients with myelodysplastic syndromes response to rHuEPO and G-CSF treatment is related to an increase of cytogenetically normal CD34 cells. Br J Haematol 2004;126:501–507.
13.
Redmond J 3rd, Kantor RS, Auerbach HE, Spiritos MD, Moore JT: Extramedullary hematopoiesis during therapy with granulocyte colony-stimulating factor. Arch Pathol Lab Med 1994;118:1014–1015.
14.
Litam PP, Friedman HD, Loughran TP: Splenic extramedullary hematopoiesis in a patient receiving intermittently administered granulocyte colony-stimulating factor. Ann Intern Med 1993;118:954–955.
15.
Glaspy JA, Golde DW: Granulocyte colony-stimulating factor (G-CSF): preclinical and clinical studies. Semin Oncol 1992;19:386–394.
16.
Becker PS, Wagle M, Matous S, Swanson RS, Pihan G, Lowry PA, Stewart FM, Heard SO: Spontaneous splenic rupture following administration of granulocyte colony-stimulating factor (G-CSF): occurrence in an allogeneic donor of peripheral blood stem cells. Biol Blood Marrow Transplant 1997;3:45–49.
17.
Falzetti F, Aversa F, Minelli O, Tabilio A: Spontaneous rupture of spleen during peripheral blood stem-cell mobilisation in a healthy donor. Lancet 1999;353:555.
18.
Tefferi A: Myelofibrosis with myeloid metaplasia. N Engl J Med 2000;342:1255–1265.
19.
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardima J, Lister TA, Bloomfield CD: World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues; report of the clinical Advisory Committee meeting. J Clin Oncol 1999;17:3835–3849.
20.
Hirri HM, Green RJ: Myelodysplasia and bone marrow fibrosis treated with calcitriol and venesection. Leuk Lymphoma 2002;43:1489–1491.
21.
Geissler RG, Schulte P, Ganser A: Treatment with growth factors in myelodysplastic syndrome. Pathol Biol 1997;45:656–667.
22.
Shih LY, Lin FC, Kuo TT: Cutaneous and pericardial extramedullary hematopoiesis with cardiac tamponade in chronic myeloid leukemia. Am J Clin Pathol 1988;89:693–697.
23.
Rice GP, Assis LJ, Barr RM, Ebers GC: Extramedullary hematopoiesis and spinal cord compression complicating polycythemia rubra vera. Ann Neurol 1980;7:81–84.
24.
Dibbern DA, Loevner LA, Lieberman AP, Salhany KE, Freese A, Marcotte PJ: MR of thoracic cord compression caused by epidural extramedullary hematopoiesis in myelodysplastic syndrome. Am J Neuroradiol 1997;18:363–366.
25.
Bastion Y, Coiffier B, Felman P, Assouline D, Tigaud JD, Espinouse D, Bryon PA: Massive mediastinal extramedullary hematopoiesis in hereditary spherocytosis: a case report. Am J Hematol 1990;35:263–265.
26.
Fukushima N, Nishina H, Koishihara Y, Ohkawa H: Enhanced hematopoiesis in vivo and in vitro by splenic stromal cells derived from the mouse with recombinant granulocyte colony-stimulating factor. Blood 1992;80:1914–1922.
27.
Haan G, Dontje B, Engel J, Loeffler M, Nijhof W: The kinetics of murine hematopoietic stem cells in vivo in response to prolonged increased mature blood cell production induced by granulocyte colony-stimulating factor. Blood 1995;86:2986–2992.
28.
Platzbecker U, Prange-Krex G, Bornhauser M, Koch R, Soucek S, Aikele P, Haack A, Haag C, Schuler U, Berndt A, Rutt C, Ehninger G, Holig K: Spleen enlargement in healthy donors during G-CSF mobilization of PBPCs. Transfusion 2001;41:184–189.
29.
Stroncek DF, Heatherman A, Shawker T, Dittmar K, Leitman SF: Transient spleen enlargement in peripheral blood donors given G-CSF. J Transl Med 2004;2:25.
30.
Brouty-Boye D, Doucet C, Clay D, Le Bousse-Kerdiles MC, Lampidis TJ, Azzarone B: Phenotypic diversity in human fibroblasts from myelometaplasic and nonmyelometaplasic hemopoietic tissues. Int J Cancer 1998;76:767–773.
31.
Koch CA, Li CY, Mesa RA, Tefferi A: Nonhepatosplenic extramedullary hematopoiesis: associated diseases, pathology, clinical course and treatment. Mayo Clin Proc 2003;78:1223–1233.
© 2006 S. Karger AG, Basel
2006
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