Verhandlungen der Deutschen Gesellschaft für Pathologie
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Verh Dtsch Ges Pathol · Jan 2007
[Colorectal serrated adenoma: diagnostic criteria and clinical implications].
More than 40 years ago Morson (1962) coined the paradigm that adenomas are the main precursors of colorectal carcinoma (CRC) whereas hyperplastic polyps are "non-neoplastic" lesions without cancer risk. Later-on (1988) this was supported by Vogelstein's molecular adenoma-carcinoma progression model with APC mutations being a key-initiating molecular event (classic adenoma-carcinoma pathway). In 1992 a new molecular mechanism, the mutator pathway of CRC was discovered in HNPCC patients. ⋯ Today four categories of serrated lesions can be delineated: (i) the most frequent classic hyperplastic polyp (HP, 80-90%), followed by (ii) sessile serrated adenoma (SSA, 15-20%) and (iii) by the rare traditional serrated adenoma (TSA, < 1%). Whereas HPP are benign, SSA are probably slowly progressing lesions and TSA as well as SSA with APC-type adenomatous atypias (iv. mixed SSA) indicate increased cancer risk. Molecularly serrated polyps seem to share a defect in apoptosis caused by either K-ras or BRAF gene mutation leading to CpG island methylation (CIMP) affecting MLHI (--> MSI type CRC) or non-MMR oncogenes (--> MSI-L or MSS type serrated CRC, Mäkinen 2007).
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Testicular germ cell tumors comprise of group of pluripotent tumors including seminomas and nonseminomas, arise from intratubular germ cell neoplasia and originate from the primordial germ cells/ gonocytes. Many well characterized markers of embryonic stem cells including CD9, PODXL and centromere-specific histone-H3-like protein CENPA are consistently expressed in TGCTs. In embryonic stem cells, pluripotency and self renewal capacities are provided by a network of OCT3/4, NANOG and SOX2. ⋯ Moreover, the genetic constitution of testicular germ cell tumors can also be linked to characteristics of embryonic stem cells, likely related to their specific inability to repair DNA damage and their high sensitivity to apoptotic cell death. In conclusion, testicular germ cell tumors represent embryonic cancers found in adults. Both the seminomas and nonseminomas have their specific population of stem cells representative of the primordial germ cells/gonocytes and for embryonic stem cells, respectively.
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While most colorectal polyps can be classified as either adenomas (AD) or hyperplastic polyps (HP), approximately 5 % have some of the features of these lesions but are distinguishable from both. These lesions include sessile serrated adenoma or polyp (SSP), mixed polyp (MP), and traditional serrated adenoma (SA). These relatively recently described entities account for only about 3%, 1% and 1% of colorectal polyps respectively. ⋯ Finally, a simple working nomenclature for the diagnostic reporting of colorectal polyps is suggested. In this system, MPs and SAs are combined as 'serrated polyps with dysplasia'. It is likely that the recognition and diagnosis of serrated polyps of the colorectum will assume increasing importance in the coming years and that their complex morphology and molecular heterogeneity will present interesting challenges for pathologists, scientists and clinicians.
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HER-2 belongs to a family of four transmembrane receptor tyrosine kinases that mediate growth, differentiation and survival of cells. HER-2 overexpression and amplification occurs in approximately 15 to 25 % of breast cancers and is associated with aggressive tumour behaviour. Herceptin (trastuzumab), a humanized monoclonal antibody directed against the extracellular domain of the HER-2 receptor, has been shown to have clinical activity in HER-2-positive advanced breast cancer when administered alone or in combination with chemotherapy. ⋯ These results caused an immediate wave of demand for Herceptin in adjuvant therapy. Results of these studies are critically reviewed. Furthermore, the available preliminary results from studies using Herceptin in the primary (neoadjuvant) therapy of HER-2-positive breast cancer are addressed and possible implications for HER-2 testing are discussed.
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Verh Dtsch Ges Pathol · Jan 2006
[Urothelial neoplasms in individuals younger than 20 years show very few genetic alterations and have a favourable clinical outcome].
Urothelial neoplasms in patients 19 years or younger are rare, with conflicting data regarding clinical outcome and no molecular data available. ⋯ Urothelial neoplasms in individuals younger than 20 years have predominantly a low grade and favourable clinical outcome. The most frequent genetic alterations found in elderly patients are extremely rare. Urothelial neoplasms in young patients could represent a biologically distinct form of bladder disease with lack of genetic instability in most cases.