Morphological aspects of basement-membranes and their receptors in benign and malignant neoplasms (review).

We review the current knowledge on alterations of the major basement membrane (BM) components and their cellular integrin receptors in benign and malignant tumors of epithelial and mesenchymal origin. While benign tumors usually exhibit a continous BM, recent analyses provide evidence that invasive growth of carcinomas coincides with (a) a loss in a proper BM, (b) changes in the type of integrin receptor expression and (c) the retained ability of certain tumor cells to synthesize matrix components. This latter aspect has been regarded as a potentially beneficial 'host' mechanism against invasive growth. This assumption is strongly supported by the finding of a positive correlation between the extent of BM loss and both a lesser degree of tumor differentiation and a worse prognosis of tumor growth. The resulting concept indicates that in carcinomas an imbalance in the cell-matrix interaction is the leading element in invasive growth. In mesenchymal tumors a somewhat different role of the BM can be observed. Thus, the qualitative and quantitative expression of major BM components in benign mesenchymal tumors closely relates to the BM pattern of normal tissues providing a histogenetically oriented classification of benign mesenchymal tumors. Most well-differentiated sarcomas retain a BM pattern close to that of the histogenetically related tissue, although in poorly differentiated sarcomas no such attribution to a histogenetic orientation of the tumor cells can be found.

Basement membrane components as differential markers for mesenchymal tumors of various origin.

We immunohistochemically analyzed the presence or absence of a pericellular basement membrane in benign and malignant soft tissue tumors of different origin--of peripheral nerve, smooth and striated muscle, fat tissue, connective tissue, blood and lymph vessels, cartilage and bone--to test the role of the expression of the BM components collagen IV, laminin, heparan sulfate proteoglycan (HSPG) and fibronectin as a differential diagnostic aid. All benign tumors revealed a BM feature corresponding to that of the normal tissue. Well differentiated sarcomas similarly showed a BM pattern close to that of the respective normal mesenchymal cells, so that these sarcomas were attributable to different histogenetic entities. Low differentiated sarcomas preserved in some, but not all, instances a typical BM pattern as well. Since the BM expression in most sarcomas of lesser degree of differentiation shows a distinctive BM pattern, we believe that the BM analysis of soft tissue sarcomas may be useful to establish a proper histogenetic classification of mesenchymal tumors.

Multiple intestinal stenoses and peripheral gangrene: a combination of two rare surgical complications in a child with Kawasaki disease.

Kawasaki disease (KD) often presents with a challenging variety of clinical symptoms. Severe gastrointestinal complications are rare and mainly appear as pseudo-obstruction. However, the authors report the unique case of a 4-month-old girl with KD suffering from a mechanical ileus. The optimal timing of surgery presented a dilemma, because she received lytic treatment for gangrenes of both her hands and feet and additionally had large coronary artery aneurysms. Finally laparotomy had to be performed while the patient was on an anticoagulant medication, and it showed a 30-cm-long jejunal segment with multiple filiforme stenoses, requiring resection and anastomosis. The postoperative course was uneventful regarding the abdominal situation; however, the left hand and left foot remained gangrenous and had to be amputated. In patients with KD, not only pseudo-obstruction, but irreversible intestinal obliteration has to be encountered. This combination of intestinal stenosis and acral gangrene has not been described before. J Pediatr Surg 36:651-653.

[Melanoma inhibitory activity (MIA). Evaluation of a new tumor-associated antigen as a serum marker for uveal melanomas]. / Melanoma inhibitory activity (MIA). Evaluierung eines neuen tumorassoziierten Antigens als Serummarker für uveale Melanome.

BACKGROUND: Currently no serological marker for the monitoring of uveal melanoma and its metastases is available. The novel tumor associated antigen Melanoma inhibitory activity (MIA) is expressed in the uveal melanoma and it's metastatic lesions. METHOD: We report about the serum samples of 38 patients with uveal melanomas. 4 of these patients had overt metastatic disease. A nonradioactive one step ELISA was used to quantify the MIA serum levels. RESULTS: In the 34 patients without overt metastatic disease the serum concentration of MIA was mean (+/- 1 SD) 3.6 +/- 1.0 ng/ml. In the 4 patients with overt metastatic disease the serum concentration of MIA was mean (+/- 1 SD) 27.7 +/- 3.0 ng/ml. The difference was statistically highly significant (student t test: p = 0.0001). CONCLUSION: MIA is expressed in primary and metastatic lesions of uveal melanomas. The elevation of MIA serum levels in patients with metastatic disease from melanomas suggests a promising role as a serum marker for monitoring patients with uveal melanoma.

[Cultivated keratinocytes on micro-carriers: in vitro studies of a new carrier system]. / Kultivierte Keratinozyten auf Microcarriern: In-vitro-Untersuchungen zu einem neuartigen Trägersystem.

Epidermal grafts from confluently cultivated keratinocytes have been used since the early eighties for the treatment of severe burns, where the shortage of donor sites for split-thickness skin grafts did not allow for adequate wound coverage. The difficult handling of these grafts as well as the advanced differentiation of their epithelial cells into a multilayer sheet poses a problem for their clinical application. The aim of the study was to characterize cultivated keratinocytes, as well as to observe their migration and proliferation from the MC onto a surface. Keratinocytes were isolated from human foreskin and cultivated in serum-free and serum-containing medium according to a modified method by Rheinwald and Green. Collagen-coated Dextran beads were used as MC. The MC were colonized with keratinocytes using the Spinner culture technique. After seeding the colonized MC into culture flasks, their migration and proliferation was monitored regularly through immunohistochemical studies and measurement of the metabolic cell activity. Immunohistological staining proved that the cells isolated from human foreskin represent keratinocytes of the basal type. Keratinocytes, cultivated with serum-containing and serum free medium, both adhered to the surface of the MC, then migrated onto the surface of the flasks and proliferated to form a multilayer of epithelial cells. In the long-term, a flexible epithelial graft consisting of poorly differentiated keratinocytes should be available, which is simple to produce and easy to handle. This would be an alternative method for treating wounds, where the conventional multilayer epithelial graft (ET) is insufficient.

Perforation of the colon: a rare complication of hepatocellular carcinoma.

Direct infiltration of the colon by hepatocellular carcinoma (HCC) is a rare condition. Only a few reports can be found in the literature. Here we present a case of direct infiltration of the ascending colon by an exophytic growing HCC of the right posterior liver lobe, in which treatment with transarterial chemoembolization (TACE) had been performed. Tumor invasion became evident by abdominal pain and lower gastrointestinal bleeding. Diagnosis was established by contrast-enhanced multidetector computed tomography (CE-MDCT), demonstrating the direct tumor invasion with concomitant perforation of the infiltrated colon segment. Based on these findings, rapid and effective surgical treatment could be achieved.

Comparison of various basement membrane components in benign and malignant peripheral nerve tumours.

Immunohistochemical methods were used to analyse benign and malignant tumours of peripheral nerve tissue. We tested for the distribution of basement membrane (BM) components collagen IV, laminin, heparan sulphate proteoglycan, fibronectin, for S100 protein and for the presence of interstitial collagens III and V. Laminin was generally noted in association with Schwann cells, but collagen IV occurred with perineural cells. When tested for BM components, fibroblasts were notably non-reactive except for fibronectin. Three specific area-dependent BM patterns were observed in the benign tumours: (a) Schwann cell-like, in fascicular areas (Antoni A areas of schwannoma, central fibrous bundles of plexiform neurofibromas and central areas of cutaneous neurofibroma), (b) perineural cell-like (capsular structures of schwannoma) and (c) fibroblast-like (myxoid and fibrously transformed areas). Most malignant tissues showed a variably fragmentary focal deposition of laminin. Other BM components were present only in well-differentiated areas. Poorly differentiated tumours demonstrated fibronectin reactivity alone. Our results provide evidence that the specific staining pattern for BM components helps to differentiate the various cellular proliferations in neurogenic tumours. Schwann cells are not only distinguishable from perineural cells by S100 protein staining, but also by their specific BM staining. In addition, perineural cells can be separated from fibroblasts, which do not express BM material. The "tropism" of laminin in normal nerves and benign neural tumours--which persists in neurogenic sarcomas--indicates preferential Schwann cell differentiation in these cells.

Distribution of basement membrane components in normal adipose tissue and in benign and malignant tumors of lipomatous origin.

Normal adipose tissue as well as 13 benign and 17 malignant lipomatous tumors (lipomas, hibernomas, lipoblastomas, and liposarcomas) were immunohistochemically analyzed for their expression of the basement membrane components collagen IV, laminin, heparan sulfate proteoglycan, and fibronectin. Monovacuolar cells in normal white fat tissue and in lipomas generally exhibited a distinctive pericellular basement membrane composed of collagen IV and laminin, whereas heparan sulfate proteoglycan and fibronectin were almost completely missing. In brown fat tissue and hibernomas the characteristic multivacuolated cells differed from the monovacuolated white fat cells by the additional content of heparan sulfate proteoglycan and fibronectin and the more intensive staining for the other components tested. In contrast, multi-/monovacuolated cells in lipoblastomas exhibited no characteristic immunohistochemical feature because they reacted irregularly and only faintly for collagen IV, laminin, and heparan sulfate proteoglycan. Spindle cell areas in benign lipomatous tumors displayed more fibronectin than laminin and heparan sulfate proteoglycan indicating a "preadipose" fibroblast-like cellular differentiation. In liposarcomas, only well-differentiated lipoma-like neoplasms revealed a basement membrane pattern resembling that of white fat tissue. Otherwise, in nonlipoma-like liposarcomas, a marked decrease particularly of collagen IV staining was evident. Poorly differentiated liposarcomas mostly failed to express any of the basement membrane components, but showed a relative increase of fibronectin. Our results provide evidence that the staining pattern of basement membrane components parallels the histogenetic derivation of benign lipomatous tumors from either brown or white adipose tissue and, additionally, may reflect such a derivation in liposarcomas.

Congenital alveolar capillary dysplasia: rare cause of persistent pulmonary hypertension.

We report on a rare case of fatal congenital alveolar capillary dysplasia. The newborn boy of a 37 weeks' normal gestation suffered from persistent pulmonary hypertension without any cardiovascular malformation and died at the age of 4 weeks despite intensive treatment. The autopsy tissue was examined histologically, immunohistochemically, and ultrastructurally. Moreover, a three-dimensional tissue reconstruction based on serial sections was performed comparing the affected lung with normal lung tissue. We observed a unique pattern of pulmonary dysplasia: An extreme decrease of capillaries was localized centrally within thickened intra-acinar septa instead of capillaries intensely neighboring pneumocytes; ectatic veins normally running in the interlobular septa were found to accompany intralobular bronchovascular bundles, denying a clear distinction between pulmonary and bronchial veins; small muscular pulmonary arteries extended to the precapillary level and type 2 pneumocytes exceeded by far the type 1 pneumocytes, inverting the normal ratio. In summary, alveolar capillary dysplasia is assumed to be a primary capillary disorder of unknown origin, which possibly involves the regular differentiation of pneumocytes, according to the close alveolocapillary relationship during pulmonary ontogenesis. We consider the venous alterations as being part of the dysplasia, whereas the arterial phenomena might occur secondarily. Recent reports on affected siblings suggest a genetic component of pathogenesis.

Age-related changes of the glenoid labrum in normal shoulders.

A growing number of labral changes are described in the literature. The purpose of this study was to evaluate the glenoid and labrum of normal shoulders at different ages and characterize any apparent age-dependent changes. We analyzed 32 normal cadaveric shoulders with a mean age of 57 years (range, 18-89 years). There were 22 male and 10 female cadavers, with 14 right and 18 left specimens. The shoulders were studied macroscopically, histologically, and radiologically. The radiologic evaluation consisted of an analysis of the subchondral mineralization of the glenoid with the use of computed tomographic osteoabsorptiometry. Macroscopically, there were no statistically significant differences among the age groups. Histopathologically, the labrum showed a significant qualitative and quantitative increase (P <.01) in lesions across all regions with increasing age. In younger individuals, lesions at the 12-o'clock position were the most prevalent, with the incidence increasing with age. The anterosuperior position was the region with the next highest prevalence. This was also the area of the highest stress distribution on the glenoid. Our studies demonstrated clear histopathologic changes of the glenoid labrum that are significantly age-related at specific sites. The earliest changes are seen close to the area of highest stress distribution of the glenoid, which could explain the progressive labral changes with increasing age. Arthroscopically detected changes of the glenoid labrum should be evaluated in the context of age-related changes in normal shoulders.