Pathology and Genetics
01 Jan 2010-pp 11-18
TL;DR: Local aggressiveness consists in the invasion of contiguous structures and organs (spleen, stomach, left adrenal gland, colon, and peritoneum), whereas distant metastases can occur in liver, lungs, adrenals, kidneys, bones, brain, and skin.
Abstract: PDAC is an aggressive disease and early infiltrates peripancreatic tissues and adjacent organs, and gives distant metastasis and peritoneal involvement, making often surgical resection impossible. About 80% of PDACs are inoperable at the time of diagnosis. However, even if radiologically resectable, some PDAC microscopically involves the resection margins (pancreatic, retroperitoneal, or biliary, the retroperitoneal being the most important because it cannot be evaluated intraoperatorially) resulting in a nonradical excision. Local aggressiveness consists in the invasion of contiguous structures and organs (spleen, stomach, left adrenal gland, colon, and peritoneum), whereas distant metastases can occur in liver, lungs, adrenals, kidneys, bones, brain, and skin.
Citations
More filters
TL;DR: At present, oral lichen planus seems to be accepted in the literature as being a potentially malignant disorder, although the risk of malignant transformation is lower than in leukoplakia, and the efficacy of follow-up of oral lichens planus is questionable.
687 citations
TL;DR: The various pathways to colorectal carcinoma are reviewed with emphasis on the serrated pathway and the implications of this pathway for coloreCTal carcinomas screening programs are evaluated.
591 citations
Medical University of Vienna1, Harvard University2, Technische Universität München3, Mayo Clinic4, National Institutes of Health5, University of Cologne6, University Of Tennessee System7, Gdańsk Medical University8, University of Salamanca9, Virginia Commonwealth University10, Ludwig Maximilian University of Munich11, University of Naples Federico II12
TL;DR: Criteria for diagnosing MCA and related disorders are defined by robust and generally applicable criteria and should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice.
Abstract: Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of ‘MCA syndromes’ (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets.
509 citations
TL;DR: There is now emerging and compelling evidence that many high grade serous carcinomas (by far the most common subtype of ovarian carcinoma) actually arise from the epithelium of the distal fallopian tube, and future studies regarding the initiating molecular events in the development of this aggressive neoplasm should concentrate on this site.
451 citations
TL;DR: Current classifications for kidney cancer have undergone dramatic changes over the past two decades, and it is stressed that each subtype harbors unique biology and thus responds differently to available treatment strategies.
392 citations
References
More filters
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
28,811 citations
TL;DR: It is found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations, which defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors.
Abstract: There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, we searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for approximately 10(6) single-nucleotide polymorphisms. We found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. Our data indicate that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis.
3,721 citations
TL;DR: Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis and a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors was found.
Abstract: Pancreatic neuroendocrine tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of 10 nonfamilial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. The most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN1, which encodes menin, a component of a histone methyltransferase complex, and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain-associated protein) and ATRX (α thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis. We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors.
1,486 citations
"Pathology and Genetics" refers background in this paper
...Mutations in oncogenes are never or rarely observed in PanNENs [31, 32]....
[...]
...A recent systematic whole-exome analysis exploiting next-generation sequencing technologies confirmed that MEN1 gene mutations are the most relevant anomalies in PanNEN [32]....
[...]
TL;DR: The tumor–node–metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference is reported.
Abstract: The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor–node–metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.
1,424 citations
"Pathology and Genetics" refers background in this paper
...The European Neuroendocrine Tumor Society (ENETS) has proposed a tumornode-metastasis (TNM)-based staging system for PanNEN [17] to which subsequent modifications have been proposed [18]....
[...]