Shi-Xuan Zhao

Invasion of Erythroblasts by Pasmodium vivax: A New Mechanism Contributing to Malarial Anemia

Severe malarial anemia causes considerable mortality and morbidity in endemic areas. Possible mechanisms underlying the anemia include lysis of parasitized and nonparasitized red cells as well as parasite product-mediated effects on erythropoiesis. The latter include suppression of erythropoiesis, dyserythropoiesis, and ineffective erythropoiesis. Present transmission electron microscope data in two cases of Pasmodium vivax malaria show a hitherto undescribed mechanism contributing to malarial anemia, namely, infection of erythroblasts by parasites and their subsequent degradation. No parasites were detected in the peripheral blood but parasites were found in the bone marrow. These findings emphasise the value of bone marrow examination in the diagnosis and eradication of malaria.

Multiple Organ Invasion by Viruses: Pathological Characteristics in Three Fatal Cases of the 2009 Pandemic Influenza A/H1N1

To further understand the pathological characteristics of multiple organ involvement of the 2009 pandemic influenza A/H1N1 infection, tissues of bronchial mucosa, lung, myocardium, gastrocnemius, and liver from 3 patients with fatal A/H1N1 infections were investigated by light microscopy and transmission electron microscopy. In all 3 patients, bronchial mucosa showed necrotizing bronchiolitis, epithelial necrosis and desquamation, and squamous metaplasia, while lung consolidation or fibrosis was identified. Myocardium and gastrocnemius exhibited focal necrosis and fibrosis, surrounded by muscle cells showing features of cell damage. In liver, there was widespread fatty degeneration and necrosis, most often around the central lobular vein and portal area. Viral particles were found in all samples, frequently located in endothelium, epithelium, and muscle cells. The observations demonstrate that in fatal cases of A/H1N1 infection, viruses not only infect the respiratory system, but also engage in multiple organ invasions, causing pathologic changes.

On the Maturation of Megakaryocytes: A Review with Original Observations on Human In Vivo Cells Emphasizing Morphology and Ultrastructure

Abstract Megakaryocytes engage in the synthesis of a variety of molecular and macromolecular constituents to build-up characteristic megakaryocyte structure and form proplatelets in a series of cells from megakaryocyte precursors to the fully matured cell. The process is illustrated in this review by light microscope morphology and transmission electron microscopy, which emphasizes new findings in human in vivo megakaryocytes, thereby making a contrast with the abundant literature on megakaryocytes from experimental animal and human in vitro material. Four stages are identified and described, based on the development of characteristic structures including α-granules, dense granules (dense-core granules), the demarcation membrane system (DMS), and proplatelets. The mechanism of DMS development is discussed, in terms of hypotheses suggesting origin from the plasma membrane, and contributions of membrane from the Golgi apparatus and endoplasmic reticulum. The formation of the marginal zone is also discussed, which is suggested to result from a circumscription of the peripheral organelle-free cytoplasmic fringe by peripheral circular cytoskeletal elements such as cytoplasmic actin and microtubules.

Congenital dyserythropoietic anemia in China: a case report from two families and a review

Congenital dyserythropoietic anemias (CDAs) are a group of hereditary disorders characterized by ineffective erythropoiesis and distinct morphological abnormalities of erythroblasts in the bone marrow. Most cases of CDA, caused by a wide spectrum of mutations, have been reported from Europe and Mediterranean countries, while a few cases have been described in China. Here, we present three cases of CDA, one from one family and two from a second unrelated family, with typical morphologic features and clinical presentations. Sequence analysis of CDA-related genes revealed that the proband with CDA Ι in the first family was a compound heterozygote of CDAN1 with mutation IVS-12+2T>C and c. 3389C>T, while both probands with CDA ΙΙ in the second family were a homozygote of the SEC23B gene with mutation c.938G>A (R313H). This study suggests that more patients with CDA, sharing a phenotype and genetic background like those of European and Mediterranean origin, remain to be diagnosed and reported in China.

Ribosome–Lamella Complex Precursors in Acute Monocytic Leukemia: A Study of 6 Cases

The ribosome–lamella complex (RLC) is a cylindrical structure composed of annular lamella associated particles, regarded as ribosomes, around a central core, which is best known in hairy cell leukemia. RLC has been presumed to originate from aggregating rER and ribosomes. Incomplete and maturing RLC structures have been called RLC precursors (pre-RLC). The present paper investigates the various architectural aspects of pre-RLC and the ultrastructural characteristics of the blasts in 6 cases of acute monocytic leukemia (M5) in which these structures occur. Blasts bearing pre-RLC contained irregular nuclei with less heterochromatin and a prominent nucleolus, and many cytoplasmic organelles in an abundant cytoplasm. The findings indicate that pre-RLC might result from an asymmetrical differentiation of organelles in blasts associated with expression of CD117 and CD56 but default of CD14 in M5.

Systematic alteration of apoptosis: a review with ultrastructural observations on leukemia cells in vivo

ABSTRACT The ultrastructural characteristics of apoptosis have been described microscopically for four decades. Alterations of nuclei, apoptotic bodies, cytoplasm, and some organelles have been illustrated and investigated during apoptosis. The successive changes of cellular components corresponding with differentiation of apoptotic cells are illustrated in the present review, based on ultrastructural observation of leukemia cells of patients in our routine clinic work by transmission electron microscopy. Most electron micrographs demonstrated that membranous components of nuclear envelop, rough endoplasmic reticulum and Golgi apparatus, and mitochondria were degenerated step by step during apoptosis. The successive images suggested that the endoplasmic reticulum and Golgi apparatus were transferred to cell surface from cytoplasm and participated in formation of apoptotic bodies in apoptosis, although relevant clinical data and more experimental evidence were needed for restraining of leukemia cases from diagnostic work randomly in recent decades.

Morphologic Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive lymphoma derived from plasmacytoid dendritic cells or precursor dendritic cells. Despite some 240 reported cases, its morphology and especially ultrastructure has not been satisfactorily studied. A case is reported of a 13 year old boy, who, despite chemotherapy, died within a 12-month period. The electron microscopy findings – microvillous processes, nuclei with slight irregularities, a moderate amount of heterochromatin, and rough endoplasmic reticulum in the form of long, narrow profiles, often in parallel arrangements – taken together, serve to distinguish BPDCN from other neoplastic cells, such as monocytes, plasma cells and the cells of chronic lymphocyte leukemia.

Ultrastructural Characteristics of Nucleated Cells in Bone Marrow of Patients with Acquired Aplastic Anemia

The objective of this study was to investigate the ultrastructural characteristics of nucleated cells in the bone marrow of patients with aplastic anemia (AA). This was done by observing the morphology of nucleated cells in bone marrow aspirates from 20 patients with AA by transmission electron microscopy. Erythroblasts were decreased in all cases and not observed in 6 cases. Nuclear abnormalities, such as pyknosis, karyolysis, karyorrhexis, apoptosis, and “Swiss cheese”-like changes, were found in 10 cases. Focal cytoplasmic necrotic changes and cytolysis were found in 3 cases. There were more megaloblasts in 4 cases. Abnormalities of granulocytes were found in 12 out of 18 cases. Megakaryocytes showed focal cytoplasmic necrotic changes. Most monocytes had dendritic features, including excessive cytoplasm, processes, and large round nuclei in all cases. Other monocytes illustrated typical monocytic features with twisted nuclei, plentiful RER, vacuoles, lysosomes, and prominent Golgi apparatus. Macrophages and hemophagocytes occurred in all cases. The incidence of lymphocytes was high in 17 out of 20 cases and occasionally lymphocytes were enlarged in 8 cases. More plasmacytes and plasmacytoid lymphocytes were found in 5 and 3 cases, respectively. The observations suggest that (1) the universal nuclear injury of erythroblasts may be related to the pathogenetic pathway of AA development; (2) the dendritic cells and hemophagocytes from the mononuclear phagocyte system may play a more critical role in hematopoietic failure of AA, directly and/or indirectly; and (3) besides T lymphocytes, increasing numbers of plasmacytes or plasmacytoid lymphocytes are associated with AA in some cases.

Ultrastructural Characteristics of Bone Marrow in Patients with Hematological Disease: A Study of 13 Cases

There are few transmission electron microscopic studies on bone marrow biopsies of patients with hematological disease owing to the difficulty of overcoming the artifacts of decalcification. Following the fixation of bone marrow biopsies thoroughly before a mild decalcification procedure, ultrastructural studies were performed on 13 patients with varied hematological diseases. Notable features included blood cell disorganization, fibroblast activation, myofibroblast transformation, as well as accumulation of collagen and extracellular amorphous matrix. In addition, excessive blood cell death in leukemia, apoptosis, and macrophage phagocytosis in myelodysplastic syndrome and polycythemia vera, as well as degranulation of eosinophils and megakaryocytes in chronic idiopathic myelofibrosis were predominant, respectively. The observations suggest that polyclonal fibroblast proliferation and extracellular matrix accumulation may result from inflammation resulting from excessive cell death and active material release of blood cells in the bone marrow of patients with hematological disease.

Histiocytic differentiation in acute monocytic leukemia

ABSTRACT Myeloid histocytes of dendritic cells (DCs), Langerhans cells (LCs), and macrophages in varied tissues, as leukemic blasts in acute monoblastic and monocytic leukemia (AML-M5a and M5b), are derived from monocyte progenitors in bone marrow. Based on DC induction from hematopoietic stem cells, myeloid progenitors, and monocytes, and occasional expressions of histocyte-related antigens (HRAs) in M5, we presume some M5 cases share histiocytic phenotypes originally. To clarify the conception, 93 M5 cases were tested with antibodies for HRAs, CD1a, CD163, S100, fascin, and langerin by immunostaining, and their morphologic characteristics were studied by light and transmission electron microscopy. The study revealed that 23 M5 cases were positive for two or more kinds of HRAs and shared a serial of histocytic immunophenotype and morphologic features, which were closely associated with M5b subtype and expression of CD14 in M5.