To the Editor:
I read the report of Krishnasamy et al[1] with great interest. The   authors   make a valid point   about management issues associated with pancreatic ductal intraepithelial neoplasia (PanIN) in their illustrative report. However, a few clarifications need to be made on surgical pathology aspect of these lesions. Without doubt, evolution of the PanIN nomenclature and classification system has led to a renewed interest in research on pancreatic cancer aimed at accurate definition and identification of the key molecular event responsible for its development. The establishment of PanIN nomenclature has helped define a genetic progression model of pancreatic cancer.[2] Moreover, the early detection and treatment of PanINs might offer an important avenue for preventing their  progression to invasive pancreatic cancer which continues to have a dismal   patient   outcome.[2]   Currently,   the   ability to clinically detect PanINs is limited therefore whether PanINs will prove equally effective in patient management remains to be seen.
First, controversy remains in the application of the original three-tier PanIN nomenclature (PanIN-1, PanIN-2 and PanIN-3) due to a lack of reproducibility between pathologists in assigning lesions to PanIN-2 category.[3] Hence, in deciding the therapeutic approach based on the grade of PanIN, a two-tier system will be needed thereby combining PanIN-1 and PanIN-2  under "low-grade PanIN " and leaving PanIN-3 as "high-grade PanIN".[3]
Next, the lack of evidence-based guidelines poses an important management issue in PanINs found at surgical margins. Generally, PanIN-1 and PanIN-2 at the margin require no therapy as they are typically incidental findings with unproven clinical significance. In view of isolated reports of PanIN-3 progressing to invasive pancreatic cancer, the resection of additional pancreatic parenchyma to achieve a margin free of PanIN-3 is recommended in a young patient with a potentially curable pancreatic lesion.[3, 4] A large invasive cancer with multiple lymph node metastases definitely poses a much greater threat to a patient's life than a PanIN-3. In such a situation, it is recommended that no additional pancreas be resected.[3]
Another important consideration that needs to be made is the distribution and extension of PanINs. Recently, Hisa et al[5] showed consecutive geographic extension and spread of PanINs-3 around the mass via the main pancreatic duct upto 25 mm (mean 10.5 mm) from the edge of the tumor. Therefore, they recommend a resection margin of 25 mm or at least >11 mm from the main tumor.