Idiopathic Acquired Sideroblastic Affaemia Transforming to Acute Myelosclerosis

J Clin Pathol: first published as 10.1136/jcp.37.9.1032 on 1 September 1984. Downloaded from

J Clin Pathol 1984;37:1032-1034

Idiopathic acquired sideroblastic affaemia transforming to acute myelosclerosis

AC BESTED,* G CHENG,t PH PINKERTON,* 0 KASSIM,t JS SENNt From the Departments of *Laboratory Hematology, tMedicine, and tPathology, Sunnybrook Medical Centre, Toronto, Ontario

SUMMARY A case of idiopathic acquired sideroblastic anaemia transforming to acute myelofibrosis is reported. The appearance of atypical megakaryocytic proliferation in idiopathic acquired sideroblastic anaemia may presage the development of an acute myelofibrotic phase of this usually chronic disease.

Idiopathic acquired sideroblastic anaemia is a disor- was hypercellular with hyperplastic erythropoiesis, der of haematopoietic stem cell differentiation and mild dysplastic changes, and numerous ring siderob- proliferation, probably representing the emergence lasts (Fig. 1). Granulopoiesis was unremarkable. of an abnormal haemopoietic clone.' While patients Megakaryocytes were clearly increased in number with this disease, usually elderly, often die of unre- with more than normal variation in size, nuclear lated causes, this disease often undergoes transfor- form, ploidy, and nuclear to cytoplasmic ratio. mation to acute leukaemia.2-7 Transformation to Idiopathic acquired sideroblastic anaemia was diag- acute myelofibrosis, however, is rare.8-10 nosed. We report a patient with idiopathic acquired The patient was given blood transfusion, but copyright. sideroblastic anaemia who developed acute otherwise his clinical and laboratory findings did not myelofibrosis." In addition to the characteristic ring change appreciably until October 1982, when neut- sideroblasts and erythroid hyperplasia, this patient's ropenia, increasing thrombocytopenia, and palpable bone marrow showed atypical megakaryocytic pro- splenomegaly were found. By January 1983, throm- liferation before progression to acute myelofibrosis. bocytopenia was severe (platelet count 20 x 109/l) and the blood film became leukoerythroblastic with Case report the presence of myelocytes (0.4 x 109/l) and occa- sional blast forms (haemoglobin concentration 7-7 http://jcp.bmj.com/ A 68 year old white man presented in April 1981 g/dl, white cell count 2-6 x 109/l). Attempts at bone with fatigue and a seven year history of insulin marrow aspiration yielded a "dry tap." Bone mar- dependent diabetes mellitus. There was no history row biopsy showed a hypercellular marrow with, as of other chronic disease, excessive use of alcohol, or before, atypical megakaryocytic proliferation now exposure to lead or relevant drugs. Physical exami- accompanied by increased reticulin and collagen nation was unremarkable, without splenomegaly or fibres (Fig. 2). Erythroid and granulopoietic ele-

lymphadenopathy. Peripheral blood findings were as ments were present with evidence of differentiation. on September 28, 2021 by guest. Protected follows: haemoglobin concentration 10-8 gIdl, white Acute myelofibrosis was diagnosed. cell count 6 2 x 109/1 (normal differential), and In March 1983 he became jaundiced. Liver func- platelet count 135 x 109/l. The blood film showed tion tests suggested hepatitis, but radioimmunoassay both hypochromic microcytic and normochromic for hepatitis B surface antigen was negative. A pro- normocytic red cells, with a few oval macrocytes. visional diagnosis of non-A, non-B hepatitis was Serum iron concentration was 32 ,umolIl (normal suggested. In early April he developed broncho- range 13-30 ,umol/l), total iron binding capacity was pneumonia. Sputum cytology showed malignant 38 ,molI (normal range 50-70 ,umol/l), with a sat- cells. A few days later he fell and suffered epidural uration of 0-84 (normal range 0.2-0.5). Serum vit- and intracranial haematomas, and he died on 7 amin B12, red cell folate, and serum ferritin concent- April. rations were within normal limits. The bone marrow Permission was obtained for a limited necropsy, which revealed the following: splenomegaly Accepted for publication 6 June 1984 (0.5 kg), with extramedullary haematopoiesis; 1032 J Clin Pathol: first published as 10.1136/jcp.37.9.1032 on 1 September 1984. Downloaded from

Idiopathic acquired sideroblastic anaemia transforming to acute myelosclerosis 1033

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Fig 1 Bone marrow film showing erythrocytes and Fig 2 Bone marrow biopsy sample showing atypical

erythroblasts containing Prussian blue positive granules megakaryocytic proliferation accompanied by increased copyright. (ring sideroblasts). Prussian blue reaction counterstained deposition ofreticulin fibres. Silver impregnation, with 1% neutral red. Original magnification X 1800. counterstained with iron haematoxylin. Original magnification x 775.

myelofibrosis of the bone marrow with atypical granulocytic, monocytic, and platelet lineages derive megakaryocytic hyperplasia and increased reticulin from a common pluripotent stem cell, marrow fibres; haemosiderosis of the liver without evidence fibroblasts are probably of separate origin.'3 http://jcp.bmj.com/ of parenchymal inflammation; and Kimmelstiel- It is rare for idiopathic acquired sideroblastic Wilson diabetic glomerulonephropathy of the kid- anaemia to. progress to acute or malignant ney. Adequate examination of the lungs and any myelofibrosis. Lewis and Szur first identified malig- examination of the brain and meninges were pre- nant myelofibrosis as a separate entity in 1963." cluded by the limited nature of the necropsy. Yeung and Trowbridge'° described the first example of idiopathic acquired sideroblastic anaemia trans- Discusson forming to acute myelofibrosis in 1977. A further on September 28, 2021 by guest. Protected case was identified by Butler et aP8 which showed Idiopathic acquired sideroblastic anaemia usually atypical megakaryocytic proliferation, and Lukow- occurs in older patients and is characterised by a icz et al9 reported two patients with idiopathic chronic course. While death often occurs owing to acquired sideroblastic anaemia who had throm- intercurrent disease, it is not uncommon for the bocytosis associated with myelofibrosis. condition to undergo transformation to acute In five cases of de novo acute myelofibrosis blast leukaemia.3- While acute lymphoblastic leukaemia cells in the peripheral blood were characterised as has been reported,'2 acute myeloid leukaemia is the being of megakaryocytic origin using the platelet usual form. The cause of the predisposition is peroxidase reaction.'5 16 Bain et al'5 postulated that unclear, but evidence indicates that both acute acute myelofibrosis is secondary to the myeloid leukaemia and idiopathic acquired sidero- megakaryocytic proliferation. In most cases of blastic anaemia may be clonal disorders originating idiopathic acquired sideroblastic anaemia transform- in pluripotent stem cells.' '4'1 While erythroid, ing to acute myelofibrosis there has been evidence of J Clin Pathol: first published as 10.1136/jcp.37.9.1032 on 1 September 1984. Downloaded from

1034 Bested, Cheng, Pinkerton, Kassim, Senn megakaryocytic hyperplasia. Platelet derived 6 Kushner JP, Lee GR, Wintrobe MM, et al. Idiopathic refractory sideroblastic anemia: Clinical and laboratory investigation of growth factor has been suggested as having 17 patients and review of the literature. Medicine a role in the pathogenesis of myelofibrosis. 1971;50 139-59. Defective megakaryoctic maturation results Lewy RI, Kansu E, Gabuzda T. Leukemia in patients with in the intramedullary destruction of developing acquired sideroblastic anemia: an evaluation of prognostic indicators. Am J Hematol 1974;6:323-31. megakaryocytes, and it has been suggested that 8 Butler WM, Taylor HG, Viswanathan U. Idiopathic acquired megakaryocytic cytoplasmic contents are released sideroblastic anemia terminating in acute myelofibrosis. into the marrow, including megakaryocytic platelet Cancer 1982;49 2497-9. derived growth factor and factor 4.5 Platelet derived Lukowicz D, Myers T, Grasso J, Albala M. Sideroblastic anemia terminating in myelofibrosis. Am J Hematol 1982; 13: 253-7. growth factor stimulates fibroblasts to proliferate '° Yeung K, Trowbridge AA. Idiopathic acquired sideroblastic and secrete collagen. Factor 4, contained in platelet anemia terminating in acute myelofibrosis. Case report and alpha granules, causes inhibition of granulocyte and literature review. Cancer 1977;39 359-65. fibroblast collagenase, which normally degrades 'Lewis SM, Szur L. Malignant myelosclerosis. Br Med J 1963;i:472-7. bone marrow collagen and reticulin fibres.'7 It is 12 Barton JC. Acute lymphoblastic leukemia in idiopathic refrac- suggested that as a result of the action of these two tory sideroblastic anemia: evidence for a common lymphoid factors, collagen and reticulin fibres are increased, and myeloid progenitor cell. Am J Hematol 1980; 9: 109-15. resulting in acute myelofibrosis.'7 3 Fialkow PJ. Clonal and stem cell origin of blood cell neoplasms. In: Lobue J, Gordon AS, Silber R, Muggia FM, eds. Contem- The presence of megakaryocytic proliferation in porary hematologyloncology. Vol 1. New York and London: sideroblastic anaemia may have prognostic poten- Plenum Medical Book Co, 1980:1. tial, indicating the likelihood of subsequent trans- McCulloch EA. Haemopoiesis in myeloblastic leukaemia. Clin formation into acute myelofibrosis and therefore Haematol 1979;8: 501-23. EBain BJ, Catovsky D, O'Brien M, et al. Megakaryoblastic predicting a poor prognosis. leukemia presenting as acute myelofibrosis-a study of four cases with platelet peroxidase reaction. Blood 1981;58:206- References 13. 16 Breton-Gorius J, Reyes F, Duhamel G. Megakaryocytic acute 'Prchal J, Throckmorton D, Carroll AJ. A common progenitor for leukemia: identification by the ultrastructural demonstration human lymphoid and myeloid cells. Nature 1978;274:590-1. of platelet peroxidase. Blood 1978;51:45-60. 2 Catovsky D, Shaw MT, Hoffbrand AV, et al. Sideroblastic '' Castro-Malaspina H, Moore MA. Pathophysiological mechan- copyright. anaemia and its association with leukaemia and myelomatosis: isms operating in the development of myelofibrosis: role of a report of five cases. Br J Haematol 1971;20:385-93. megakaryocytes. Nouv Rev Fr Hematol 1982;24:221-6. Cheng DS, Kushner JP, Wintrobe MM. Idiopathic refractory sideroblastic anemia: incidence and risk factors for leukemic transformation. Cancer 1979;44: 724-31. Dameshek W. Sideroblastic anaemia, is this a malignancy? Br J Requests for reprints to: Dr PH Pinkerton, Department of Haematol 1965; 11: 52-8. Laboratory Hematology, Sunnybrook Medical Centre, Dameshek W. The Di Gugliemo syndrome revisited. Blood 2075 Bayview Avenue, Toronto, Ontario, Canada 1969; 34:567-72. M4N 3M5. http://jcp.bmj.com/ on September 28, 2021 by guest. Protected