Biomedical subjects
Publications and source records attributed to J Smolle.
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We report on a 74-year-old woman showing a reddish infiltration of the tip of the nose, which had appeared 3 months ago. Clinically, we considered the following differential diagnoses: sarcoidosis, rosacea, pseudolymphoma, and metastasis. Histological and immunohistological investigation proved a cutaneous metastasis of carcinoma of the breast. Our case report gives evidence of the fact that cutaneous metastases of systemic malignancies are frequently located in acral regions of the skin.
We report on an 82-year-old woman with typical features of Reiter's disease. Up to now, Reiter's disease has been considered to affect almost exclusively male patients in the third and fourth decades of life. Our observation and several recent reports in the literature suggest that Reiter's disease must also be considered in aged female patients.
The clinical diagnosis of cutaneous pigmented tumors is often difficult. Surface microscopy represents an interesting approach to this problem. For this in vivo investigation, a stereomicroscope, a glass slide and immersion oil are used. In order to improve the clinicopathological correlation of pigmented skin lesions, morphological criteria discerned by surface microscopy--such as pigment network or black dots--were compared with the corresponding histological features. Surface microscopy opens a new dimension for the diagnosis and differential diagnosis of malignant melanomas, dysplastic nevi, or non-melanocytic pigmented tumors, and allows a better pre-operative assessment of these lesions.
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Benign congenital melanocytic nevi, removed shortly after birth, may histologically be misinterpreted as malignant melanomas. We present the criteria for the differential diagnosis. As a name for these unusual melanocytic tumors, which belong to the large group of pseudomalignancies of the skin, we suggest the term 'congenital pseudomelanoma'.
With regard to certain clinical features, polymyalgia rheumatica (PR) may closely resemble dermatomyositis. In contrast to dermatomyositis, PR usually does not show any cutaneous manifestations, although there might be seen concomitant giant cell arteritis. Furthermore, we do not find muscle enzymes in the serum with PR, and there is no histologic evidence of myositis. In rare cases, however, PR may be associated with cutaneous drug eruption and/or non-specific increase of muscle enzymes, which might cause considerable difficulties regarding the diagnostic differentiation from dermatomyositis.
Cutaneous melanoma, stage I, from 35 survivors at 5 year follow-up and 16 non-survivors were studied. Mean nuclear area in the superficial layer was significantly larger than in the deep layer both in survivors and non-survivors, but the ratio between nuclear area in superficial and deep layers (so-called maturation index) did not differ between survivors and non-survivors. In comparison with the survivors, the mean nuclear area of non-survivors was significantly larger both in the superficial (51.1 microns2 vs 43.7 microns2, p less than 0.01) and deep (42.9 microns2 vs 36.4 microns2, p less than 0.05) layer. This points to a general increase in nuclear areas in metastasizing tumors. Furthermore, the coefficient of variation of nuclear area [(standard deviation/mean) x 100] was not different between survivors and non-survivors, either in the superficial or in the deep layer. Inspection of histograms of areas of 1000-2000 nuclei per case in 20 random cases (10 survivors and 10 non-survivors) showed a homogeneous increase in nuclear area in non-survivors. None of the histograms revealed a cell clone with especially large nuclei. These data show that the increased mean nuclear area in non-survivors is due to a homogeneous increase of all nuclei throughout the tumor and not to a special cell clone with large nuclei within nuclei of otherwise normal size. The difference in mean nuclear area in superficial and deep layers indicates that careful selection of nuclei in either of these layers is essential to obtain reproducible and comparable results with interactive morphometry.
The present study examines the distribution of blood vessels in melanocytic skin tumors. Fresh frozen sections of 11 cases each of benign nevocellular nevus, primary malignant melanoma and metastatic malignant melanoma were stained with the endothelium-specific monoclonal antibody BMA 120 and evaluated by an automated image analysis system. Additionally, the proliferative activity was assessed in parallel sections using Ki 67 monoclonal antibody. There were only slight differences between the diagnostic groups as to the vascular distribution in the tumor center, but there were remarkable differences in the connective tissue at the base of the lesions: The area occupied by small vessels (minimum diameter less than 20 microns) was 0.3 +/- 0.05% in benign nevi, 0.6 +/- 0.05% in primary malignant melanoma, and 1.2 +/- 0.10% in metastatic malignant melanoma (U-test: p less than or equal to 0.05). The proliferative activity within each lesion showed a strong positive correlation with the number of small vessels at the base of the tumor (linear regression analysis: r = 0.86; p less than or equal to 0.0001). The findings demonstrate that neovascularization in malignant melanocytic tumors takes place predominantly in the surrounding host tissue and is closely related to the proliferative activity.
In various tumors, proliferative activity has been demonstrated to be closely related to the degree of malignancy. In the present study, we examined the proliferative pool in a total of 25 melanocytic (nevocytic) skin tumors by immunohistochemical staining with Ki 67 monoclonal antibody (labeling the G1, S, G2-phase of the cell cycle) and quantitative morphological evaluation. There were highly significant differences in the numerical density of Ki 67-positive cells between nevocellular nevi (number of positive cells: 2.2 +/- 0.7 X 10(3)/mm3), primary malignant melanoma (6.3 +/- 1.9 X 10(3)/mm3), and metastatic malignant melanoma (47.0 +/- 9.2 X 10(3)/mm3). Within the malignant melanoma group, there was a significant correlation between proliferative activity and maximum tumor thickness (r = 0.85; p less than 0.05). Comparison with previous studies using tritiated thymidine labeling and colony-forming efficiency shows that the stereological evaluation of Ki 67 staining in melanocytic skin tumors provides a reliable estimate of proliferative activity, which might be of prognostic value.
A 31-year-old man with multiple cystic tumors symmetrically distributed on his eyelids is presented. Histopathology and immunohistochemistry suggest the diagnosis of apocrine hidrocystomas. Apocrine hidrocystomas occur frequently on the face, but multiple and symmetrical occurrence on the eyelids has not been reported up to now.
Proliferative activity and morphometric data have previously been shown to be related with the degree of malignancy in melanocytic skin tumors. In the present study, the proliferative activity, as defined by Ki 67 monoclonal antibody (reactive with all actively cycling cells), has been determined by immunohistologic and morphometric methods in cutaneous melanocytic tumors. Quantitative morphologic features of Ki 67-positive and Ki 67-negative nuclei were separately assessed using computer-assisted image analysis. Comparing morphometric features and proliferative activity, the most significant correlation was found between mean nuclear volume and the percentage of Ki 67-positive nuclei in each lesion (linear regression analysis: r = 0.73; p = less than 0.05). On multidimensional discriminant analysis, tumors with high proliferative activity (more than 5 X 10(3) Ki 67-positive cells per mm3 tumor tissue) were detected at a specificity of 92% and a sensitivity of 75%. Within one lesion, Ki 67-positive nuclei showed an increase in nuclear volume (Wilcoxon test: p = less than 0.05), a more spheroid shape (p = less than 0.05), and a wider dispersion of nuclear volume values (Siegel-Tukey test: p = less than 0.05) than negative nuclei. Discriminant analysis on the basis of nuclear volume density functions facilitated an estimation of the proliferative state (resting or cycling) of a given nucleus. The results are consistent with increased cellular synthetic activity in highly proliferating lesions and particularly in actively cycling cells. The association of proliferative activity and quantitative nuclear features may be helpful in the interpretation of morphometric studies concerning melanocytic skin tumors.
The term 'multinucleate cell angiohistiocytoma' was first introduced by Smith and Wilson Jones in 1985. We report the clinicopathological, immunohistological and ultrastructural findings observed in two patients. Multinucleate cell angiohistiocytoma occurs mainly in middle-aged women and is usually located at acral sites, particularly the distal extremities. Grouped, brown-red, slightly elevated, asymptomatic papules slowly develop over several months until further growth ceases. There is no evidence of systemic disease. Histologically, the dermis shows numerous well developed capillaries with prominent endothelia, large bizarre basophilic and often multinucleate cells with a sparse lymphohistiocytic infiltrate. The immunohistological and ultrastructural findings suggest a fibroblastic differentiation of the large multinucleate cells.
Morphometry was carried out on H&E stained paraffin sections of 29 cases of contact dermatitis (CD) and 35 cases of mycosis fungoides (MF) (patch stage 12; plaque stage 11; tumor stage 12); 9 nuclear parameters, mean thickness of the infiltrate and 5 stereological parameters were assessed for each slide. Application of a non-parametric discriminant analysis (k-nearest neighbour method) which is based on median of nuclear areas, mean maximal nuclear diameter, volume density and numerical density of nuclei provided discrimination between CD and patch stage MF at an efficiency of 82.9% (specifity 86.7%, sensitivity 61.5%). Efficiency of discrimination between CD and plaque stage was 92.5% (specifity 89.7%, sensitivity 91.7%) and between CD and tumor stage 100% when discriminant analysis was based on the mean thickness of the infiltrate. Although unequivocal discrimination between CD and MF cannot be achieved in each individual case, morphometry on routine paraffin material obviously provides additional objective criteria for the diagnosis of early MF.
The distribution of OKM 5-positive dendritic cells in the epidermis was investigated in 75 cases of inflammatory dermatoses and in 14 cases of normal human skin by immunohistochemical and morphometric methods. Furthermore 6 cases of normal human skin, 14 cases of nevocellular nevi, 26 cases of malignant melanoma, 7 cases of contact dermatitis and 6 cases of mycosis fungoides have been examined with special emphasis on the expression of OKM 5 antigen on keratinocytes. OKM 5-positive dendritic cells were present in normal human epidermis at a density of 46 +/- 3.4 cells/mm2 section area. However, there was a significant increase in cutaneous drug eruptions (166 +/- 17.2 cells/mm2; U-test: p less than or equal to 0.05). Concerning OKM 5-positive keratinocytes, a mean percentage of 10.2% +/- 5.0% OKM 5-positive keratinocytes was found in nevocellular nevi, compared to 0.5% +/- 0.5% in the adjacent skin. The corresponding values for malignant melanomas were 52.5% +/- 3.4% (lesional epidermis) and 7.1% +/- 2.2% (adjacent epidermis). There were significant differences of both lesional and adjacent epidermis between nevi and melanomas (U-test: p less than or equal to 0.05). Our cases of contact dermatitis revealed a mean percentage of 19.3% +/- 6.7% OKM 5-positive keratinocytes, whereas in mycosis fungoides the corresponding value represents 42.7% +/- 6.2%. The differences between the percentage of OKM 5-positive keratinocytes in normal epidermis and contact dermatitis as well as mycosis fungoides were significant (U-test).(ABSTRACT TRUNCATED AT 250 WORDS)
The cellular reactivities with the monoclonal antibodies OKT9 and Ki 67 have been demonstrated to be closely related to proliferation in various malignant neoplasms. In this study a total of 25 melanocytic skin tumors was examined immunohistochemically with both antibodies and the results were evaluated semiquantitatively for OKT9 and quantitatively for Ki 67 by stereological methods. All cases of primary and metastatic malignant melanoma expressed a strong stainability for OKT9, whereas benign melanocytic nevi were almost completely negative. Our results with the monoclonal antibody Ki 67 revealed highly significant differences in the numerical density of Ki-67-positive cells between metastatic malignant melanoma (number of positive cells: 47.0 +/- 9.2 X 10(3)/mm3), primary malignant melanoma (6.3 +/- 1.9 X 10(3)/mm3) and benign melanocytic nevi (2.2 +/- 0.7 X 10(3)/mm3). Correlation analysis between mean percentage of OKT9-positive cells and numerical density of Ki-67-positive cells revealed a significant correlation of both parameters (r = 0.58; p less than or equal to 0.05), indicating a positive relationship of OKT9 and Ki 67 expression. Especially in primary malignant melanoma, however, the amount of OKT9-positive cells considerably exceeds that of Ki-67-positive cells. The monoclonal antibodies OKT9 and Ki 67 reflect 'proliferative activity' in melanocytic skin tumors, as both are expressed in significantly higher amounts in primary and metastatic malignant melanomas. The combined application of these antibodies in cutaneous melanocytic lesions might be of diagnostic and prognostic value.
Prostatic carcinoma accounts for about 1% of all cancers that metastasize to the skin. The regions most frequently involved are the genital region, the head and the trunk. Clinically the lesions present as nodules; less often diffuse infiltrates, red macules and papules or tumors of an angiomatous appearance occur. Histopathological examination of skin biopsy specimens can reveal gland-like, epithelial or anaplastic differentiation of tumor cells. Prostatic origin can be proven by the immunohistological demonstration of acid prostatic phosphatase or prostatic specific antigen in paraffin-embedded specimens taken for routine histological examination.
40 cases each of malignant melanoma. Spitz's nevus and benign intradermal nevus were examined using an interactive image analysis system. 60 consecutive nuclei were evaluated in the upper and lower portion of the melanocytic lesions. Besides basic karyometric data, a 'maturation parameter' (MP) expressing the previously described 'maturation to the depth' was assessed in each individual case, by calculating the ratio of the nuclear area in the deep portion and in the superficial portion. When the three parameters (superficial nuclear area, deep nuclear area and maturation parameter) were evaluated separately (k-nearest neighbour method), the efficiency of the superficial nuclear area was only 19%, compared with 72% for the deep nuclear area and 94% for the maturation parameter. Combination of the maturation parameter and the deep nuclear area provided an efficiency of 98% with a sensitivity of 98% and a specificity of 97%. The results indicate that the maturation parameter is superior to conventional karyometric data in the differentiation between benign and malignant melanocytic lesions.