[Centrifugal plaques with central atrophy and peripheral scale on the scalp]. / Zentrifugale Plaques mit zentraler Atrophie und peripherem Hornwall am Capillitium.

A 62-year-old man presented with slowly progredient, centrifugal, peripherally hyperkeratotic, centrally atrophic, slightly pruritic lesions on his scalp for at least 9 months. A punch biopsy stained with hematoxylin-eosin (HE) revealed minimal epidermal acanthosis and chimney-like parakeratosis (cornoid lamella) around a follicle. Discrete spongiosis of the epidermis was observed, as well as a lymphocytic cell infiltration in the papillary dermis. Based on the clinical picture and the histopathological examination the diagnosis of porokeratosis of Mibelli was made. Topical treatment was started using an urea and vitamin A acid preparation.

[Extranodal Rosai Dorfman disease (sinus histiocytosis with massive lymphadenopathy). Report of 5 cases]. / Extranodale Rosai-Dorfman-Erkrankung (Sinushistiozytose mit massiver Lymphadenopathie). Ein Bericht über fünf Fallbeobachtungen.

Sinus histiocytosis with massive lymphadenopathy (SHML) was described in 1969 by Rosai and Dorfman as an benign disorder of the lymph nodes. Involvement of extranodal sites by SHML may occur as part of a generalized disease involving lymph nodes as well as independently of the lymph node status. The clinical course is mostly benign and indolent, but in rare cases the SHML can cause death. We report 5 cases of extranodal Rosai Dorfman disease (ENSHML). The lesions were localized in the soft tissue of the extremities, the head and the skeleton. Histopathological examination revealed a lymphoplasmacellular infiltration and numerous histiocytes with an eosinophilic cytoplasma and vesicular nuclei with basophilic nucleoli. The histiocytes showed emperipolesis with multiple lymphocytes within the cytoplasm and occasionally phagocytosis of other inflammatory cells. The histiocytes were immunohistochemically positive for S 100 protein and macrophage-specific antibodies, but in paraffin material negative for CD1a. We briefly discuss aspects of differential diagnosis of this lesion, too.

Pansclerotic morphea in childhood: a case report.

Scleroderma can be differentiated into progressive systemic and circumscript forms. The extensive form with lethal outcome is known from case reports of children and adolescents. The present case report concerns a boy who died at 16 years of age. In the 5th year of life, he experienced weight loss and developed multiple, firm, partially atrophic plaques in the skin of the extremities. These plaques gradually became confluent and extended over the whole torso and head. Plaque ulceration resulted in massive mutilations to the body. Later the patient's cachexia worsened and he developed keratose, moderately differentiated squamous cell carcinoma of the right leg. The prognosis of pansclerotic morphea for children is worse than for adults. No successful therapy is known.

[Sclerosing epithelioid fibrosarcoma]. / Sklerosierendes epitheloides Fibrosarkom.

The sclerosing epithelioid fibrosarcoma (SEF), defined as an entity by Meis-Kindblom et al. in 1995 [15] is now considered to be a variant of fibrosing fibrosarcomas. It is a rare tumor with an intermediate malignant potential leading to local recurrences in one third and to metastases in about 40% of the cases. We report six cases of this entity. At the time of diagnosis two patients of our series already showed metastases in the lungs. The tumors were located in the deep soft tissue and measured between 2.5 and 17 cm. The histology is characterized by small epithelioid cells that are arranged individually or in cords and nests and set typically in a hyaline sclerotic matrix. By immunohistochemistry, all cases were vimentin positive, however EMA positive cells are also possible. The differential diagnosis includes metastases of carcinoma, benign and malignant soft tissue tumors. The distinction of SEF from fibromatosis, fibrous histiocytomas, ossifying fibromyxoid tumors, clear cell sarcomas, epithelioid sarcomas, synovial sarcomas and extraskeletal osteosarcomas is discussed.

Large-scale methylation analysis of human genomic DNA reveals tissue-specific differences between the methylation profiles of genes and pseudogenes.

Cytosine in CpG dinucleotides is frequently found to be methylated in the DNA of higher eukaryotes and differential methylation has been proposed to be a key element in the organization of gene expression in man. To address this question systematically, we used bisulfite genomic sequencing to study the methylation patterns of three X-linked genes and one autosomal pseudogene in two adult individuals and across nine different tissues. Two of the genes, SLC6A8 and MSSK1, are tissue-specifically expressed. CDM is expressed ubiquitously. The pseudogene, psi SLC6A8, is exclusively expressed in the testis. The promoter regions of the SLC6A8, MSSK1 and CDM genes were found to be essentially unmethylated in all tissues, regardless of their relative expression level. In contrast, the pseudogene psi SLC6A8 shows high methylation of the CpG islands in all somatic tissues but complete demethylation in testis. Methylation profiles in different tissues are similar in shape but not identical. The data for the two investigated individuals suggest that methylation profiles of individual genes are tissue specific. Taken together, our findings support a model in which the bodies of the genes are predominantly methylated and thus insulated from the interaction with DNA-binding proteins. Only unmethylated promoter regions are accessible for binding and interaction. Based on this model we propose to use DNA methylation studies in conjunction with large-scale sequencing approaches as a tool for the prediction of cis-acting genomic regions, for the identification of cryptic and potentially active CpG islands and for the preliminary distinction of genes and pseudogenes.

Genetic alterations in metastatic renal cell carcinoma detected by comparative genomic hybridization: correlation with clinical and histological data.

In order to optimize the management of patients with renal cell carcinoma (RCC) it is important to define the genetic risk for metastatic disease. In this study we performed comparative genomic hybridization (CGH) on metastatic tumors aiming at the identification of genetic alterations associated with metastatic disease. We analyzed 46 renal tumors along with their metastases, and 15 non-metastatic renal tumors. Tumors were classified pathologically according to the Heidelberg classification of RCC, and staged according to the TNM-system. Standard CGH was performed using microdissected archival tissues and DOP-PCR. The average numbers of chromosomal aberrations per tumor were 3.0, 2.1 and 3.9 in patients without metastasis, in patients who developed metastases after a two-year latency period (late onset of metastatic disease) and in patients who developed metastases within two years after therapy of the primary tumor (early onset of metastatic disease). CGH revealed chromosomal aberrations in 91% of primary metastatic tumors. Deletions or losses of chromosomes 9 (26% vs 6%), 10 (21% vs 6%) and 18 (23% vs 0) and 17 (28% vs 7%) occurred more often in metastatic tumors than in non-metastatic tumors. Furthermore, these aberrations were more common in patients with early metastases. CGH analysis of 40 pairs of primary RCCs and their corresponding metastasis revealed similar aberrations in 70% of cases. In 30%, however, metastases showed additional chromosomal aberrations not detected in the corresponding primary tumors. In conclusion, we identified genetic alterations associated with metastatic disease in RCC which could be useful for predicting prognosis. Genetic changes leading to metastases occurred early in tumorigenesis of metastatic tumors.

The correlation of p53 protein overexpression and p53 antibodies in serum of patients with transitional cell carcinoma of the urinary bladder.

BACKGROUND: Mutations of p53 gene were demonstrated in many solid tumors with varying frequency. We analyzed the relationship between p53 protein expression in bladder cancer tissue, p53 autoantibodies in serum and the clinical course of 32 patients with and 10 patients without transitional cell carcinoma of the urinary bladder. MATERIALS AND METHODS: In the 32 patients studied, bladder cancer was diagnosed as pTaG1-2 in 8 cases, pT1G2 in 6, pT1G3 in 7, pT2G2-3 in 7, pT3G2-3 in 3 and pT4 in 1 patient. Anti-p53 antibodies were detected by an enzyme-linked immunosorbent assay. Immunohistochemical staining was performed using a standardized alkaline phosphatase monoclonal anti-alkaline phosphatase method. To prove the statistical significance of tumor grading and staging, the Kruskal-Wallis test was applied (p < 0.01). The mean follow-up was 26 months. RESULTS: We found 12.5% p53 autoantibody-positive sera without a statistically significant correlation with tumor grade (p = 0.0569) and category (p = 0.612). Three of 4 patients who had p53 autoantibody-positive sera died within 9 months. All of these sera-positive patients had p53 protein-positive tumor tissue. Control sera were all negative for p53 autoantibodies. CONCLUSION: This study shows a strong relationship between p53 protein overexpression and the occurrence of p53 autoantibody in bladder cancer. The expression of p53 autoantibodies seems to be an event in cases of bladder cancer with an unfavorable tumor-specific outcome. Because of the small number of cases and the short follow-up time, further quantitative studies will hopefully demonstrate whether this might be of prognostic importance.

Genetic characterization of multifocal tumor growth in renal cell carcinoma.

The primary cancer found in the kidney is renal cell carcinoma (RCC), which does not as yet have a delineation of the types of lesions that progress to tumor malignancy. We studied tissues from primary tumors and secondary lesions, and compared it with the surrounding normal kidney tissue using comparative genomic hybridization to determine their potential for malignancy. Although our sample size was small, we found that small multifocal tumors have the same potential as primary carcinoma to lead to RCC malignancy. Further genetic studies in a larger sample of patients is necessary before the risk of different lesions to remain benign or progress to RCC can be defined absolutely.

[Tyrosine-rich crystalloids in a myoepithelioma of the minor salivary glands in the smooth palate]. / Tyrosinreiche Kristalloide in Einem Myoepitheliom der kleinen Speicheldrüsen des Gaumens.

Tyrosine-rich crystalloids in tumors of the salivary glands are rare and have been reported mainly in specimens from Black African patients. The pathogenesis of these structures is still unclear, but pathological secretion by neoplastic myoepithelial cells is supposed. Millon's staining and ultrastructural examinations are used for confirming the diagnosis. We present the case report of a 59-year-old woman with a myoepithelioma of the minor salivary glands in the smooth palate containing tyrosine-rich crystalloids as an example of this rare phenomenon.

Differentiation of multifocal renal cell carcinoma by comparative genomic hybridization.

Multifocality occurs in 12-22% of all renal cell carcinoma (RCC) cases. In order to differentiate multifocal RCC, we performed comparative genomic hybridization (CGH) and correlated the results with histopathological and clinical data. After histopathological examination of multifocal tumors, tumor areas were dissected from histopathological sections. Isolated DNA was amplified by DOP-PCR. CGH was performed according to standard protocols. Twenty cases were analyzed. In eight cases, at least one identical aberration was detected in the related tumors. Another eight cases showed different chromosomal changes in tumors of the same kidney. In the small additional clear cell tumors typical genetic alterations of clear cell carcinomas were detected whereas in the chromophilic tumors aberrations characterizing both adenomas and carcinomas were found. From these results we conclude that multifocal RCC represents a heterogeneous group of tumors. The malignant potential of small additional tumors in multifocal RCC cannot be excluded.

Synthesis and protein distribution of the unspliced large tenascin-C isoform in oral squamous cell carcinoma.

The inclusion or omission of the alternatively spliced region in the tenascin-C (Tn-C) mRNA gives rise to the large (Tn-C(L)) or small (Tn-C(S)) variant, respectively. Tn-C(L) is thought to be a typical component of provisional extracellular matrices (ECMs) and is expressed during tumour stroma remodelling. Tn-C(L) synthesis has been studied using RNA/RNA in situ hybridization, and Tn-C(L) protein distribution, using immunohistochemistry (clone BC-2), in 18 oral squamous cell carcinomas (OSCCs) of different grades of malignancy. While the Tn-C(L) protein was demonstrated within the whole stromal compartment regardless of grade of malignancy, the majority of the Tn-C(L) mRNA signal-bearing cells were carcinoma cells. Only a few stromal myofibroblasts were able to synthesize Tn-C(L), as revealed by alpha-smooth muscle actin double staining. In well-differentiated carcinomas (G1), the Tn-C(L) synthesizing carcinoma cells were localized as a single positive cell layer in the tumour stroma interface, particularly in invasive areas. A higher grade of malignancy (G2/G3) is associated with a significantly increased number of Tn-C(L) synthesizing carcinoma cells randomly distributed within the invading tumour areas. Double-staining experiments (Tn-C(L) mRNA ISH/BC-2 immunohistochemistry) indicate that these cells are capable of organizing and depositing a three-dimensional Tn-C(L) matrix. Even though an instructive and/or inductive role of the carcinoma cells in tumour stroma formation cannot be excluded, these results demonstrate that carcinoma cells can directly produce the ECM components of tumour stroma.

Quantitative evaluation of apoptosis and proliferation in renal cell carcinoma. Correlation to tumor subtype, cytological grade according to thoenes-classification and the occurrence of metastasis.

To analyse growth characteristics of human renal cell tumors, 66 renal cell carcinomas and one oncocytoma were investigated concerning the proliferative activity by immunohistochemical demonstration of the Ki-67 antigen (clone MIB1) and the apoptotic rate using the terminal deoxynucleotidyl-transferase mediated dUTP-fluorescin nick end labelling (TUNEL) method. The TUNEL method indicates DNA double strand breaks considered as a hallmark of programmed cell death (apoptosis). Apoptotic cells were observed in 57 of 67 cases. The apoptotic rate (percentage of stained tumor cells) varied from 0% to 54.1%. GI carcinomas possessed a statistically significant higher apoptotic rate than GII/GIII carcinomas. The proliferation index (percentage of Ki-67 labelled cells) ranged from 0.09% to 22.3%. The well differentiated carcinomas (GI) showed statistically lower proliferative activity than moderate and poorly differentiated carcinomas (GII/GII). The clear cell variant of renal cell carcinoma expressed a higher apoptotic rate than the chromophilic variant. A statistical correlation between apoptosis/proliferation and occurrence of metastasis could not be established. In progression from well to less differentiated renal cell carcinoma the decrease of apoptotic rate, as well as the increase of the proliferative activity, contributes to a rapid tumor growth.