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Biomedical subjects

Brian Eyden

Publications and source records attributed to Brian Eyden.

18 recordsLinked to original sources
PubMed2007

Rhabdomyoblastic differentiation in malignant melanoma in adults: report of 2 cases.

Two cases of malignant melanoma are reported in adults exhibiting rhabdomyoblastic differentiation to alert pathologists to this rare variant of malignant melanoma. One of the cases presented as a metastasis in a submandibular lymph node, and the other was a primary skin melanoma. There are only a few published reports on melanocytic tumors with rhabdomyoblastic differentiation, mainly occurring in giant congenital nevi. Both cases reported here were confirmed by immunohistochemistry. Both cases were also studied by electron microscopy, and one showed distinctive ultrastructural features of striated muscle.

Adult↗
PubMed2006

TGF-beta1 drives partial myofibroblastic differentiation in chondromyxoid fibroma of bone.

Chondromyxoid fibroma (CMF) is a rare benign cartilaginous bone tumour with a lobular architecture containing stellate and myofibroblast-like spindle cells. The aim of this study was to investigate the presence, spatial distribution, and extent of myoid differentiation in CMF and to evaluate a possible causative role for TGF-beta1 signalling, which is known to promote smooth muscle actin (SMA) expression. Twenty cases were studied for immunoreactivity for muscle-specific actin (MSA), SMA, desmin, h-caldesmon, calponin, TGF-beta1, and plasminogen activator inhibitor type 1 (PAI-1). The extent of myofibroblastic differentiation was further investigated ultrastructurally, including immuno-electron microscopy using antibodies against MSA and SMA, focusing upon the different cell types in CMF. The expression of potential genes driving this process was quantified by Q-RT-PCR (TGF-beta1, fibronectin, its EDA splice variant, and PAI-1). Tumour cells, especially those with a spindled morphology, showed diffuse immunoreactivity for MSA, SMA, TGF-beta1, and PAI-1, while desmin, h-caldesmon, and calponin were absent. Ultrastructurally, neoplastic cells showed the presence of myofilaments and rare dense bodies, which were more prominent in spindle cells and less so in chondroblast-like cells. Immuno-electron microscopy confirmed the actin nature of these myofilaments. No fibronexus was identified. The functional activity of TGF-beta1 was demonstrated by the identification of PAI-1, a related downstream molecule both immunohistochemically as well as by Q-RT-PCR. There was a linear correlation between TGF-beta1 and PAI-1 expression. Fibronectin-EDA levels were low. We have therefore substantiated the presence of morphological, immunohistochemical, and immuno-electron microscopic partial myofibroblastic differentiation in CMF, driven by TGF-beta1 signalling.

Actins↗
PubMed2003

Electron microscopy in the study of myofibroblastic lesions.

Electron microscopy in the diagnosis and academic study of myofibroblastic lesions is discussed. Myofibroblasts from granulation tissue and tumor stroma are regarded as the nearest equivalent to a "normal" myofibroblast population with which to define myofibroblastic differentiation in tumoral and pseudotumoral lesions. Histological features include a plump-spindle-cell morphology, with an ill-defined cytoplasm paler and less fibrillar than in smooth-muscle cells, and matrix collagen. Myofibroblasts stain for alpha-smooth-muscle actin, fibronectin, and vimentin. Desmin is found in some lesional myofibroblasts. The main ultrastructural features are prominent rough endoplasmic reticulum, modestly developed myofilaments with focal densities ("stress fibers"), and fibronexus junctions. The latter are foci on the cell surface where intracellular myofilaments and extracellular fibronectin filaments converge. Myofibroblastic lesions vary in the extent to which they mirror this overall phenotype. Hypertrophic scar, Dupuytren's disease, nodular fasciitis, the fibromatoses, and inflammatory myofibroblastic tumors have the most developed myofibroblastic features. Keloid, postoperative spindle-cell nodule, and fibroma of tendon sheath are less well differentiated. Myofibroblastoma is among many lesions described as myofibroblastic which, however, appear to show a kind of smooth-muscle differentiation. Some spindle-cell malignancies express myofibroblastic features.

Actin Cytoskeleton↗
PubMed2002

Spindle-cell squamous carcinoma exhibiting myofibroblastic differentiation. A study of two cases showing fibronexus junctions.

The features of two spindle-cell carcinomas of the dermis are described with special reference to the presence of fibronexus junctions in tumour cells. The cases were of a 78-year-old man with a left eye-lid tumour and a 78-year-old woman with a naso-labial fold tumour, who had been given radiotherapy 13 years earlier for a clinically diagnosed basal cell carcinoma. Both specimens were slightly ulcerated and polypoid. Histologically, invasive tumour consisted of interlacing fascicles of plump spindled and oval cells, which were positive for several anti-cytokeratin antibodies, epithelial membrane antigen, vimentin and smooth-muscle and muscle-specific actins. Ultrastructurally, tumour cells in both cases contained rough endoplasmic reticulum (prominent in case 1), tonofibrils, desmosomes and smooth-muscle type myofilaments with focal densities. Fibronexus junctions were also present, which correlated with positive staining for fibronectin. This is the first documentation of the fibronexus in epithelial tissue in vivo, and the first unambiguous demonstration in a spindle-cell carcinoma. It extends the known distribution of the fibronexus and expands the ultrastructural spectrum of squamous carcinoma.

Aged↗
PubMed2002

Postmortem diagnosis of "occult" Klinefelter syndrome in a patient with chronic renal disease and liver cirrhosis.

This report describes a patient not suspected of having Klinefelter syndrome during life but diagnosed with it following postmortem examination using fluorescent in situ hybridization (FISH) for sex chromosomes and hormone serum analysis. A 49-year-old Japanese man had a history of nephrosis, heavy alcohol consumption, diabetes mellitus, and liver cirrhosis and had been undergoing dialysis for 10 years. He died of ruptured esophageal varices. Autopsy revealed hypogonadism, suggesting Klinefelter syndrome. This was confirmed by FISH, which showed a mosaic 46XY, 47XXY karyotype, and by serum analysis, which revealed high luteinizing hormone and follicle-stimulating hormone and low testosterone levels. Autopsy also revealed a nodular, bilateral, testicular Leydig cell hyperplasia. This report illustrates the value of postmortem laboratory investigations, particularly FISH for sex chromosomes and serum hormone analysis, for the demonstration of clinically uncertain or "occult" Klinefelter syndrome.

DNA↗
PubMedDate not supplied

Contribution of electron microscopy to understanding cellular differentiation in mesenchymal tumors of the gastrointestinal tract: a study of 82 tumors.

Eighty-two mesenchymal tumors of the gastrointestinal tract were examined by electron microscopy for the purposes of subtyping for diagnostic precision and of understanding cellular differentiation. Tumors were subclassified into leiomyoma/leiomyosarcoma, tumors of the interstitial cell of Cajal (equivalent to traditionally defined GISTs [Miettinen et al. Hum Pathol. 1999; 30:1213-1220; Mod Pathol. 2000; 13:1134-1142]), gastrointestinal autonomic nerve tumors (GANTs), and fibroblastic and myofibroblastic tumors, using criteria from the literature. Leiomyoma/leiomyosarcoma were diagnosed by myofilaments, attachment plaques, plasmalemmal caveolae, and lamina; GIST by processes or cell bodies full of intermediate filaments, solitary focal densities amid intermediate filaments, attachment plaques with incomplete lamina, scarce myofilaments, and smooth endoplasmic reticulum; GANTs by neuroendocrine granules, cell bodies/processes full of intermediate filaments (more rarely microtubules), and smooth endoplasmic reticulum; fibroblastic/myofibroblastic tumors by abundant rough endoplasmic reticulum, myofilaments, and fibronexuses. Seventy-three tumors (89%) were successfully subclassified, as 5 leiomyoma/leiomyosarcoma (6%), 36 GISTs (44%), 22 GANTs (27%), 10 fibroblastic and myofibroblastic tumors (12%). Results indicated overlap between poorly differentiated leiomyosarcoma and GIST, and between GIST and GANT. GANT is emphasized as a neuronal tumor identifiable by electron microscopy, and thereby distinguishable from GIST.

Aged↗
PubMedDate not supplied

Leiomyosarcoma showing partial synthetic-phase differentiation.

An unusual leiomyosarcoma in the thigh of a 53-year-old woman is described. Tumor cells were spindled and positive for muscle immuno-markers. Some cells exhibited typical smooth-muscle ultrastructure--abundant myofilaments, focal densities, attachment plaques, plasmalemmal caveolae, and lamina. Others had fewer myofilaments and prominent rough endoplasmic reticulum. These features indicated a variable phenotype that included synthetic-phase (matrigenic) differentiation. Synthetic-phase cells were distinguished from myofibroblasts by typical smooth-muscle surface features in the absence of fibronexus junctions. In a subset of cells myofilaments were absent, but structures resembling solitary focal densities were identified. These are discussed as possible indicators of a primitive level of smooth-muscle differentiation.

Biomarkers, Tumor↗
PubMedDate not supplied

An immunohistochemical and ultrastructural study of pancreatic microcystic serous cyst adenoma with special reference to tumor-associated microvasculature and vascular endothelial growth factor in tumor cells.

Pancreatic microcystic serous cyst adenomas are rare exocrine tumors composed of small cysts lined by glycogen-rich cells. The disease may be sporadic or present as part of von Hippel-Lindau (VHL) syndrome. Four sporadic cases of pancreatic serous cyst adenoma were examined by conventional histological, immunohistochemical, and ultrastructural methods. In the present study, new findings include the immunohistochemical identification of vascular endothelial growth factor (VEGF) and the lack of PDX-1 (putative master transcriptional factor in pancreatic stem cells) in the epithelial tumor cells. Ultrastructurally, many small blood vessels were intimately associated with epithelial tumor cells and adjacent fibroblastic cells. The observations suggest the possibility that VEGF-containing tumor cells act in a paracrine fashion to stimulate neovascularization; that peripheral blood in the vascular lumen might be filtered or processed by the endothelial and epithelial tumor cells; and that filtrates might therefore be stored as serous inclusions. It is hypothesized that pancreatic serous cyst adenomas might be under the abnormal regulation of the VHL gene, just like VHL disease itself and certain types of renal cell carcinoma, showing the distinctive histology of a rich vascularity intimately related to epithelial lining cells of cysts accompanied by stromal fibroblasts/myofibroblasts and collagenous stroma.

Aged↗
PubMedDate not supplied

Metastatic small cell malignant melanoma: a case requiring immunoelectronmicroscopy for the demonstration of lattice-deficient melanosomes.

A case of metastatic malignant melanoma exhibiting small cell morphology is described. The patient had had a previous primary nodular small cell melanoma. The metastatic tumor was examined by conventional histology, light microscope immunohistochemistry, conventional electron microscopy, and ultrastructural immunolabeling. It consisted of small cells, which, however, varied in size and were present in distinct but merging areas. Tumor cells were negative for S-100 protein and very focally positive for cytokeratin: these findings in combination with small cell morphology suggested the possibility of small cell carcinoma. However, other melanocytic markers were positive. Neuroendocrine markers were negative. By electron microscopy, tumor cells lacked unambiguous melanosomes but contained paranuclear aggregates of nondescript granules. Following ultrastructural immunolabeling, these were found to be decorated with gold-labeled HMB-45 antibodies, thereby confirming them as lattice-deficient melanosomes. This tumor is an uncommon example of malignant melanoma where immunoultrastructural analysis helped clarify the nature of otherwise nondescript granules as true but lattice-deficient melanosomes. This is also the first case of small cell melanoma to be studied by electron microscopy.

Aged↗
PubMedDate not supplied

An ultrastructural and immunohistochemical study of microcystic meningioma with emphasis on matrix proteins and connexin 26 type gap junctions.

Although the histopathological subtypes of meningioma do not themselves appear to have prognostic significance, they are collectively important for defining the overall histopathological entity of microcystic meningioma (MCM) and allowing a distinction from other intracranial tumors, such as capillary hemangioblastoma, glioma, and metastatic renal cell carcinoma showing similar histology. Four cases of MCM were analyzed by conventional histology, immunohistochemistry, and electron microscopy. The present series of MCM was characterized by spindle- or cobweb-shaped tumor cells, characteristically associated small blood vessels, and a peculiar microcystic pattern. Among the microcystic meningeal tumor tissue, small areas of conventional subtypes were identified. Immunohistochemically, tumor cells showed the mesenchymal features of vimentin positivity and a rich distribution of matrix proteins around tumor cells. They lacked epithelial marker positivity but were faintly EMA positive. Ultrastructurally, primitive cellular junctions, desmosomes, and gap junctions were frequently seen between tumor cells. The gap junctions correlated with connexin 26 immunoreactivity. Although lacking an obvious epithelial nature, these features could be interpreted as showing an abortive differentiation mimicking meningothelial (arachnoidal) cells, which, physiologically, regulate cerebrospinal fluid between blood vessels and brain parenchyma.

Aged↗
PubMedDate not supplied

Ultrastructural preservation of ovarian cortical tissue cryopreserved in dimethylsulfoxide for subsequent transplantation into young female cancer patients.

Cytotoxic therapy in young women with cancer may cause loss of ovarian function, and ovarian cryopreservation has been proposed as a means of preserving fertility. The objective of this study is to assess ultrastructural preservation of follicles in frozen-thawed ovarian cortical strips, previously cryopreserved using dimethylsulfoxide and a standard slow-cool/rapid-thaw protocol. Ovarian cortical strips (patients, n=7) were thawed and fixed in glutaraldehyde for epoxy resin embedding electron microscopy according to conventional procedures. Oocytes were generally well preserved, on the basis of plasma-membrane integrity, uniformity of chromatin pattern, mitochondrial and rough endoplasmic reticulum (rER) cisternal integrity, and absence of cytoplasmic and intranuclear clear spaces. Frequently, rER cisternae were distended and intramitochondrial matrices lost. Granulosa cells showed somewhat variable preservation. Some were dark-staining; others exhibited washed-out cytoplasm containing damaged or artifactually expanded organelles. The consistently good preservation of oocytes and the good but more variable preservation of granulosa cells provides scientific validation of one component in the overall clinical procedure of attempting to reestablish fertility in young female patients after cytotoxic therapy for cancer.

Adult↗
PubMedDate not supplied

Fibroblast phenotype plasticity: relevance for understanding heterogeneity in "fibroblastic" tumors.

Cellular transformations, reflecting phenotypic plasticity, characterize embryonic life, would-repair, physiological adaptation, and neoplasia. Fibroblastic tumors show a range of cellular differentiation, which can be rationalized in terms of phenotypic plasticity of the "normal" fibroblast. In this paper, the various kinds of fibroblast transformation are discussed, and some insights provided into the molecular mechanisms involved. Comparable molecular events may take place in neoplastic fibroblasts to produce the heterogeneous tumors nevertheless identified as fibroblastic. The following transformations are discussed: histiocytic, and fibrohistiocytic tumors; adipocytic, and lipogenic tumors; myofibroblastic, and myofibroblastic tumors. A definition of the fibroblast is required. This consists of spindle-cell morphology, vimentin-staining, and abundant rough endoplasmic reticulum. Transformation to histiocytic, lipogenic and myofibroblastic phenotypes requires the development of lysosomes, lipid droplets and lamina, and peripheral myofilaments and fibronexuses respectively. These occur in non-malignant transforming (transdifferentiating) fibroblasts, and also in tumors identified as fibrohistiocytic, lipogenic and myofibroblastic. The molecular basis of the myofibroblast transformation is probably the best studied. It is driven primarily by transforming growth factor beta. Investigations into the mechanisms of differentiation in normal fibrobiasts could prove fertile ground for defining comparable differentiation in tumors. In this respect, there are very few publications on the presence of growth factors in tumors or tumor-like lesions. There is, however, increasing investigation into gene expression and gene products in tumors, which bear on the differentiation process. Ultimately, our understanding of the molecular events controlling differentiation in cancer will lead to control, cure and prevention.

Cell Transformation, Neoplastic↗
PubMedDate not supplied

Soft-tissue extrarenal rhabdoid tumor with a unique long-term survival.

Rhabdoid tumors of kidney and extrarenal rhabdoid tumors are identified by a round-epithelioid cell morphology and a bland immunophenotype, but a distinctive ultrastructure dominated by paranuclear whorls of intermediate filaments, most usually of vimentin. These tumors are also known to be highly aggressive malignancies, which, typically, bear a poor prognosis, frequently measured in months following initial presentation. The authors record the case a soft-tissue rhabdoid tumor in a 12-year-old boy with a unique long-term survival in excess of 16 years. The features of this case are documented, with a brief summary of histological, immunohistochemical, ultrastructural, and genetic characteristics of this entity.

Antineoplastic Combined Chemotherapy Protocols↗