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H Kerl

Publications and source records attributed to H Kerl.

At least 199 records · Page 11Linked to original sources

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↗

Acral pseudolymphomatous angiokeratoma. A variant of the cutaneous pseudolymphomas.

APACHE (acral pseudolymphomatous angiokeratoma of children) is a recently described benign cutaneous condition. Only a few cases have been documented to date. The disease has been previously reported in children between 2 and 13 years of age as unilateral eruptions of multiple angiomatous papules on acral sites of the hands and feet. We herein report two cases of APACHE, one occurring in a 16-year-old boy and the other in a 64-year-old woman. Unlike the previously reported cases, our female patient presented in adulthood with a single lesion on the back. Histopathologic and immunohistochemical investigations reveal characteristic features, allowing APACHE to be included among the group of cutaneous pseudolymphomas.

Adolescent↗

Classification of cutaneous lymphomas.

Despite the many distinct features of cutaneous lymphomas, they are best classified according to the Kiel classification and the Working Formulation for clinical usage. T-cell lymphomas predominate (65%); however, there are a significant number of primary B-cell lymphomas of the skin (25%). Moreover, there are a variety of unusual and rare manifestations and nosologic entities of cutaneous lymphomas that cannot be seen in the lymph node owing to the peculiarities of the skin as a distinct homing organ and vice versa (10%). It is important to note that some cutaneous lymphomas have a better prognosis when occurring primarily in the skin than their corresponding entity in the lymph node.

Humans↗

The use of monoclonal antibodies on paraffin sections in the diagnosis of cutaneous lymphoproliferative disorders.

Immunohistochemistry provides a new powerful tool for the diagnosis and classification of cutaneous lymphoid infiltrates. The use of a panel of monoclonal and polyclonal antibodies on routinely-fixed, paraffin-embedded tissue sections allows the correct classification of most cutaneous T-cell and B-cell lymphomas and of specific cutaneous manifestations of Hodgkin's disease and of "true" histiocytic lymphoma.

Antibodies, Monoclonal↗

Therapeutic approaches in cutaneous lymphoma.

Standard therapy of the CTCL MF and SS consists of topical glucocorticosteroids, PUVA, topical chemotherapy, and total skin electron beam irradiation in stages Ia and IIa; local radiation or total skin electron beam irradiation in stage IIb; and systemic chemotherapy in stages III and IV. The experimental treatment modalities, interferon-alpha and retinoids, especially arotinoid, are most effective in early stages of CTCL; in advanced stages, the effectiveness can be increased by combination regimens. Up to now, the most promising results are obtained by combination therapy of interferon and PUVA. When serotherapy is considered as a therapeutic alternative for patients in stage IIb to IVb, the benefit/risk ratio must be carefully analyzed. Anti-thymocyte-globulin and monoclonal antibodies, either alone or conjugated to radioisotopes or toxin, have shown some therapeutic effect but are still under investigation. Extracorporal photopheresis is well established in erythrodermic patients. Initial reports also have shown encouraging results with this treatment for stage Ib and in combination with methotrexate or interferon. Hexadecylphosphocholine, a new, well-tolerated topical agent, induced a remission rate of 50%, with 25% complete remission in CTCL patients of stage Ia to IIb.

Antineoplastic Agents↗

Specific skin manifestations in acute leukemia with monocytic differentiation. A morphologic and immunohistochemical study of 11 cases.

BACKGROUND: Monocytic differentiation is present in the myelomonocytic (M4) and monocytic (M5) type of acute myeloblastic leukemia. Infiltration of the skin in acute myelomonocytic leukemia occurs in 10-20% of patients, the skin lesions occasionally being the first symptom, even preceding monocytosis. METHODS: Eleven patients with myelomonocytic (n = 2) and monocytic leukemia (n = 9) were studied who had skin manifestations. RESULTS AND CONCLUSIONS: Clinically, all patients showed disseminated papules or nodules that corresponded histologically to nodular or diffuse infiltrates of monocytoid cells, occasionally displaying a whorled pattern. The currently available antibodies for paraffin-embedded sections (lysozyme, elastase, leukocyte common antigen (CD45), MT1 (CD43), Leu-M1 (CD15), LN2 (CD74), MB2, MB1 (CD45RA), LN1 (w75), Mac387, L26 (CD20), UCHL1 (CDR0), MT2 (CD45RA), and KP-1 (CD68)) and chloracetate-esterase are not more helpful in diagnosis than are the histologic findings. By contrast, the antibodies used on frozen sections (Leu-4 (CD3), Leu-3a (CD4), BA1 (CD24), B4 (CD19), Leu-M5 (CD11c), Vim12 (CD11b), VimD5 (CD15), KiM6 (CD68), KIM7 (CD68), My7 (CD13), and My9 (CD33) allow the definition of a reaction pattern that is diagnostic for acute myeloid leukemia with monocytic differentiation.

Adult↗

Inhibition of K1735-M2 melanoma cell invasion in vitro by retinoic acid.

Melanoma cell invasion in vitro was tested by means of confrontation cultures of melanoma multicellular spheroids with rounded fragments of embryonic chick heart tissue. Quantitative determination of invasion was performed using a computerized image analysis program, facilitating the evaluation of the efficacy of potentially anti-invasive compounds. Retinoic acid (RA; 1 microM) [corrected] considerably impaired K1735-M2 melanoma cell invasion, as demonstrated by various measuring parameters. Parameter TUMAREA, expressing the amount of tumor tissue, indicates a growth inhibitory effect and the invasion parameter STRCSTR shows that after treatment with RA the stromal component was better preserved than in untreated controls. Besides the inhibitory effect of RA on melanoma cell invasion in confrontation cultures, RA increased the dynamics of adhesion of melanoma cells to the extracellular matrix components type I collagen and laminin, and slightly impaired melanoma cell directional migration. Fluorescence microscopy using rhodamine-labeled phalloidin showed that RA also modulated the organization of the actin cytoskeleton by inducing the formation of actin-containing stress fibers. Our data show that 1 microM RA exhibited a pronounced anti-invasive effect on highly metastatic melanoma cells in vitro. Impairment of host tissue degradation, altered adhesion abilities, changes in the actin cytoskeleton, as well as the antiproliferative effect may all account for inhibition of melanoma cell invasion.

Actin Cytoskeleton↗

Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid. An alternative treatment modality for solar keratoses, superficial squamous cell carcinomas, and basal cell carcinomas?

BACKGROUND: Topical photodynamic therapy with endogenous porphyrins consists of irradiation of a tumor with visible light after the application of exogenous 5-aminolevulinic acid. OBJECTIVE: To assess the effectiveness of this modality, patients with precancerous conditions and various skin cancers were treated. METHODS: Thirteen patients with 70 skin lesions were enrolled. Standard treatment involved the topical application of 20% 5-aminolevulinic acid in an oil-in-water emulsion. The emulsion was applied under an occlusive dressing for 4 to 8 hours before exposure to photoactivating light. RESULTS: We observed a complete response after a single treatment for all 9 solar keratoses, 5 of 6 early invasive squamous cell carcinomas, and 36 of 37 superficial basal cell carcinomas. Only 1 of 10 nodulo-ulcerative basal cell carcinomas completely resolved. Eight cutaneous metastases of malignant melanoma were therapeutic failures. CONCLUSION: Topical photodynamic therapy with endogenous porphyrins is effective for superficial epithelial skin tumors.

Administration, Cutaneous↗

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↗

Molecular detection of clone-specific DNA in hypopigmented lesions of a patient with early evolving mycosis fungoides.

A specific molecular probe for the malignant lymphoid clone of lesions of a patient with mycosis fungoides was developed. As a clone-specific marker the junctional region of rearranged T-cell-receptor-gamma (TCR-gamma) genes was used. An oligonucleotide primer complementary to these sequences was designed. Using this primer and polymerase chain-reaction technology, early hypopigmented lesions of the patient, which were previously unclassifiable by conventional microscopy, were analysed. The study demonstrates, on the molecular level, that these hypopigmented lesions contain tumour clone-specific DNA and may represent early manifestations of mycosis fungoides.

Adult↗

Cutaneous immunocytomas: a clinicopathologic study of 26 cases.

The clinical and histological features of 16 patients with a primary cutaneous immunocytoma and 10 patients with a secondary cutaneous immunocytoma are reported. In all cases the diagnosis was based on the presence of monotypic plasma cells or lymphoplasmacytoid cells. Our data show that primary cutaneous immunocytomas are a distinct type of cutaneous lymphoma, characterized by (a) the presence of solitary or localized skin lesions (13 of 16 cases); (b) preferential localization on arms and legs (15 of 16 cases); (c) excellent response to local treatment (15 of 16 cases) and (d) a favourable prognosis. Histologically, these primary cutaneous immunocytomas are characterized by the presence of nodular or diffuse infiltrates with monotypic lymphoplasmacytoid/plasma cells located at the periphery of the infiltrates. Important clinical and histological differences were noted between primary and secondary immunocytomas. In the latter group more widespread skin disease was seen, often in the presence of paraproteins and/or autoimmune diseases. In contrast with the peripheral localization of the monotypic cells in primary cutaneous immunocytomas the monotypic lymphoplasmacytoid/plasma cells in secondary immunocytomas formed diffuse infiltrates or these cells were found dispersed throughout the infiltrate. There were no differences in clinical presentation or course between the different subtypes of cutaneous immunocytomas (lymphoplasmacytic, lymphoplasmacytoid and polymorphic immunocytomas). The differential diagnosis between primary cutaneous immunocytomas and cutaneous plasmacytomas, primary follicular centre cell lymphomas and cutaneous 'pseudolymphomas' is discussed.

Adult↗

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↗

Verrucous cysts: histopathologic characterization and molecular detection of human papillomavirus-specific DNA.

Verrucous cyst is an uncommon newly described benign epithelial cyst which may be associated with human papillomavirus infection. The purpose of this project was to study the clinicopathological features of verrucous cysts and to demonstrate human papillomavirus (HPV) by polymerase chain reaction (PCR) in these lesions. We have analyzed 5 examples of verrucous cysts: the age range of the patients was between 37-82 years and the most common locations were face and extremities. Clinically the lesions were interpreted as cyst (2), dermatofibroma (2) and basal-cell carcinoma (1). Histopathologic examination of the biopsy specimens showed in all cases an intradermal infundibular cyst lined by a papillated and/or digitated epithelium with focal prominent hypergranulosis and irregular keratohyalin granules. Furthermore, numerous whorls of keratinocytes (so-called squamous eddies) were present within the squamous areas of the hyperplastic epithelium of the cyst, morphologically reminiscent of inverted follicular keratosis. Architectural and cytological features of malignancy were not present. Sections of paraffin-embedded tissue of the 5 verrucous cysts and of 5 "conventional" follicular cysts, infundibular type, were investigated for the presence of HPV DNA sequences by PCR using consensus primers. In all 5 cases of verrucous cysts, HPV-specific DNA sequences were detected, whereas all follicular cysts, infundibular type, were negative. These results support the concept that verrucous cysts can be added to the large spectrum of HPV-induced cutaneous neoplasms. Further studies are needed to identify the specified HPV-type in these distinctive benign cystic proliferations.

Adult↗

Inhibition of melanoma cell directional migration in vitro via different cellular targets.

In malignant melanoma active movement of cancer cells is considered to be essential for tissue invasion. Various mechanisms, such as the Ca(2+)-calmodulin-proteinkinase C cascade or G-protein-dependent processes are considered to play a role in tumor cell functions. The assay of directional migration, combined with computer-assisted image analysis, was used to evaluate the antimigratory efficacy of drugs interfering with different steps of signal transduction pathways. Treatment with different compounds showed a more or less concentration-dependent reduction of migration rates: The Ca(2+)-channel blockers verapamil and devapamil showed a slight reduction of motility. The effect was more pronounced when the calmodulin antagonist flunarizine was used or the proteinkinase C inhibitors dequalinium, tamoxifen and H-7 were applied. A marked inhibition of motility was found with the G-protein antagonist L 651582. Thus, our results indicate that different signal transduction pathways are involved in the regulation of directional migration of K1735-M2 melanoma cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Notalgia paresthetica, "posterior pigmented pruritic patch" and macular amyloidosis. Three stages of a disease].

We report on nine cases of notalgia paresthetica, a cutaneous condition that has rarely been described in the dermatological literature and is characterized by localized pruritus, burning and hyperesthesia and/or paresthesia on the back. Histological and immunohistochemical studies have not clarified the pathogenesis of this disease. Several factors might be involved in various cases, including increased cutaneous innervation and neuropathy. The so-called posterior pigmented pruritic patch and macular amyloidosis may be considered as progressive evolutional stages of notalgia paresthetica.

Adult↗

[Surface microscopy of pigmented cutaneous tumors].

BACKGROUND: Clinical guidelines for the diagnosis of pigmented lesions of the skin are not always reliable. Especially the differential diagnosis between benign dysplastic nevi (Clark's nevi) and early melanomas, as well as between melanocytic and nonmelanocytic skin tumors (seborrheic keratoses, pigmented basal cell carcinomas and angiokeratomas) is often difficult. OBJECTIVE: Surface microscopy, which is performed today under various synonyms (dermoscopy, dermatoscopy, epiluminescence microscopy, incident light microscopy, skin microscopy), has been shown to provide additional features and subtle clues for the assessment of pigmented skin lesions. METHODS: The pigmented lesions are covered in vivo with a drop of immersion oil and a glass slide, and observed in incident light by using a stereomicroscope (magnification 6- to 40-fold) or a hand-held instrument called dermatoscope (magnification 10-fold). The immersion oil renders the stratum corneum translucent and allows a better observation of distinctive alterations of the dermoepidermal junction and the papillary dermis. RESULTS: The various criteria of surface microscopy (e.g. pigment network, black dots or irregular extensions) that cannot be discerned by the naked eye are summarized and discussed in detail. The diagnostic significance but also the limitations of this technique are emphasized. CONCLUSION: Surface microscopy opens up a new dimension of clinical morphology for the diagnosis of pigmented skin tumors and facilitates a more reliable assessment of the lesions.

Angiokeratoma↗

Tumor cell proliferation and motility estimates are prognostic factors in malignant melanoma.

Metastatic spread of solid tumors depends on a complex metastatic cascade. Metastatic tumor cells must therefore express a variety of biological properties including the ability to proliferate and the ability to migrate. In the present study, the prognostic significance of both parameters was investigated in 184 cases of malignant melanoma of the skin. Proliferative activity was assessed by mitotic counts, the degree of cell motility was estimated by comparing the histological pattern of the tumor with patterns obtained by computer simulations with predefined values of cell motility. Follow up of surviving patients was at least 5 years. Statistical analysis was done using classification and regression tree (CART) analysis combining mitotic counts and motility estimates. As far as overall survival was concerned, mitotic counts were the most significant variable separating one group of patients with mitotic counts < 17/mm2 and a 5-year survival rate of 82% and a group with mitotic counts > or = 17/mm2 and a 5-year survival rate of 52%. Within the group with low mitotic counts, motility estimates found a subgroup of patients with a coefficient of motility > or = 126, which had a 5-year survival rate of 55% similar to those patients with high mitotic counts. Corresponding results were obtained in the assessment of metastasis-free interval. The data show that not only proliferation as assessed by mitotic counts, but also estimates of tumor cell motility based on image analysis and computer simulations provide prognostic information in primary malignant melanoma of the skin.

Cell Division↗