Kutane Sarkome.

Cutaneous sarcomas comprise a heterogeneous group of mesenchymal spindle cell tumors of the dermis and subcutis, one of the best-known entities being dermatofibrosarcoma protuberans. Other sarcomas addressed in this review include a typical fibroxanthoma, cutaneous undifferentiated pleomorphic sarcoma, leiomyosarcoma, liposarcoma, and angiosarcoma. With the exception of dermatofibrosarcoma protuberans, which has its peak incidence in middle-aged adults, cutaneous sarcomas usually occur in elderly individuals starting in the sixth or seventh decade of life. The pathogenesis of the various disease entities is not uniform and has not been definitively ascertained. Histology is the key to arriving at a correct diagnosis, and should always include ruling out other dermal neoplasms such as melanoma. In recent years, molecular genetic methods have provided greater insight into the pathogenesis, thus paving the way for new targeted therapies. Treatment of choice for cutaneous sarcomas is excision with sufficient surgical margins. Adjuvant and neoadjuvant therapeutic concepts include radiation therapy and the use of targeted therapies or chemotherapies. Local recurrences have frequently been reported in cutaneous sarcomas. Unlike soft tissue sarcomas, the prognosis in terms of survival - with the exception of angiosarcoma - is very good if treated adequately, a fact that should be emphasized to patients.

Cutaneous sarcomas.

Cutaneous sarcomas comprise a heterogeneous group of mesenchymal spindle cell tumors of the dermis and subcutis, one of the best-known entities being dermatofibrosarcoma protuberans. Other sarcomas addressed in this review include atypical fibroxanthoma, cutaneous undifferentiated pleomorphic sarcoma, leiomyosarcoma, liposarcoma, and angiosarcoma. With the exception of dermatofibrosarcoma protuberans, which has its peak incidence in middle-aged adults, cutaneous sarcomas usually occur in elderly individuals starting in the sixth or seventh decade of life. The pathogenesis of the various disease entities is not uniform and has not been definitively ascertained. Histology is the key to arriving at a correct diagnosis, and should always include ruling out other dermal neoplasms such as melanoma. In recent years, molecular genetic methods have provided greater insight into the pathogenesis, thus paving the way for new targeted therapies. Treatment of choice for cutaneous sarcomas is excision with sufficient surgical margins. Adjuvant and neoadjuvant therapeutic concepts include radiation therapy and the use of targeted therapies or chemotherapies. Local recurrences have frequently been reported in cutaneous sarcomas. Unlike soft tissue sarcomas, the prognosis in terms of survival - with the exception of angiosarcoma - is very good if treated adequately, a fact that should be emphasized to patients.

Fast raster-scan optoacoustic mesoscopy enables assessment of human melanoma microvasculature in vivo.

Melanoma is associated with angiogenesis and vascular changes that may extend through the entire skin depth. Three-dimensional imaging of vascular characteristics in skin lesions could therefore allow diagnostic insights not available by conventional visual inspection. Raster-scan optoacoustic mesoscopy (RSOM) images microvasculature through the entire skin depth with resolutions of tens of micrometers; however, current RSOM implementations are too slow to overcome the strong breathing motions on the upper torso where melanoma lesions commonly occur. To enable high-resolution imaging of melanoma vasculature in humans, we accelerate RSOM scanning using an illumination scheme that is coaxial with a high-sensitivity ultrasound detector path, yielding 15 s single-breath-hold scans that minimize motion artifacts. We apply this Fast RSOM to image 10 melanomas and 10 benign nevi in vivo, showing marked differences between malignant and benign lesions, supporting the possibility to use biomarkers extracted from RSOM imaging of vasculature for lesion characterization to improve diagnostics.

Expression patterns of transcription factors in progressively transformed germinal centers and Hodgkin lymphoma.

The World Health Organization (WHO) classification of Hodgkin lymphoma (HL) distinguishes two types: Classical Hodgkin lymphoma (CHL) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). Both groups have in common that they mostly derive from B cells with rare classical cases originating from T cells. They differ in their histomorphology, immunophenotype, and clinical behavior. One of the subtypes of CHL, designated as lymphocyte-rich classical Hodgkin lymphoma (LRCHL), shares some morphological features with NLPHL. The transcription factors BSAP, BOB.1, Oct2 and MUM1 are sequentially expressed in normal B-cell development. In order to investigate the relationship between the CHL subgroups and NLPHL, we examined the protein expression of these transcription factors using immunohistochemistry in 15 reactive processes and 4 different subtypes of 58 HL cases. Our findings underline the B-cell origin of HL, without evidence, that reactive processes like progressively transformed germinal centers (PTGCs) are precursor lesions of HL. Furthermore, they demonstrate that LRCHL is distinct from NLPHL and that it is closely related to the mixed cellularity CHL (MCHL) in respect of BSAP, BOB.1, and Oct2 expression. It therefore occupies an intermediate position between MCHL and NLPHL. Based on MUM1 staining, LRCHL exhibits a more mature phenotype than NLPHL.

Expression of ZAP-70 protein correlates with disease stage in chronic lymphocytic leukemia and is associated with, but not generally restricted to, non-mutated Ig VH status.

The mutational status of immunoglobulin variable region genes (Ig VH) is a well established prognostic parameter in chronic lymphocytic leukemia (CLL). Recently, a subset of genes with a characteristic expression profile correlating with the mutational status of B-CLLs has been identified. One of the overexpressed genes in the prognostically unfavorable group of CLL patients with unmutated Ig VH genes encodes for the protein tyrosine kinase ZAP-70, which is physiologically involved in T-cell signaling. Since ZAP-70 has been described to be prognostically relevant in CLL, we analyzed the possible relationship of its expression to the mutational status of Ig VH genes as well as to other prognostic factors in CLL and indolent lymphomas. The mutational status of Ig VH genes was analyzed by seminested PCR, direct sequencing and comparison with the sequences of the EMBL databases in 60 samples of patients with B-CLL and 18 samples of patients with indolent B-cell malignancies. ZAP-70 protein expression was assessed in all samples by immunoblotting and for semiquantitative analysis the ratio of ZAP-70 to tubulin expression was calculated. ZAP-70 protein was found to be expressed in all investigated B-cell malignancies. Expression levels varied within a wide range in each entity. The highest mean level of ZAP-70 expression was observed in unmutated B-CLLs, however, with broad expression variability. High levels of ZAP-70 expression correlated with higher stage Binet B or C and with unmutated Ig VH genes. Overall survival rates estimated by Kaplan-Meier curves did not differ among patients with high or low ZAP-70 expression. We conclude that ZAP-70 is associated with the mutational status of Ig VH genes, but this expression pattern is not present in all individual cases. Furthermore, high levels of ZAP-70 correlated with Binet stages B or C indicating an involvement of ZAP-70 in mechanisms promoting growth of B-CLL cells.