Role of pancreatic juice cytology in diagnosis of high-grade pancreatic intraepithelial neoplasia

Abstract

High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and it does not exhibit mass lesions. It is suspected based on changes in the main pancreatic duct in magnetic resonance cholangiopancreatography. Sometimes only an unclear duct shows in magnetic resonance cholangiopancreatography with no focal strictures and upstream dilatation of the main pancreatic duct. Serial pancreatic juice cytology is valuable in diagnosis of those patients.

Key Words: High-grade pancreatic intraepithelial neoplasia; Pancreatic cancer; Magnetic resonance cholangiopancreatography; Endoscopic retrograde pancreatography; Pancreatic juice cytology; Pancreatic ductal adenocarcinoma

Core Tip: Early diagnosis of pancreatic ductal adenocarcinoma may be challenging. The tumor may start with pancreatic intraepithelial neoplasia, that when detected, could be an opportunity for an early curative surgery. Serial pancreatic juice cytology is a valuable diagnostic modality in high-grade intraepithelial neoplasia of the pancreas, especially in cases with unclear main pancreatic duct without focal strictures and dilatation.

TO THE EDITOR

In this article, we comment on the article by Furuya et al[1] which was published in the World Journal of Clinical Cases. We discuss the significance and importance of the early diagnosis of high-grade pancreatic intraepithelial neoplasia. Pancreatic cancer is one of the most fatal malignancies worldwide. It was ranked as the 11^th most common cancer in the world in 2018 based on data from the Global Cancer Observatory[2]. In 2020, approximately 500000 new cases of pancreatic cancer were reported, with about 470000 related deaths. The pancreatic cancer incidence worldwide in the same year was 4.9 per 100000, while the mortality rate was 4.5 per 100000[3]. Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second most common cause of cancer-related death by 2030[4]. Pancreatic adenocarcinoma has a very poor prognosis with an age-adjusted net survival rate after 5 years of diagnosis of less than 15% in most countries[5]. The disease is commonly diagnosed at a late stage with a large tumor size, local vascular invasion, or distant metastasis, which markedly affect the disease outcome, as such cases mostly preclude curative surgery[6]. PDAC constitutes more than 90% of all pancreatic cancer cases[7]. The early detection of PDAC and carcinoma in situ is of utmost importance, as the 5-year survival rate can be as high as 80% if curative measures are applied when the tumor is less than 10 mm[8].

Summary of the case

The patient[1] was 60 years old and had pancreatic cysts accidentally discovered by computed tomography scan during a follow-up assessment for uterine cancer. Her magnetic resonance cholangiopancreatography (MRCP) results showed an unclear area of the main pancreatic duct (MPD) without distal upstream dilatation. A follow-up assessment after 24 months showed distal MPD dilatation and a larger pancreatic cyst. Endoscopic retrograde pancreatography (ERP) and serial pancreatic juice cytology (PJC) revealed atypical cells. Distal pancreatectomy was performed, which showed a high-grade pancreatic ductal carcinoma in situ (PanIN) which required curative resection.

Diagnostic challenges

PanINs exhibit no mass lesions and are suspected on the basis of focal strictures and distal dilatation of the MPD. PJC and pathological analysis after curative resection are used to confirm the diagnosis. Thus, at this early stage one should not expect a mass lesion and should be highly alert in evaluation of the MPD itself for the presence of any focal strictures or upstream dilatations. In the presented case, there was no early distal dilatation during neoplasia development. MRCP is a non-invasive modality that can accurately delineate both the biliary and the pancreatic duct systems. It is included as the first modality in the evaluation of the pancreatic ductal system by the Japan Pancreatic Society[9]. If it shows a clear localized structured area of the MPD, with upstream dilatation, the correct action is to proceed with endoscopic ultrasonography, and if no masses are detected, ERP and pancreatic juice analysis should follow. The published case had an area of unclear MPD without early distal dilatation of the MPD. It may be suggested to proceed directly with ERP. However, an unclear MPD may occur as a normal finding and ERP is not a procedure without potential complications. The authors preferred to follow the patient up, which was the correct decision[1]. The follow-up showed the aforementioned changes, which warranted ERP, leading to the detection of atypical cells.

Comparison with previous cases

The authors presented a review of previous similar cases that showed that the absence of MPD stricture and distal dilatation is an uncommon occurrence[1]. They provided an explanation of that based on the histopathological pattern of the PanIN and whether cells are flat or low papillary[1].

Future directions

Would the presence of a concomitant cyst together with an unclear area of MPD warrant a more expedited diagnostic approach rather than a routine follow-up? In Japan, cyst aspirations are not performed for fear of needle tract seeding. Future research on safe diagnostic modalities to help differentiate mucinous from non-mucinous and benign from malignant pancreatic cystic neoplasms may affect decision making for such cases. Would secretin-enhanced MRCP be of value in such gray-zone cases early in the course of the disease? That study could dynamically evaluate the MPD diameter and show focal dilatation of the MPD behind an abnormal area, which wouldn’t have the same compliance as normal MPD. Until now, this has not been an approved indication for that study, but it could open an area for future research for such rare presentations.

Conclusion

PanIN is a challenging diagnosis with the potential for the prevention of pancreatic cancer if properly diagnosed and managed. We should be vigilant to all MRCP abnormalities of the MPD, even if only unclear with the absence of strictures, as they may show up as PanIN in follow-up assessments. Although PJC has high false-negative rates, it should be considered in the diagnostic work-up for cases with MPD abnormalities depicted in MRCP.