Abstract
Purpose
To assess the role of endoscopic ultrasound (EUS) in the initial evaluation and follow-up of incidental pancreatic cystic lesions (PCL).
Methods
Retrospective analysis of patients with incidental PCL on imaging who were evaluated by EUS and had a minimal follow-up of 1 year.
Results
There were 62 patients (40 females and 22 males). The mean patient age was 67.7 years (range, 30–89). The Median follow-up was 24 months (range, 12–72). The mean PCL size was 21.6 mm. In all, 13 patients underwent surgery (20.9%). Diagnosis included a mucinous cystic tumour (7), mucinous adenocarcinoma (2), intraductal papillary mucinous neoplasm (1) and a cystic neuroendocrine tumour (1). The overall malignancy rate among patients who underwent surgery was 15.3% (two patients). The mean carcinoembryonic antigen (CEA) level from PCL fluid analysis was also significantly higher in surgically treated group (7760) vs. the stable group (184.7) vs. the enlarging PCL group (361.1). A CEA level above 192 ng/ml predicted mucinous PCL with a sensitivity of 90%.
Conclusions
EUS with cystic fluid analysis can be successfully used to rule out pancreatic neoplasms and to follow-up incidentally discovered PCL.
Keywords: cystic tumours, pancreatic neoplasia
The ubiquitous use of cross-sectional imaging has led to the discovery of incidental pancreatic cystic lesions (PCL) in about 1–1.2% of all studied populations.1 Among other pancreatic cysts, pancreatic cystic neoplasms are encountered in 10–15% and may represent malignant or premalignant entities.2 Endoscopic ultrasound (EUS) and cystic fluid analysis have become powerful tools in the differential diagnosis of incidental PCL. Relatively few studies have described the natural history of PCLs, not related to acute or chronic pancreatitis. In the present study, the results of analysis of our retrospective study of patients with PCL followed by EUS and cystic fluid analysis are presented.
Materials and methods
Patients, who have been found to have incidentally discovered PCLs on imaging [computed tomography (CT) or magnetic resonance imaging (MRI)] done for unrelated reasons, were retrospectively identified in the hospital database. Patients with a current or past history of pancreatitis were excluded. Only patients with the above-mentioned findings who underwent EUS with cystic fluid analysis and minimum follow-up of 1 year were selected for analysis. The current study was approved by the Danbury Hospital Institutional Review Board.
All patients were evaluated according to previously established protocol (Fig. 1). The procedure included EUS with fine needle aspiration (FNA). Cystic fluid was sent for carcinoembryonic antigen (CEA) and cytology. If there were findings suggesting neoplasm during initial EUS (CEA elevated above 192 ng/ml, presence of malignant cells on cytology or/and solid mass), patients were referred to a HPB surgeon for possible resection. Otherwise, patients with PCL underwent pancreas-specific MRI or CT every 6–12 months. In cases where the PCL increased in size, EUS was repeated and a decision made depending on updated findings.
Figure 1.
Protocol for management of incidental pancreatic cystic lesions
Results
There were 62 patients (40 females and 22 males). All patients were asymptomatic. The mean patient age was 67.7 years (range, 30–89). The median follow-up was 24 months (range, 12–72). Overall, 22 cystic lesions were located in the area of the pancreatic head (35.4%), 20 cystic lesions were located in the body of pancreas (32.2%) and 20 in the pancreatic tail (32.2%). Mean PCL size was 21.6 mm (range, 6–51 mm). Mean cystic CEA level was 2166 (range, 0.4–32056) ng/ml. Cytology was negative in the majority of the specimens and positive for adenocarcinoma in one patient in which initial EUS demonstrated a solid component within a cystic mass. In 41 (66.1%) patients, PCL were characterized as non-mucinous (CEA < 192 ng/ml), remained stable and did not require surgical evaluation. EUS was repeated in eight cases (12.9%) as a result of an increase in size. In patients with enlarging PCL, the mean CEA level value was 361.1, characteristic for mucinous neoplasms. This group included patients who were not resected because of severe co-morbidities or refusal of surgical resection. Thirteen patients or 20.9% underwent surgery and neoplastic PCL were found in 11 patients (84.6%) and included nine mucinous cystic tumours (seven mucinous cystic neoplasms and two mucinous cystic adenocarcinomas), one case of an intraductal papillary mucinous neoplasm (IPMN), one serous cystadenoma, one lymphoepithelial cyst and one low grade neuroendocrine cystic neoplasm. The cystic fluid CEA was elevated above the cut-off value in all but one resected patient with confirmed diagnosis of mucinous cystic neoplasm, resulting in overall sensitivity of 90% and specificity of 84%, positive predictive value (PPV) of 90%, negative predicted value (NPV) of 66% and accuracy of 84%. The role of cytology was limited in the present study, with a sensitivity of only 50% for cancer (positive in one out of two cases of cystadenocarcinoma). The overall malignancy rate among patients who underwent surgery was 15.3% (two patients).
There were nine distal pancreatectomies, two pancreatoduodenectomies, one median pancreatectomy and one exploratory laparotomy (as a result of unresectable pancreatic cancer found intra-operatively) performed. There was no mortality among resected patients. Details of the patients who underwent surgical resection are presented in Table 1. The mean PCL size was larger in the surgical group (27.8 mm) vs. the stable group (18.8 mm) vs. the enlarging PCL group (17.8 mm). The mean cyst fluid CEA level was also significantly higher in the surgically treated group (mean, 7760) vs. the stable group (184.7) vs. the enlarging group (361.1).
Table 1.
Surgical interventions in incidental pancreatic cystic lesions
| Age/gender | Size, mm | Location | Cyst EUS data | Cyst CEA level | Reason for surgery/ pre-operative dx | Surgical procedure | Surgical pathology result |
|---|---|---|---|---|---|---|---|
| 73M | 31 | Tail | Simple cyst with solid component | 32056 | Adenocarcinoma per FNA | Laparatomy | Mucinous adenocarcinoma |
| 80F | 16 | Tail | Septated cyst | 25085 | Mucinous neoplasm/possible malignancy | DP | MCA |
| 76M | 35 | Tail | Cyst+mass | 22000 | Mucinous neoplasm/concern for malignancy | laparatomy | Mucinous adenocarcinoma |
| 30F | 20 | Body | Septated cyst | 2886 | Mucinous neoplasm | DP | MCA |
| 38F | 45 | Tail | Simple cyst | 81 | Increase in size | DP | MCA |
| 40F | 51 | Tail | Simple cyst | 564 | Mucinous neoplasm | DP | MCA |
| 58F | 28 | Tail | Simple cyst | 27301 | Mucinous neoplasm | DP | MCA |
| 68M | 17 | Body | Septated cyst | 35000 | Mucinous neoplasm | DP | MCA |
| 60M | 45 | Tail | Septated cyst with solid component | 0.3 | Concern for malignancy | DP | Lymphoepithelial cyst |
| 78M | 27 | Tail | Simple cyst with solid component | 2.4 | Concern for malignancy | DP | Neuroendocrine neoplasm |
| 67M | 28 | Head | Simple cyst and MPD dilatation | 389 | IPMN | Pancreatoduodenectomy | IPMN |
| 81F | 23 | Head | Simple cyst | 733 | Mucinous neoplasm/increase in size | Pancreatoduodenectomy | MCA |
| 78F | 22 | Tail | Simple cyst | 738 | Mucinous neoplasm/increase in size | DP | Simple cystadenoma |
M, male; F, female; MCA, mucinous cystoadenoma; IPMN, intraductal papillary mucinous neoplasm; DP, distal pancreatectomy, FNA, fine needle aspiration.
Discussions
Pancreatic cystic neoplasms represent up to 15% of all incidental PCL. According to the WHO classification, pancreatic cystic neoplasms are further divided into serous cystic neoplasms, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms and solitary pseudopapillary neoplasms.1 Malignant potential is quite variable, with up to 42% of the cystic neoplasms having premalignant changes and up to 17% harbouring in situ cancer.1 The group-specific malignancy rate is from 6% to 36% in cases of mucinous cystic neoplasms, 65% to 46% in branch-type IPMN and 60% to 92% in main duct-type IPMN.2 Taking into account that roughly 50% of all cystic neoplasms are completely asymptomatic, appropriate evaluation and follow-up are important. EUS with FNA and cystic fluid analysis is currently the state-of-art of evaluation in the case of the suspected pancreatic cystic neoplasms. With an overall complication rate of 1–2%, it allows for differentiation between neoplastic and non-neoplastic cysts if the amount of aspirated fluid is sufficient for analysis.3,4 Among the most powerful markers, CEA has a pooled sensitivity of 75% and specificity of 84% if using a level of >192 ng/ml as a cut-off value for detection of mucinous neoplasms.5 Levels <5 ng/ml suggest non-mucinous cyst- serous or pseudocyst. EUS characteristics of the cystic lesions: microcystic vs. macrocystic, monocystic vs. ‘honeycomb’ appearance, presence of stellate scar, associated mural nodule or solid component and presence of pancreatic duct dilatation) can provide additional diagnostic information. Cytology is specific but has a low sensitivity.6 The presence of mucin, cystic fluid CA19-9 levels, k-ras mutation and DNA analysis could enhance diagnostic value of the PCL aspirate but is not available at all institutions.7 In univariate analysis of 153 patients who underwent EUS for suspected pancreatic cystic neoplasms, older age, male gender, jaundice, a history of another malignancy, associated solid component and positive cytology were associated with an increased risk of cancer.8 All mucinous cystic neoplasms should be resected if feasible. In the case of IPMN, consensus guidelines recommend resection in the case of main pancreatic duct dilatation >10 mm, branch size lesions >3 cm in diameter, a presence of a mural nodule or cytology suspicious for malignancy.9,10 All symptomatic lesions should be also resected. The size of lesions is not always valid criteria in decision making because even smaller lesions can have malignant potential.11
In spite of the the fact that PCL can be adequately imaged using conventional CT/MRI protocols, EUS has a significant advantage in its ability to perform guided FNA for subsequent cystic fluid analysis. It was decided to use a CEA cut-off value of 192 ng/ml in the present study because it correlates better than EUS morphology or cytology in differentiating between mucinous and non-mucinous cystic lesions.5 In the present study, a pre-determined CEA cut-off level resulted in an ability to diagnose mucinous cystic neoplasm with high sensitivity and specificity (90% and 84%, respectively). All PCL with a CEA level below the cut-off value remained stable within the follow-up period.
In conclusion, EUS with FNA can be successfully used for initial work up and follow-up of incidental pancreatic lesions and allows for differentiation of neoplastic from non-neoplastic cysts. The cystic fluid CEA levels >192 ng/ml can be used to reliably distinguish between mucinous and non-mucinous PCL.
Conflicts of interest
None declared.
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