Crystalloid-Containing Giant Granules in Leukemic Monoblasts

Abstract

Giant granules (≥1 μm in diameter), Auer rods, and unique giant granules that contained crystalloid material were investigated in monoblasts from a patient with acute monocytic leukemia using ultrastructural and cytochemical techniques. The latter granule type differed from abnormal granules previously described in leukocytes. In Wright's stained preparations, these granules appeared to be crystalloid-containing vacuoles and were observed in approximately 10% of the blasts. Ultrastructural examination of this granule type revealed a limiting membrane enclosing a variably dense matrix and a central crystalloid. Some giant granules contained multiple crystalloids. Giant granules, Auer rods, and both the matrix and the crystalloid of the crystalloid-containing giant granule possessed heavy acid phosphatase and peroxidase reactivity. At the electron microscope level, 45% of the monoblasts contained abnormal granules. Auer rods were observed in 1% of monoblasts, giant granules in 26% of monoblasts, giant crystalloid-containing granules in 10% of monoblasts, and 8% of monoblasts demonstrated both giant granules and crystalloid-containing giant granules. Auer rods were not observed in cells containing giant granules or crystalloid-containing giant granules. Neither phagocytosis of Auer rods nor autophagy was observed, and the transition of Auer rods to giant granules or crystalloid-containing giant granules could not be demonstrated. Genesis of giant granules appeared to result from fusion of small Golgi-derived precursor granules, azurophilic granules, and giant granules with each other. Crystalloid formation was only observed after substantial granule enlargement. These findings detail multiple abnormalities of granule genesis in leukemic monoblasts, which are comparable but distinctly different from abnormalities previously reported in leukocytes from patients with the Chediak-Higashi syndrome or in leukemic cells.