[Histopathologic characteristics of bone marrow in patients with aplastic anemia].

INTRODUCTION: Histopathologic findings in bone marrow biopsies in patients are with aplastic anaemia crucial for the diagnosis of the disease. Changes observed by the examination of bone marrow such as cellularity, histopathologic type, presence of irregular cells maturation in all three blood lineages, condition of medullar stroma can be of great prognostic significance [1, 2, 4, 5]. The aim of the study was to make histopathological analyses in patients with aplastic anaemia and to establish parameters significant for the prognosis of the disease.

PATIENTS AND METHODS: Thirty-three patients with aplastic anaemia treated in the Institute of Haematology, Clinical Centre of Serbia, from 1988 to 1995 were included in the study. Bone marrow specimens were analysed for: cellularity, number of megakaryocytes, condition of medullar stroma, presence/absence of blood and oedema, lymphoid elements, presence of plasma and reticular cells, and determination of histopathologic type on the basis of bone marrow changes. For data description we used the arithmetic mean and standard deviation for parametric results. Results of analyses were explained by Kaplan-Mayer's method and two factors analysis of variance.

RESULTS: In all analysed marrow biopsy specimens a 100% hypocellularity was observed: 1. Weak hypocellularity in two specimens (6%); 2. Mild hypocellularity in six cases (19%); 3. Severe hypocellularity in 24 (75%), In one case (3%) the finding was not known. In 25 specimens (75%) megakaryocytes were not found, in 5 (16%) they were rare; in two cases (6%) they were numerous. Medullar stroma changes were not found in 30 (94%) byopsies, but in two (6%) they were found. Blood and oedema liquid were found in 26 (81%) cases and not in 6 (19%). Lympho-plasmocytic bone marrow infiltration was found in 23 specimens (72%) and not in nine (28%). First histopathologic types two (one-a and one-b) were present in 25 (78%) cases, histopathologic type two in 5 (16%) and type three in 2 (6%) specimens. The two factors analysis of variance regarding proportions between dead and alive patients revealed a significant difference in proportions according to histopathologic types (FD = 7.52; DF = 2; p = 0.002). Significant statistical differences were found between alive and dead patients in all three histopathologic types, tip one (one-a and one-b) (FD = 8; DF = 1; p = 0.06); type two (FD = 4.286; DF = 1; p = 0.041) and type three (FD = 4.762; DF = 1; p = 0.031). Histopathologic type two had the best prognosis regarding survival probability; p = 0.800; in histopathologic type two survival prognosis was worse p = 0.300, and type three it was the worst, p = 0.000. With regard to survival time, there was no statistical difference in patients with weak and mild bone marrow hypocellularity (p = 0.487). We also compared patients with severe bone marrow hypocellularity with patients with weak and mild hypocellularity. The difference in survival was statistically significant (p = 0.026), Consequently, survival was shorter in patients with severe bone marrow hypocellularity.

DISCUSSION: Bone marrow biopsy and histopathologic examination are necessary for definitive diagnosis of aplastic anaemia [1-3]. Cellularity estimation in bone marrow based on biopsy and histopathologic examination is more reliable than that made by bone marrow aspiration [7]. Aplastic anaemia is a disease that can be associated with abnormal clones development. Most frequently paroxysmal nocturnal haemoglobinuria, acute leukaemias and myelodysplastic syndrome occur. Therefore, repeated bone marrow biopsies are necessary to follow-up the course of the disease [10, 11]. The presence of megakaryocytes in bone marrow specimens has favourable prognostic significance. Their appearance is a reliable sign of disease improvement [6, 7]. However, lymphocytosis, plasmocytosis and damaged marrow stroma are markers of bad prognosis [7]. (ABSTRACT TRUNCATED)