A 41 yo 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 following:
Your diagnosis is:
- Adenocarcinoma, pancreas
- Neuroendocrine cancer, pancreas
- Adenocarcinoma, intestine
- Hamartoma, intestine
Genetic studies of this patient would most likely reveal:
- STK11/LKB1 mutation
- P53 mutation
- K-Ras mutation
- All of the above
Scroll below for answers.
Answer 1: a, Adenocarcinoma, pancreas.
Answer 2: 4, All of the above.
Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disease in which most cases (estimated from 66-99%) contain a mutation of STK11/LKB1, a tumor suppressor gene. PJS is typified by GI 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 90-95% 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.
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses. Sian Jones et al, Science 321:pp1801-1806, 26 Sept 2008, DOI:10.1126science.1164368
Distinct Populations of Cancer Stem Cells Determine Tumor Growth and Metastatic Activity in Human Pancreatic Cancer, Hermann, Patrick C. et al, Stem Cell, 2007, DOI10.1016/j.stem2007.06.002
High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Aretz S. et al. Hum Mutat. 2005;26:513–9.
Genotype-phenotype correlations in Peutz-Jeghers syndrome. Amos CI , et al .J Med Genet. 2004;41:327–33
Powered by Facebook Comments
- Slide of the Week Answers: Stomach Mass, September 19th, 2011
- Slide of the Week: Li-Fraumeni Syndrome, October 17th, 2011
- Slide of the Week: Clear Cell Carcinoma, Kidney, May 3, 2011
- Slide of the Week: Stomach Mass, September 19th, 2011
- Slide of the Week: Young Female with Breast Mass, October 31st, 2011