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.