A Proposed Histopathologic Grading System Derived from a Study of KIT and CK19 Expression in Pancreatic Endocrine Tumors
LN Dao, TC Smyrk, RV Lloyd, CM Lohse, L Zhang. Mayo Clinic, Rochester, MN
Background: Predicting the behavior of pancreatic endocrine tumor (PET) in the absence of local invasion or metastasis is difficult. We recently identified KIT as an independent prognostic marker for PET and proposed an immunohistochemical classification system based on a combination of KIT and CK19 expression: low risk (KIT-/CK19-); intermediate risk (KIT-/CK19+); high risk (KIT+/CK19+). Survival, metastases, and recurrence of PET were significantly different between the three groups. In this study, we sought to correlate histopathologic features with the immunohistochemical categories.
Design: We compared pathologic findings of 97 PETs which had been classified into three groups based on KIT/CK19 expression. Clinicopathological associations with prognosis were evaluated using Cox proportional hazards regression models.
Results: Tumor size, mitosis, necrosis, tumor border, extrapancreatic extension, and perineural invasion were significantly different between the three groups. A scoring system using mitosis, necrosis, and tumor border was developed as following: mitosis (per 50 HPF): 0 (0), 1 (1-3), 2 (≥4); necrosis: 0 (absent), 1 (present); tumor border: 0 (non-infiltrating), 1 (infiltrating), giving a possible histology score of 0 to 4. While there was an overall difference in disease-specific survival between the groups, there was not a statistically significant difference between patients with scores of 0 and 1 or with scores of 3 and 4. Therefore, a three-tiered grading system was developed by combining score 0/1 tumors as grade 1, score 2 tumors as grade 2, and score 3/4 tumors as grade 3. There was a significant difference in outcome between the three grades. We also compared grade to tumor metastasis and recurrence. Nineteen percent of grade 1 PET had metastasis at the time of surgery, compared to 73% and 99% of grade 2 and 3 tumors. Tumor recurred in 6% grade 1 patients, compared to 46% of those with grade 2 or 3 tumors.
Conclusions: This histopathologic grading system derived from KIT/CK19 expression correlates with clinical behavior of PET. The use of reproducible parameters (mitosis, tumor necrosis, infiltrative border) makes this an easy grading system for pathologic evaluation of PET.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 92, Monday Morning