Cyst Probe and Monitoring --10 errors in pancreatic cystic tumor diagnosis

Articles by J. E. Dominguez-Muñoz

Pancreatic cystic neoplasm (PCN) is a common and clinically challenging disease. The prevalence of PCN increases with age and the report estimates that PCN may occur in 2-45% of the general population.

In addition, the biological behavior of each type of PCN varies (from benign to malignant, see table 1), requiring different monitoring and treatment approaches. Therefore, proper management of PCN is essential not only to avoid cancer progression, but also to avoid unnecessary close and long-term follow-up, unnecessary invasive diagnostic surgery and overtreatment.

table 1 

In this article, we discuss possible and relevant errors in PCN diagnosis, monitoring, and management, and suggest strategies to avoid them. The sources of these strategic recommendations are based primarily on the recently published PCN evidence-based guidelines in Europe.

Error 1

Each pancreatic cystic lesion was evaluated to determine the type of lesion.

Computed tomography (CT), magnetic resonance imaging (MRI/MRCP), and cholangiography (MRI/MRCP) are accurate methods of detecting PCN, with MRI and MRCP being the most frequently used.

However, the accuracy of these methods in identifying specific types of PCN is relatively low. If a specific diagnosis cannot be confirmed by CT scan and further diagnosis does not change clinical management (for example, if there are definite surgical indications or contraindications, or if there are small cysts but no surgical indications, no further examination is required.)

Error 2

Cystic fluid analysis was used to diagnose specific types of PCN.

Although CEA and amylase or lipase improve the accuracy of endoscopic ultrasound (EUS) in differentiating mucous and non-mucous PCN, the diagnostic accuracy of these biomarkers is too low to determine the specific type of PCN.

Furthermore, CEA is neither used to identify mucinous cystic tumors (MCN) from intraductal papillary myxomatosis (IPMN), or benign mucinous cysts from highly atypical hyperplasia or cancer.

Therefore, the diagnosis of specific types of PCN by cysts fluid CEA is unreliable, and CEA level can only be used as an auxiliary indicator for imaging and cytological characteristics of cystic lesions.

Error 3

EUS-FNA cytological sampling was performed for each cystic lesion.

Fluid analysis should include amylase or lipase, CEA, and cytology. Compared with EUS alone, cytological examination of EUS-FNA can improve the accuracy of differentiating mucilaginous and non-mucilaginous PCN and benign and malignant PCN. However, cytology in this case is highly specific but insensitive. (Histology EUS-FNB should be considered.)

Error 4

Each PCN patient was monitored over a long period of time.

PCN monitoring depends on the risk of progression to cancer. Patients clearly diagnosed with serous PCN do not need to be monitored because these lesions are benign in nature.

In contrast, mucinous PCN (including MCN and IPMN) develops over time into highly atypical hyperplasia and an increased risk of cancer. Therefore, patients with MCN or IPMN should be followed up for a long time if there is no indication of surgery.

However, long-term follow-up is not appropriate for patients with MCN or IPMN who have comorbidity and are not eligible for surgery.

Error 5

CT scans were used to monitor PCN patients.

Multiphase pancreatic CT scan is very accurate for the characterization of PCN. In order to comply with the multiphase pancreatic protocol CT, the examination shall include the thin-layer reconstructed images obtained during the scanning phase of the pancreatic parenchyma (≤ 2.5mm section thickness).

Nevertheless, magnetic resonance imaging/biliopancreatic magnetic resonance imaging (MRI/MRCP) remains the preferred monitoring method to avoid repeated radiation exposure during long-term follow-up. In addition, MRI/MRCP is more sensitive than CT scan in identifying relevant PCN characteristics, such as mural nodules (associated with a high risk of dysplasia or cancer), intracyst septa (which may contribute to specific diagnosis of PCN), and polycysts (which support the diagnosis of multilateral IPMN).

Error 6

Only IPMN patients were monitored when appropriate surgical indications were available.

Among patients with IPMN who are eligible for surgery, there are several absolute surgical indications: jaundice (tumor related), cytological positive for highly atypical hyperplasia or cancer, solid mass or contrast enhanced mural nodules ≥5 mm, or main pancreatic duct dilatation ≥10 mm (figure 1). It is appropriate to monitor surgically appropriate IPMN patients only in the absence of any indication of surgery.

figure 1 

In a relatively surgical indications (such as: growth rate reach or exceed 5 mm/year), without jaundice with elevated serum level of CA19.9, main pancreatic duct of 5-9.9 mm in diameter, the cyst size reaching or higher than 40 mm, new occurred diabetes, IPMN caused by acute pancreatitis, or contrast enhanced wall nodule < 5 mm), for patients with obvious complications or short life expectancy monitoring is appropriate, but for those who have no obvious complications or for those who have two or more relevant indications of surgery ,monitor is not appropriate. It is also important to emphasize that the more indications associated with surgery, the higher the likelihood of malignancy.

Error 7

Patients with IPMN or MCN were followed up for 3-5 years and no significant changes were observed. Then the monitoring of patients was interrupted.

The risk of IPMN or MCN developing highly atypical hyperplasia or cancer increases over time, and the chance of developing surgical indications (both clinical and image-based) increases over time.

Therefore, the monitoring of patients with IPMN or MCN but no indication of surgery should not be interrupted as long as they are suitable for surgery, even if no significant changes are observed after 3-5 years.

Error 8

Patients with IPMN are operated too early or too late.

IPMN resection should not be delayed in patients with absolute or relative indications that IPMN is associated with a higher risk of cancer.

In contrast, patients with IPMN have a lower risk of developing highly atypical hyperplasia or cancer in the absence of associated risk factors, although malignancy cannot be definitely excluded prior to histological examination of surgically resected specimens.

On this basis, as a general rule, patients without indications for surgical excision (i.e., small cysts with no risk factors for malignancy) should not be operated on unless they have developed a surgical indication during follow-up. In such cases, factors such as life expectancy, patient compliance and willingness, and surgical risk are important for rational clinical decision-making.

Error 9

Parenchyma preserving pancreatectomy was performed in patients with IPMN indications.

Parenchyma preserving pancreatectomy is a non-neoplastic surgery, and its incidence is equal to or even higher than that of neoplastic pancreatectomy.

Patients with IPMN indications should not undergo this non-neoplastic procedure. Due to its risk of cancer or highly atypical hyperplasia, IPMN should be operated by tumor resection plus standard lymph node resection.

Error 10

Neglect the long-term monitoring of patients with undefined cysts.

The type of small cyst may remain unclear after appropriate diagnostic examination. However, an ambiguous cyst may be mucous, and the risk of malignant transformation may increase over time.

Therefore, the criteria for surgical excision or monitoring of undefined cysts may follow the same general rules as for branched-type IPMN (bd-ipmn).

However, in the absence of any risk factors for malignancy, small pancreatic cysts that have not been identified are common and usually have no impact on patient survival.

On this basis, the European Pancreatic Cystic Cancer research group recommends that undefined cysts of less than 15 mm in size be re-examined annually in the absence of risk factors for malignancy. If it is stable for 3 years, as long as the patient is still suitable for surgery, the examination period can be adjusted to re-examination every 2 years.

If there are no risk factors for malignancy and the diameter of undefined cysts is ≥15 mm, follow-up should be conducted every 6 months in the first year and annually thereafter.