Answer 1: A. Adenocarcinoma, pancreas.
Answer 2: D. All of the above.
A 41-year-old male carrying the diagnosis of Peutz-Jeghers syndrome complains of upper abdominal pain radiating to the back and a 15-pound weight loss. Laboratory studies and imaging prompt surgery. Tissue obtained from the surgery reveals the slide above.Comment: Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease in which most cases (estimated from 66% to 99%) contain a mutation of STK11/LKB1, a tumor suppressor gene. PJS is typified by gastrointestinal symptoms including obstruction, abdominal pain, rectal bleeding, multiple polyps within the jejunum and colon, and abnormal mucocutaneous pigmentation. Of interest, the intestinal polyps are typically hamartomas. However, these patients also, when compared to the general population, have a 15-fold increased risk of developing intestinal cancers, of which 36% are pancreatic. About 90% to 95% of human pancreatic carcinomas are ductal. Human pancreatic adenocarcinomas have a high mutation rate of the oncogene K-ras and also either overexpression or mutation of the tumor suppressor p53 gene. Of interest, overexpression has been attributed to survival difference but the association is still controversial.
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Reference:
1. Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321:1801-1806. PMID: 18772397
2. Hermann PC, Huber SL, Herrler T, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007;1:313-323. PMID: 18371365
3. Aretz S, Stienen D, Uhlhaas S, et al. High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat. 2005;26:513-519. PMID: 16287113
4. Amos CI, Keitheri-Cheteri MB, Sabripour M, et al. Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet. 2004;41:327-333. PMID: 15121768
5. Tuveson DA, Hingorani SR. Ductal pancreatic cancer in humans and mice. Cold Spring Harb Symp Quant Biol. 2005;70:65-72. PMID: 16869739
6. Hruban RH, Adsay NV, Albores-Saavedra J, et al. Pathology of genetically engineered mouse models of pancreatic exocrine cancer: consensus report and recommendations. Cancer Res. 2006;66:95-106. PMID: 16397221
