Trypsin Expression in Pancreatic Neuroendocrine Carcinomas: Potential Diagnostic Pitfall and Prognostic Marker
Rondell P Graham, Thomas C Smyrk, Lizhi Zhang. Mayo Clinic, Rochester, MN
Background: Trypsin immunohistochemical stain is considered a specific marker for acinar cell carcinoma of pancreas. However, in our consultation practice, we have seen cases of metastatic pancreatic neuroendocrine carcinoma (PNECs) which label strongly and diffusely with chromogranin and synaptophysin showing focal trypsin expression. The significance of focal trypsin positivity in PNEC is unknown. In this study, we sought to determine the clinicopathologic characteristics of PNEC with focal trypsin expression and compared them to those without trypsin expression.
Design: We retrieved 132 PNECs from our database and obtained clinical and follow up data. Immunohistochemistry for trypsin was performed. For each trypsin positive case, a PAS-Diastase stain was done and confirmatory electron microscopy (EM) was performed on a single case. Trypsin–positive cases were compared to trypsin-negative cases for differences in survival and other clinicopathologic features. Available metastases associated with trypsin-positive primary tumors were also evaluated with the trypsin stain.
Results: Of the 131 cases of PNEC, 9 (6.8%) showed focal trypsin expression in tumor cells. There were 8 men and 1 woman with a median age of 58 years. The trypsin-positive cases all had some cells with PAS-D positive cytoplasmic granules, and the single case assessed by EM revealed tumor cells with zymogen granules. Four of 5 metastases tested also showed focal trypsin positivity. The trypsin-positive tumors were functional in 6 of 7 cases, the median Ki-67 was 3.3% (range 1.4-7) and they were associated with liver metastases in 7 of 9 cases. By comparison, trypsin-negative tumors were functional in 56% of cases, had a median Ki-67 of 2.5% (range 0-25) and were complicated by metastases in 48%. Follow up data were available for 129 of 131 cases. At 5 and 10 years, tumor specific survival for patients with trypsin-positive tumors were 38% and 38% compared to 85% and 56% for those with trypsin-negative tumors (log-rank test p=0.035).
Conclusions: Rare PNEC may show focal trypsin positivity, which can be a potential diagnostic pitfall when evaluating small biopsies. We do not consider these tumors a type of mixed acinar-neuroendocrine carcinoma because of very focal trypsin expression in a background of nearly 100% cells positive for neuroendocrine cell markers. Still, when compared to trypsin-negative tumors, these tumors seem to have more aggressive clinical behavior. We hypothesize that trypsin expression in PNEC may represent an exocrine phenotype which portends a worse prognosis.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 212, Tuesday Morning