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Biomedical subjects

B Eyden

Publications and source records attributed to B Eyden.

At least 19 recordsLinked to original sources
PubMed2005

Malignant melanoma with neuroendocrine differentiation: clinical, histological, immunohistochemical and ultrastructural features of three cases.

AIM: To document the clinical, histological, immunohistochemical and ultrastructural features of three malignant melanomas showing neuroendocrine differentiation. METHODS AND RESULTS: Three patients, two with primary cutaneous melanoma and one with nasal mucosal melanoma, subsequently developing or simultaneously presenting with metastatic malignant melanoma, were studied by conventional histological technique, immunohistochemistry of formalin-fixed paraffin-wax embedded tissues, and electron microscopy of epoxy-resin-embedded tumour tissue. Tumours showed either small cell or conventional malignant melanoma cell morphology. One of the three primary melanocytic lesions (the nasal melanoma) exhibited neuroendocrine differentiation immunohistochemically. All three metastatic malignant melanomas showed, in varying combinations, immunohistochemical and ultrastructural evidence for neuroendocrine differentiation: they were positive for the melanocytic markers, S100 protein, HMB-45, Melan-A and tyrosinase, and the neuroendocrine markers chromogranin, synaptophysin and neurofilament protein. Ultrastructural study in two of the metastases revealed neuroendocrine granules but no lattice-bearing melanosomes. CONCLUSIONS: The cases described are the most comprehensively investigated malignant melanomas showing neuroendocrine differentiation to date, and the first to document neuroendocrine differentiation ultrastructurally in these tumours. Malignant melanoma with neuroendocrine differentiation therefore needs to be recognized among the other, better known variants of malignant melanoma.

Adult↗
PubMed2005

Foci of amorphous/granulofilamentous matrix in the extracellular domain of tumours. 2. Immunohistochemical and immunogold characterization of a fibronectin-rich matrix component.

The term FEAM (foci of extracellular amorphous matrix) has been used for discretely outlined areas of moderately dense material having a filamentous/granular substructure located in the extracellular matrix of tumours. In spite of being widespread in mesenchymal tumours especially, and often abundant, they have received little attention in terms of structure, composition and origin. Mostly, they have been regarded as a variant or a product of lamina ('basement membrane material'). However, they also appear in tumours whose cells should and do lack a lamina, such as giant-cell fibroblastoma and solitary fibrous tumour. This paper describes their fine structure in a variety of predominantly mesenchymal tumours, and documents their composition using light microscope immunostaining and immunogold labelling. Small amounts of type IV collagen and laminin were found focally and inconsistently among the five tumours by light microscope immunostaining, but fibronectin was strongly and consistently identified. Strong fibronectin staining was also identified by immuno-electronmicroscopy. These data suggest that FEAM represent a fibronectin-rich matrix constituent, which might be a common final product of either lamina or the external component of the subplasmalemmal linear density (focal adhesion). There is little support light microscopically for a relationship to immune-complexes or cryoglobulins.

Biomarkers, Tumor↗
PubMed2005

The myofibroblast: a study of normal, reactive and neoplastic tissues, with an emphasis on ultrastructure. Part 1--normal and reactive cells.

The myofibroblast is essential for the integrity of the mammalian body by virtue of its role in wound-healing, but it can also threaten it by its ability to promote tumour progression. It is an almost universal cellular component in mammalian lesions, but not a typical component of normal untraumatised tissues. Partly because of its absence from normal tissue, it has not been part of conventional histology teaching. This has contributed to difficulties in appreciating the nature of the myofibroblast and defining it by scientists interested in the mechanism of disease and pathologists wanting to diagnose myofibroblastic rumours. This paper documents the features of the myofibroblast with an emphasis on ultrastructure. A base-line of understanding is first provided by a description of normal cells found in untraumatised tissues, from which the myofibroblast has on occasion been postulated as arising, or with which, to varying degrees, the myofibroblast has been confused--fibroblasts, smooth-muscle cells, endothelium, pericytes, myoepithelium and lymphoid reticulum cells. The biology, light microscopy features and ultrastructure of the myofibroblast are then documented for comparison. Features emphasised for defining the myofibroblast include: a spindled cell morphology, an abundant matrix, immunostaining for alpha-smooth-muscle actin (in the absence of desmin and h-caldesmon) and the ED-A splice variant of cellular fibronectin, rough endoplasmic reticulum, peripherally located smooth-muscle type myofilaments, a Golgi apparatus producing collagen-secretion granules, gap junctions and fibronexus junctions. The fibronexus is emphasised as a distinctive organelle for identifying the myofibroblast and lamina is emphasised as absent. The mechanism by which myofibroblasts arise in granulation tissue and promote tumour progression is discussed briefly, and an appendix provides summaries of the involvement of myofibroblasts in non-neoplastic diseases.

Animals↗
PubMed2005

The myofibroblast: a study of normal, reactive and neoplastic tissues, with an emphasis on ultrastructure. part 2 - tumours and tumour-like lesions.

This paper describes the ultrastructure of the commoner myofibroblastic tumours and tumour-like lesions. The objective is to complement mainstream pathology texts, which have concentrated on the clinical and light microscopy features of these lesions and which have arguably but understandably somewhat neglected electron microscopy as an ancillary diagnostic tool and a technique for investigating tumour cell biology. Ultrastructural features are described of nodular fasciitis, the myofibromatoses (including Dupuytren's disease), inflammatory myofibroblastic tumour, post-operative spindle cell nodule, fibroma of tendon sheath, fibrous pseudotumour, benign fibrous histiocytoma, atypical fibroxanthoma, dermatofibrosarcoma protuberans, myofibrosarcoma (myofibroblastic sarcoma), malignant fibrous histiocytoma (pleomorphic myofibrosarcoma), epithelioid sarcoma and spindle-cell carcinoma. Fibrosarcoma and leiomyosarcoma are illustrated for comparison. The fibronexus is emphasised as an important marker for the most confident diagnosis of myofibrosarcoma. Some pathologists accept a light microscope definition, which includes alpha-smooth-muscle actin positivity, h-caldesmon negativity and, in some cases, desmin positivity. Caution in the interpretation of desmin staining in a possible myofibroblastic lesion is urged, since, in combination with an ultrastructurally identified lamina, it more probably suggests true smooth-muscle differentiation. Myofibroblastoma and angiomyofibroblastoma are examples of tumours argued on the basis of ultrastructural findings (sometimes in combination with desmin staining) to be primitively differentiated smooth-muscle cell rather than myofibroblastic proliferations.

Adolescent↗
PubMed2003

Foci of amorphous/granulofilamentous matrix in the extracellular domain of tumours: a study of 34 cases. 1. Ultrastructural characterisation.

The distribution and the appearance of foci of extracellular amorphous/granulofilamentous material (FEAM) in 34 human tumours are described. FEAM were rounded to oval, or more elongated or irregular elements of discretely delineated dense material lying in the extracellular space of tumours. They varied in size and abundance, sometimes coalescing into more extensive areas of dense material. At high magnification, FEAM exhibited a granular and finely filamentous substructure. Variations in the electron-density of FEAM were noted. Some FEAM were found associated with the surfaces of tumour cells, on occasion with subplasmalemmal linear densities. FEAM was also sometimes associated with matrix filaments, often collagen. Material of similar substructure and density was also associated with some vessels. FEAM were mostly found in tumours showing mesenchymal differentiation. The nature and origin of FEAM is discussed.

Adolescent↗
PubMed2003

The ultrastructure of human tubulo-interstitial fibrosis.

Tubulo-interstitial fibrosis, comprising tubular atrophy, infiltration by inflammatory cells, accumulation of extracellular matrix, and proliferation of mesenchymal cells in the interstitium, is a major characteristic of most progressive chronic renal diseases leading to end-stage renal failure, regardless of cause. All of the ultrastructural characteristics of tubulo-interstitial fibrosis can correlate with clinically defined features of chronic renal dysfunction. The present review illustrates ultrastructural features, emphasising some novel findings, in tubulo-interstitial fibrosis, including widespread expression of actin filaments, fatty degeneration of tubular epithelial cells, presence of cilia, and infiltration of leukocytes into the tubular lumen. The hypothesised development of interstitial myofibroblasts from tubular epithelial cells, and the relationship between tubule injury and capillary abnormality are also discussed.

Epithelial Cells↗
PubMed2003

Actin filaments in human renal tubulo-interstitial fibrosis: significance for the concept of epithelial-myofibroblast transformation.

Epithelial-myofibroblast transformation has been argued as playing a role in tubulo-interstitial fibrosis. To investigate this hypothesis, we examined 9 renal biopsy specimens from patients with chronic renal disease by light and electron microscopy. In all cases, electron microscopy confirmed light microscope observations in relation to tubulo-interstitial fibrosis-tubular atrophy, accumulation of extracellular matrix and of mesenchymal interstitial cells, and infiltration by inflammatory cells. Tubular epithelial cells (TECs) contained bundles of actin filaments: mostly lacking the focal densities typical of smooth-muscle myofilaments. The interstitium contained collagen and inflammatory cells. Some endothelial cells showed bundles of myofilaments. Free mesenchymal cells in the matrix were spindled and had sparse rough endoplasmic reticulum (rER), small attachment plaques, few actin filaments and no lamina. In one case, myofibroblasts (defined by abundant rER, myofilaments and fibronexuses) were present. Most of the mesenchymal cells, therefore, did not correspond to myofibroblasts, nor to classical fibroblasts because of the sparse rER and the presence of actin filaments. We therefore called these cells myoid stromal cells, regarding them as stromal mesenchymal elements showing partial activation towards a smooth-muscle phenotype. This paper demonstrates a greater phenotypic complexity of actin-containing stromal cells in the interstitium than previously appreciated, with only a minority conforming to true or fully differentiated myofibroblasts. The widespread presence of actin (as filaments or immunoreactivity) in both TECs and interstitial cells, combined with the absence of evidence of intermediate forms or of migration from epithelium into interstitium, may point to epithelium and interstitium as separate targets for actin upregulation as an alternative hypothesis to epithelial-myofibroblast transformation.

Actin Cytoskeleton↗
PubMed2002

Amphicrine carcinoma of breast with giant granules: an immunohistochemical, histochemical and ultrastructural study.

A moderately differentiated grade 2 invasive ductal carcinoma was diagnosed in the right breast of an 81-year-old woman. The uniform nuclear profiles and moderately abundant granular cytoplasm suggested a neuroendocrine tumour and a Grimelius stain was positive. Neurone specific enolase, synaptophysin and somatostatin stained positively, and casein was interpreted as positive although with some background staining. By electron microscopy, tumour cells possessed desmosomes, tonofibrils, intercellular lumina, lamina and dense granules. Rounded dense granules 160-480 nm in diameter resembled neuroendocrine granules. They were found in both luminal and basal areas. Fewer and much larger ('giant') granules had a rounded profile and were up to 5 microm across. The smaller cytoplasmic granules were mostly Grimelius-positive while giant granules were negative. The smaller granules were also uranaffin-positive, but no uranaffin-positive cytoplasmic giant granules were encountered. Both small and giant granules were observed in lumina, and here both were uranaffin-positive. Intraluminal giant granules had a substructure of small pale lipid-like lacunae, and some had irregular profiles. The exceptional size of these exocrine granules is emphasised, and the nature of both the small and giant granules discussed in this amphicrine carcinoma.

Aged↗
PubMed2001

Structural variations of collagen in normal and pathological tissues: role of electron microscopy.

The spectrum of ultrastructural appearances assumed by collagen in normal and pathological tissues is illustrated using techniques of thin section transmission electron microscopy and computer-assisted analysis. The normal fibrillar collagen types are described in order to provide a basis for comparing other normal and abnormal forms. In normal tissues, the anchoring fibril and basal lamina (basement membrane) represent tissue structures largely containing collagen but differing significantly in organisation from normal types I to III fibrillar collagen. In pathological tissue, deviations from normal fine structure are reflected in abnormal aggregates of collagen fibrils (amianthoid and skeinoid fibres) and abnormalities in fibril diameter and cross-sectional profile. Fibrous and segment long-spacing collagen represent two further organisational variants of collagen, the former found widely in pathological tissues, the latter very rarely. Much remains to be discovered about these abnormal collagen variants-their mode of formation, the cells that produce them, and their roles. They also present a challenge for the collagen biologist formulating hypotheses of collagen fibril assembly and molecular organisation.

Animals↗
PubMed2001

Monotypic angiomyolipoma of the nasal cavity: a heretofore undescribed occurrence.

A monotypic angiomyolipoma of the nasal cavity in a 34-year-old woman is described. Tumor cells were spindled or epithelioid and contained glycogen and diastase-resistant PAS-positive granules. There were few mitoses, and necrosis was absent, indicating a benign tumor. The stroma was markedly vascular, and a few adipocytes were seen in one area. Cells were positive for melanocyte and muscle markers. Electron microscopy revealed abundant dense granules. Although melanin was absent histochemically, it was present using a chemical assay, and the granules may, therefore, be atypical melanosomes. Fine actin filaments, attachment plaques and lamina were present. Initial assessment of the lesion indicated malignant melanoma, but the immunostaining and histologic features indicated monotypic angiomyolipoma. To the best of our knowledge, this is the first such case in the nasal cavity.

Actins↗
PubMed2001

The fibronexus in reactive and tumoral myofibroblasts: further characterisation by electron microscopy.

Forty two surgical specimens containing myofibroblasts were studied to clarify the criteria for identifying the fibronexus, an ultrastructural feature regarded as a marker for myofibroblastic differentiation. Granulation tissue, tumour stroma, fibro-proliferative lesions (nodular fasciitis, myofibromatosis, inflammatory myofibroblastic tumour) and malignancies (myofibrosarcoma and fibrosarcoma) were studied. Comparable results were found throughout these specimens, although fibronexus junctions were better developed in reactive compared with tumoral myofibroblasts. By electron microscopy, myofibroblasts were identified by abundant rough endoplasmic reticulum, peripheral smooth-muscle myofilaments with focal densities, and fibronexus junctions. The latter were recognised as the points of convergence on the myofibroblast surfaces of intracellular myofilaments and extracellular fibronectin fibrils. The fibronectin fibrils were often co-linear with myofilaments. Also, fibronectin fibrils were dark-staining, straight and rigid-looking, and had a longitudinal filamentous substructure. A striking feature was the tendency of fibronectin fibrils to project into the surrounding extracellular space, away from the myofibroblast surface: in these respects, they differed significantly from lamina ("basement membrane"). The presence of fibronectin fibrils correlated positively with fibronectin immunostaining by light and electron microscopy. Laminin and collagen IV showed variable and weak staining in the intercellular spaces in a minority of cases and never strongly stained myofibroblast surfaces. The data emphasise that the fibronexus has a number of distinctive features permitting identification, and constitute a reference-point for pathologists wishing to use electron microscopy to refine light microscopy diagnoses of putative myofibroblastic lesions. The role of the fibronexus in the definition of the myofibroblast is discussed.

Carcinoma, Squamous Cell↗
PubMed2000

Giant-cell fibroblastoma: a case report emphasising the presence of hyperplastic subplasmalemmal linear densities in continuity with granular matrices in the extracellular space.

The histological, immunohistochemical and ultrastructural features of a case of giant-cell fibroblastoma from the soft tissues of the chest wall in a 48-year-old female are described with special reference to the cell surface and matrix. Subplasmalemmal linear densities (SLDs) characterised cell surfaces, and exhibited excessive development of the dense external component: foci of identical dense material were present in the matrix. The nature of these dense foci, both the external component of the SLD and those free in the extracellular space, was investigated by light microscope immunostaining for fibronectin, laminin and collagen IV. All three proteins stained vessels. There was weaker but positive staining for tumour cell surfaces and matrix, consistent with the widely dispersed nature of the dense foci. Given their fine structural appearance, these dense foci can be referred to as granular matrices. Given also that the matrix protein immunostaining pattern is consistent with the distribution of these granular matrices as observed by electron microscopy, they may be provisionally interpreted as a kind of basement-membrane-related granular matrix. The presence of these proteins emphasises the point that, while giant-cell fibroblastoma fibroblasts lack a lamina, they nevertheless bear basement-membrane-related proteins organised, however, in a non-laminate fashion. The observations reinforce the need to qualify immunostaining results by ultrastructural investigation in order to understand the organisation of immuno-detected proteins and are discussed in terms of their diagnostic and possible biological significance.

Basement Membrane↗