Ultrastructural characteristics of therapy-related acute nonlymphocytic leukemia: evidence for a panmyelosis

Leukemic cells from 13 patients with therapy-related acute nonlymphocytic leukemia (ANLL) were studied by electron microscopy. All of the patients had radiotherapy, and/or alkylating agent chemotherapy for other neoplastic disease 25 to 182 months prior to the diagnosis of ANLL. All cases manifested ultrastructural evidence of a panmyelopathy. All marrow cell lines exhibited nuclear--cytoplasmic asynchrony and abnormalities of cell size. Developing granulocytes exhibited decreased primary and/or secondary granule formation and abnormal granules characterized by irregular shape, large size and internal membranous lamellae. Monocytes showed perinuclear bundles of microfilaments. In some cases, the predominant leukemic blasts showed evidence of early basophil granule development which was not appreciated in light microscopy. Abnormalities in erythroid cells included abundant intracristal mitochondrial iron, large vacuoles, infoldings of redundant membrane and membrane-bound nuclear blebs and intranuclear clefts. Megakaryocytes manifested decreased numbers of granules and demarcation membranes. Excessively large platelets with decreased or abnormal granules were identified; giant compound granules with irregular contour and variable electron density were present. Several of the changes in the developing hematopoietic cells were similar to those described in preleukemia and in certain nonneoplastic disorders. The consistent panmyelosis in therapy-related ANLL together with several uniform clinical features defines a specific clinicopathologic entity.