Ultrastructure of bone marrow tissue in so-called primary (idiopathic) myelofibrosis-osteomyelosclerosis (agnogenic myeloid metaplasia). I. Abnormalities of megakaryopoiesis and thrombocytes.

An electron microscopic study was conducted with the aim to analyze abnormalities of the megakaryopoiesis in bone marrow tissue of patients suffering from so-called primary (idiopathic) myelofibrosis-osteomyelosclerosis. In comparison with control specimens and in confirmation of light microscopical findings, a pronounced pleomorphism of the megakaryocytic cell line could be observed consisting of giant forms, micromegakaryocytes and naked (pyknotic) nuclei. Further atypias were expressed by a dissociation of nuclear-cytoplasmic maturation. These included particularly the amount of dense granules, and the development of the demarcation membrane system as well as the occurrence of emperipolesis (i.e. internalization of hematopoietic cells) already in immature or megakaryoblastic elements. In these specimens there was a striking variety in the appearance of dense granules of the alpha or bull's eye type revealing frequent elongated roll- and dumbbell-like shapes and a doubling of the nucleoids. Thrombocytes showed giant forms with either hypertrophy of the open canalicular system or abundance of dense granules and beta-glycogen accumulation. Remarkable was a focal sponge-like proliferation of the open canalicular system in many of the large platelets and giant and fused granules of the alpha and osmiophilic type. The abnormalities disclosed in megakaryo- and thrombocytes may have certain functional implications, i.e. to hemorrhage and thrombosis which are often encountered out of proportion to the platelet counts in this disorder. Moreover, those anomalies indicate a disorganization of megakaryopoiesis which may contribute to the abnormal release of factors (platelet-derived growth factor and factor 4) predominantly involved in the process of myelofibrosis.