Myeloid dysplasia (MD): a hematological disorder preceding acute and chronic myeloid leukemia. A morphological study on sequential core biopsies of the bone marrow in 27 patients.

Abstract

Light- and electron microscopic appearances of core biopsies of the bone marrow in 27 selected patients out of about 195 cases with a clinically suspected preleukemic syndrome. The correct diagnosis of “ preleukemia” was established retrospectively by sequential biopsies of the iliac crest or autopsy in those patients who developed overt leukemia in periods ranging from 2 to 36 months. As a final diagnosis chronic myelogenous leukemia (CML) was established in 10, with accompanying blast crisis in 6 and acute non-lymphocytic leukemia (ANLL) in 11 cases. Histomorphology of the resin embedded cores of bone marrow showed hypercellularity in 21 specimens, a hypocellular marrow in 5 and a normal bone marrow in 1 case. There was also a conspicuous macrocytic or megaloblastoid maturation of erythropoiesis with frequent sideroblasts. Ultrastructural abnormalities included atypical nuclear clefts, dense iron deposits in the mitochondrial matrix and an increase of ferritin uptake. Neutrophilic granulopoiesis showed a shift to the left and often a remarkable aberration of nuclear segmentation consistent with a pseudo-Pelger-Huet anomaly. Electron microscopy displayed atypias of granulogenesis in comparison with maturation and segmentation of the nuclei, abnormal nuclear loops and blebs and very conspicuous nuclear fibrillar appendages (so called Nebenkerne). There was also an increase in eosinophilic granulocytes, monocytic elements, edema and a remarkable perivascular plasmacytosis of the myeloid stroma. Our results suggest that characteristic morphological features of the bone marrow exist before onset of overt, acute and chronic leukemia. These alterations are identical in CML and ANLL and are the morphological substrate of a maturation defect of hematopoiesis which precedes the establishment of the leukemic clone. The clinical term preleukemia should be replaced by myeloid dysplasia (MD), thus indicating transformation into overt leukemia in only a certain proportion of patients (only 27 of 195 clinically suspected patients who displayed an identical histopathology of MD in the bone marrow in 93 cases to date) and has to include ANLL as well as CML.