Applied pathology最新文献

The classical morphological criteria in the diagnosis of hepatocellular carcinoma (HCC) include: (a) the similarity of tumor cells to hepatic cord cells; (b) the trabecular nature of the growth with capillary and canaliculi formation, and (c) the intravascular growth of trabecular carcinoma. These criteria apply to the most common variants of HCC but they do not suffice in all cases. That makes additional criteria and certain refinements necessary. A promising approach to the diagnosis of HCC is that based upon consideration by the pathologist of some relevant aspects of the natural history of this tumor. A panel of tests exploring the various functions and properties of liver cells should be set up. Tests for bile and fibrinogen synthesis are most important because they reflect specific and exclusive properties of the original cell line. Bile synthesis in tumor tissue is reflected by the finding of cholecholatestasis, namely bilirubinostasis and retention of copper and copper-binding proteins. The positive immunostaining for fibrinogen may appear in the form of cytoplasmic granules occurring in 50% of HCC, or in the form of fibrinogen-ground-glass (G-G) inclusions, representing a specific feature of HCC. During neoplastic transformation oncofetal proteins may reappear, alpha-fetoprotein (AFP) being very common. Despite sensitivity of AFP, this test, similar to alpha-1-antitrypsin (AAT), has very low specificity, because of the widespread occurrence of these proteins in a variety of tumors. The selection of special 'clones' such as Mallory bodies and fibrinogen-G-G is of particular value, because of the specificity of these peculiar cytoplasmic changes. Although rare, the presence of HBV antigens in tumor tissue is virtually pathognomonic for HCC. The availability of nonneoplastic liver tissue for morphological examination is of great help, because it may carry key information or markers of the development stages of HCC: cirrhosis, liver cell dysplasia, HBV antigens, congenital metabolic disorders, such as hemochromatosis and AAT deficiency. The two latter conditions represent the link with the last working hypothesis of the present study, i.e. that during neoplastic transformation hepatocytes may 'switch' their 'phenotype' thus escaping the storage phenomena, which continue to occur in nonneoplastic hepatocytes. This study provides a guideline to a dynamic approach to the diagnosis of HCC. The rationale is listed in 5 points; among them, bile production, fibrinogen synthesis, Mallory body and fibrinogen-G-G selection, HBV antigen expression can be considered at present as confident markers for the morphological diagnosis of HCC.

Hepatocellular dysplasia, first described by Anthony et al. [J. clin. Path. 26: 217-223, 1973], is considered a peculiar pattern of proliferation process mainly observable in cirrhotic nodules in patients with hepatocellular carcinoma. Its precancerous meaning has been variously evaluated in the past. In the present study, immunohistochemical data concerning the presence of alpha-fetoprotein, alpha 1-antitrypsin, carcinoembryonic antigen, hepatitis B surface antigen and hepatitis B core antigen did not show meaningful differences between carcinomatous cells and normal and dysplastic hepatocytes. On the contrary, morphometric analysis seems to be useful to discriminate dysplastic cells by means of parametrical indexes of shape and symmetry of the nuclei and could probably offer in the future an objective evaluation of hepatocellular dysplasia.

A detailed morphological study concerning the liver of 71 patients suffering from idiopathic haemochromatosis was carried out. These patients were subjected to long-term venesection therapy, which lasted from 1 to 12 years. The mean duration of therapy was 7 years for each patient. The material consisted of needle biopsies of the liver. Three to seven biopsies were performed in each patient; the initial biopsy, the biopsy following venesection therapy, and the follow-up biopsies. In 30 cases the follow-up was performed in autopsy material. It was found that the final histological appearance of the liver remained unchanged in 44 (62%) cases, became worse in 23 (32%) cases, and improved in 4 (5%) cases. However, the change for the worse is generally retarded and consequently the mean survival of the patients is increased. Two out of 4 cases that showed improvement (i.e. changing from cirrhosis to fibrosis) are strongly supported by the fact that the follow-up study was performed in autopsy material after 2-5 needle liver biopsies. A high incidence of hepatocellular carcinoma (18%), as well as of a malignant neoplasia in another organ (8.4%), was noted in spite of the long-term venesection therapy. It follows therefore that the longer survival of patients with idiopathic haemochromatosis increases the possibility of hepatocellular carcinoma or of a malignancy in another organ.

Soft tissue sarcomas are capable of causing diagnostic bewilderment for the surgical pathologist, because of their diversity of differentiation and overlapping histologic appearances. Immunohistochemical studies provide a means whereby this confusion can be resolved in many cases, and electron microscopy also may play a useful role in this process. This overview presents a summary of results of these 2 adjuvant modalities of pathologic analysis, as applied to the spectrum of malignant soft tissue neoplasms.

In pathological conditions, vascular modifications occur in various stages involving both vessel structure and adjacent extracellular matrix. The relationships between vascular cells and surrounding microenvironmental stroma are mediated by cytoskeleton. Our investigation showed a high number of vimentin- and actin-positive cells in the vascular cutaneous bed, mainly related to reactive vascularization phenomena, whereas vessel cells with a desmin-positive reaction were barely detectable. Furthermore, in newly formed vessels ultrastructure showed that basement membrane synthesis strictly depends on close contact between the endothelium and extracellular matrix. Our data give structural evidence of the close morphofunctional interactions existing between vascular cells and extracellular matrix.

The pathologic and clinical aspects of benign tumors and pseudotumors of the liver are reviewed. They are classified according to the tissue of organ into epithelial (further subclassified into tumors of hepatocellular and cholangiocellular origin), mesenchymal or mixed derivation, and a miscellaneous group. Some of the tumors and pseudotumors, e.g. bile duct adenoma, small focal nodular hyperplasias and cavernous hemangiomas, and focal fatty change, are of no clinical significance. Others, such as nodular regenerative hyperplasia, hepatocellular adenoma and giant hemangioma, can be manifested by portal hypertension, hemoperitoneum or a hemorrhagic diathesis respectively. Cognizance of the histopathologic criteria for diagnosis, the radiologic features and the varied clinical manifestations are essential for management. The malignant potential of some of the benign tumors is briefly touched upon.

Quantitative pathology is a rapidly growing field of pathology. This field is developing methods allowing greater objectivity and better reproducibility in diagnostic decisions. The introduction of quantitative pathology as a teaching subject in medical education will help this field to become more widely and more correctly applied. Courses on quantitative pathology are organized yearly by the Department of Pathology at the University of Ancona. The 1986 course emphasized training of students in understanding basic problems such as variation caused by tissue processing, instrumentation, data handling and interpretation, and variation between observers. In this paper we describe experiments performed during the course on identification and quantitation of mitoses in malignant glial tumors. The participants, i.e. students of the postgraduate Pathology School, could identify mitoses with a 'substantial' reproducibility. However, when the observers were allowed freely to choose the fields to count, the reproducibility was 'slight'. The study suggests that sampling rules should be applied which secure reproducible application of morphometric method also on condition of free selection of fields. Because the application of such rules needs expertise in histopathology, it seems that morphometric method can best be applied by histopathologists themselves.

Fibrolamellar carcinoma (FLC) of the liver is a clinicopathologic type of hepatocellular carcinoma (HCC) with a favorable prognosis with long-term survival. At variance with the usual HCC, FLC occurs predominantly in young people, both male and female, usually without preexisting liver disease. The distinctive pathologic features of FLC are presented and reviewed. Both gross and microscopic findings suggest that FLC is the malignant counterpart of focal nodular hyperplasia that may arise from preexisting focal nodular hyperplasia. The storage of copper and fibrinogen inside tumor cells is a peculiarity of FLC, and it appears to be in a close relationship with the oncocytic appearance of FLC cells having a deeply eosinophilic, finely granular, mitochondrion-rich cytoplasm. All other immunohistological and ultrastructural findings strongly support the high degree of differentiation of FLC.

First a brief delineation of the general ultrastructural characteristics of the human primary hepatocellular carcinomas (PHCs) is given. This is followed by a detailed survey of the electron microscopic findings concerning the cytoplasmic inclusions, cell junction structures and hepatitis B virus components seen in the PHC cells. Then the ultrastructural features of certain newly recognized subtypes (fibrolamellar, clear-cell types and primary endocrine liver tumor) of PHCs are described. Finally the importance of electron microscopy in the differential diagnostics of the liver tumors and its contribution to our knowledge concerning the morphology and etiopathogenesis of the PHCs are emphasized.