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Biomedical subjects

B P Eyden

Publications and source records attributed to B P Eyden.

At least 19 recordsLinked to original sources

Cardiac sarcoma showing bone formation and neurogenic markers: report of a case.

A 54 year-old Japanese female with cardiac insufficiency was found to have a left atrial mass and smaller masses on the mitral valve. Excisional surgery of the masses and mitral valve replacement were carried out. In spite of intensive post-operative radiation therapy, the patient died of intra-atrial recurrence and brain metastases after 8 months. Tumour cells were spindled to oval, were positive for vimentin, S100 protein and neurone specific enolase. Laminin and fibronectin were also demonstrated. Bone formation and myxoid areas were present. An ultrastructurally identifiable stromal component, possibly responsible for laminin and fibronectin staining, was also present. The merits of the two main diagnostic possibilities - a mesenchymal/fibroblastic sarcoma showing bone and aberrant S100 protein, and a malignant peripheral nerve sheath tumour with bone - were discussed. In practical terms, the tumour was given the diagnosis of unclassifiable sarcoma of the left atrium. Atrial sarcomas showing neural markers and bone formation are exceedingly rare, and this report adds a further exceptionally uncommon case to the literature.

Biomarkers, Tumor↗

A study of four cases of extra-orbital giant cell angiofibroma with documentation of some unusual features.

AIMS: To document the clinical, light microscopic, immunohistochemical and ultrastructural features of four cases of extra-orbital giant cell angiofibromas. METHODS AND RESULTS: Sections of formalin-fixed paraffin-embedded specimens were studied by haematoxylin and eosin, reticulin and immunohistochemical stains. Electron microscopy was carried out in two cases on tissue fixed in formalin. The age of the patients ranged from 30 to 41 years. Two patients presented with a soft tissue swelling in the left groin, one patient had a left axillary soft tissue lump and one patient presented with a parotid lump. All lesions were well circumscribed and contained variably cellular and vascularized tissue composed of round to spindle cells with a patternless arrangement, scattered multinucleate giant cells and pseudovascular spaces conforming to the description of giant cell angiofibroma. Mononuclear and multinucleate tumour cells were both positive for vimentin and CD34; one tumour exhibited focal S100 protein and GFAP positivity. Both of the tumours examined by electron microscopy showed fibroblastic features, but in addition one contained cells having Schwannian features. All four patients were well without recurrent disease on follow-up (average 25 months). CONCLUSION: Giant cell angiofibroma shares many features with solitary fibrous tumour and giant cell fibroblastoma and shows a wider distribution than initially recognized. Rarely, Schwannian differentiation may be observed in these tumours.

Adult↗

Evidence of nerve sheath differentiation and high grade morphology in sclerosing epithelioid fibrosarcoma.

Sclerosing epithelioid fibrosarcoma is a recently described sarcoma in which ultrastructural evidence of fibroblastic differentiation forms part of the diagnostic criteria. This report describes a further case of this tumour, which showed evidence of both fibroblastic and perineurial differentiation by immunohistochemistry and electron microscopy, and which had areas of high grade morphology. The tumour metastasised and the patient died of disease 12 months after presentation. The relevance of these findings to diagnosis and differentiation in these tumours is discussed.

Cell Differentiation↗

Mesotheliomas with deciduoid morphology: a morphologic spectrum and a variant not confined to young females.

Deciduoid mesotheliomas are rare with only four previously reported cases, all affecting the peritoneum of young females. We describe another six cases (three men and three women; age range 52-65 yrs, median 55 yrs; five peritoneal and one pleural). Three patients had an occupational history of asbestos exposure. The deciduoid appearance predominated in four cases, whereas in two it represented a minor component within conventional tubulopapillary epithelioid mesothelioma. All tumors were strongly cytokeratin-positive (including CK5/6) and all showed at least focal staining for thrombomodulin, HBME-1, and calretinin. All were negative for epithelial mucin (D/PAS), CEA, BerEP4, LeuM1 (CD15), CD21, CD35, and S100 protein. Five of six cases (83%) were vimentin-positive and two (33%) were focally positive for alpha-smooth muscle actin. A differential diagnosis of gastrointestinal autonomic nerve tumor (GANT) had been initially considered from the morphology of one case, and we found positivity for some of the "neuronal" markers described in GANTs. This prompted us to apply such a panel to the other five tumors, accepting that the cytokeratin positivity encountered in all of our cases would exclude GANT. All cases of deciduoid mesothelioma (100%) were positive for PGP 9.5 and NSE and four of six (66%) were positive for NKI/C3. Weak focal staining (<5% cells) for synaptophysin was seen in two of six tumors. All cases were chromogranin-negative. All cases examined by electron microscopy showed desmosomes and smooth microvilli without rootlets but no neuroendocrine granules. In conclusion, a deciduoid morphology appears to be part of the histopathologic spectrum encountered in epithelioid mesothelioma. This variant is not confined to female patients and occurs over a wider age range than previously recognized. The overlapping immunophenotype with GANTs illustrates that caution should be exercised when interpreting positivity for "neuronal" markers in this context. An immunohistochemical panel that includes cytokeratins should always be used.

Aged↗

Extraskeletal myxoid chondrosarcoma with neuroendocrine differentiation: a pathologic, cytogenetic, and molecular study of a case with a novel translocation t(9;17)(q22;q11.2).

A case of extraskeletal myxoid chondrosarcoma (EMC) in which there was histochemical, immunohistochemical, and ultrastructural evidence of neuroendocrine differentiation is reported. Genetic investigations showed the recently described novel translocation t(9;17)(q22;q11.2) and associated fusion of the CHN and RBP56 genes, contrasting with the translocation t(9;22)(q22;q12) and EWS/CHN gene fusion found in the majority of EMCs.

Biomarkers, Tumor↗

Malignant melanoma showing ganglioneuroblastic differentiation: report of a unique case.

We report a case of metastatic malignant melanoma in an inguinal lymph node, expressing ganglioneuroblastic differentiation. This was characterized by the presence of discrete nests and islands of large ganglion cells with abundant cytoplasm and eccentric nuclei with prominent nucleoli admixed with smaller primitive neuroblasts. The cells were separated by pale pink fibrillar material representing neuritic cell processes. These foci of ganglioneuroblastoma were seen over a background of an otherwise typical metastatic epithelioid, focally melanotic, malignant melanoma. Immunohistochemistry showed positivity for neurofilament, synaptophysin, chromogranin, vasoactive intestinal peptide, and glial fibrillary acidic protein in the areas with ganglioneuroblastic differentiation, but not in the melanocytic component. Conversely, HMB45 positivity was expressed by the melanocytic cells only. S-100 protein and Melan-A, a putative melanocytic marker, showed positivity in both melanocytic and ganglioneuroblastic components. Ultrastructurally, neuritic cell processes and dense core neurosecretory granules were identified in the ganglionic and neuroblastic cells. A subsequent nodal metastasis in the same region showed focal neuroblastic differentiation without the ganglionic element. No evidence of neuronal or ganglionic differentiation was seen in the primary skin melanoma.

Adult↗

Sclerosing epithelioid fibrosarcoma: a study of five cases emphasizing diagnostic criteria.

AIMS: To study the clinical and histopathological features of sclerosing epithelioid fibrosarcoma, and to define diagnostic criteria for this uncommon soft-tissue tumour. METHODS AND RESULTS: Standard histological, immunohistochemical and ultrastructural techniques were applied to five tumours from head and neck, chest wall and groin. Tumours consisted of groups of monomorphic rounded/epithelioid cells surrounded by a prominent collagenous stroma. Tumour cells showed positive vimentin staining but were negative for other markers. They contained prominent rough endoplasmic reticulum and a large Golgi apparatus which in one case was producing collagen secretion granules, an ultrastructural marker for collagen production. Three patients had medium to long-term survival (3-7 years). Of these, one was disease-free for 3 years, and two experienced multiple recurrences: one of the latter died of metastatic disease. CONCLUSION: Criteria for diagnosing this uncommon tumour include: small to medium cell size, clear or pale cytoplasm, cellular arrangement in cords and strands, dense collagenous stroma; vimentin staining; rough endoplasmic reticulum and a Golgi apparatus producing, in well preserved examples, collagen secretion granules. The paper emphasizes the value of electron microscopy, supporting an appropriate histological picture and immunophenotype, in identifying these relatively low-grade sarcomas.

Adult↗

Schwannoma with features mimicking neuroblastoma: report of two cases with immunohistochemical and ultrastructural findings.

OBJECTIVE: A study of two cases of a rare variant of benign schwannoma showing areas mimicking neuroblastoma/peripheral primitive neuroectodermal tumour (PNET). METHODS: Sections of formalin fixed, paraffin embedded specimens were studied by tinctorial stains and immunohistochemistry, and the tissue retrieved from formalin was examined by electronmicroscopy in one case. RESULTS: The tumours were small and subcutaneous. Both showed features of benign schwannoma; one had a multinodular plexiform pattern. In addition, rosette-like structures consisting of collagenous cores surrounded by small round cells or slightly larger epithelioid cells were present. Tumour cells were positive for S100 protein, Leu7, and in one case GFAP, but were negative for neurofilament protein, synaptophysin, and MIC2. Type IV collagen surrounded individual cells. Electronmicroscopy in case 2 confirmed schwannian features (lamina, processes) and failed to show features of neuroblastoma (neuroendocrine granules). CONCLUSIONS: Benign schwannomas may contain rosette-like structures mimicking neuroblastoma/PNET. The techniques used confirmed schwannian differentiation only and eliminated neuroblastoma/PNET. These uncommon variants should be recognised by practising histopathologists to avoid erroneous diagnoses and inappropriate treatment.

Adult↗

Characterisation of breast stromal fibroblasts: cell surface distribution of collagen type IV, laminin and fibronectin.

A number of cells--fibroblasts, chondrocytes and osteoblasts for example--lack the conspicuous cell surface specialisation known as lamina: instead, they possess subplasmalemmal linear densities (SLDs). These have been documented ultrastructurally as having a lamina-like external component but the extent to which they resemble true lamina in terms of protein composition has not been investigated. The relationship of the external component of the SLD to true lamina was examined in this study by light microscope immunostaining, conventional transmission electron microscopy and immuno-electronmicroscopy in intralobular stromal fibroblasts. These were studied in normal peri-tumoral breast tissue in 17 patients undergoing surgery for breast lesions. For ultrastructural immunostaining the indirect immunoperoxidase procedure was used on cryostat sections followed by embedding in epoxy resin. To varying degrees, collagen type IV, laminin and fibronectin antibodies stained fibroblasts and macrophages at the light microscope level. Using immuno-electronmicroscopy, all three antibodies localised as foci on fibroblast and macrophage surfaces. These occurred with a frequency comparable to that of SLDs as seen in non-immunostaining ultrathin sections. These observations represent a first attempt to define the protein composition of SLDs in fibroblasts in vivo. They provide an opportunity of comparing these structures with true lamina and form a basis for understanding how fibroblasts interact with their environment.

Adult↗

Gap junctions and nerve terminals among stromal cells in human fallopian tube ampullary mucosa.

The purpose of the present study is to investigate the ultrastructure and immunohistochemistry of the stromal cells and terminal nerve fibers in human fallopian tube ampullar mucosa to achieve a detailed characterization of this tissue to permit a better assessment of possible functions. Tissues were obtained during surgery or at autopsy from 26 patients. Specimens were studied by the conventional histologic technique, immunohistochemistry (Cx43, synaptophysin, neurofilament proteins, and S-100 protein), and electron microscopy. Gap junction and nerve terminal frequency between stromal cells were studied by direct assessment on ultrathin sections in the transmission electron microscope. Gap junctions were observed between the cytoplasmic processes of subepithelial stromal cells. There were approximately 23 gap junctions per 73 nucleated stromal spindle cells. Immunohistochemistry using Cx43 antibody confirmed the dot-like distribution of gap junctions. The frequent and intimate association of stromal cell processes with nerve terminals was also demonstrated. Nerve terminals were immunostained by antibodies to nerve-specific molecules and ultrastructurally as axonal profiles containing dense-cored granules or empty vesicles. Analysis of nerve terminal frequency revealed 18 nerve profiles containing 51 axonal profiles per 73 nucleated stromal spindle cells. The present paper documents the participation of autonomic nerve endings and gap junctions in the stromal cell network in human fallopian tube stroma. Similarities to the unique anatomical unit referred to as the 'neuro-reticular complex' in bone marrow tissue (Yamazaki and Allen, 1990) are discussed.

Adult↗

Adenomyoepithelioma of the skin: a case report with immunohistochemical and ultrastructural observations.

AIMS: The histological, immunohistochemical and electron microscopic features of a primary adenomyoepithelioma of skin, a rare sweat gland tumour, are reported. METHODS AND RESULTS: The tumour occurred on the back of a 92-year-old woman. It was composed of well-formed tubules lined by epithelial cells surrounded by clear or spindled myoepithelial cells. Immunohistochemically, the epithelial cells exhibited strong cytokeratin (CAM5.2) and weak carcinoembryonic antigen positivity. The myoepithelial cells showed diffuse positivity for smooth muscle actin and focal positivity for S100 protein. Ultrastructurally, the myoepithelial cells contained myofilaments with focal densities and hemidesmosomes. They were limited by well-formed basal lamina. The tumour was associated with a small eccrine spiradenoma. CONCLUSION: We predict that the tumour will behave in a benign fashion. There is no evidence of recurrence or metastasis 28 months later.

Actins↗

Clinicopathological characteristics of peripheral primitive neuroectodermal tumour of skin and subcutaneous tissue.

AIMS: To study the clinical and pathological features of primary malignant peripheral primitive neuroectodermal tumours (PNETs) of the skin and subcutaneous tissue, to discuss the differential diagnosis, and to review the existing literature on these tumours. METHODS AND RESULTS: Eight cases of PNETs presenting in the skin and subcutaneous tissue were identified from the pathology records of the Christie Hospital, Manchester. Detailed immunohistochemical studies were performed on all cases and seven tumours were subjected to electron microscopic examination. Detailed clinical and follow-up information was obtained on seven cases. Six tumours occurred in children and adolescents and two were seen in young adults (age range, 8-36 years). No sex or site predilection was observed. Five tumours occupied the dermis and subcutis and three were entirely located in the subcutaneous tissue. Microscopically, they were composed of small round cells and seven tumours contained glycogen. Only one tumour focally exhibited Home-Wright rosettes and neuropil. Two tumours contained rhabdoid or plasmacytoid cells in places and all cases showed microcystic and pseudovascular spaces. Immunostains revealed MIC2 (8/8), NSE (7/8), PGP9.5 (7/8), beta 2 microglobulin (7/8), neurofilament protein (6/8), S100 protein (3/8), synaptophysin (2/8) and Leu-7 (1/8) positivity. Anomalous cytokeratin (4/8), desmin (2/8), myoglobin (2/8), NKIC3 (4/8) and GFAP (1/8) staining was also noted. Ultrastructurally, neuroendocrine granules were detected in five cases and one case exhibited microtubules in processes. Adequate follow-up information was available in four cases. One patient died of metastatic disease. One child developed axillary lymph node metastasis but is alive with no evidence of disease 96 months after treatment. Two other patients are alive with no residual or recurrent disease 44 and 52 months after excision and radio/chemotherapy. CONCLUSION: PNETs are rare malignant small round cell tumours of the skin and subcutaneous tissue which are probably underdiagnosed. A correct diagnosis can be made on light microscopic features, demonstration of neuroendocrine granules on electron microscopy and a combination of MIC2, beta 2 microglobulin, and more than one neural marker positivity. These neoplasms should be differentiated from other cutaneous neoplasms composed of small round cells. The number of cases of cutaneous PNETs studied so far is rather small, and no firm conclusion can be drawn about their behaviour but long-term survival is possible in some cases.

12E7 Antigen↗

Nodular erythema elevatum diutinum mimicking cutaneous neoplasms.

AIMS: We describe the cutaneous pseudoneoplastic lesions in two patients with nodular erythema elevatum diutinum, a rare chronic disorder in which polymorph nuclear fragmentation (leukocytoclasis) is present within dermal nodules showing spindle cells and fibrosis. In both cases diagnostic difficulty was encountered clinically and pathologically and various benign and malignant neoplasms were considered in the differential diagnosis. METHODS AND RESULTS: Immunohistochemically the spindle cells were negative for CAM5.2, AE1/3, S100 protein and desmin (D33). They were positive for vimentin and focally positive for CD34 and alpha-smooth muscle actin. Some of the spindle cells were positive for Mac 387 and KP1(CD68). By electron microscopy, the lesions were shown to consist of fibroblasts/myofibroblasts and fusiform macrophages. CONCLUSIONS: Increased awareness of the features described will help to avoid misdiagnosis as a neoplastic process.

Adult↗

Angio-tumoral complex in human malignant melanoma characterised by free laminin: ultrastructural and immunohistochemical observations.

Neo-vessel density in primary tumours as a prognostic factor for metastasis has been questioned. For this reason we have investigated qualitative aspects of tumour vascularity and particularly the association of cancer cells with endothelium, focussing on the peri-endothelial matrix. We have examined the matrix between endothelium and tumour cells in human invasive and metastatic malignant melanoma using transmission electron microscopy and immunohistochemistry. We have identified a hitherto unrecognised image (the angio-tumoral complex) in which the tumour cell and endothelium are in direct contact via an amorphous matrix. This amorphous matrix lacks an organised lamina and contains predominantly laminin with noticeably less collagen type IV. In this image endothelial cells showed no signs of physiological damage, no tumoral intravasation, and tumour cells occupied a pericytic location. This typical image was absent from naevi. We regard the laminin in this amorphous matrix as "free' laminin as distinct from laminin integrated into an organised lamina. We discuss the role of this free laminin in promoting the migration of melanoma cells in contact with vessels and suggest the possibility that this angio-tumoral complex represents a marker for metastasis.

Humans↗