Gastro-intestinal stromal tumors: an ultrastructural reinterpretation of the clear cell component.

The histology, immunohistochemistry and ultrastructure of six gastro-intestinal stromal tumors of the stomach (GSTs) showing a focal to diffuse clear cell component are reported. At light microscopy, all GSTs had typical histopathological features with one case additionally displaying stromal myxoid changes and scattered multinucleated giant cells. Immunohistochemically, 6 of 6 GSTs stained positive for vimentin, 2 of 6 for smooth muscle specific actin and 1 of 6 for desmin. At electron microscopy, GSTs showed microfilaments with focal densities as well as other smooth muscle features, such as subplasmalemmal linear densities and foci of external lamina. Ultrastructural appearances of tumor cells with clear cell features showed these not to be an artifact of fixation, but the expression of an unusual cytophagocytic activity. Inclusions of auto- and heterophagocytic nature were found responsible for the origin of the large, mostly lipidic vacuoles which displaced cell nuclei peripherally in a signet-ring fashion. It is concluded that such previously unrecognized features are ultrastructural aspects of GSTs with smooth muscle differentiation.

Origin of unreactive hyaline bodies from erythrocytes in genital tumors.

Two genital tumors, one a lipid virilizing cell tumor of the ovary, the other an ovarian Sertoli-Leydig cell tumor with retiform pattern, were studied focusing attention on the numerous eosinophilic hyaline bodies that were present both in the extracellular spaces and within the cytoplasm of the proliferating cells. Histochemistry and immunohistochemistry revealed that they were PAS positive and alpha-1-fetoprotein negative. Under electronmicroscopy these hyaline bodies appeared to correspond to variably altered red blood cells: red blood cell ghosts, erythrocytes with Heinz bodies, phagocytosed erythrocytes. Our findings could explain the origin of at least a part of the hyaline bodies found in similar or in other unrelated pathologies.

Epithelioid leiomyoma of the breast with granular cell change: a case report.

A 42-year-old woman with an epithelioid granular cell leiomyoma of the right breast is reported. The cells were spindle to polygonal and displayed finely granular cytoplasm. The smooth muscle differentiation of this tumor was shown by the immunohistochemical positivity of the neoplastic cells with anti-alpha smooth actin and antidesmin antisera. Microfilaments with focal densities were present in the cytoplasm at an ultrastructural level. The granular cytoplasmic changes are related to a relevant number of lysosomes within the neoplastic cells.

Human cytomegalovirus nuclear and cytoplasmic dense bodies.

One of the characteristic features of cytomegalovirus (CMV) replication is the formation of cytoplasmic dense bodies. Recent findings revealed similar structures also in the nuclei of CMV-infected cells. By transmission electron microscopy, immuno electronmicroscopy, and cytochemistry, we have studied the morphogenetic steps and macromolecular composition of both structures. Our results show that both structures contain DNA, RNA and viral antigenic proteins. Nuclear dense bodies are probably an expression of a stimulated cellular metabolism, while cytoplasmic dense bodies may represent the site where surplus cellular and viral molecules are stored before being eliminated.

Human cytomegalovirus structural components: intracellular and intraviral localization of p38.

Rabbit antisera raised against the product of ORF UL 80 of human cytomegalovirus (CMV) genome (HindIII L fragment of AD169 strain) as well as IgM from acutely infected patients recognize an antigen of Mr 38 kDa. In the viral particle this antigen is bound via S-S bridge to a lower Mr compound to form a final complex of 62 kDa that is also recognized by rabbit antisera as well as patients' IgM. P38 is present both in the nucleus and in the cytoplasm of CMV-infected cells starting from 24 h p.i. and increasingly thereafter. Immunoelectron microscopy revealed that this antigen is mainly associated with the internal portion of viral capsids both in the nucleus and in the cytoplasm.

Brenner tumor of the ovary: a correlative histologic, histochemical, immunohistochemical, and ultrastructural investigation.

The histologic, histochemical, immunohistochemical, and ultrastructural features of Brenner tumor (BT) were studied. BT was compared with transitional bladder cells, and close similarities between the two tissues were identified. Abundant glycogen in all cellular layers, an alcianophilic/sialomucinic surface mucous coat, and argyrophilic cells characterized both BT and bladder epithelium. Immunohistochemically, chromogranin and neuron-specific enolase reactivity was observed in all cases examined. An additional relevant finding was the presence of serotonin-storing cells in both BT and urothelium. Moreover, carcinoembryonic antigen, epithelial membrane antigen, and keratin reaction were found in BT and urothelium, indicating an additional antigenic similarity. Additionally, malignant Brenner tumor was ultrastructurally found to share many common features with the bladder tissue. The distinct histochemical, ultrastructural, and antigenic pattern of BT, primarily of the transitional type, is emphasized.

Ependymoma of the foramen of Monro: ultrastructural characterization.

The characteristics of clear cells of an ependymoma of the foramen of Monro have been studied by electron microscopy to precisely define its organellar composition and to establish the tumor histogenesis. Our data confirm that the once-thought oligodendroglial is, in fact, an ependymal tumor. Both the scarce number of organelles, owing to the low degree of differentiation, and the abundance of hyaloplasmic lipid vacuoles can account for the clear appearance of these tumor cells.

Elastofibroma: an in vivo model of abnormal neoelastogenesis.

Thirteen cases of elastofibroma have been studied by conventional light and electron microscopy, as well as by histochemistry and immunohistochemistry. By light microscopy elastinophilic material appeared as huge fibers crossing collagen bundles. Immunohistochemistry demonstrated a strong positivity for elastin in numerous and circumscribed areas of the extracellular matrix. By electron microscopy, collagen consisted of 40-50-nm wide fibrils, and elastin was made of large aggregates of moderately electron-dense material surrounding a very thin, apparently normal, elastin core. At high magnification these aggregates consisted of short tubules, often in regular arrays, surrounded by microfibrils and microfilaments. These data, associated with selective digestions on thin sections with elastase, purified collagenase, hyaluronidase, and chondroitinase ABC, revealed that elastic fibers in elastofibroma seem to be made of true elastin surrounded by an enormous amount of hydrophilic material, in which some elastin, chondroitin sulfates, and collagenase type-VII sensitive material are aggregated forming a rather ordered array of short tubules.

Ultrastructural and immunohistochemical contribution to the histogenesis of human cardiac myxoma.

The ultrastructural features of 8 human cardiac myxomas were analyzed and correlated with immunohistochemical data, with the aim to clarify the characteristics of the cell lines involved in the tumor genesis. Immunohistochemical studies were performed to detect the presence and the distribution of intracytoplasmic filaments (vimentin, desmin, actin, myosin) as well as myoglobin and factor VIII-related antigen, albumin, and lysozyme. Eighty percent of myxoma cells were simultaneously positive for vimentin, desmin, and actin, whereas 30% of them stained with antifactor VIII and antivimentin antibodies. The submicroscopic analysis revealed two main cell populations: (1) one composed of stellate-shaped cells with scanty organelles and sparse hyaloplasmic filaments scattered throughout the myxoid stroma and forming a loose network with their projections; (2) another one included cells with more cytoplasmic organelles, intermediate filaments, and myofilaments arranged either singly or in both solid and hollow cord-like structures. Our results support the hypothesis that cardiac myxoma may originate from a reserve multipotent mesenchymal cell able to differentiate more or less completely along two major evolutional lines: myoid and endothelial. The tumor tissue thus seems to be involved in vessel formation, suggesting a growth pattern akin to that manifested in other forms of endocardial pathological reactivity in which reserve mesenchymal cells are engaged.

Human cytomegalovirus morphogenesis: an ultrastructural study of the late cytoplasmic phases.

The late cytoplasmic phases of human Cytomegalovirus (HCMV) morphogenesis in cultured fibroblasts have been studied by transmission electron microscopy focusing attention on the relationship between the viral particles and host cell organelles. The results obtained largely reflect changes in cells subjected to sublethal injurious stimuli induced by many viruses as well as different noxious agents. A great increase in the number of Golgi apparatuses and lysosomes was observed, both of them interacting with the viral progeny. HCMV seems to acquire its final envelope from Golgi-derived structures and, less frequently, from the plasma membrane.

Human cytomegalovirus structural components: intracellular and intraviral localization of p28 and p65-69 by immunoelectron microscopy.

Using specific monoclonal antibodies, we have localized two structural proteins (p65-69 and p28) of human cytomegalovirus in infected cells and in virions and/or virus-related particles by immunoelectron microscopy using protein A-gold. Protein p65-69 is present in some roundish structures in the nuclei, often in contact with the viroplasm, and in the cytoplasm, exclusively within the dense body matrix. Protein p28 is present only in the outline of cytoplasmic capsids, and reaches the highest density in the large aggregates of virions and dense bodies which are particularly numerous during the late phases of the viral replication cycle.

Structural components of human cytomegalovirus: in situ localization of the major glycoprotein.

The localization of the major cytomegalovirus glycoprotein, both in the viral particle and in the cell membrane, was studied by means of indirect immunofluorescence and immunoelectron microscopy using a guinea pig anti-glycoprotein hyperimmune serum recently obtained by Gonczol et al. [1986]. By indirect immunofluorescence a slight and uneven positivity was observed on the plasma membrane of unfixed cells starting from 72 h postinfection (p.i.) until the end of our observation time (7 days p.i.). At immunoelectron microscopy the plasma membrane proved positive only where the virus and dense bodies budded through the membrane to form their own envelope. Extracellular viral particles (both viruses and dense bodies) appeared very strongly labeled on the external surface.

Bone metastases of neuroblastoma: the role of the orthopaedic surgeon.

The authors report 38 cases of bone metastases of neuroblastoma. They discuss the problems of diagnosis and treatment from the point of view of the orthopaedic surgeon, who is frequently confronted with a patient with localised bone symptoms in whom the primary neuroblastoma has not previously been diagnosed. The authors propose a diagnostic protocol and discuss the situations in which operative intervention by the orthopaedic surgeon may be indicated.

Stromal cells in primary myelofibrosis: ultrastructural observations.

The bone marrows of five patients with primary myelofibrosis at different stages of the disease have been studied. In the myelofibrotic bone marrow, associated with "reticulum cells", two other cell types have been identified, namely fibroblast-like and myofibroblast-like reticulum cells, as well as a spectrum of transitional forms. Our findings suggest that reticulum cells may represent a reserve stromal cell pool (i.e. primitive reticulum cells) able to modulate themselves and to transform differently according to functional requirements. Some suggestions regarding the functional significance of fibroblast-like and myofibroblast-like reticulum cells in primary myelofibrosis are suggested.