摘要:

We analyzed three Merkel cell carcinomas (MCC), applying comparative genomic hybridization (CGH) with DNA from paraffin‐embedded and cultured tumor material as the probes. By this method, numerous changes in chromosome copy numbers were observed in each tumor investigated. Recurrent gains of chromosomes 1, 6, 18q and 20 were detected in two tumors. A third tumor showed complex chromosomal copy number changes, including gain of chromosome 8 and 9. These gains, as well as gain of chromosome 1 in the first two tumors, were confirmed by fluorescence in situ hybridization to paraffin tissue sections. Our results support the view that important genes for MCC development may be located on chromosomes 1, 6, 18q and 2

ISSN:0303-6987    

DOI:10.1111/j.1600-0560.1996.tb01428.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Two cases of acquired reactive perforating collagenosis with poorly controlled diabetes mellitus were studied by histochemistry and by electron microscopy. In excoriated wounds, the necrotic mass on the bottom of the ulcer contained the collagen bundles which were continuous with the collagen bundles in the reticular layer. In the developing stage, the epidermis regenerated between the necrotic mass and the reticular dermis, and the collagen bundles in the reticular dermis were in continuity with those in the necrotic mass through the epithelial tunnels. The collagen in the epidermal channels did not degenerate ultra‐structurally. In the mature lesion, collagen bundles being eliminated through the epidermis were surrounded by the fibroblasts at the basal cell layer. Collagen fibers were seen in the cytoplasm of these fibroblasts. From these findings, the mechanisms of the formation of the eruption in acquired reactive perforating collagenosis might be as follows: 1) In the developing stage, the regeneration of epidermis progresses between the necrotic mass and the reticular dermis, and among the collagen bundles. As a result, the collagen bundles remain in the channels of the epidermis. And then, 2) the regenerated epidermis makes the thick horny layer. As a result, the necrotic masses are lifted up and the collagen bundles are pulled up from the dermis through the epidermal channel

ISSN:0303-6987    

DOI:10.1111/j.1600-0560.1996.tb01429.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Retinoids are potent cell growth and differentiation modulators, but cellular effects of therapeutic retinoids in psoriasis are unknown. We studied the effects of etretinate on pathological activation of keratinocytes and lymphocytes in patients treated systemically with this agent for 8 weeks. Ten patients with extensive psoriasis vulgaris were treated with etretinate at 0.75 mg/kg for 8 weeks. Skin biopsies obtained before and at 8 weeks of treatment were studied using immunohistochemical markers for keratinocyte proliferation or differentiation and for the presence of T‐lymphocyte subsets or associated inflammatory proteins. During 8 weeks of treatment, the clinical severity decreased by a mean of 64% (p<0.001). Compared to a similar group of patients treated with bath PUVA, psoriatic plaque erythema resolved more slowly and less completely (p<0.05), but improvements in plaque thickness and scale were not significantly different between etretinate and PUVA treatments. Etretinate produced a 44% decrease in epidermal thickness (p<0.001) and a 62% reduction in keratinocyte proliferation (p<0.001) after 8 weeks of treatment. Unexpectedly, keratinocyte differentiation was enhanced following etretinate treatment as indicated by increased filaggrin production, increased number and size of keratohyaline granules, greater abundance of keratin filaments, and increased secretion of intercellular lipids from Odland bodies. The stratum corneum in resolving psoriatic lesions was unusually thin, probably caused by retinoid‐induced shedding of corneocytes. “Regenerative” epidermal growth was maintained during etretinate treatment, as marked by continued expression of keratin 16 and a3‐integrin by suprabasal keratinocytes. Surprisingly, the inflammation‐associated proteins HLA‐DR and ICAM‐1 were no longer produced by epidermal keratinocytes following etretinate treatment, and CD3+, CD8+, and CD25+ T‐lymphocyte subsets were reduced by 50‐65% in lesional tissue (p<0.01). Etretinate shows unexpected anti‐inflammatory and pro‐differentiation actions in psoriasis. Etretinate appears to function as a disease suppressive agent which improves hyperplasia, keratinocyte differentiation and tissue inflammation mediated by c

ISSN:0303-6987    

DOI:10.1111/j.1600-0560.1996.tb01430.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Psoriasis is characterized by immune activation, increased proliferation and abnormal differentiation of keratinocytes. The reported anti‐psoriatic mechanisms of actionin vivoof vitamin D analogues include reduction of keratinocyte proliferation and induction of keratinocyte terminal differentiation.We investigated whether the anti‐psoriatic effect of the natural active vitamin D analogue, calcitriol, applied topically, is due to direct effects on keratinocytes alone or also due to immunoregulatory effects of calcitriol.Psoriasis patients were treated with topical calcitriol (0.005%) and a vehicle control for 8 weeks. Disease activity was assessed by a severity index and quantitative histopathological markers.In vitrostudies of lymphocyte proliferation and gamma interferon secretion and of keratinocyte proliferation complemented the clinicohistopathologic studies.A heterogeneous response to calcitriol treatment could be segregated based upon elimination of K‐16 keratin expression. Calcitriol treatment decreased keratinocyte proliferation, normalized keratinocyte differentiation and decreased immune activation in plaques.The histologic response to vitamin D treatment of psoriasis includes suppression of both immune and keratinocyte activationin situ. These studies provide a basis for rational combination of anti‐psoriatic treatments and for the design of new vitamin D analogues to treat ps

ISSN:0303-6987    

DOI:10.1111/j.1600-0560.1996.tb01431.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Cyclosporin is a very effective treatment for severe psoriasis, but its exact mechanism of action in this disease is not completely understood. It has been hypothesized that the drug could act through (lie inhibition of the expression of certain cell adhesion molecules on the keratinocytes prior to the reduction in the number of epidermal inflammatory cells. Several studies have focused on ICAM‐1 changes on keratinocytes and endothelial cells after cyclosporin treatment in psoriatic patients but their results have been somewhat contradictory. We examined changes in T‐cell markers and adhesion molecules among keratinocytes, enclothelial and inflammatory cells after low‐dose cyclosporin treatment for severe psoriasis.We performed a histological and immunohistochemical study on psoriatic skin among 10 patients (7 males and 3 females; mean age 37 years) treated with low‐dose (2.5 mg/kg/day) cyclosporin, prior to therapy, after 1 month, and after 3 months of treatment. The mean PASI (Psoriasis Area and Severity Index) before treatment was 23±4, 13±7 after the first month of therapy, and 8±2 at the end of the third month of therapy. Pretherapy samples showed a moderate to severe inflammatory infiltrate mainly clue to T‐lymphocytes expressing a T‐cell memory (UCHL‐1) and helper/inducer (CD4) phenotype. Most of these cells also expressed HLA‐DR and LFA‐1 and ICAM‐1 antigens. Alter the treatment, an overall reduction in the degree of epidermal hyperplasia was seen (p=0.01). The severity of the infiltrate was clearly reduced (p=0.05), but no significant changes in the phenotype profile were observed. Although slightly reduced, endothelial ICAM‐1 expression persisted after cyclosporin therapy. Keratinocyte ICAM‐1 expression was uniformly and significantly reduced after 1 month and 3 months of therapy (p=0.01). These results support the hypothesis that cyclosporin interferes with the expression of keratinocyte adhesion molecules

ISSN:0303-6987    

DOI:10.1111/j.1600-0560.1996.tb01432.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Six solitary, dermal or subcutaneous lesions occurring in adult patients are presented. These masses had a circumscribed, lobulated configuration; they were composed of fusiform and epithelioid cells that lacked atypical nuclear features. The pattern of growth featured fascicles and nests, a myxofibrous stroma, and prominent blood vessels with a focally “hemangiopericytoid” appearance. Immunohistochemical analyses showed uniform reactivity for vimentin and alpha isoform‐actin, with negativity for desmin and neural determinants. The overall appearance of the lesions was similar to that of “infantile myofibromastosis,” and corresponded to previous descriptions of “solitary myofibroma(tosis)” in adults. Immunophenotypic and ultra‐structural support exists for a proposed myofibroblastic nature for such proliferations. Differential diagnostic considerations include neurothekeomas, plexiform fibrous histiocytomas, nodular fasciitis, cutaneous inflammatory pseudotumors, dermatomyofibromas, leiomyomas, and other forms of fibromatosis affecting the skin and superfici

ISSN:0303-6987    

DOI:10.1111/j.1600-0560.1996.tb01433.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Infantile myofibromatosis is a distinctive type of fibromatosis that usually develops during the immediate perinatal period. There are variants with solitary and multiple tumors. Lesions confined to the skin, soft tissue, and bone carry a good prognosis, showing spontaneous regression. The prognosis, however, is much less favorable when visceral lesions are present and the outcome may be fatal. Only recently it became obvious that there is an adult counterpart of infantile myofibromatosis, characterized by solitary lesions that have a predilection for involve the dermis and show no tendency to regression, although they have an entirely benign biological behavior. These lesions have been named cutaneous myofibroma or solitary myofibroma of adults.We have studied the clinical, histopathological and immunohistochemical characteristics of 53 examples of cutaneous adult myofibroma. In addition, 2 cases were examined ultrastructurally. The patients were mostly adults with ages ranging from 6‐83 years. The lesions presented as solitary, usually painless nodules of variable duration on the skin, usually located on the extremities. Histopathologically, four patterns were identified: nodular or cellular type, multinodular or biphasic type, leiomyoma‐like or fascicular type, and vascular type. A correlation between the histopathologic pattern and the lesional age was observed: vascular type of cutaneous adult myofibroma in early lesions, nodular and multinodular lesions in fully developed lesions, and leiomyoma‐like or fascicular type in late lesions. Immunohistochemically, the spindle cells were desmin negative, but expressed immunoreactivity for vimentin, pan‐smooth muscle actin, and alpha‐smooth muscle actin. Ultrastructurally, neoplastic cells showed characteristics of undifferenciated mesenchymal cells with features of fibroblasts, myofibroblasts and pericytes. Primitive vascular formations were seen in the form of irregular clefts between adjoining cells.We conclude that cutaneous adult myofibroma is a little‐known benign vascular neoplasm probably derived from m

ISSN:0303-6987    

DOI:10.1111/j.1600-0560.1996.tb01434.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Superficial leiomyosarcomas are rare tumours. The lesions confined to the dermis, contrary to those involving the subcutis, have been reported to carry a favourable prognosis.A retrospective study of 41 consecutive cases of surgically treated intradermal and subcutaneous leiomyosarcomas was undertaken in order to determine the prognostic factors that may influence the survival of these patients. Seven tumours were predominantly intradermal and 34 involved the subcutaneous tissue. Fifty‐four percent of the tumours were located in the lower extremities. All cases stained positively for smooth muscle antigen and 66% for desmin. The tumours were classified with regard to tumour grade I (low grade, 3%), II (intermediate, 12%), IIIA (high grade, 46%) and IIIB (high grade, 39%). In all patients, follow‐up information was available. Mean follow‐up time was 5 years. The patients with intradermal tumours were all alive without signs of recurrence, whereas 14 of those with leiomyosarcomas involving the subcutis have died with pulmonary metastases.Our study confirms that “pure” intradermal leiomyosarcomas independent of tumour grade behave in a benign fashion, probably due to small tumour size. Tumour size ≥ 5 cm, deep localization with fascia involvement, and high malignancy grade (IIIB) were found to deteriorate survival based on a univariate analysis. However, in a multivariate analysis only tumour size was found to be an independent progno

ISSN:0303-6987    

DOI:10.1111/j.1600-0560.1996.tb01435.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Kaposi's sarcoma (KS) is a heterogeneous tumor where spindle cells are predominant and macrophages and factor XIIIa positive dendrocytes are abundant. The origin of the macrophages and dendrocytes is unclear, although their numbers suggest a critical role in KS pathogenesis. To determine if KS macrophages are recruited from the blood stream or proliferate on‐site, we examined biopsy specimens 1) for expression and distribution of vascular adhesion molecules (PECAM‐1, ELAM‐1, ICAM‐1, VCAM‐1, P‐selectin, L‐selectin) and the macrophage‐associated adhesion‐molecule ligand, VLA‐4; 2) for dual expression of proliferation (Ki‐67) and lineage‐associated markers (KP‐1, CD34, factor XIIIa, LCA); and 3) for dual expression of macrophage (KP‐1) and endothelial cell (CD34) associated markers. Avidin‐biotin peroxidase techniques were used. Resident vessels were found to strongly express PECAM‐1, ELAM‐1, ICAM‐1, P‐selectin, and moderately express VCAM‐1 and VLA‐4. Tumor spindle cells showed less intense expression of ELAM‐1, ICAM‐1 and P‐selectin. The most frequent double‐stain combination was Ki‐67+CD34‐K In contrast, the combinations of Ki‐67+KP‐l+, Ki‐67+XIIIa+ and KJ‐67+LCA+ were rarely seen. The enhanced expression of adhesion molecules on resident vessels and the lack of evidence of macrophage proliferation suggest that the a

ISSN:0303-6987    

DOI:10.1111/j.1600-0560.1996.tb01436.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Inflammation and ulceration at the epithelium‐connective tissue interlace, a characteristic of erythema multiforme (EM), may be associated with altered molecular attachment of basal keratinocytes. To determine the expression of basal keratinocyte‐associated integrins and their basement membrane ligands in oral EM, specimens of clinically and microscopically confirmed EM (n=12) and mucosal controls (n=7) were stained immunohistochemically for the integrins α3, β6, β1, and β4 and for extracellular matrix proteins laminin 1, laminin 5, collagen IV, and collagen VII using a standard avidin‐biotin‐peroxidase technique. In EM, results showed increased staining intensity for all integrins studied in basal and suprabasal keratinocytes. Basement membrane‐associated staining of a6 and b4 was intense, but disrupted and fragmented. In EM, integrin staining was most marked at the summit of the connective tissue papillae. Laminin 5 staining was more intense than in controls, was frequently fragmented, and extended into the lamina propria. Laminin 1 staining was discontinuous and was frequently less intense than in controls. Collagen IV staining in EM was interrupted along the basement membrane. Collagen VII staining was fragmented but unchanged in intensity. These alterations in interface adhesion molecules suggest that hemidesmosome‐associated molecules are important in the pathogenesis of EM. The staining intensities and patterns of expression of these adhesion molecules suggest that oral EM is initially focused in the connective

ISSN:0303-6987    

DOI:10.1111/j.1600-0560.1996.tb01437.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY