Biomedical subjects
Publications and source records attributed to H Kerl.
A patient with artificial penile nodules and ulcerative plaques on the penis is described. Clinical course, histology and serological examination revealed a diagnosis of secondary syphilis. The differential diagnosis of the ulcerative genital lesions in the presence of artificial penile nodules is discussed.
The expression of the proto-oncogene c-myc was studied in tumorous skin lesions of (cutaneous) lymphoproliferative diseases (3 cases of pseudolymphoma, 8 cases of non-Hodgkin lymphoma and 1 case of lymph node involvement in mycosis fungoides) in a total of 12 patients. c-myc mRNA levels were quantified by Northern blot analysis followed by densitometric evaluation of the specific bands. Higher levels of c-myc mRNA expression were observed in lymphomas as compared with pseudolymphomas (p greater than 0.05). No significant differences in c-myc mRNA values were detected between B and T cell pseudolymphomas. Our results suggest that c-myc mRNA overexpression is associated with malignant lymphomas of the skin. We conclude that the measurement of c-myc mRNA levels may contribute to further characterize cutaneous lymphoproliferative diseases.
A 25-year-old man who survived carbon monoxide intoxication presented erythematous cutaneous lesions with blister formation in pressure areas. Histologic examination revealed subepidermal vesicles with extensive sweat gland necrosis. We discuss the clinicopathological findings of carbon monoxide poisoning. Similar cutaneous features have been observed in patients with various kinds of drug-induced coma.
Epidemiological and histological data of 1368 patients with invasive malignant melanoma treated at the Department of Dermatology between 1970 and 1989 were analysed retrospectively. Frequency of melanoma increased from 103 cases between 1970 and 1974 to 593 between 1985 and 1989. The male/female ratio was 1/1.5 and did not change during the study period. Mean age of patients at the time of primary operation was 56.1 years and was approximately the same for males and females (males 55.8, females 56.3 years). The predominant site was the trunk in males (58.7 per cent) and the lower leg in females (41.6 per cent). There was a relative increase of melanomas of the back in males and the lower leg in females at the expense of melanomas of the face. The Breslow index was significantly higher in males than in females. In patients older than 69 years, the proportion of thick melanomas was above average. During the study period, the frequency of thick melanomas (greater than 1.5 mm) showed an encouraging decrease in both sexes. In 1989, 50 per cent of all melanomas were thinner than 1.01 mm. This can be interpreted as a successful outcome of efforts in preventive medicine.
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The architecture of the tumour margin is an essential feature for the histological diagnosis of certain neoplasms. In a previous study we have shown by computer simulations, that the degree of tumour cell motility and proliferation influences qualitative morphological criteria of the tumour border. Here we propose a method for an objective, quantitative description of the tumour cell distribution at the tumour-stroma border. 100 morphological patterns generated by computer simulation with different preset degrees of motility and proliferation were evaluated. On a measuring path starting at the most peripheral cell and going towards the tumour centre, the density of tumour cells for each distance from the tumour margin was calculated from the number of cells within a 5 x 5 matrix around each measuring point. An exponential regression function was adapted to the measured density distribution. The parameters of the regression curve and 'the goodness of fit' were tested for correlation with the preset simulation parameters. It was found that the degree of motility and proliferation can be deduced from the quantitative descriptors of the tumour margin (linear regression of the preset values and of the values estimated from the morphological analysis: r = 0.903; t = 20.7; P less than 0.001). Besides the evaluation of computer-simulated morphological patterns, the same measuring procedure can also be applied to histological slides of melanocytic skin tumours using automated image analysis.
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A panel of antibodies reactive in routinely fixed, paraffin-embedded tissue sections was compared with a panel of antibodies reactive in frozen sections for the immunophenotyping of cutaneous lymphoproliferative disorders. Three T cell-associated markers (UCHL1, MT-1, MT-2, six B cell-associated markers (MB-1, MB-2, LN-1, LN-2, L-26, 4KB5), immunoglobulin heavy and light chains, anti-LCA antibody, two markers for Reed-Sternberg cells (Ber-H2, Leu-M1), one marker for macrophages (Mac-387) and anti-S-100 protein antibody were tested on normal skin, inflammatory skin diseases, and cutaneous lymphomas and pseudolymphomas. On the basis of the results in frozen sections, 12 inflammatory T cell diseases, 14 T cell lymphomas and pseudolymphomas, and 10 B cell lymphomas and pseudolymphomas were identified. In addition, two cases of specific skin infiltrates of Hodgkin's disease have been examined. Among T cell markers, the greatest sensitivity was exhibited by UCHL1, which stained all but one specimen of T cell infiltrate; it was negative in one specimen of mycosis fungoides that progressed into a T-immunoblastic lymphoma. The combined use of MB-2, LN-2, and 4KB5 identified all B cell proliferations. LN-1 marked germinal centers in all cases of follicular lymphoma and pseudolymphoma. Ber-H2 stained the Reed-Sternberg cells in both cases of Hodgkin's disease and the large cells in the histiocytic type of lymphomatoid papulosis. Mac-387 and anti-S-100 protein antibody recognized macrophages and T-zone histiocytes (Langerhans cells and interdigitating cells), respectively. A panel of antibodies reactive in routinely fixed, paraffin-embedded tissue sections is proposed that facilitates the identification of most B and T cell infiltrates in the skin.
Four cases of large eccrine acrospiroma (three benign, one malignant) are reported. The benign tumors involved the lower extremities of two women and one man (73 to 89 years of age). The duration of the lesions ranged from 10 to 20 years. The malignant tumor involved the left side of the chest of a 60-year-old man. Its occurrence in a lesion that had been present for 40 years suggested malignant transformation of a pre-existing benign eccrine acrospiroma. Each tumor showed little to no cellular atypia. Mitotic rates (mitotic figures per 10 high-power fields) varied both between and within lesions. Average mitotic rates did not differentiate the benign from the malignant tumors. The most important distinguishing features of large benign eccrine acrospiromas are the relative circumscription, the lack of cellular atypia, and the absence of stromal, perineurial, and angiolymphatic invasion.
Tumor growth is considered to depend on tumor cell proliferation and on tumor cell motility. The present study investigates in which way these two cellular properties influence the evolving morphological pattern. Computer simulations were performed, where cells were either dividing or moving for a variable distance at a present probability. The simulation parameters (probability of motility, maximum moving distance) were set interactively. The resulting patterns were evaluated by binary morphological criteria, 13 of 17 binary criteria showed a significant relationship with the simulation parameters (median test: p = less than 0.05). Discriminant analysis of two sets of simulations with different simulation parameters provided a correct classification with an efficiency of 100% (k-nearest-neighbour method; jack-knife-procedure). The results indicate that cell proliferation and motility affect morphological patterns in a reproducible way and that the patterns in turn provide morphological clues for the quantitative estimation of motility and proliferation.
The microtubulus system as a part of the cellular cytoskeleton contributes to cell movement. Microtubulus assembly and disassembly is considered to be essential for tumor invasion and serves as a target for tumor chemotherapy. Using immunohistochemical methods, we investigated the distribution of tubulin in normal skin and 34 melanocytic skin tumors. In normal skin, tubulin was strongly expressed in dermal nerves, melanocytes, fibroblasts within the papillary dermis and in myoepithelial cells. In melanocytic skin tumors, nevus cells and melanoma cells stained positive, particularly at the periphery of the lesions, where there were single cells and small nests. The main difference between benign and malignant melanocytic tumors was found in the stromal cells: In melanocytic nevi, the stromal fibroblasts were entirely tubulin negative; whereas, adjacent to the invasive edge in primary and metastatic malignant melanoma, the stroma fibroblasts were strongly positive. Our results show that tubulin is regularly expressed in melanocytic skin tumors and may serve as a prerequisite for cell movement. The pronounced expression of tubulin in fibroblasts surrounding malignant melanocytic skin lesions reflects a stromal alteration that might contribute to tumor invasion.
Checking consecutively sampled routine sections of 206 melanocytic lesions with a maximum vertical diameter of at least 1 mm (133 benign dermal nevi, 20 Spitz's nevi, 53 primary malignant melanomas), we measured the morphometric features of at least 60 nuclei each from the superficial and the deep dermal tumor portion using a computer-assisted interactive image analysis system. Furthermore we calculated the so-called maturation parameter (MP) in each case as the ratio of the mean nuclear area in the deep portion and the superficial portion. When we compared the results with those obtained in a training set, we found that the lowest evidence for the discrimination of benign and malignant melanocytic lesions resulted from the application of the mean values of the nuclear area in the superficial layer (efficiency = 62.1%). The efficiency was higher when we used the mean values of the nuclear area in the deep layer (96.1%) and the maturation parameter (85.4%). By applying the mean nuclear area in the deep portion and the maturation parameter simultaneously, we gained the highest efficiency, specificity, and sensitivity for the distinction between benign dermal nevi and malignant melanomas (0.968, 0.955, 1) as well as for the distinction between Spitz's nevi and malignant melanomas (0.986, 0.950, 1). Our study shows that morphometry provides reliable diagnostic results in routinely sampled melanocytic skin tumors.
We examined the influence of different staining techniques [(three-step immunoperoxidase technique (IP); alkaline phosphatase-anti-alkaline phosphatase technique (APAAP)] on the quantitative evaluation of Ki-67-labeled nuclei. We studied five melanocytic skin tumors. From each case, five parallel sections were prepared and stained using the peroxidase-antiperoxidase (PAP) technique (slide 1) and the APAAP technique once (slide 2). Slide 3 consisted of a single repetition of the APAAP technique, slide 4 was a double repetition, and slide 5 was a third repetition. We assessed the volume fraction (VV) of Ki-67-positive nuclei using computer-assisted image analysis. For each staining group, the mean value and standard deviation of VV were calculated. Comparing VV values obtained from the different staining groups we did not find a statistically significant difference between the IP and the various APAAP steps (Wilcoxon test, p = less than 0.05). However, the staining procedure influenced the quantitative results to some extent. The mean VV of the five staining groups ranged in our study from 0.10 to 0.17%, which is narrow compared with the overall variability among different cases (dermal melanocytic nevus, 0.01%; metastatic malignant melanoma, 0.43%). Therefore, we can state that for a rough evaluation of Ki-67-positive nuclei, the influence of different staining methods is negligible; for a subtle quantitative analysis, however, it would nevertheless be preferable to always apply the same staining technique.
Tumor invasion is a crucial feature of tumor growth in vivo. Confrontation cultures of multicellular melanoma spheroids and embryonic chick heart fragments provide a model for invasive growth in vitro. We have developed an image analysis method, which facilitates the objective measurement of tumor cell invasion in this model. Cryostat sections of confrontation cultures were immunohistochemically stained with an antiserum directed against the stromal component for automated recognition of the stroma tissue. The slides were automatically processed by a grey level based computerized image analysis system. On Spearman's rank correlation test, 25 out of 39 parameters correlated with the reference value of invasion, which was derived from the subjective evaluation of five independent observers. Two parameters combining the stroma margin and the total amount of stroma tissue completely reproduced the judgement of the morphologists in our test set. The quantitative evaluation of tumor invasion in vitro by automated image analysis may be helpful in pharmacologic and pathogenetic studies of tumor growth.
Eight patients with skin tumor lesions composed of dense, predominantly plasma cell infiltrates were studied. Primary cutaneous plasmacytoma can be reactive (polyclonal) or neoplastic (monoclonal). In four of the patients skin lesions were associated with multiple myeloma. Specific skin lesions usually consisted of reddish or purple nodules located on the trunk. In one case the cutaneous lesions developed at the site of previous herpes zoster. Histologically, the cutaneous plasmacytic infiltrate was mainly diffuse and monomorphous. Most of the plasma cells were mature, but in some cases immature immunoblasts and mitoses were observed. Serum immunoelectrophoresis findings correlated with the monoclonality or polyclonality of the plasmacytoma. Presence or absence of systemic involvement cannot be predicted from the appearance of clinical lesions or from maturity of plasma cell infiltration in the skin.