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Thirty-six lesions in six patients who died from cerebral Aspergillus infection after bone marrow transplantation (BMT) were studied with regard to signal intensity, contrast enhancement, size, and location. The diagnosis was confirmed in all cases by autopsy. Retrospective correlation of histopathological and radiological findings was possible for 14 lesions. Most of the lesions (22/36) had isointense to low signal intensity on T2-weighted images (T2WI). Histopathologically, hemorrhagic necrosis was determined in three of them. Areas of high signal intensity on T1-weighted images (T1WI) were related to gross hemorrhage. Two infarctions showed intravascular accumulation of fungal hyphae with secondary thrombosis of the vessel. The remaining 12 lesions had high signal intensity on T2WI and low on T1WI. Histopathologically, four were infectious and four were unspecific demyelinated lesions. In conclusion, cerebral aspergillosis typically presented with large lesions showing isointense to low signal intensity on T2WI that could have areas of high signal on T1WI. Contrast enhancement was only visible in 15 lesions, and the predominant locations were the subcortical white matter, the cerebellum, and the basal ganglia. Small lesions with high signal on T2WI and low signal on T1WI could not necessarily be related to Aspergillus infection.

Cadherins are a family of glycoproteins that are associated with cell adhesion mechanisms. They are divided into subclasses. The E- and P-cadherins are regarded as the epithelial subtype. Their expression has been demonstrated in many different carcinoma types. Using immunomorphological techniques, we studied the expression of E-cadherin in a series of 145 human brain tumours with the monoclonal antibody 5H9. Western blot analysis was used to confirm the immunohistochemical data. The tumour types represented were astrocytoma WHO I (n = 7), astrocytoma WHO II (n = 6), astrocytoma WHO III (n = 14), glioblastoma WHO IV (n = 8), oligodendroglioma WHO II (n = 5), ependymoma WHO II (n = 5), choroid plexus papilloma WHO I (n = 5), pineoblastoma WHO IV (n = 5), medulloblastoma WHO IV (n = 5), neurinoma WHO I (n = 5), meningioma WHO I and WHO III (n = 75) and pituitary adenoma WHO I (n = 5). Only choroid plexus papillomas (5/5) and meningiomas showed E-cadherin expression. In benign meningiomas (n = 45; 100%), positive E-cadherin immunoreactivity was found regardless of the histomorphological subtype. E-Cadherin was also expressed in 21 WHO I meningiomas (100%) invading dura, bone, brain, and muscle. In contrast, E-cadherin was absent from the majority of morphologically malignant meningiomas (6/9, 66.6%). In addition, in recurrent meningiomas (n = 9), E-cadherin expression in the recurrent tumours was identical to that in the primary neoplasm except in cases with malignant progression, where the malignant recurrent tumour was E-cadherin negative. In 2 cases of metastasizing meningiomas, no E-cadherin immunoreactivity was found in the primary tumours or their metastases.

The monoclonal antibody HMB45 is used to detect an epitope specific for melanocytes, malignant melanomas and melanoma metastases. Using the PAP method, we observed consistent expression of HMB45 in 19 metastases of melanotic and amelanotic malignant melanomas of the central nervous system, while metastases of 32 adenocarcinomas, 10 squamous cell and 8 small cell carcinomas were negative except for 2 cases of breast cancer. Differential diagnosis between cancer and melanoma metastases can be made using cytokeratins as an additional immunocytochemical marker protein. Ten meningeomas and 5 pineocytomas were also negative. Even though it is not absolutely specific, we consider the HMB45 immunoreaction diagnostic for a metastasis of a malignant melanoma if the tumour is cytokeratin negative and HMB45 positive in a large number of tumour cells.

The development of human cancer is a multistep process that entails a progressively more malignant phenotype through the evolution of cellular subsets with increasing numbers of genetic alterations. Here we review the molecular genetics of human cancer predisposition and progression and describe paradigmatic cancer types and cancer syndromes. We also briefly consider the future impact of molecular biology on cancer diagnosis and treatment.

Concanavalin A (Con A) acceptors have been demonstrated in large differentiated neurons in a previous paper. In order to elucidate the correlation between Con A binding in normal and neoplastic neurons and lectin binding dependence upon the differentiation grade, 26 tumours of the neuronal series were examined using formalin fixed and paraffin embedded biopsy specimen. The neoplasms included 3 gangliocytomas, 7 gangliogliomas, 1 central neuroblastoma, 11 medulloblastomas, 2 retinoblastomas, and 2 sympathicoblastomas. Well differentiated neurons in gangliocytomas and gangliogliomas expressed a high intracytoplasmic Con A acceptor density comparable to the feature in large non-neoplastic neurons. Less differentiated neurons and neuroblasts showed a weak perinuclear fine granular binding or an absolute lack of binding molecules, respectively. Our results suggest that in a variety of tumours, Concanavalin A receptor density in neurons depends upon the degree of differentiation of the cell. Well differentiated cells have a higher density than poorly differentiated neoplastic neurons.

Peanut lectin (PNL) binding to a total of 13 granular cell tumours was examined by means of the peroxidase antiperoxidase technique. The tumours included six tumourettes of the neurohypophysis, one malignant granular cell tumour of the brain, and six peripheral tumours of distinct locations. Every tumour studied showed intracytoplasmic fine granular PNL binding; after pretreatment with neuraminidase, the weakly positive reaction was enhanced to a great extent. In all tumours simultaneous examination for the detection of lysozyme and glial fibrillary acidic protein (GFAP) was also carried out. Lysozyme was negative in all cases, whereas GFAP expression could be demonstrated at the periphery of the malignant granular cell tumour of the brain. The data presented clearly demonstrate that PNL can be used as a histochemical marker for granular cells regardless of their location. The fact that the presence of lysozyme could not be proved does not support the view of a histiocytic origin for granular cells, whereas the expression of GFAP in some immature granular cells of the brain tumour examined is considered to be an argument in favor of its glial origin.

We have correlated the light-microscopic features in the unmyelinated hypothalamus with gonadal atrophy in 15 women of 30-111 years of age and in 7 men between 29 and 82 years. In the postmenstrual cases there is a distinct concordance of gonadal atrophy and the manifestation of nucleolar changes (augmentation, multiplication and vacuolization) in many nerve cells of the arcuate and subventricular nuclei. In younger, still fertile women this nucleolar finding was seen only rarely and sporadically, was limited to the arcuate nucleus and was absent in the subventricular nucleus. We interpret this nucleolar finding as a feedback effect. In man, too, this coincidence is obvious with age and in gonadal atrophy, with fewer nucleolar changes in old age than are seen in women. This difference is probably caused by a more rapid drop of the estradiol than of the testosterone level. - The hypertrophy of the subventricular nucleus (Sheehan and Kovacs) was also observed in our postmenstrual cases.

Ten tumours of tonsillar or epipharyngeal localization showing the histological picture of "lymphoepithelial carcinoma" (Schmincke 1921) were examined immunohistochemically using Peanut lectin, Ulex europaeus lectin-I and an antiserum to S-100 protein. The findings suggest a close relationship of this type of carcinoma to the normal tonsillar crypt epithelium. The majority of tumour cells are UEA-I-positive and PNL-negative, as is the crypt epithelium, while oral mucosa is both PNL- and to a lesser extent UEA-I-reactive. Tumour areas expressing this pattern contain a large number of asteroid-shaped PNL-positive histiocytes and arachnoid-shaped histiocytes reacting with anti-S-100 protein; both cell types being probably identical and representing typical elements of the normal tonsillar crypt epithelium. Consequently, the WHO-term "nasopharyngeal carcinoma, undifferentiated type" seems to be inadequate for this type of tumour.

The distribution of selective cytokeratin polypeptides, vimentin, and glial fibrillary protein (GFP) in 5 human cystadenolymphomas of the parotid gland was compared with normal human parotid (n = 5) and submandibular (n = 4) glands using a panel of monoclonal antibodies against diverse and selective cytokeratin polypeptides, vimentin and glial fibrillary protein (GFP). A biotinstreptavidin method was used on cryostat sections. The immunocytochemical finding of identical cytokeratin polypeptides Nos. 7, 8, 18 and 19 and basal cells selectively labeled by the monoclonal antibody KS 8.58, in both the epithelial part of the cystadenolymphomas and in the duct epithelium of the parotid gland, confirms the hypothesis that the epithelial compartment of cystadenolymphomas is derived from the duct system. The triple expression of cytokeratin, vimentin and GFP in myoepithelial cells of the parotid gland is discussed.

Synaptophysin is an acidic, integral membrane glycoprotein (Mr 38,000) of presynaptic vesicles in various neurons and neuroendocrine cells, and in tumours derived from such cells. By indirect immunofluorescence microscopy of cryostat sections, using the monoclonal antibody SY 38 to synaptophysin, a consistent positive immunoreactivity was observed in all medulloblastomas (n = 6) and neuroblastomas (n = 3) as well as a ganglioneuroma and a glioneuronal hamartoma. The presence of synaptophysin in medulloblastomas was confirmed biochemically by immunoblotting experiments. For purpose of comparison, the expression of intermediate-sized filament (IF) proteins was also examined. While neurofilament proteins were consistently expressed in the neuroblastomas (3/3), the ganglioneuroma and the glioneuronal hamartoma, IF distribution in medulloblastomas was variable. A neurofilament-positive type of tumour (1/6) could be distinguished from vimentin-expressing neoplasms (4/6) by immunocytochemistry. These data indicate that synaptophysin is a reliable marker for medulloblastomas as well as other differentiated and undifferentiated neuronal tumours and in this respect is superior to the more heterogeneous expression patterns of IF proteins in these tumours.

The expression of intermediate-sized filaments (IF) was examined by immunocytochemical methods in 40 primary renal cell carcinomas and compared with the IF distribution in the normal adult human kidney. All tumours stained positively with cytokeratin IF antibodies. Co-expression of cytokeratins and vimentin was observed in 21/40 (52,5%) renal carcinomas. Double immunofluorescence labelling demonstrated that in most of these cases tumour cells contained both cytokeratin and vimentin type IF. In normal human kidneys, cells of the various tubular segments disclosed a positive reaction with cytokeratin antibodies in a different intensity and intracellular localization. Co-expression of cytokeratin and vimentin IF in normal adult human kidneys has never been observed. From a histogenetic point of view, co-expression of cytokeratins and vimentin in renal cell carcinoma obviously represents an atavistic phenomenon since vimentin is re-expressed by these tumour cells during neoplastic transformation. This finding indicates the metanephric origin of the renal parenchyma. In surgical pathology the possibility of very rare co-expression of cytokeratin and vimentin IF within tumour cells should be considered, particularly in the differential diagnosis of clear cell carcinomas.