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Biomedical subjects

M Guarino

Publications and source records attributed to M Guarino.

At least 37 records · Page 2Linked to original sources

Neurological complications of liver transplantation.

We examined 199 consecutive patients who underwent 220 liver transplantations, to define the type, frequency and aetiology of posttransplant neurological complications and their prognostic value. We found neurological complications in 63 patients (32%), mostly involving the central nervous system. The most frequent complications were mental status changes ranging from delirium to coma and seizures. The aetiology was multifactorial, cyclosporin A neurotoxicity being the main cause. Patients with neurological complications had a higher mortality rate than those without. In our series, neurological complications represented a major medical problem with increased morbidity and mortality.

Adolescent↗

Sarcomatoid carcinomas: pathological and histopathogenetic considerations.

Malignant tumors with a mixed phenotype are a controversial field of pathology. In this article the morphological aspects and the immunohistological characterization of sarcomatoid carcinomas are presented. These uncommon neoplasms show both carcinomatous and sarcomatous features, and have been described in the past under a variety of different names causing great uncertainty about their classification and histogenesis. They can occur in various anatomical sites and exhibit a wide range of microscopic appearances, but some features are quite characteristic and are found in many cases. Morphological "transition" between carcinomatous and sarcomatous tissue, and detection of epithelial characteristics by electron microscopy or immunohistochemistry in the sarcomatous component, are very peculiar features of these neoplasms, providing both helpful clues for pathological diagnosis and important insights into histogenesis. Here a unifying histopathogenetic mechanism based on the phenotypic conversion of carcinoma into sarcomatoid tissue is proposed and supporting literature data from both experimental systems and clinicopathological observations are reviewed and discussed.

Carcinoembryonic Antigen↗

Experimental induction of epithelial-mesenchymal interconversions.

Under some in vitro conditions, such as exposure to collagen, growth factors and related molecules, and agents affecting DNA methylation, a cell phenotype shift can be observed from an epithelial to a mesenchymal state of differentiation. The reverse process, a mesenchymal-to-epithelial conversion can likewise be obtained by certain experimental manipulations. In some instances the change is fully reversible by removing the inducer substances, but in others the conversion appears to be stable and irreversible. Only a partial modulation of the cell phenotype is often seen, but sometimes a complete switch to a new phenotype occurs, and morphological, biochemical and functional characteristics of the parent cells can be abrogated. In some in vivo models development of sarcomatous tumours can be seen in animals transplanted with several types of carcinoma, and it is possible that in some of these experiments an epithelial-to-mesenchymal conversion has occurred too. In normal embryonic development as well as in pathological lesions including tissue repair, tumour invasion, and some malignant biphasic tumours, changes similar to the ones observed in experimental epithelial-mesenchymal interconversion seem to take place. Therefore, it is conceivable that experimentally-induced phenotype conversions reflect an inherent potential of cells, and that under some experimental circumstances normally silent genetic programs for epithelial or mesenchymal differentiation are activated, thus recapitulating a phenomenon that occurs in physiopathological circumstances in vivo.

Animals↗

No neurological improvement after liver transplantation for Wilson's disease.

Orthotopic liver transplantation (OLT) represents the sole etiological treatment for Wilson's disease (WD), but its efficacy in resolving the neurological symptoms is still a matter of debate. We present the case of a young male affected with WD with hepatic and neurological involvement, who underwent OLT for subacute liver failure. Clinical, neuropsychological and neuroradiological assessment were performed before and after OLT. OLT had no effect on neurological symptoms, suggesting that the basal ganglia damage may be irreversible. Nineteen months after OLT, the patient went on to develop new permanent extrapyramidal symptoms. We postulate a sequela of an early post-operative central pontine and extrapontine myelinolysis.

Adult↗

Epithelial-to-mesenchymal change of differentiation. From embryogenetic mechanism to pathological patterns.

In embryonic morphogenesis, dramatic changes from one state of differentiation to another take place, and some epithelia transform into mesenchymal cells endowed with the ability to migrate and to form connective tissue. In vitro model systems have been developed which have provided new insights into crucial aspects of this differentiation change. Triggered perhaps by either extracellular matrix or growth factors, this phenotypic conversion involves a reorganization of the cytoskeleton, and changes in both cell-cell and cell-matrix interactions. As embryonic and adult tissues contain the same, albeit differently expressed, genetic information, one could expect, under particular circumstances, conversion to mesenchyme from epithelium to occur in adult tissues too. Indeed, there is evidence that this change really occurs in human diseases: some tissue reactions to injury; the process of tumour invasion and metastasis; and the development of carcinosarcomas, are all pathological conditions in which an epithelial conversion into mesenchyme probably plays a role. Here, recent observations on embryonic and in vitro epithelial-mesenchymal conversion are reviewed, and these data are compared with findings from some pathological situations. Many similarities emerge which further strengthen the belief that this change in differentiation is involved in the pathogenesis, and underlies the pathological pattern of some diseases.

Adult↗

Immunohistochemical analysis of extracellular matrix components in synovial sarcoma.

Little attention has been paid to the composition of the extracellular matrix in synovial sarcoma, a tumour showing both epithelial and mesenchymal phenotypes. As extracellular matrix participates actively in interactions between epithelial and mesenchymal tissues, further knowledge of the pathogenesis of this tumour may be provided by the study of extracellular matrix components. Therefore, we have analysed the immunohistochemical distribution of type I, III, and IV collagen, fibronectin, laminin and tenascin in four cases of synovial sarcoma. The pattern of immunoreactivity for these molecules varied according to the tissue phenotype of the tumour. Mesenchymal tissue labelled mainly for type I and III interstitial collagen and fibronectin. The epithelial component was surrounded by a laminin and type IV collagen-positive basement membrane, but punctate pericellular reactivity for laminin and type IV collagen was also detected among some mesenchymal cells. Tenascin was strongly expressed in the mesenchymal tissue immediately around epithelial structures and weakly or not at all expressed in the monophasic tumours and in mesenchymal tissue distant from epithelial elements in the biphasic tumours. These results suggest some resemblances between synovial sarcoma and the embryonic development of epithelia from mesenchymal cells, providing further support for the concept of an epitheliogenesis from the mesenchyme in these tumours.

Adult↗

Post-traumatic retrograde amnesia with selective impairment of autobiographical memory.

A selective, temporally limited retrograde amnesia, confined to autobiographical memory, was the only sequela of a "minor" head trauma in two young men. The retrograde memory gap covered about one year of life before the trauma and persisted for several months, without any anterograde deficit or other cognitive disturbances. This unusual pattern of retrograde amnesia deserves close consideration and points to the dissociation of memory subsystems and mechanisms.

Adult↗

Fibronectin, laminin, type IV collagen distribution, and myofibroblastic stromal reaction in aggressive and nonaggressive basal cell carcinoma.

The stromal myofibroblastic reaction and extracellular matrix in a series of 19 morphologically and clinically aggressive basal cell carcinomas (BCC) were examined by an immunohistochemical staining panel for myofibroblastic markers (vimentin, actin, and desmin), for basement membrane components (laminin and type IV collagen), and for fibronectin. Results were compared with a series of 19 nonaggressive BCC. The aggressive BCC showed discontinuous staining for laminin and type IV collagen, a marked myofibroblastic response, and increased stromal fibronectin. Conversely, the nonaggressive BCC showed a continuous basement membrane and a total lack of staining for fibronectin and myofibroblastic markers in all but three cases. This report suggests that a combined analysis of extracellular matrix components and myofibroblastic markers may be useful for evaluating the clinical behavior including the metastatic capability of aggressive BCC.

Aged↗

[Primary embryonal rhabdomyosarcoma of the breast. Description of a case].

Authors report a case of embryonal rhabdomyosarcoma of the breast occurring in a 16-year-old girl. To date, 26 cases have been described in the literature of which only 4 in girls younger than 16 years. Histological features, immunohistochemical findings and differential diagnosis are discussed.

Adolescent↗

Immunohistochemical distribution of basement membrane type IV collagen and laminin in synovial sarcoma.

AIMS: To investigate the distribution of basement membrane components type IV collagen and laminin in synovial sarcomas. METHODS: Paraffin sections from synovial sarcomas were studied by the peroxidase-antiperoxidase procedure using specific antibodies to type IV collagen and laminin. RESULTS: Type IV collagen and laminin immunoreactivity was confined around epithelial areas in biphasic tumors. Several interruptions and discontinuities of the linear basement membrane profile were seen in sites of transition between mesenchymal and epithelial tissue. Moreover, a spot-like immunoreactivity was often observed in the spindle cell component of biphasic tumors. Monophasic tumors were either negative or showed a pericellular staining for both type IV collagen and laminin. CONCLUSIONS: The distribution of basement membrane components is clearly related to the formation of epithelial elements in biphasic synovial sarcoma. The spot-like immunoreactivity of the spindle cell component, and the basement membrane interruptions at the boundary between mesenchymal and epithelial tissue, are both consistent with early basement membrane formation by developing epithelium. These findings support the concept that synovial sarcomas are basically soft tissue carcinosarcomas and that the epithelial component of the tumors develops by conversion of mesenchyme to epithelium.

Adult↗

The basement membranes in sarcomatoid carcinomas. An immunohistochemical study.

AIMS: Eight sarcomatoid carcinomas from various anatomical locations were investigated by immunohistochemical staining to laminin, type IV collagen and heparan sulfate proteoglycan, to study the characteristics of basement membranes at the interface between carcinomatous and sarcomatous tissues. METHODS: Paraffin wax embedded tissue sections from representative tumor samples have been stained with specific antibodies, using the peroxidase-antiperoxidase technique. RESULTS: In all cases several interruptions or discontinuities of the basement membrane staining pattern were seen. In 4 cases, larger defects or complete loss of staining was also noted. At these places, the boundaries between carcinomatous and sarcomatous tissue were often blurred. CONCLUSIONS: Disruption and loss of basement membranes at interface between carcinomatous and sarcomatous tissues is a frequent finding in sarcomatoid carcinomas. These changes could be consistent with an epithelial origin of the sarcomatous component in these tumors by means of an epithelial-mesenchymal conversion mechanism.

Aged↗

The extracellular matrix in sarcomatoid carcinomas of the breast.

The distribution of the main extracellular matrix components has been investigated immunohistochemically in four cases of breast sarcomatoid carcinomas. The histogenesis of these tumours is still unclear, but most evidence suggests that the sarcomatous component originates from mesenchymal conversion of carcinomatous cells. We found that carcinomatous portions of the tumours were associated with linear basement membrane-like deposition of laminin, type IV collagen and heparan sulphate proteoglycan that partially circumscribed the epithelial nests. The sarcomatous components produced an extracellular matrix immunoreactive to fibronectin, type I, III and VI collagens and tenascin. However, in two cases, in some sarcomatous areas, focal pericellular staining for antibodies to laminin and type IV collagen was seen. These results indicate that modifications observed in the double tissue component of these tumours involve not only the cell shape and the cytoskeleton, but also the components of the extracellular matrix. The significance of these findings and their relevance in the understanding of the phenotypic pattern changes of these biphasic tumours are discussed.

Aged↗

Ductal adenoma of the breast. An immunohistochemical study of five cases.

The immunohistochemical features of 5 ductal adenomas of the breast were investigated. The tumours were composed by tubular glands lined by cells with both luminal and basal/myoepithelial immunophenotypes. Tubules were encircled by an intact basement membrane as demonstrated by staining for laminin and type IV collagen. Areas of dense fibrosis, a usual finding in these lesions, stained for fibronectin, type III collagen and contained vimentin and actin positive spindle cells, consistent with myofibroblasts. These observations confirm a double epithelial and myoepithelial differentiation in these lesions and seem to support the suggestion that ductal adenomas result from sclerosis of ductal papillomas.

Adult↗

Plexiform schwannoma. Immunohistochemistry of Schwann cell markers, intermediate filaments and extracellular matrix components.

An immunohistochemical study using a comprehensive panel of antibodies to Schwann cell markers, intermediate filaments and extracellular matrix components has been performed on three cases of plexiform schwannoma. All tumour cells expressed S 100 protein, Leu 7-HNK 1 antigen and vimentin; glial fibrillary acidic protein was detected in many tumour cells. In addition, expression of cytokeratin was also demonstrated in one case. The associated extracellular matrix was found to be reactive with antibodies to laminin, heparan sulfate proteoglycan, fibronectin, type I, III, IV and VI collagen. It is concluded that Schwann cells producing their own extracellular matrix are the main components of these tumours. The significance of the cytokeratin expression and the possible role of the extracellular matrix in regulating Schwann cells' proliferation in peripheral nerve tumours are discussed.

Adult↗

Carcinosarcoma of the oesophagus with rhabdomyoblastic differentiation.

We report a case of oesophageal carcinosarcoma with prominent rhabdomyoblastic differentiation. Immunohistochemically, the rhabdomyblasts were mainly reactive to vimentin, cytokeratin, desmin, muscle-specific actin, myosin, and myoglobin, and were surrounded by laminin and type IV collagen-positive basement membranes. The tumour had dual differentiation, carcinomatous and sarcomatous, but also showed evident features of transition between the two components; suggesting a common origin. An epithelial-mesenchymal conversion could be the pathogenetic mechanism involved in the histogenesis of this lesion. The word carcinosarcoma, from a descriptive point of view, seems the most suitable to describe a tumour composed of both carcinomatous and true sarcomatous elements.

Aged↗