Presence of small pancreatic cystic lesions should not preclude liver transplantation.

Abstract

Potential conflict of interest: Nothing to report. See Article on Page 324 Identification of a pancreatic cyst on abdominal imaging is not infrequent during evaluation for liver transplant with estimated pancreatic cyst prevalence of 15% in cirrhotic pretransplant patients.1 The first issue is how to correctly classify the cyst type for malignant potential, and second is whether therapeutic immunosuppression increases the risk of malignant transformation. Pancreatic cysts are generally being recognized more frequently with increased use of computed tomography and magnetic resonance imaging. They have an increased prevalence in patients older than 60 years of age. The most frequent pancreatic cyst types are intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms, serous cystadenomas, simple cysts, and a plethora of other lesions, with IPMNs accounting for the majority of incidentally discovered asymptomatic pancreatic cysts.2 Cysts with malignant potential include IPMNs and mucinous cystic neoplasms. The initial approach to a pancreatic cyst is based on cyst size, imaging characteristics, and presence of symptoms. Asymptomatic cysts of < 2 cm without high‐risk features such as mural nodules or wall thickening on imaging can be followed with imaging, whereas those over 2‐3 cm in size or with high‐risk features require endoscopic ultrasound (EUS) with fine‐needle aspiration (FNA) for characterization. EUS may detect mural nodules in approximately 30% of cysts in which they were not appreciated on initial imaging.3 FNA of cyst fluid is usually analyzed for carcinoembryonic antigen (CEA), cytology, and genetic studies for mutations including V‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and possibly guanine nucleotide binding protein, alpha stimulating complex locus (GNAS). CEA < 5 ng/mL is almost confirmatory of a nonmucinous cyst, whereas higher levels over 109.9 ng/mL are compatible with mucinous cysts. The presence of abnormal cytology suggests a mucinous cyst and/or neoplasm, as does the presence of KRAS mutations. In the current issue of Liver Transplantation, a retrospective study by Vidhyarkorn et al. addresses the effect of immunosuppression on pancreatic cysts in a liver transplant population.4 They excluded cysts present on initial imaging with a high potential of being malignant, including only pancreatic cysts lacking mural nodules or calcification, a group with an overall low malignant potential. In addition, they were small, with an average diameter of 8 ± 4.9 mm. Of 58 patients with cysts found on preoperative evaluation, 12 (21%) underwent pretransplant EUS‐FNA reflecting the overall small cyst size. The remaining 12 patients had cysts identified after transplantation, and 8 of these underwent subsequent EUS. Initial imaging of the total cohort classified the cysts as mostly being indeterminate—“nonspecific benign cysts” in 40/70 (57%) with only 7/70 (10%) classified as IPMNs. Thus, their population of very small pancreatic cystic lesions had only a small number of premalignant lesions, and a corresponding low risk of progression to malignancy. There was an increase in size of the pancreatic cysts over a mean follow‐up time of 64 months (standard deviation, ± 39 months; range, 6‐147 months), with a mean cyst size increase of 4.5 mm (6.0 ± 5.9 mm to 10.5 ± 6.6 mm), which were still under 2 cm in size. This is similar to other studies in which pancreatic cysts in post–liver transplantation patients increase in size during follow‐up, comparable with nonimmunosuppressed controls.5 A total of 323 patients in 6 studies with small pancreatic cysts without high‐risk features, though IPMNs were included, have been followed after liver transplantation or after solid organ transplantation.4 Overall, 23 of 323 (7%) patients in follow‐up were found to develop worrisome or high‐risk features, indication for surgical resection, or pancreatic malignancy during follow‐up. Importantly, only 1 patient developed a pancreatic malignancy, while another patient had high‐grade dysplasia. It appears liver transplant patients with pancreatic cysts who developed features which would usually prompt surgical interventions, undergo operations less often than nontransplanted patients with pancreatic cysts, as surgery was performed in only a minority (2 patients; 1 with IPMN with high‐grade dysplasia, and 1 with indication for resection without malignancy on pathology) of the 23 patients.6 Reassuringly, 4 of 6 transplant studies had comparable control populations with no increased risk detected despite immunosuppressive therapy. It seems that immunosuppressive therapy does not increase the risk of malignant change in pancreatic cysts that are vigorously screened and found to have low malignant potential before transplantation. Thus, our primary attention should be on pretransplant patient evaluation including dedicated cross‐sectional imaging and EUS‐FNA if indicated, with subsequent appropriate imaging follow‐up after solid organ transplantation.