Thirty-nine cases of acute promyelocytic leukaemia (APL) were divided into two morphological subgroups, typical hypergranular APL (31 cases) and microgranular APL (eight cases, 21%). The leukaemic cells in the microgranular APL cases were characterized by striking nuclear folding or lobulation; granulation was present in most of these cells but was less abundant and finer than in typical APL. In three microgranular APL cases a distinctive small leukaemic promyelocyte with unusual nuclear lobulation and deeply basophilic cytoplasm containing few or no visable granules was the predominant leukaemic cell. This small hyperbasophilic promyelocyte was also present as a minor population of cells in the other five microgranular APL case and in 28 of the 31 typical APL cases. Ultrastructurally the most abundant promyelocytes in microgranular APL had smaller and usually fewer granules than in typical APL; other characteristic ultrastructural features of APL were found with equal frequency. The median blood leucocyte count was significantly higher in microgranular APL, 83.0 x 10(9) x 10(9)/l, than in typical APL, 1.8 x 10(9)/l (P less than 0.01). The median duration of complete remission (CR) for microgranular APL, 6.5 months, was shorter than the 21 + month median CR for typical APL. The morphological characteristics of microgranular APL may mimic those of myelomonocytic leukaemia; however, the presence of cells with multiple Auer rods, large inclusions of Auer-like material and the small hyperbasophilic promyelocytes are important distinguishing features. In equivocal cases cytochemistry, electron microscopy and cytogenetic studies may verify the diagnosis.
A cell line, designated RS4;11, was established from the bone marrow of a patient in relapse with an acute leukemia that was characterized by the t(4;11) chromosomal abnormality. The cell line and the patient's fresh leukemic cells both had the t(4;11)(q21;q23) and an isochromosome for the long arm of No. 7. Morphologically, all cells were lymphoid in appearance. Ultrastructurally and cytochemically, approximately 30% of the cells possessed myeloid features. The cells were strongly positive for terminal deoxynucleotidyl transferase. They were HLA-DR positive and expressed surface antigens characteristic for B lineage cells, including those detected by anti-B4, BA-1, BA-2, and PI153/3. Immunoglobulin gene analysis revealed rearrangements of the heavy chain and kappa chain genes. The cells lacked the common acute lymphoblastic leukemia antigen and antigenic markers characteristic of T lineage cells. The cells reacted with the myeloid antibody 1G10 but not with other myeloid monoclonal antibodies. Treatment with 12-O-tetradecanoyl- phorbol-13-acetate induced a monocyte-like phenotype demonstrated by cytochemical, functional, immunologic, and electron microscopic studies. The expression of markers of both early lymphoid and early myeloid cells represents an unusual phenotype and suggests that RS4;11 represents a cell with dual lineage capabilities. To our knowledge, RS4;11 is the first cell line established from t(4;11)-associated acute leukemia.
The authors describe eight cases of acute basophilic leukemia. In six of the eight cases, basophilic involvement was not apparent by light microscopic examination. The cases were identified on the basis of ultrastructural evidence for basophil/mast cell differentiation of the blasts with little or no differentiation into other lineages. Ultrastructural analysis revealed immature basophil granules in blasts in all eight cases and theta granules in blasts in four cases. In three cases, ultrastructural evidence of mast cell differentiation also was present, with rare cells showing evidence for both basophil and mast cell differentiation. No clinical features distinguished this group of patients from others with acute myeloid leukemia. Cytogenetically, the cases were heterogeneous. Three had a Philadelphia chromosome; none had a t(6;9). The authors conclude that ultrastructural analysis usually must be used to diagnose acute basophilic leukemia, that acute basophilic leukemia is associated frequently with the Philadelphia chromosome, and that the ultrastructural findings provide evidence for a common origin of basophils and mast cells.
Ultrastructural studies of intranuclear inclusions in plasma cells and lymphocytes from patients with different forms of monoclonal gammopathies are presented. The inclusions occurred as two distinct morphologic and ultrastructural types. In three patients, two with IgA myeloma and one with Waldenström's macroglobulinemia, the inclusions were variably PAS-positive in routine sections and composed of electron-light amorphous material ultrastructurally. In one patient with an IgG monoclonal gammopathy, the plasma cells contained inclusions that were PAS negative by light microscopy and primarily osmiophilic ultrastructurally. One patient with an immunoblastic sarcoma and an IgM monoclonal had plasma cells with numerous inclusions of both types. There was a distinct spatial relationship between the electron-light amorphous material and the osmiophilic deposits in many of the inclusions in cells from this patient. In cells from two patients in which osmiophilic inclusions were found, they were present in the cytoplasm as well as the nucleus. The intranuclear inclusions appeared to develop from accumulation of material in the perinuclear cisterna, resulting in single or multiple invaginations of the nuclear structure.
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