[Scientific medicine and alternative medicine--are we failing to communicate?].
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Complementary Therapies↗
Biomedical subjects
J Smolle
Publications and source records attributed to J Smolle.
Pathology of tumor-stroma interaction in melanoma metastatic to the skin.
Tumor invasion and metastasis formation largely depend on tumor-stroma interaction. In the present study morphological correlates of tumor-stroma interaction were examined in 344 melanoma lesions metastatic to the skin. In particular, the presence of simple infiltration into the surrounding dermis or subcutis without evident stromal reaction, the incorporation of pre-existent dermal collagen or subcutaneous fat cells into the tumor bulk, and the formation of a peritumoral capsule or intratumoral fibrous septa were evaluated. Our results showed that simple infiltration into the surrounding tissue as well as the incorporation of pre-existent stroma tissue without destruction is associated with poor outcome, whereas capsule and fibrous septa are favorable prognostic signs, particularly in subcutaneous lesions. Remarkably, simple infiltration is a prognostic indicator independent of the location of the metastasis (locoregional or distant), as shown by multivariate analysis. These data indicate that morphological aspects of tumor-stroma interaction in metastatic skin lesions of melanoma may reflect biological behavior of the tumor cells, may facilitate a pathological subclassification of metastatic melanoma in addition to clinical data, and are directly related to the patient's outcome.
Adult↗
Computer simulations of histologic patterns in melanoma using a cellular automaton provide correlations with prognosis.
Computer simulations have been used frequently in the life sciences to investigate the mechanisms of morphologic pattern formation. The cellular automaton program SMN5 is designed to simulate tumor growth and to estimate biologic properties by comparing real tumor patterns with computer-simulated reference patterns. This method was applied to 195 cases of primary melanoma of the skin. S-100-stained sections were evaluated by image analysis and compared statistically to a reference set of 4000 simulated patterns. Estimates of tumor cell proliferation, motility, cell loss, cohesion, stroma destruction, and intercellular signals (autocrine and paracrine factors affecting growth, motility, and cell loss) were calculated. Twelve of 18 estimated parameters correlated significantly with tumor progression, as indicated by vertical tumor thickness (linear regression analysis: p < or = 0.05), and 13 of 18 parameters carried prognostic significance (log rank test: p < or = 0.05). Poor prognosis was associated particularly with a pronounced increase in the estimates of proliferation, tumor cell motility, and stromal degradation. Poor prognosis was also associated with a decrease in the estimates of cell loss, tumor cell cohesion, and paracrine growth factor dependence. In multivariate analysis using Cox's proportional hazard model, stromal degradation and motility showed prognostic information in addition to conventional prognostic parameters. The study shows that analytical comparison of real tumors with computer-simulated patterns of a cellular automaton facilitates a functional interpretation of tumor morphology, which carries prognostic significance in cutaneous melanoma.
Computer Simulation↗
Ultraviolet irradiation induces acute changes in melanocytic nevi.
Ultraviolet (UV) light represents one of the factors that might play a role in the initiation and promotion of malignant transformation of human melanocytes. To determine the short-term effects of UV irradiation on melanocytic nevi in vivo, we investigated one half of symmetric melanocytic nevi after a single UV exposure with double the patient's minimal erythema dose. This half was compared with the nonirradiated, shielded half of the same nevus. The different parts were examined histologically for differences and immunohistochemically for the presence of HMB-45 antigen and proliferating cell nuclear antigen. The features were assessed quantitatively by image analysis. One week after the single UV irradiation, we observed a significant increase of suprabasally located melanocytes and a markedly enhanced expression of HMB-45, whereas proliferative activity of the cells was unchanged. In nevi that were excised 2 or 3 weeks after irradiation, no significant differences were observed between the irradiated and the nonirradiated part. The results indicate that a single UV irradiation may induce transient melanocytic activation with morphologic and histologic changes. Although these data do not formally assess resemblance to melanoma, these changes may be similar to those of melanoma in situ.
Adolescent↗
Multinucleate cell angiohistiocytoma: treatment with argon laser.
Multinucleate cell angiohistiocytoma mainly affects middle-aged women, and usually presents as grouped reddish-brown papules. Histopathological features include the presence of multinucleate cells in the reticular dermis, and numerous dilated dermal vessels. The lesions are benign, and may persist for years. Treatment is needed for cosmetic reasons. We report the successful use of the argon laser to treat two patients who had multinucleate cell angiohistiocytoma.
Adult↗
Confocal laser scanning microscopy: a new optical microscopic technique for applications in pathology and dermatology.
Confocal laser scanning microscopy (CLSM) is a new optical microscopic technique, which offers significant advantages over conventional microscopy. CLSM is microscopy of optical sections. Light, which is emitted from regions other than the focal plane, is cut off by introducing a diaphragm in the beam path. The result is an optical "slice", which shows more details because the blurring from out of focus haze disappears. It has been repeatedly used in experimental, but also in diagnostic dermatopathology. The "in vivo" confocal microscopy, applied directly to the intact skin provides details of living cells in the superficial layers comparable to that of fixed and stained tissue. While the extent of its future applications is hard to predict, its potential for applications in dermatology appears enormous, particularly for studies of fixed or living tissues, where it is desirable to obtain clear images many micrometers below the surface of the tissue under examination.
Animals↗
Approach to diagnostic image analysis of melanocytic tumors.
Numerous attempts have been made to apply image analysis in dermatopathology. The technics used comprise measurement of nuclear size, shape, chromatin content, and texture, evaluation of immunohistological slides, assessment of proliferation, pattern analysis, and tumor volume estimation. For commonly accepted routine use, however, image analysis research has to be extended to large numbers of cases, using straightforward and reproducible measuring procedures, and to the development of ready-to-use equipment for specific tasks. In this way, image analysis in dermatopathology might supply useful diagnostic tools in addition to conventional microscopy, and may increase our understanding of morphology as a whole.
Diagnosis, Differential↗
Diagnostic reliability of dermoscopic criteria for detecting malignant melanoma.
BACKGROUND: Recently a new standardized terminology in dermoscopy has been provided by a Consensus Meeting held by the Committee on Analytical Morphology of the Arbeitsgemeinschaft Dermatologische Forschung in Hamburg in order to be applied to further studies in this field. OBJECTIVE: In this study on 159 pigmented skin tumors including 65 melanomas, the validity of various dermoscopic criteria proposed by the Consensus Meeting for detecting melanoma was evaluated. METHODS: In each lesion, a detailed clinical and dermoscopic examination, photographic documentation of the clinical and dermoscopic appearance, surgical excision and histopathologic evaluation were performed. Statistical analyses including chi 2 statistics, logistic regression analysis and CART (classification and regression tree) analysis were applied. RESULTS: The diagnosis of melanoma using dermoscopy could be obtained easily, if combinations of the following criteria were observed: whitish veil, pigment network alterations (e.g. irregular pigment network, narrow pigment network, broad pigment network), irregular extensions, black dots and gray-blue areas. Interestingly, however, clinical and dermoscopic examination to detect melanomas yielded the same results, namely a sensitivity of 94%. The combined use of both methods led to an increase in the diagnostic sensitivity of 95%, whereas the combination of clinical and dermoscopic examination with logistic regression analysis of dermoscopic criteria enabled us to detect all 65 melanomas in our data set, thus providing a sensitivity of 100%. Furthermore, an algorithm for the classification of melanoma based on the evaluation of dermoscopic criteria has been constructed by CART analysis showing that the presence of a whitish veil in combination with a pigment network inevitably indicates melanoma. CONCLUSION: The validity of the various dermoscopic criteria set forth by the Consensus Meeting could be demonstrated as some criteria (e.g. whitish veil, irregular pigment network, irregular extensions) were observed with a significant higher frequency in melanomas.
Algorithms↗
[Skin symptoms in extracutaneous lymphomas, leukemias and plasmacytomas].
In neoplastic diseases of the haemopoietic and the lymphatic system, the skin may be infiltrated specifically by neoplastic cells or may display 'nonspecific' cutaneous reactions, frequently associated with a systemic malignancy. Acute febrile neutrophilic dermatosis associated with myeloproliferative disorders and scleromyxedema, lichen myxedematosus, diffuse plane xanthomas and necrobiotic xanthogranuloma associated with paraproteinemia may serve as examples. These conditions as well as several other, often atypical cutaneous manifestations should rise suspicion as to the potential presence of some underlying systemic neoplastic disorder.
Humans↗
[Retinoids in chemoprevention of tumors of the skin and mucous membranes. Theoretical principles and practical applications].
Chemoprevention, the use of drugs to prevent invasive neoplasia, has gained increasing significance in recent years. Especially for the skin, chemoprevention will become of importance, because large areas of the skin are exposed to environmental carcinogenic factors. Furthermore, many skin diseases predispose to the development of multiple skin tumors. One group of chemopreventive agents are the retinoids, which are effective modulators of cell proliferation and differentiation in normal as well as in transformed tissues. Though the mechanism of action of retinoids is not yet fully understood at the molecular level, chemoprevention studies have demonstrated the ability of retinoids to prevent the development of skin cancer, particularly in patients with xeroderma pigmentosum, multiple basal cell carcinoma and oral leukoplakia. A better understanding of the carcinogenic process should improve our ability to develop effective chemoprevention strategies.
Animals↗
[Pacemaker erythema with telangiectasis ].
Pacemaker erythema is a rare, irreversible side effect of cardiac pacemakers, clinically characterized by epifocal teleangiectatic erythema. Histology reveals teleangiectatic vessels in the superficial dermis and a slight perivascular infiltrate. We report on three patients presenting with pacemaker erythema following either pacemaker or defibrillator implantation. The pathogenesis of this histopathologically uncharacteristic lesion is unknown. In contrast to peri- or postoperative pacemaker infections, physical irritation can be considered a possible triggering mechanism. Allergic reactions to the implanted material have been ruled out by negative patch test results.
Aged↗
Evaluating intraoperative radiation therapy (IORT) and external beam radiation therapy (EBRT) in non-small cell lung cancer (NSCLC). Five years experience.
A pilot study on intraoperative radiation therapy (IORT) combined with external beam radiation therapy (EBRT) in nonresectable non-small cell lung cancer (NSCLC) was performed in 31 patients (mean age: 66.2 years, range: 51-80; 10 anatomically and functionally, 21 functionally, nonresectable; 20 squamous-cell, 11 adenocarcinoma). The tumor was exposed by lateral thoracotomy and a staging lymph node dissection was performed (final staging 7 T1, 16 T2, 8 T3; 11 nodal positive). Ten to 20 Gy IORT (energy: 7-20 MeV electrons) were delivered to the tumor. Unilateral continuous positive airway pressure ventilation of the diseased lung was used to reduce the amount of healthy lung tissue in the IORT port and to minimize the ventilatory movement. Secondary collimation and direct shielding of radio-sensitive structures within the IORT port by aluminium sheets were used to further reduce collateral damage. Four weeks after IORT, 46 Gy EBRT (2 Gy/day 5 times a week; 8-23 MeV photons) were administered to the mediastinum and to the tumor-bearing area on an outpatient basis. In nodal positive cases the mediastinal dose was increased to 56 Gy. Twenty-three patients were evaluable. In 13 complete, in 8 partial (50-97% regression) and in 2 minor response has been achieved. Five patients experienced a recurrence (local only: 2; local and distant: 1; distant only: 2). Twelve patients died of underlying cardio-respiratory disorders within 6 to 25 months after IORT; 7 died of cancer. The overall 5-year survival rate including the incidental deaths is 14.7%. The recurrence-free survival rate is 53.2%.
Adenocarcinoma↗
Quantitative assessment of melanoma single-cell motility in vitro.
Cell motility is a crucial property of tumor cells during invasion and metastasis. In this study we developed a computer assisted system to measure translocation and stationary motility of single cells and used this procedure to evaluate the influence of cytochalasin A (CA) on single-cell motility parameters of K1735-M2 mouse melanoma cells. The cells were seeded at low density into a microincubator. Time lapse microcinematography was performed every 20 seconds from a high power field to assess stationary motility and every 10 minutes with a screening objective to measure translocation. 1 muMol CA was added to the medium 48 hours before measurement. Calculation of stationary motility was performed by subtraction of subsequent images and the resulting image difference was used for quantitative evaluation. Three different measuring windows were drawn to discriminate between membrane ruffling, intracellular organelle transport and overall stationary motility. For each cell we measured change of density (CD), area of change (AC), perimeter of area of change (PC), area of ruffling (AR), number of ruffling sites (NR), change of intracellular organelles (CIO) and number of changing intracellular organelles (NIO). In order to quantify translocation, the center of gravity of each cell was assessed subsequently and the velocity was calculated by connecting the centers of gravity. CA-treated cells showed a significantly lower stationary motility and membrane ruffling compared to the untreated cells (U-test: p < = 0.01), but there was not significant difference concerning the intracellular organelle transport.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Spitz's nevus arising on a nevus spilus.
The first case of a solitary dermal Spitz's nevus arising on a nevus spilus is described. The special variant of a combined Spitz's nevus may cause difficulties in differential diagnosis from malignant melanoma in association with a nevus spilus.
Adolescent↗
Pattern interpretation by cellular automata (PICA)--evaluation of tumour cell adhesion in human melanomas.
In routine pathology, the evaluation of the pattern of a tumour at scanning magnification often reveals diagnostic and prognostic features indicating that the biological properties of the tumour cells are related to the morphological pattern. For further evaluation of the relationship between functional properties of the cells on the one hand and the pattern on the other, we propose the pattern interpretation by cellular automata (PICA) procedure. The PICA system consists of an import module transferring real histological images into the data structure of a cellular automaton, a measurement module generating a comparable quantitative description of real and simulated images, a cellular automation designed to simulate tumour growth and invasion at the histological level, a database consisting of the morphological results obtained in simulated patterns, an interpretation module linking real histological images to the knowledge stored in the database and an image synthesis and display module. By comparing real images to computer-simulated patterns, PICA facilitates an estimation of functional properties based on the static histological pattern of a given tumour. Using the example of tumour cell adhesion, it is demonstrated that the degrees of tumour-tumour and tumour-stroma adhesion significantly affect the resulting simulated patterns, that, in turn, the morphological evaluation of the patterns enables a reproducible estimation of adhesion and that estimates of adhesion in real images of malignant melanoma of the skin are of prognostic significance. PICA may serve as an additional in situ evaluation technique linking morphological features to functional properties.
Cell Adhesion↗
Computerized video image analysis in dermatopathology.
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Computer Systems↗
Proliferative activity in Spitz's naevi compared with other melanocytic skin lesions.
Proliferative activity has been shown to correlate with the degree of malignancy in various human neoplasms. Immunostaining with the monoclonal antibody PC10 binding to proliferating cell nuclear antigen (PCNA) facilitates the assessment of proliferation in routinely fixed, paraffin-embedded tissue sections. In this study we investigated the expression of PCNA in 29 Spitz's naevi in comparison with 43 primary malignant melanomas (MM), 18 cutaneous metastases of malignant melanoma (MMM) and 16 benign melanocytic naevi (BMN). After selection of the microscopic field with the highest number of PCNA-positive nuclei, the nuclear density (NDmax) of PCNA-stained nuclei in this field was assessed using interactive image analysis. The mean value of NDmax (given as 1000 nuclei/mm3 tissue) of SN was 27.9 (+/- 16.7) and differed significantly from that of MM (48.1 +/- 40.5; U-test: p < 0.05) and that of MMM (114.4 +/- 56.3; p < 0.01). Comparing NDmax of the subgroups of MM according to their maximal vertical tumour thickness with NDmax of SN we found significant differences only between SN and MM > 1.5 mm thick (n = 14; NDmax = 67.8 +/- 36.1) but not between SN and MM < or = 1.5 mm thick (n = 29; NDmax = 38.8 +/- 39.3). PCNA expression in SN did not differ from that of BMN (NDmax 23.8 +/- 28.5). Proliferative activity as assessed by measurement of PCNA expression therefore showed significant differences between BMN, SN and thin primary melanomas on one hand and thick primary melanomas and cutaneous metastases of malignant melanomas on the other hand.
Antigens, Neoplasm↗
Comparison of proliferative activity as assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 monoclonal antibodies in melanocytic skin lesions. A quantitative immunohistochemical study.
Immunostaining with the monoclonal antibodies PCNA and Ki-67 provides a simple method for the assessment of growth fractions of tumors. Contrary to Ki-67, PCNA antibody can be applied on aldehyde- or alcohol-fixed and paraffin-embedded tissues, thus allowing studies on archival material. For 77 melanocytic skin lesions, we compared PCNA immunostaining on formalin-fixed tissue with Ki-67 immunostaining on frozen material of the same lesion. 16 benign melanocytic nevi (BMN, from 16 patients), 43 primary malignant melanomas (PMM, 42 patients), and 18 skin metastases of malignant melanoma (MMM, 12 patients) were included in the study. Maximum nuclear density (NDmax) of PCNA- and Ki-67-positive nuclei was assessed using interactive image analysis. NDmax values for both PCNA and Ki-67 differed significantly between the three diagnostic groups (Kruskal-Wallis H-test: p << 0.001). Mean values (given as 1000 nuclei/mm3 tissue) increased considerably from benign to malignant lesions (PCNA: BMN: 23.8 +/- 28.4 [mean +/- standard deviation], PMM: 48.1 +/- 41.0, MMM: 117.0 +/- 64.6; Ki-67: BMN: 6.4 +/- 3.3, PMM 25.0 +/- 31.1, MMM: 95.2 +/- 47.2). Correlation between NDmax values of PCNA- and Ki-67-positive nuclei was significant (Linear regression analysis: r = 0.51, p << 0.001). Furthermore, for PMM a significant correlation between histologic parameters related to prognosis (Breslow index and mitotic rate) and PCNA as well as Ki-67 expression was found (PCNA-Breslow index: r = 0.42, p < 0.01; Ki-67-Breslow index: r = 0.60, p << 0.001; PCNA-mitotic rate: r = 0.40, p < 0.01; Ki-67-mitotic rate: r = 0.50, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Monoclonal↗