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Jalal et al. J Cancer Metastasis Treat 2023;9:11 https://dx.doi.org/10.20517/2394-4722.2022.122 Page 7 of 11

[33]
identified malignant cysts with a 91% sensitivity and a 93% specificity . Mutations in KRAS were found in
IPMNs and MCNs, whereas GNAS is frequently mutated IPMNs [56,57] . IPMNs with high-grade dysplasia or
[58]
malignancy were found to have mutations in TP53, PIK3CA, PTEN and/or AKT1 . A study that analysed
pancreatic fluid for genetic mutation using next-generation sequencing found that KRAS/GNAS mutations
were highly sensitive for IPMNs and specific for mucinous cysts .
[58]
Through-the-needle micro-forceps biopsy
TTNB devices (Moray Micro-forceps, US Endoscopy, Mentor, Ohio, USA) have demonstrated their
superiority over standard FNA with accuracy, sensitivity, and specificity of 78.8%, 82.2%, and 96.8%,
respectively, in diagnosing pancreatic cyst subtypes . Three passes on average have yielded adequate
[59]
histology results. The TTNB offers an assessment of the cyst wall, which, when combined with the
cytological and biochemical assessment of the aspirated fluid, improve diagnostic accuracy. The major
drawback of this technique is that it only allows sampling of the posterior wall of the cyst from the point of
entry of the needle. Therefore, the acquired tissue may not represent the actual dysplasia. The reported
adverse events were bleeding (2%-4%) and pancreatitis (2%) [59,60] .

Confocal laser endomicroscopy
nCLE is another novel technique that can be combined with EUS to enable imaging lesions at the
subcellular level and to provide an optical biopsy [61,62] . It has been used in diagnosing lesions in different
parts of the gastrointestinal tract. It involves passing a nCLE through a 19 G needle, which enables real-time
microscopic visualisation of tissue. Pooled data produced a sensitivity of 82.4%, a specificity of 96.6%, and a
diagnostic accuracy of 88.6% in diagnosing pancreatic cyst subtypes% . The adverse events reported were
[63]
mild bleeding, infection, and mild pancreatitis (1.4%-7%).

Pancreatoscopy
Per-oral pancreatoscopy (POP) has also been employed in the diagnostic work-up of MD-IPMNs or during
intraoperative mapping . It offers intraductal visualisation of the pancreatic duct. The reported malignant
[64]
[65]
features in IPMNs were fish-egg-like projections with vascular images, villous types, and vegetative types .
The reported cannulation rate was 86%-100%. Although POP is reported to achieve technical success, its
main disadvantage is the reported high rate of adverse events of 12%, with post-procedure pancreatitis at up
[64]
to 10% . Due to its high risk of associated pancreatitis, POP should be performed only after a diagnostic
work-up using EUS and tissue sampling and after multidisciplinary discussion. Its role should be to help
decide in equivocal cases, to assess the presence of malignant changes, and to guide the choice of the margin
of resection of IPMNs .
[64]

Endoscopic retrograde cholangio-pancreatography
Endoscopic retrograde cholangio-pancreatography (ERCP) can help to confirm communication between a
pancreatic cyst and the main pancreatic duct. The potential use of ERCP is to inform the differentiation of
an MD-IPMN from chronic pancreatitis, but given the high risk of pancreatitis following ERCP, it is
reserved for therapeutic purposes only [28,66] .

CONCLUSION
Patients who have PCLs often undergo several tests to categorise their cysts and detect premalignant or
malignant changes. Some of these tests can be invasive and pose the risk of developing complications. The
assessment of PCLs often requires a combination of more than one test to achieve adequate diagnostic
accuracy. The challenges in managing PCLs are mainly in differentiating mucinous from non-mucinous
cysts and in detecting high-grade dysplasia or early cancer.