We report three cases of fundic gland polyposis in the stomach identified in three patients who were related. Grossly the numerous polyps covered an area limited to the body and fundus of the stomach, no polyps were found in the antrum, duodenum, colon, or rectum, and histologically, the gastric lesions consisted of numerous hamartomatous polyps, characterized by proliferation of the fundic and cystic glands. The gastric lesions were identified in families without polyposis coli. This type of fundic gland polyposis has never been documented before in the literature.

We present a undescribed condition in a girl who died at 8 years of hypertrophic cardiomyopathy. Muscle and endomyocardial biopsies disclosed a selective loss of thick filaments ultrastructurally. In muscle biopsy histochemical abnormalities of myofibrillar AT-Pase were confined to type 1 fibres. Gel electrophoresis of muscle homogenate showed no qualitative abnormalities of slow and fast myosin heavy chains (MHC) and light chains, and the amount of the different myosin isozymes was in agreement with histochemical myofibrillar ATPase findings. The pathogenetic mechanisms have not been elucidated in this case but we suspect an abnormality of the beta-cardiac MHC gene, the only gene expressed in the heart and in type 1 skeletal muscle fibres.

Stromal-epithelial interactions as expressed by alpha-smooth muscle actin (alpha-SM actin) collagen type IV, fibronectin, laminin and tenascin were studied in normal and pathological endometrial mucosa. There was complete or incomplete cuffing of scattered endometrial glands by alpha-SM actin mostly in the basal layer of endometrial mucosa and in dilated or cystic glands. Individual adenocarcinomatous glands were not encircled by alpha-SM actin-positive cells. Collagen type IV and laminin were found surrounding all glands irrespective of the presence of periglandular alpha-SM actin. Fibronectin was diffusely present in the stroma. Tenascin was identified, albeit not exclusively, in a periglandular location similar to that of alpha-SM actin. We conclude that the periglandular cells staining for alpha-SM actin, which were negative for cytokeratins, are probably myofibroblasts (MFs). Since this phenomenon was most commonly observed in dilated and cystic glands, we suggest that stromal cells immediately surrounding these glands may be subjected to mechanical or other stress resulting, as in other situations of tissue remodelling, in the development of MFs. This may also explain the appearance of tenascin in the same location. Thus, our finding may represent a further example of the local modulation of stromal cell phenotype, possibly under the action of micro-environmental factors.

In order to clarify the sites of predilection for foamy spheroid bodies (FSBs) their regional distribution was studied in 56 persons (30-98 years) without neurodegenerative diseases. Variable amounts of FSBs were observed in approximately 30% of cases and favoured the rostro-ventral parts of the globus pallidus (GP), including the ventral pallidum, and/or the substantia nigra pars reticulata (SNr). The results strongly suggest that FSBs develop during aging and are a hitherto undescribed pathological hallmark for degeneration of the GP and the SNr.

To elucidate the significance and nature of calcium oxalate crystals in the thyroid, we studied these crystals clinicopathologically and immunohistochemically in 182 normal thyroids from patients autopsied within 5 h of death. Under polarized light, calcium oxalate crystals showed brilliant birefringence and were invariably found within the colloid. The crystals were found in 73.1% of all cases but were more prevalent and denser in older individuals, with the highest prevalence (85.2%) being observed in those over 70 years of age. No crystals were seen in those under 10 years of age. Although underlying diseases seemed to have little influence, post-mortem delay apparently affected the prevalence and density of occurrence since the crystals tended to disappear with hours after death. An immunohistochemical study using anti-thyroid hormone antibodies revealed that the crystals were within negatively or weakly stained colloid and were not common in strongly stained colloid. These findings support the hypothesis that the occurrence of calcium oxalate crystals in normal human thyroid is associated with a low functional state of the thyroid follicles.

Intima formation in vessels, spontaneous or experimentally induced, is generally characterized by the presence of longitudinally oriented smooth muscle cells (LSMC). During an experiment of neo-intima induction in carotid arteries in rabbits, by application of a non-constrictive silastic cuff, a study was performed to investigate the presence of LSMC in the systemic and pulmonary circulations, in both elastic and muscular arteries. Three patterns could be distinguished: intimal cushions in muscular arteries, single or small groups of LSMC in the intima in elastic and larger muscular arteries, and intra-medially located layers or columns of LSMC in the aorta, the pulmonary artery, at the bifurcation of the aorta and around orifices of branches. In order to understand this peculiar orientation a biomechanical approach was used: this showed that near the lumen the circumferential stress is 4.5 times higher than the longitudinal. Because the cell surface of the smooth muscle cells exposed to this stress per unit vessel length is much less in the longitudinal than in the circular direction we conclude that the LSMC align in the direction which allows them to cope most effectively with the mechanical stresses.

The cell-mediated immune reaction was studied in the cutaneous lesion of chromomycosis, using monoclonal antibodies against polymorphonuclear neutrophils, macrophage and lymphocyte subsets, endothelial and fibroblast cells. In addition, immunostaining of the main degradative enzymes (neutrophil elastase and interstitial collagenase) and certain important cytokines (transforming growth factor-beta, tumour necrosis factor-alpha and interferon-gamma) suggested an explanation for the granulomatous reaction and the associated tissue remodelling. The distribution pattern of neutrophils and macrophage subsets, observed by computer-aided image analysis, suggests that the in situ persistence of fungi is the main pathological factor.

The tumour suppressor gene product p53 is believed to play an important role in the progression of human malignant tumours through mutation and over-expression. Using a microwave oven heating method, we have detected over-expression of p53 in buffered-formalin fixed, paraffin-embedded sections of oesophageal carcinomas immunohistochemically and examined the relationship between the p53 over-expression and postoperative survival. Employing a monoclonal antibody (pAb1801), nuclear p53 was detected in 56 of 105 (53%) tumour specimens. Homogeneous, heterogeneous, and focal immunostaining patterns were noted. No immunostaining was found in adjacent benign tissues. The results in buffered-formalin fixed sections were similar to those in the frozen sections. The cumulative survival rate of patients with p53 expression was significantly lower than that of the patients without expression (P < 0.05), even though there were no significant differences between the clinicopathological features of the two groups. The results indicate that the nuclear accumulation of p53 might be an independent prognostic factor in patients with oesophageal squamous cell carcinomas.

We present the first ultrastructural study of liver and spleen from a 20-week fetus with Niemann-Pick disease type C in correlation with lipid studies of these tissues. The lipid storage pattern was characteristic of the disease and although the distribution of the lipid storage was similar to that of affected children, ultrastructural studies emphasized that many inclusions were qualitatively different. These are discussed. Concomitant with this complex lipid storage, ultrastructural evidence of cholestasis was observed and the early hyperplasia of pericanalicular microfilaments leads us to question the presence of a toxic metabolite which might induce cholestasis by acting upon microfilaments.

A case of parachordoma of the left calf in a 19-year-old Chinese female is reported. The tumour showed multinodular growth pattern and consisted of round or oval tumour cells with abundant eosinophilic cytoplasm and myxoid matrix. Tumour cells formed small nests and sometimes showed concentric arrangement. Physaliferous-like cells and undifferentiated spindle cells were occasionally observed among the cell nests. The myxoid matrix was positive for high-iron diamine stain, indicating the presence of chondroitin 4- and 6-sulphates and keratan sulphate. Ultrastructurally, well-developed rough endoplasmic reticulum, abundant intermediate filaments, microvillous cytoplasmic processes, pinocytic vesicles, and desmosome-like junctional structures were found. Tumour cells were positive for S-100 protein and vimentin, but negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and desmin. These results are consistent with the definition of parachordoma as a soft tissue neoplasm consisting of cells with histology and ultrastructure similar to those of chordoma cells but with immunohistochemistry similar to that of chondroid tumour cells.

An ultrastructural study of amyloid deposits in four cases of squamous cell carcinoma of uterine cervix was performed. The amyloid deposits reacted with anti-keratin antiserum on frozen sections. Amyloid deposits showed nodular (4 cases) and star-like forms (3 cases). Nodular amyloid deposits were composed of slightly whorled fibrils, measuring 7-10 nm in width. Some of them contained cellular debris and thicker, more electron-dense filaments than amyloid fibrils. In three cases, filamentous tumour cells and filamentous masses were observed together with amyloid. Star-like amyloid deposits were composed of bundles of straight amyloid fibrils. Some of the tumour cells in contact with star-like amyloid deposits had deep cytoplasmic invaginations, where closely packed amyloid fibrils were arrayed in parallel fashion. In addition, a few tumour cells had membrane-bound amyloid fibrils in the cytoplasm. It is suggested that nodular amyloid deposits are derived from the tumour cells through filamentous degeneration. Amyloid fibrils in star-like amyloid deposits are thought to be formed within the cytoplasm or in the vicinity of invaginated cytoplasmic membranes of the tumour cells.

Renal cell carcinoma is known to metastasize early independent of tumour grade. Invasion of the renal vein plays an important role in the prognosis. Cell adhesion molecules have been investigated, including the expression of alpha-2, alpha-5, and alpha-6 integrin, E-cadherin, neural-cell adhesion molecule and CD-44 in 34 renal cell carcinomas, using the alkaline phosphatase-anti-alkaline phosphatase technique. Our results indicate a differential expression of these cell adhesion molecules (alpha-2, alpha-5 and E-cadherin) depending on histological type and tumour grade.

Papillary cystic tumour (PCT) is a rare, low-grade malignant pancreatic neoplasm, in which the histological criteria for malignancy are still uncertain. We performed a histological examination of 3 metastasizing PCTs, while comparing them with 18 non-metastasizing PCTs, using a computed image analyser. The mean maximum nuclear diameter, the mean standard deviation (SD) of the nuclear diameter, the mean nuclear area and the nuclear-nonnuclear (N/NN) ratio obtained by the image analyser of the metastasizing PCTs (7.23 microns, 2.21 microns, 30.45 microns2, 36.41%) were all significantly larger than those of the non-metastasizing PCT (6.34 microns, 1.59 microns, 23.66 microns2, 23.74%; P < 0.005, P < 0.005, P < 0.005, P < 0.001 respectively). However, there were no statistical differences in either the nuclear ellipsoidity or nuclear regularity. These results suggested that nuclear morphometry might be a useful parameter to define metastatic potential, in addition to histological variables such as venous invasion, nuclear grade and mitotic rate.

beta 1 Integrins were examined immunohistochemically in normal and mastopathic mammary glands, 12 benign tumours and 90 carcinomas of the breast using monoclonal antibodies against beta 1 and alpha 1 to alpha 6 subunits. When compared with epithelial cells of non-neoplastic mammary glands and of benign tumours, carcinoma cells showed considerable quantitative changes in the pattern of alpha 2, alpha 3 and alpha 6 subunit expression. In contrast, the distribution pattern of beta 1, alpha 1, alpha 4 and alpha 5 antigens corresponded to the situation observed in non-neoplastic mammary gland epithelium in most instances. An abnormal expression of alpha 2 was found in 71.0% of the carcinomas ranging from a remarkably low number of alpha 2-positive tumour cells in 27.5% of the cases to a complete absence of the alpha 2 molecule in 43.5% of the carcinomas. Of the carcinomas 39.9% exhibited quantitative changes in alpha 3 expression with an abnormally low content of alpha 3-positive neoplastic cells in 15.4% and a complete absence of this molecule in 24.5% of the cases. Expression of alpha 6 was abnormal in 73.2% of the carcinomas, consisting in a greater number of alpha 6-negative tumour cells in 31.9% and in a complete absence of alpha 6 in 41.3% of the tumours. The abnormally low expression/absence of alpha 2 and alpha 3 subunits correlated with oestrogen receptor negativity (P < 0.033 and P < 0.04, respectively). In addition, abnormally low expression/absence of alpha 2 correlated with poor differentiation of the tumours (P < 0.014). The quantitative changes in the expression pattern of beta 1-associated alpha subunits in breast carcinomas may cause a disturbed cell-cell and/or cell-matrix interaction that increases the invasive and migratory property of the tumour cells.