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J Smolle

Publications and source records attributed to J Smolle.

At least 145 records · Page 8Linked to original sources

Quantitative evaluation of the tumour-stroma border by exponential regression analysis.

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.

Cell Division↗

Immunophenotyping of cutaneous lymphoid infiltrates in frozen and paraffin-embedded tissue sections: a comparative study.

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.

Antibodies, Monoclonal↗

Intraoperative radiation therapy combined with external irradiation in nonresectable non-small-cell lung cancer: preliminary report.

Twenty-one patients with nonresectable non-small-cell lung cancer (15 squamous-cell, 4 adeno, 2 large-cell; T1-T3, N0-N2, all M0) underwent lymph node dissection and intraoperative irradiation of the tumor (IORT) with doses between 10 and 20 Gy (energies: 7 to 20 MeV electron beam). Postoperatively, 46-56 Gy external beam irradiation (8 or 23 MeV photon beam) were delivered to the mediastinum and 46 Gy to the tumor bearing area. Fifteen patients were available for follow-up investigations. The CT-scan tumor volumetry 4 weeks postoperatively showed a significant overall decrease (Wilcoxon test: p less than 0.05) with eight minor responses (MR) (tumor regressions between 4 and 45%) and six partial responses (PR) (between 50 and 84%). One case was not evaluable. A second volumetry after external irradiation was done in 14 patients, 18 weeks after IORT, showing 3 complete responses, 10 partial responses (62 to 84%), and 1 minor response (28%). The recent volumetries (10 patients) between 4.5 and 16.5 months after IORT showed 7 complete responses and 3 partial responses (63 to 94%). One patient died from intrabronchial hemorrhage at 7 weeks. Three others died from unrelated causes, 6, 12 and 14 months, respectively, after IORT and in one further case the cause of death at 15 months was local tumor regrowth. Within the median time elapsed since IORT (12 months) only this one case of local regrowth and one further case of distant spread were observed.

Aged↗

Intraoperative radiation with external irradiation: an alternative for nonresectable non-small-cell lung cancer?

In 15 patients with nonresectable non-small-cell lung carcinoma (NSCLC) (10 squamous, 1 large cell, 4 adenocarcinomas; T1-T3, N0-N2, all M0), lymph node dissection and intraoperative irradiation of the tumour (IORT) with doses between 10 and 20 Gy (11-20 MeV electron beam) was performed. Four weeks postoperatively 46-56 Gy external irradiation (8 or 23 MeV photons) was delivered to the mediastinum and 46 Gy to the tumour-bearing area. Four weeks postoperatively, 8 minor responses (MR, tumour regression between 4% and 45%) and 6 partial responses (PR, 50%-84%) were found. In 1 case, CT was inconclusive. Eighteen weeks after IORT, volumetry showed 3 CR, 9 PR (62% to 94%) and 1 28% MR. One patient died from intrabronchial hemorrhage 7 weeks after IORT (50% PR). Two others (both CR) died from unrelated causes, 6 and 12 months, respectively, after IORT. One patient (62% PR) died after 14 months from an unknown cause. Another patient died at 15 months from local relapse after CR. The latest CT volume assessment between 7.5 and 21.5 months, respectively, yielded 8 CR, and 1 63% PR. One further case of local CR has developed contralateral pulmonary metastasis after 10 months. All these patients are alive and well. The median time elapsed since IORT is 12.5 months, 10 patients have survived more than 12 months.

Aged↗

Computer simulation of tumor cell motility and proliferation.

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.

Cell Division↗

Tubulin expression in melanocytic skin tumors. An immunohistochemical study.

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.

Fibroblasts↗

Morphometric diagnosis of melanocytic skin tumors.

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.

Humans↗

The influence of staining procedures on the assessment of cell proliferation as defined by the monoclonal antibody Ki-67.

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.

Antigens, Surface↗

Quantitative evaluation of melanoma cell invasion in three-dimensional confrontation cultures in vitro using automated image analysis.

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.

Animals↗

Clinicopathologic study of cutaneous plasmacytoma.

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.

Aged↗

Immunohistochemical classification of cutaneous pseudolymphomas: delineation of distinct patterns.

Because of the broad spectrum of clinical and histological features, cutaneous pseudolymphomas are difficult to classify. To delineate objective criteria for classification, we investigated the immunoarchitecture of 53 cases of pseudolymphomas; 29 were classified as T cell pseudolymphomas. The immunohistologic characteristics were the absence of B cell compartments, the predominance of T helper-inducer cells and the presence of Langerhans cells/indeterminate cells. Lymphomatoid contact dermatitis showed the bandlike (superficial) T cell pattern. Lymphocytic infiltration of the skin, lymphomatoid papulosis, lymphomatoid drug reactions, and persistent nodules following assaults by arthropods revealed a nodular T cell pattern. Twenty-four cases represented B cell pseudolymphomas containing a nodular arrangement of B lymphocytes. In 6 lesions, there were B cell aggregates without the association of dendritic reticulum cells (non follicular B cell pattern); in 18, the B cell clusters were associated with dendritic reticulum cells and a typical expression of IgM and IgD, thus forming fully developed germinal centers (follicular B cell pattern). The B cell clusters were always surrounded by distinct T zones. B cell patterns were present in lymphadenosis benigna cutis, large cell lymphocytoma and occasionally, in persistent nodules, following assaults by arthropods.

Adolescent↗

Cutaneous metastases of a giant cell tumor of bone: case report.

A 47-year-old patient with the previous history of a giant cell tumor of the left femur presented with 3 cutaneous nodules located on the face. Histologic examination revealed skin metastases of a giant cell tumor of bone, with dermal and subcutaneous nodules characterized by multinucleate giant cells and mononuclear cells. The patient died 10 months later from widespread metastases to the lung and brain. A panel of enzymo- and immunohistochemical markers reactive and osteoclastic, fibroblastic and histiocytic determinants was tested on the cutaneous lesions. The results indicated osteoclastic lineage of the multinucleate giant cells whereas the mononuclear cells showed features of fibroblastic differentiation. Cutaneous metastasis from a giant cell tumor of bone is an extraordinary event and so far has only been reported once.

Bone Neoplasms↗

Early 'invasive' malignant melanoma of the glans penis and the male urethra. Report of a case and review of the literature.

A 40-year-old male with early 'invasive' malignant melanoma of the glans penis and meatus urethrae externus is presented. Early stages of primary melanoma of the glans penis and the male urethra are distinctly rare and are often clinically indistinguishable from penile lentigo, melanosis and melanocytic nevus on the genitalia. In order to avoid large and useless surgery on such a delicate location we propose a punch biopsy with subsequent histological examination prior to definitive surgical procedure. Whereas malignant melanoma of the penis with a thick Breslow index is treated with extended surgical management, only local excision of the tumor without groin dissection was performed in our patient.

Adult↗

[Cowden syndrome].

A patient with multiple hamartoma syndrome or Cowden's disease with multiple gastrointestinal polyps and malignant melanoma is presented. The syndrome is characterized by hamartomatous tumors of the skin, fibrocystic disease of the breasts, gastrointestinal polyps and disease of the thyroid gland such as goiter and adenoma. In addition, other abnormalities and malformations occur in the skeletal system, central nervous system and urogenital tract. Recognition of this syndrome is important because of the association with malignant tumors of the breast and thyroid gland and with malignant melanoma. Gastrointestinal hamartomatous polyps may lead to the diagnosis of Cowden's disease which must be separated from other intestinal polyposis syndromes.

Adenomatous Polyposis Coli↗

[Acute febrile neutrophilic dermatosis (Sweet syndrome). A retrospective clinical and histological analysis].

Acute febrile neutrophilic dermatosis (Sweet's syndrome) was first described in 1964. The condition presents with rapidly developing inflammatory plaques, a neutrophilic dermal infiltrate, fever and leucocytosis. In this study, clinical and histological features of 18 patients with Sweet's syndrome have been analysed. The arms (83%), face (67%) and legs (67%) were the most common sites of involvement. Morphologically, plaques, nodes and pseudo-vesicles prevailed. Elevated ESR (89%), fever (72%) and peripheral blood leucocytosis (44%) were noted in many, but not all, cases. Histology revealed a dermal infiltrate with numerous neutrophils (100%) without vasculitis. Nuclear dust (72%) and extravasation of erythrocytes (44%) were also encountered. Collagen degeneration was not observed. Differential diagnosis included erythema multiforme, erythema nodosum and adverse drug reaction. Possible causative factors observed were upper respiratory tract infection, gastrointestinal infection, and malignancies. Sweet's syndrome may be considered as an extreme manifestation within a continuous spectrum of cutaneous reactions to various stimuli or as an ill-defined entity that has some overlap with other dermatoses.

Acute Disease↗