Concordance between preoperative imaging and surgical specimen size in the evaluation of intraductal papillary mucinous neoplasms of the pancreas

Introduction

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are mucin-producing cystic neoplasms with malignant potential (1,2). Cystic lesions of the pancreas are being detected more often due to the increase in the use of diagnostic cross-sectional abdominal imaging (3,4). IPMNs are the most frequently incidentally identified pancreatic cystic lesions (3). The incidental finding of pancreatic cystic lesions has a prevalence of 2.3% for computed tomography (CT) and 19% for magnetic resonance imaging (MRI) (4). The incidence of IPMN varies depending on age and has been reported as over 10% in patients aged 70 years or older (5).

The management of IPMN, especially the decision to proceed with surgery or continue surveillance, is largely guided by the cyst’s radiologic features (i.e., size, growth kinetics over time). The International Association of Pancreatology (IAP) guidelines describe worrisome features (WF) and high-risk stigmata (HRS) based on radiologic, biochemical, and clinical characteristics of the IPMN (5,6). The use of MRI and endoscopic ultrasound (EUS) is recommended for patient follow-up since the majority of IPMNs are not surgically resected but surveyed (5). However, previous research has suggested that there are clinically relevant differences in reported cyst size when comparing MRI and EUS findings (7).

The current study aims to evaluate the concordance of MRI and EUS with surgical pathology measurements of resected IPMNs. We hypothesized that a clinically significant difference would exist between all imaging modalities and the actual size of the cyst.

Methods

Study design

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This is a retrospective study derived from a single academic quaternary medical institution IPMN registry of patients who underwent resection of an IPMN between 2014 and 2023. This study was approved by the Institutional Review Board of Hartford Hospital (IRB No. HHC-2020-0278). Given its retrospective nature, the requirement for informed consent was waived. This study aimed to evaluate the concordance of surgical pathology measurements with radiologic measurements through MRI and EUS.

The measurements used for analyses were obtained from radiology and pathology reports, respectively. We recorded the radiological tumor size as the maximal measurement on cross-sectional diameter by an experienced radiologist on MRI and/or EUS by an experienced gastroenterologist, as measured by the reporting radiologist. Surgical pathology measurement was also defined as the largest transverse diameter reported by the pathologist’s examination. For patients with multifocal tumors, we only recorded the largest tumor on imaging and pathology reports. We extracted demographic data for all patients from the database, including age, sex, and race, as well as tumor histology and presence of adenocarcinoma in situ.

Analyses were performed on records of patients at least 18 years old with pathology-proven IPMN who then underwent surgical resection. Exclusion criteria included a diagnosis of invasive pancreatic adenocarcinoma or other pancreatic malignancies without IPMN, pancreatic cystic neoplasms without IPMN, and metastatic disease.

Statistical analysis

A descriptive analysis was provided for the sample. Continuous data were presented as a mean and standard deviation (SD). Categorical data were presented as frequencies, using percentages.

The methodology of Jeffery et al. was followed (8). A paired t-test was used to evaluate if there was a significant difference between each of the three measurements, independently, and the pathological tumor size. A difference in both underestimation and overestimation (using the pathological/actual size as the “gold standard”) was calculated for the sample, using Student’s t or a Mann-Whitney U, and the percentage of each was presented.

All analyses were conducted with SPSS v.29 (IBM, Armonk, NY, USA; 2022). An alpha level of 0.05 was used such that all results yielding P<0.05 were deemed statistically significant. All reported P values are two-sided tests.

Results

Among the 72 patients captured by the registry, 15 records were excluded from analyses because they did not have an EUS for analysis, and 57 records were included in the analyses (Figure 1). The mean age ± SD of the sample was 71.3±10.0 years old. Most of the sample was male (32, 56.1%) and White (26, 45.6%). Interestingly, 25 (54.4%) had a history of tobacco use. The majority of the cohort, 31 (54.3%), underwent a Whipple procedure for resection. Upon histological evaluation, the most frequent epithelial cell type observed in the tumors was gastric cells (20, 41.7%), and 12 (21.1%) patients had adenocarcinoma in situ.

Figure 1 Flow chart of patient enrollment.

Concordance between radiologic and pathologic measurements

Each imaging modality was independently compared to surgical pathology. These analyses revealed that when comparing the mean difference between each imaging modality and pathology size, both modalities underestimated actual IPMN size, and a significant difference was determined for EUS measurements (−1.0±2.7 cm, P=0.01) but not on MRI (−1.2±3.0 cm, P=0.06) (Table 1).

Subsequently, patients were classified into under- and overestimate subgroups to be compared with pathology measurements. When comparing mean size for underestimate groups in both EUS and MRI categories, both groups demonstrated a statistically significant difference with surgical measurements. Similarly, the overestimation groups for both EUS and MRI showed a significant difference when compared to surgical measurements (Table 2). However, the most impressive difference was again displayed by the underestimate group for EUS (−2.1±2.6 cm, P<0.001).

A Pearson coefficient was calculated to determine the correlation between imaging and surgical pathology measurements. Neither imaging modality showed a statistically significant correlation; however, EUS had a numerically better positive correlation with actual specimen size than MRI (r=0.074, P=0.61 vs. r=0.050, P=0.81, respectively).

Discussion

This study compared measurements from the recommended imaging modalities for evaluation of IPMN to surgical pathology in a retrospective analysis of data from patients who underwent surgical resection of IPMN. We determined that both MRI and EUS underestimate the size of the neoplasm; however, through independent analyses, only EUS underestimation proved to be statistically significant. It is important to note that, albeit not statistically significant, there was a trend toward statistical significance when analyzing MRI data, which may have reached significance had the study included a larger sample size. Current guidelines recommend EUS and MRI for patient evaluation and surveillance, but no standardization exists.

Tumor size is an important indicator for surgery in the context of IPMN due to its correlation with high-grade dysplasia and malignancy (5,6,9,10). Current guidelines differ when advocating for an imaging modality to assess and follow-up patients with IPMN. The American Gastroenterological Association (AGA) guidelines recognize that CT, MRI, and EUS have suboptimal sensitivity to IPMN; however, they recommend MRI for pancreatic cysts <3 cm (11). Furthermore, both the 2013 European consensus on cystic tumors of the pancreas and the 2023 Kyoto guidelines consider both CT and MRI as primary modalities in the evaluation of IPMNs (5,12). The lack of standardization in the work-up of patients with IPMNs may lead to untimely interventions and suboptimal patient outcomes.

Various past studies have evaluated the agreement between imaging modalities for a variety of high-risk features and anatomic disposition of IPMNs but there is not a consensus on the ideal modality for the evaluation of these patients. A study by Uribarri-Gonzales et al. evaluated the agreement between MRI/magnetic resonance cholangiopancreatography (MRCP) and EUS in branched-duct IPMNs (BD-IPMN). They determined that there was disagreement when evaluating solid components, main pancreatic duct (PD) dilation, and enhancing mural nodules, especially in the proximal pancreas (13,14). Different from our results which showed that all imaging modalities underestimated the size of cyst when compared to surgical pathology, past studies evidenced that CT and MRI overestimated IPMN size and only EUS underestimated the cyst when compared to pathology measurements (15,16).

The incidence of IPMNs appears to be rising due to improvements in imaging technology and the more frequent use of these resources by clinicians (17,18). Recent advances in EUS technology have improved the diagnostic evaluation of pancreatic cystic lesions. Needle-based confocal laser endomicroscopy (nCLE) has demonstrated high specificity (90.5%) and overall diagnostic accuracy (83%) for identifying premalignant or malignant features, offering real-time imaging of epithelial architecture and dysplasia (19). Similarly, advancements in sampling techniques such as through-the-needle microforceps biopsy (TTNB), which has shown excellent interobserver agreement among pathologists in assessing epithelial dysplasia and mucinous differentiation, have the potential to aid in complex decision making when refining cyst classification and management (20).

Since the management of IPMNs is largely dependent on the cyst’s radiographic appearance, accuracy in estimating the size of the cyst and identifying other clinically relevant characteristics is of utmost importance. The decision to proceed with surgical intervention for IPMN should be based on the patient’s appropriateness for surgery and the degree of suspicion for in-situ carcinoma or high-grade dysplasia. As previously mentioned, the presence of WF or HRS can assist with the surgical decision-making. HRS includes obstructive jaundice in a patient with a cystic lesion in the pancreatic head, an enhancing mural nodule greater than 5 mm or a solid component, a main PD diameter exceeding 10 mm, or positive/suspicious cytology. If any of these HRS are present and the patient is deemed fit for surgery, operative management is generally warranted. In contrast, WF—which may be clinical or radiographic—do not represent an absolute indication for surgery but should prompt further evaluation and consideration within a multidisciplinary context (5). The present study suggests that the modalities used to evaluate IPMNs underestimate size, and therefore caution and clinical judgment should be exercised. Most importantly, this study demonstrates that no imaging study is perfect. In our results, while MRI tended to overestimate size compared to EUS, it is important to note that both MRI and EUS underestimate size compared to surgical pathology. Therefore, it appears that while we previously thought EUS may have been the better modality to estimate size of IPMN, it seems as though MRI may be most closely aligned with surgical pathology true size.

The study is not without limitations. The small sample size limits our ability to present more robust statistical analyses and draw stronger conclusions. Since it is a retrospective review, its validity due to lack of subject randomization and prospective evaluation is reduced. Measurement acquisition represents a key limitation of this study, as EUS is operator-dependent and lacks standardized measurement protocols. Measurements are often not obtained in the same imaging plane, contributing to variability. This potential inconsistency, along with the inherent limitations of EUS accuracy, may have influenced the results. Furthermore, patients with IPMN managed at our institution do not receive protocolized imaging which contributed to the lack of consistency in modality selection for evaluation.

Conclusions

This retrospective study sought to compare the concordance between radiologic and surgical pathology measurements in patients with resected IPMNs. Our findings suggest that both MRI and EUS tend to underestimate the actual size of IPMN, with EUS showing a statistically significant underestimation. We believe that this could potentially impact clinical decision-making, given that tumor size is a critical factor in determining the need for surgical intervention. Our results align with previous research showing variability in imaging accuracy, emphasizing the importance of integrating multiple modalities and correlating with clinical findings to enhance diagnostic yield.

Future research through prospective randomized trials should be conducted to refine imaging protocols and improve clinical guidelines for IPMN management. Improving the accuracy of preoperative imaging could lead to better patient outcomes by ensuring timely surgical intervention.

Acknowledgments

This work was presented as a podium presentation in the Hepatobiliary Surgery section of the American College of Surgeons Clinical Congress 2024.

Footnote

Data Sharing Statement: Available at https://apc.amegroups.com/article/view/10.21037/apc-25-6/dss

Peer Review File: Available at https://apc.amegroups.com/article/view/10.21037/apc-25-6/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apc.amegroups.com/article/view/10.21037/apc-25-6/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective chart review study was approved by the Institutional Review Board of Hartford Hospital. IRB approval was obtained prior to data collection (IRB No. HHC-2020-0278). Given the nature of the study, the requirement for informed consent was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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