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Pleomorphic reticulum cell sarcoma, monoclonal gammopathy and amyloidosis: an immunoperoxidase study.

Pleomorphic reticulum cell sarcoma, a histologic variant of the histiocytic lymphomas, presented as an abdominal mass in a 52-year-old woman. Extensive amyloid deposition was present within the tumor mass and an M-component (IgG Lambda) was identified in the serum. Direct immunoperoxidase staining of tissue sections demonstrated the same monoclonal immunoglobulin to be present within the neoplastic cells, presumptive evidence of their ability to both synthesize and secrete immunoglobulin. The presence of amyloid within this patient was probably the direct result of the tissue deposition of this monoclonal immunoglobulin and may be related to the amyloidogenic nature of Lambda light chains. Immunoglobulin production is a specific property of the B lymphocyte series. Transforming B lymphocytes and their differentiating progeny are engaged in active immunoglobulin synthesis and thus may be distinguished from morphologically identical but functionally distinct cells. The demonstration of cytoplasmic monoclonal immunoglobulin within these "malignant reticulum cells" strongly supports the assertion that at least some "histiocytic lymphomas" are neoplastic analogues of transformed B lymphocytes, and are not derived from phagocytic histiocytes, as previously believed.

Amyloidosis

Pleomorphic B cell neoplasm with monoclonal IgA secretion: a case report.

A case of non-myelomatous malignant disease with IgA paraproteinemia is described. A pleomorphic lymphoid/plasmacytoid infiltrate was found in the bone marrow. While the cells studied had some ultrastructural characteristics closer to myelomatosis than Waldenström's macroglobulinemia, immunofluorescence showed IgA in both the cytoplasm and at the cell surface, as seen with IgM in macroglobulinemia but not with IgA in typical IgA myelomatosis. This case illustrates that IgA paraproteinemia may be produced in association with pleomorphic B cell proliferative diseases as well as myelomatosis. There is probably a spectrum of disease states as with IgM paraproteinemia.

Adult

Effects of cigarette smoke on elastase secretion by murine macrophages.

Mice were chronically exposed to cigarette smoke for various time periods up to 4 weeks. As a consequence of the exposure, there was an increase in the number of alveolar macrophages obtained from the lungs of these mice. Light microscopic examination of cultured cells revealed increased numbers of highly pleomorphic cells filled with pigmented residues of cigarette smoke. These cells were more mitotically active, with a five fold increase in the number of alveolar colony-forming cells compared to the controls. When macrophages derived from mice exposed to cigarette smoke were cultured at high density in the absence of serum, they secreted significantly greater amounts of elastase than did the same number of control macrophages. At concentrations as low as 0.50 micrograms/ml, cycloheximide reversibly inhibited elastase secretion from both the control and experimental cultures. The effects of cigarette smoke inhalation on elastase secretion by alveolar macrophages do not appear to be a direct effect of cigarette smoke on these cells. Exposure of normal mouse macrophages in vitro to pulses of aqueous extracts of cigarette smoke, while significantly increasing secretion of elastase by peritoneal exudative macrophages, did not augment that of resident or exudative alveolar macrophages. These results suggest that the increased elastase secretion observed with the use of cultured macrophages derived from mice exposed to cigarette smoke is the result of either indirect activation of resident macrophages or the recruitment of a highly activated exudative population into the lungs of the exposed animals.

Animals

Canine atypical malignant lymphoma.

An instance of canine malignant lymphoma with some similarities to human Hodgkin's disease is described. Although the clinical data were all within normal limits, the histopathologic changes indicated that in many organs, the normal cell architecture was replaced by a pleomorphic cell population.

Animals

Giant cell tumors of tendon sheath. An electron microscopical study of 11 cases.

Light and electron microscopy of 11 giant cell tumors of tendon sheath revealed a pleomorphic cell population in which the giant cells had similarities to osteoclasts, and the stromal cells had similarities to primitive mesenchymal cells, osteoblasts, fibroblasts, and histiocytes. I suggest that giant cell tumors of tendon sheath are derived from mesenchymal cells with partial osseous differentiation.

Adult

Primary Cerebral Pleomorphic-Myxoid Sarcoma With Many Hyaline Globules.

A case of primary sarcoma that arose in the right temporal lobe of a 59-year-old man is reported. The patient had a history of resection of a "pituitary tumor" and postoperative radiotherapy about 40 years earlier. The cerebral tumor consisted of loose and diffuse proliferation of large pleomorphic cells in a matrix showing a markedly myxoid change and containing a variable amount of delicate collagen fibers. Some tumor cells had a large intracytoplasmic vacuole containing acid mucopolysaccharide, thus featuring "pseudolipoblasts." Differentiation along other specific mesenchymal lineages was not found. Many tumor cells contained densely eosinophilic hyaline globules in the cytoplasm. Tumor cells showed a loss of the nuclear expression of H3K27me3. Although cerebral sarcomas showing similar histopathological features have not been previously reported, a markedly myxoid change of the stroma admixed with delicate collagen fibers and "pseudolipoblasts" suggests a close pathological kinship to myxofibrosarcoma. Another notable finding was the appearance of many hyaline globules, which has been considered a characteristic finding of primary intracranial sarcoma, DICER1-mutant. In the cytogenetic study of the present case, however, no DICER1 gene mutations were demonstrated.

Humans

Fine structure of cells and their histologic organization within internodal pathways of the heart: clinical and electrocardiographic implications.

The fine structure of the normal internodal pathways was studied in 1 human and 2 canine hearts and correlated with histologic observations on more than 100 human and 10 canine hearts. From the electron microscopic studies six different kinds of myocardial cells were classified from two locations: the Eustachian ridge (posterior internodal pathway) and the Bachmann bundle (anterior internodal pathway). Five of the six kinds of cells (working myocardial cells, Purkinje-like cells, either broad or slender transitional cells and P cells, all previously described) were present in both locations. A sixth cell, pleomorphic and dark in appearance, with a special intertwined relation to P cells, is newly designated as an ameboid cell. It was found solely in the Eustachian ridge. In the same area a rare direct contact between a nerve and a myocardial cell was observed. The importance of these different kinds of cells, their respective cell connections, and their topographic locations inside the internodal pathways are discussed relative to certain functions such as rapid conduction and subsidiary pacemaking. The possible influence of these factors on clinical electrocardiographic changes is considered.

Animals

Induction of some features of glial differentiation in primary cultures of human gliomas by treatment with dibutyrl cyclic AMP.

Explants from 18 gliomas were cultured for periods up to 7 weeks and studied by light microscopy scanning and transmission electron microscopy. Well-differentiated tumor tissue gave rise to early outgrowths of stellate cells showing process orientation. Poorly-differentiated tissue produced a more haphazard out-growth of pleomorphic cells with few processes and flattened pseudopodia. Mean circadian cell displacement was several times greater in poorly-differentiated cells, but was significantly and reversibly reduced by treatment and dibutyryl cAMP (5 X 10(-4)M) for 48 h. Reduction in motility was directly correlated with a change in cell morphology to a more stellate form. Well-differentiated cells had a smooth surface with ruffling restricted to the ends of processes and highly orientated glial filament and microfilament bundles. The poorly-differentiated cell surface had a microvillous, blebbed appearance and ruffling regularly occurred around the edge of the cytoplasm. Glial filaments and microfilaments were fewer and less well orientated in the poorly-differentiated cells; sites of adhesion to the substratum were fewer than in well-differentiated cells. Treatment of malignant cultures with dibutyryl cAMP resulted in smoothing of the cell surface, retraction of processes into thin pseudopodia and the appearance of microfilament bundles within the cells. These features marked the apparent cyto-differentiation. However, there was a loss of attachment, disappearance of microtubules and loss of glial filaments in the cytoplasm which was not compatible with differentiation. Intracellular recordings of membrane potentials gave a significantly higher mean value for well-differentiated cells. The mean membrane potential and input resistance of poorly-differentiated cells was unchanged by the addition of dibutyryl cAMP. The results of this study suggest that some, but not all, features of mature glia are restored in malignant tumour cells by cAMP treatment.

Brain Neoplasms

Myxoid variant of malignant fibrous histiocytoma.

It has been generally recognized that malignant fibrous histiocytoma (MFH) may assume a highly myxoid, hypocellular appearance. Eighty cases of malignant fibrous histiocytoma having varying degrees of myxoid change were reviewed. These tumors typically arose on the extremities (leg, 61%; arm, 21%) of adults (peak age incidence, 60-69 years). They were usually attached to fascia (31%) or involved skeletal muscle (51%) and had a mucoid or translucent appearance. The myxoid areas consisted of widely spaced spindled and pleomorphic cells embedded in a matrix of acid mucopolysaccharides. The cellular areas were indistinguishable from those of the typical pleomorphic MFH. The rate of local recurrence of these tumors was 61%, and of metastasis, 23%, but metastasis was less likely when the tumor was small, superficially located, or had a prominent myxoid component. In fact, the degree of myxoid change was inversely related to the rate of metastasis. Therefore, because of the more favorable prognosis of the myxoid variant, it seems appropriate to separate it from the usual nonmyxoid form of MFH. The myxoid variant must also be clearly distinguished from benign myxoid lesions such as myxoma or nodular fasciitis, with which it is often confused.

Adult

The development of experimental brain tumours a sequential light and electron microscope study of the subependymal plate. II. Microtumours.

Pregnant BD-IX rats were given a single intraperitoneal injection of 30 mg of N-ethyl-N-nitrosourea (ENU) per kg of body weight on the 15th day of gestation. The offspring were killed at fortnightly intervals between 2 and 20 weeks of age. The subependymal plate region adjacent to the lateral ventricles was examined by light and electron microscopy to study the early stages in the development of brain tumours. Microtumours, composed of subependymal plate cells, glioblasts and various glial cells at different stages of maturation, were found in 16-, 18-, and 20-week-old rats. The most common site for microtumours was the angle of the lateral ventricles between the corpus callosum and caudate nucleus; others were located at the lateral aspect of the ventricles. It is suggested that most, if not all, cerebral gliomas originate from the undifferentiated cells of the subependymal plate: these mitotically active stem cells provide a susceptible target for the carcinogenic stimulus. The morphology of the gliomas developed is determined by the diverging processes of differentiation and anaplasia resulting in a pleomorphic cell population. The relevance of this experimental model to the pathogenesis of human gliomas is discussed.

Animals

Temperature-sensitive 6-aminopenicillanic acid-resistant mutants of Escherichia coli.

Wild-type Escherichia coli cells became spherical in the presence of low concentrations of 6-aminopenicillanic acid (APA). Higher concentrations of APA caused inhibition of cell division (filamentation) and lysis. Spontaneous temperature-sensitive APA-resistant mutants were isolated and characterized. These mutants also possessed increased resistance to mecillinam but not to benzylpenicillin, ampicillin, and cephaloridine. They formed round or pleomorphic cells at the nonpermissive temperature and possessed thermolabile penicillin-binding protein 2 activity. Temperature-resistant revertants of these mutants had normal rod-shaped morphology, normal levels of sensitivity to APA and mecillinam, and thermostable penicillin-binding protein 2 activity. The mutation conferring APA resistance cotransduced with lip and mapped, therefore, close to 14 min on the E. coli linkage map. APA appears to be more specific than mecillinam as a selective agent for the isolation of penicillin-binding protein 2 mutants.

Drug Resistance, Microbial

Feline anaplastic giant cell adenocarcinoma of the thyroid.

An 8-year-old castrated, male, domestic short-haired cat had anaplastic giant cell adenocarcinoma in the thyroid gland. The cat had difficulty in breathing and swallowing because of a rapidly growing mass in the left thyroid region that partially enclosed the trachea and esophagus and had evidence of diffuse discrete interstitial pulmonary metastases. The neoplasm, which was locally invasive, was formed by groups of pleomorphic cells arranged in an endocrine-like pattern. The cells were found, spindle, fusiform or irregular; some were large and multinucleated with up to 50 nuclei. Metastases were in the lungs, pleura and regional lymph nodes. Microscopically, both thyroid glands were involved; areas of transition from a well differentiated papillary adenocarcinoma to an anaplastic form were seen.

Adenocarcinoma

An electron-microscopic study of human thyroid cancer.

Authors studied the ultrastructural characteristics of the following thyroid cancer: papillary carcinoma, follicular carcinoma, undifferentiated carcinoma and medullary carcinoma. Some specific ultrastructural-functional correlations for each type of thyroid cancer could be established. Papillary and follicular carcinoma had some common features: larger nuclei than in benign lesions, a highly increased number of mitochondria, a reduced endoplasmic reticulum, cell junctions between the cells and an intact basal lamina. In addition, papillary carcinoma presented stage I and stage II nuclear inclusions, and nuclear invaginations that contained cytoplasm. The higher malignancy of follicular carcinoma compared with that of papillary carcinoma was assigned to less differentiated areas corresponding to the compact fields. Undifferentiated carcinoma consisted of large pleomorphic cells (spindle and giant cells) with abundant mitochondria, a flat rough endoplasmic reticulum, scanty secretory granules and lysosomes, cell junctions, all suggesting their common epithelial origin. Ultrastructure of medullary carcinoma contributed to the explanation of the amyloid origin and of granule types in correlation with hormone storage in cells.

Adenocarcinoma

Two types of congenital hydrocephalus induced in rats by X-irradiation in utero: electron microscopic study on the telencephalic wall.

Stage-specific incidences of congenital hydrocephalus induced by X-irradiation of pregnant rats showed a bimodal distribution. At a dose level of 200 R, 100% hydrocephalic offspring were obtained by irradiation at embryonic days 11 and 14. When pregnant rats were subjected to 200 R X-irradiation at embryonic day 11, numerous ventricular cells of the telencephalic wall of the embryo became necrotic during the first 2 hours post-irradiation, but the paraventricular cell-to-cell interconnexions made up of zonulae adhaerentes were less affected. Mitosis took place in the surviving paraventricular surface cells throughout subsequent development. The full-term fetus exhibited little change in the cytoarchitectural arrangement of neural cells and neuropils, although it was only about half the thickness of the untreated control. After 200 R X-irradiation at embryonic day 14, most of the ventricular cells became necrotic within 6 hours. The paraventricular cell-to-cell interconnexions were completely destroyed, and never repaired in subsequent development. Mitosis took place either freely in cell clusters, or in rosettes which formed randomly in the telencephalic wall between 48 and 72 hours post-irradiation. The resulting telencephalic wall of the full-term fetus was also about half the thickness of the control. In the outer part of the tissue, the cortical plate made up of differentiating neuroblasts was hypoplastic, but the inner half was filled with numerous heterotopic masses of pleomorphic cells and bundles of primitive axons. The ependymal layer at the paraventricular surface was never formed. Whether the paraventricular zonulae adhaerentes were destroyed or not by X-irradiation was considered to be an important factor in the determination of the subsequent cytoarchitectural organization of the telencephalic wall.

Animals

Malignant haemangioblastoma (haemangiosarcoma) of the meninges.

The present paper is a report of two cases of malignant haemangioblastoma (haemangiosarcoma) of the meninges. Evidence was found of a tumour made up of vascular proliferation and pleomorphic cells. In case 1 the meningeal tumour had the ultrastructural characteristic of a malignant haemangioendothelioma. In this patient, a spinal tumour found a year later presented the features of a mixed malignant haemangioblastoma. The origin of the tumour in case 2 is the capillary pericyte, the lesion being a malignant haemangiopericytoma. We discuss ultrastucture and properties of the pericyte, its relationship to the cerebral reticulohistiocytic system, and the relationship of malignant haemangiopericytoma with the tumours considered to represent cerebral reticulosis and reticulum cell sarcomas.

Adult

Morphologic aspects of the neurofibrosarcoma (neurogenic sarcoma).

Two cases of malignant tumours of the nerve sheaths are reported. In the first patient, who had von Recklinghausen's disease, light- and electron-microscopic investigations showed an undifferentiated mesenchymal tumour of the radial nerve with the property of producing collagen fibres, an aspect characteristic of sarcoma of the fibroblastic type. In the second case a pleomorphic cell sarcoma of the cranial nerves of the left cerebellopontine angle was present. The morphologic aspects of these tumours show them to be primary mesenchymal tumours of the nerve (neurofibrosarcoma, neurogenic sarcoma) originating in the fibroblastic-like elements of the nerve sheaths. The clinical and nosologic framework of this type of malignant tumour of the nerve sheaths is discussed.

Adult

Virus particles in the basal plate of rhesus monkey and baboon placenta.

C-type virus particles and particles, approximately 35 nm in diameter, were present in the region of the basal plate from the placenta of a rhesus monkey and two baboons. Both particles appeared to bud from the plasma membrane of the cytotrophoblast: large, pleomorphic cells with cytoplasmic extensions, indented nuclei, well-developed endoplasmic reticulum, and glycogen deposits. Extracellular particles were enmeshed within a fibrous matrix. Particles were also observed in the junctional zone, but not in the decidua. C-type virus particles from the rhesus monkey and baboons differed in ultrastructure from each other and from C-type mouse leukemia virus particles. The 35-nm-type particle was spherical with a dense central core.

Animals

Malignant melanoma of choroid developing in the eye of a three-year-old boy.

An apparently normal, healthy 3-year-old boy developed redness of the left eye. An ophthalmologist discovered an intraocular tumor which he believed arose from the choroid. The child's 17-year-old mother developed osteosarcoma of the right femur during pregnancy and died a short while after his birth. Because of the rarity of malignant melanoma of the choroid in this age group, an exhaustive study was made resulting in firm evidence that this was probably a melanoma. The eye was enucleated. Pathologic study demonstrated a malignant melanoma with unusually pleomorphic cells.

Adolescent