ROLE OF NUMBER AND SIZE OF NERVES INVOLVED BY PANCREATIC ADENOCARCINOMA IN PREDICTING RECURRENCE AND SURVIVAL
Simran Mashiana*, Joseph Rohr, Benjamin J. Swanson, Chandrakanth Are, Quan P. Ly, Kelsey Klute, Mridula Krishnan, Chi Lin, Audrey J. Lazenby
University of Nebraska Medical Center, Omaha, NE
Background
For pancreatic adenocarcinoma (PA), surgical resection is considered as the only potentially curative therapy, but a vast majority of these patients succumb, with local recurrence or metastatic disease. Although PA shows a high prevalence of perineural invasion (PNI), results in the literature vary on the importance of PNI for survival and recurrence. The current NCCN guidelines do not include PNI as a marker for postoperative adjuvant therapy. The current College of American Pathologists template only specifies PNI as "not identified" or "present." The purpose of this study was to provide additional detail on PNI (number and size of involved nerves) and correlate this with clinicopathologic data including recurrence and overall survival (OS).
Design
A retrospective review of 93 resections for PA from January 2014 to December 2017 was conducted. 36 cases were excluded due to lack of complete follow up or non-availability of all slides. Of the 57 cases, 27 were males and 30 females, with age from 37 to 85 years. 13 patients (22.8%) had received neoadjuvant therapy. We performed detailed examination of PNI for number, location and diameter of the nerves involved. PNI was defined as the presence of tumor cells within a nerve, in the perineural space, or adherent to a nerve, causing deformation. The diameter of the largest nerve for each case was used for analysis. The number of blocks with tumor and PNI were also noted. Clinical data were collected from medical records. Spearman rank correlation and log-rank (Mantel-Cox) tests were performed.
Results
Of 57 cases, 49 (85.96%) showed PNI (Figure 1). A median of 4 nerves per case (range: 1-65) were involved, with maximum diameters of 0.03 -3.05 mm. A median of 8 paraffin blocks (range: 1-32) showed tumor. There was an inverse correlation between presence of PNI and OS (r=-0.4383, p=0.0013). Patients with involvement of three or more nerves had shorter OS (p=0.0046) and recurrence intervals (p=0.0027) (Figure 2). Diameter of the largest involved nerve did not predict outcome, but tumor involvement of larger nerves correlated with the presence of tumor at the resection margin (r=0.3574, p=0.0063). Extra-pancreatic PNI was identified in 25 cases (43.85%) and its presence showed significant correlation to the number of nerves involved (r=0.4228, p=0.0020). There are significant correlations between size of tumor and number of blocks as well as blocks with PNI, which is a confounding factor.
Conclusion
Our results suggest that not just the presence, but also the number of nerves involved (three or more), is a negative predictor of time to recurrence and OS. The size of nerves involved correlated with margin status but did not predict recurrence or OS. Remarkably, these findings are inextricably linked to the number of blocks, suggesting that tumor sampling may have influenced the results.
Figure 1: Malignant glands surrounding the nerve and invading the perineural space, consistent with perineural invasion (H&E, 20x).
Figure 2: Outcomes by number of nerves involved by pancreatic adenocarcinoma. The presence of three or more nerves with perineural invasion discriminated overall survival (2A; p=0.0046) and recurrence (2B; p=0.0027).
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