Mucinous pancreatic cysts should be considered for surgical resection due to their malignant potential [
The present study included patients preoperatively diagnosed to have mucinous cystic lesion (both side branch-intraductal papillary mucinous neoplasms (SB-IPMN) and mucinous cystic neoplasms (MCNs)) and referred to surgery based on EUS findings. We correlated EUS morphologic findings with surgical pathology and then determined which findings were most helpful in identifying mucinous cysts that will benefit from surgical resection.
This was a retrospective cohort study of patients with a cystic pancreatic lesion on EUS performed for the evaluation of a focal pancreatic lesion found on a CT scan/MRI/ultrasound between March 2002 and May 2013 at Saint Louis University Hospital and Missouri Baptist Hospital (
Study cohort. Mucinous cyst criteria: (1) aspiration of thick mucus from the cyst, (2) CEA > 192
Medical records of all the patients who were referred for surgery (
Demographic characteristics, EUS findings, and patient symptoms were tested for significance for their association with a final diagnosis of mucinous adenocarcinoma using univariate analysis. Chi-square test was used for categorical variables, and
We compared the characteristics of 78 patients who were included for analysis and the remaining 77 patients who had no surgery data (Table
Comparison between patients with surgery data available and patients who did not have surgery or surgery data not available.
Indication for surgery | Patients who had surgery data |
Patients who did not have surgery or no surgery data available |
---|---|---|
Size ≥ 3 cm | 42 (53.8%) | 45 (58.4%) |
Focal wall thickness | 49 (62.8%) | 33 (42.8%) |
Thickened septa | 25 (32.1%) | 14 (18.2%) |
Atypia/adenocarcinoma | 39 (50%) | 33(42.8%) |
Atypia | 19 (25.6%) | 11 (14.3%) |
Adenocarcinoma |
20 (25.4%) | 22 (28.6%) |
CEA > 500 | 32 (41%) | 11 (14.3%) |
PD dilation | 22(28.2%) | 25(32.5%) |
People with only 1 indication for surgery | ||
|
20 (25.6%) | 40 (51.9%) |
Size ≥ 3 cm | 7 (9%) | 21 (27.3%) |
Focal wall thickness | 1 | 4 (5.2%) |
Thickened septa | 0 | 1 |
Atypia/adenocarcinoma | 3 (3.8%) | 3 (3.9%) |
CEA > 500 | 9 (11.5%) | 11 (14.3%) |
Table
Final diagnosis of surgically resected patients.
Patients selected | Total = 78 |
---|---|
Pseudocyst | 3 (3.85%) |
IPMN low grade | 25 (32.05%) |
IPMN intermediate grade | 14 (17.95%) |
MCN low grade | 12 (15.38%) |
MCN intermediate grade | 1 (1.28%) |
Mucinous solid-cystic lesion of indeterminate type | 1 (1.28%) |
Serous cyst | 2 (2.56%) |
Mesenteric cyst | 1 (1.28%) |
Adenocarcinoma | 17 (21.79%) |
IPMN high grade | 2 (2.56%) |
IPMN: intraductal papillary mucinous neoplasm; MCN: mucinous cystic neoplasm.
All patients included in this study were preoperatively diagnosed to have mucinous cystic lesions based on EUS-FNA. The EUS-FNA cytology was diagnostic of adenocarcinoma in 20 patients, benign in 39 patients, and atypical in 19 patients. Table
Characteristics of patients who underwent surgery.
Patients selected ( |
Adeno Ca |
Adeno Ca |
|
Total = 78 |
---|---|---|---|---|
Gender | ||||
Female | 6 (31.57%) | 36 (61.01%) | 0.035 | 42 (53.9%) |
Male | 13 (68.43%) | 23 (38.98%) | 36 (46.1%) | |
Symptoms | ||||
Abdominal pain | 5 (26.31%) | 19 (32.20%) | 0.77 | 24 (30.8%) |
Weight loss | 6 (31.57%) | 12 (20.33%) | 0.35 | 18 (23.1%) |
Jaundice | 3 (15.78%) | 2 (3.38%) | 0.09 | 5 (6.4%) |
Acute pancreatitis | 3 (15.78%) | 9 (15.25%) | 1.00 | 12 (15.4%) |
|
|
|
||
Age (years) | 66.82 (8.48) | 65.27 (10.75) | 0.56 | 65.6 (10.22) |
|
|
|
|
Total = 78 |
Cyst size ≥ 3 cm | 15 (78.94%) | 27 (45.76%) | 0.016 | 42 (53.8%) |
Thickened septa | 8 (42.10%) | 17 (28.81%) | 0.39 | 25 (32.1%) |
Focally thickened cyst wall | 18 (94.73%) | 31 (52.54%) | 0.0008 | 49 (62.8%) |
Dilated PD | 10 (52.63%) | 11 (18.64%) | 0.0067 | 21 (26.9%) |
Atypia/adenocarcinoma on cytology | 18∗ (94.73%) | 21∗∗ (35.59%) | 0.0001 | 39 (50.0%) |
Logistic regression of adenocarcinoma.
Patients selected ( |
Odds ratio | 95% CI |
|
---|---|---|---|
Adenocarcinoma | |||
Thick cyst wall | 12.59 | 1.49–106.43 | 0.020 |
Size ≥ 3 cm | 4.02 | 1.07–15.00 | 0.038 |
Dilated PD | 2.68 | 0.76–9.33 | 0.12 |
Adenocarcinoma includes pts with adenocarcinoma and high grade atypia noted on cytology. PD: pancreatic duct; CI: confidence interval.
Figure
Correlation of EUS findings of focal wall thickening, cyst size ≥ 3 cm, and PD dilation with malignant, borderline, and benign pancreatic cysts.
Endoscopic ultrasound imaging in a patient presenting with mucinous cystic lesion showing focal wall thickening.
In this study, we performed a clinicopathologic correlation in patients who underwent surgery based on the preoperative EUS-FNA diagnosis of mucinous cystic lesions with suspicion of malignancy. Amongst 78 study patients, 34 had lesions that warranted surgery (19 cancer and 15 borderline lesions). We found no correlation between patient age and symptoms and the likelihood of adenocarcinoma. Focal wall thickening (≥3 mm), cyst size ≥ 3 cm, and dilated PD were associated with higher likelihood of adenocarcinoma on univariate analysis, but only focal wall thickening and size ≥ 3 cm were independent predictors of adenocarcinoma on multivariate analysis. Eighteen of 49 patients with focal wall thickening and one of 29 patients without identifiable focal wall thickening on EUS were found to have adenocarcinoma. Cyst size and PD dilation were however useful adjunctive findings. None of patients lacking all three of these findings was found to have adenocarcinoma in our cohort.
Surgery is considered appropriate in patients with malignant or borderline pancreatic mucinous cysts with high near- or medium-term risk of malignant transformation [
Most published data on predictors of malignancy in pancreatic cysts is derived from patients from surgical databases [
Even though we used commonly accepted and rather conservative criteria to diagnose mucinous cysts, not all patients preoperatively diagnosed to have mucinous cysts actually had a mucinous lesion; false-positive diagnosis included patients with serous cystadenoma, pseudocyst, and mesenteric cyst and one patient with a solid-cystic lesion whose etiology could not be determined even on surgical pathology. These data illustrate the limits of criteria used currently for diagnosing a mucinous cyst—a mucinous cyst aspirate, high CEA levels in cyst fluid, and presence of mucinous epithelium. Since mucinous cysts are more sinister clinically than the other types of pancreatic cysts and require surgery or surveillance, we believe that it is better that a few lesions that closely mimic mucinous cysts preoperatively be diagnosed as mucinous cysts rather than a mucinous cyst being missed due to the use of more stringent criteria.
In the present cohort, pancreatic adenocarcinoma/HGD was diagnosed preoperatively by EUS-FNA in 16 of 19 patients. Conversely, of the 20 patients preoperatively diagnosed to have cystadenocarcinoma/HGD (not just atypia), 16 were confirmed based on surgical pathology. The sensitivity for diagnosing malignancy is much higher than has been reported earlier by several groups [
In our clinical practice, we perform FNA of the cyst only at the time of initial evaluation of the cyst. We repeat FNA of the cyst at the time of follow-up EUS only when there is identifiable focal wall thickening. The purpose of EUS surveillance of mucinous pancreatic cysts is to identify not only cysts with overt malignancy but also borderline cystic neoplasms, which have the potential to turn malignant in the near or medium term. We, therefore, recommend surgery for patients with pancreatic cystic lesions with abnormal EUS morphology (particularly those with focal wall thickening) even if the cytology is just atypical or nondiagnostic. We interpret the absence of malignant epithelial cells in these lesions as suggestive of a borderline cystic neoplasm and do not discount the possibility that HGD or carcinoma in situ may be present in another part of the cyst. An effective surveillance of mucinous cysts would identify these lesions at a stage when they are borderline and precancerous (and have nonmalignant cytology) rather than when they turn frankly malignant. Our data provides support that EUS morphology of the mucinous cysts can be helpful in identifying these lesions and selecting patients who would benefit most from surgical resection.
Our cohort of patients with mucinous pancreatic cysts included those with SB-IPMN and MCNs, and we did not make a distinction in their management as suggested by the Sendai criteria. This is in part because our cohort included patients whose diagnosis predated development and general acceptance of the Sendai criteria. As per these criteria, surgery is recommended for a patient with MCN which is different in view of the younger age and the cumulative risk associated with surveillance. There is considerable overlap between SB-IPMN and MCN in terms of the communication between the PD and the cyst, making it difficult to reliably distinguish them preoperatively. There is no data to suggest that the EUS morphologic criteria that suggest malignancy differ between the MCN and SB-IPMN.
The present study has limitations inherent to its retrospective design. However, it is based on the cohort of patients who were referred for surgery based on the preoperative EUS-FNA diagnosis. The patients used in the final analysis were derived from 937 patients with pancreatic cystic lesions evaluated in our clinical practice over 10 years. The subset of patients who were referred for surgery but were excluded for analysis was similar to that of those who were included (Table
To conclude, EUS morphologic findings including focal wall thickening, cyst size ≥ 3 cm, and PD dilation can help identify patients likely to have malignant or borderline mucinous pancreatic cysts. These findings are helpful for EUS surveillance in patients with mucinous pancreatic cyst(s) and are useful adjunct to cytology in the determination of malignancy in a pancreatic cyst.
Carcinoembyronic antigen
Endoscopic ultrasound
Fine-needle aspiration
Pancreatic duct
Mucinous cystic neoplasm
Intraductal papillary mucinous neoplasm
Standard deviation.
This paper was presented as a poster at Digestive Disease Week, May 3–6, 2014, Chicago, Illinois, USA, and at American Pancreas Association 2014 Annual Meeting at Kohala Coast, Hawaii.
The authors disclose no conflicts.
Siddharth Javia, Satish Munigala, and Banke Agarwal are responsible for the study concept and design, statistical analysis, and administrative support. Siddharth B Javia, Satish Munigala, Sushovan Guha, and Banke Agarwal are responsible for the analysis and interpretation of data and critical revision of the manuscript for important intellectual content and approved the final draft of this study. Banke Agarwal is responsible for the supervision of the study.
The authors would like to thank Dr. Mohit Mehra for his assistance with data and abstract preparation.