Multiple KRAS mutations in the non‐mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas

Abstract

Aims Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian‐type stroma. Although a non‐MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian‐type stroma and NMLE should be classified as MCNs or separately designated is debated. Methods and results To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low‐grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92% (11/12) of NMLE foci and 89% (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low‐grade dysplasia. Conclusions Clonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.

Pancreatic Cysts after Endoscopic Ultrasonography-Guided Ethanol and/or Paclitaxel Ablation Therapy: Another Mimic of Pancreatic Pseudocysts

“…In present study, 84% (10/12) of cases had a clinical impression of pancreatic cysts, mainly MCNs based on pretreatment imaging studies. As is well-known, ovarian-type stroma is a distinct histologic features of MCNs [28]. As expected, we found ovarian-type stroma in about half (5/12, 42%) of the cases, and all 5 cases with ovarian-type stroma had residual lining mucinous epithelia.…”

“…Similar to our results, Oh and colleagues [14] reported that 75% (3/4) of the cases showed marked epithelial ablation (range, 25–100%) in resected pancreatic cysts after ablation. In contrast, in nontreated MCN cases before surgical resection, approximately half of the neoplastic epithelial lining was eroded [28]. Therefore, pancreatic cysts treated with EUS-guided ablation therapy may have a wider area of the cystic wall without covering lining epithelial cells after ablation.…”

Significance of KRAS mutation testing in biliary brushing cytology specimens: A 10‐year retrospective review

“…34,38 In Cancer Cytopathology July 2022 pancreatic cystic fluid, the presence of KRAS mutation has been suggested as a highly specific test for mucinous cyst, with a reported sensitivity of 77%. 33,35,36 These results suggest that KRAS mutational analysis has lower sensitivity and specificity in detecting malignancy in biliary tract brushing compared with that in pancreatic solid or cystic lesion FNAs. 24,33,34,38 The differences may be explained by a lower incidence of KRAS mutation rate in cholangiocarcinoma (5%) compared with pancreatic adenocarcinoma (66%), the inclusion of nonmalignant cytology cases in our study cohort, and the nature of overall limited cellularity in bile duct brushing specimens.…”

“…In contrast, KRAS mutation testing in pancreatic FNA biopsy was reported to have overall sensitivity and specificity of 79% and 100%, respectively 34,38 . In pancreatic cystic fluid, the presence of KRAS mutation has been suggested as a highly specific test for mucinous cyst, with a reported sensitivity of 77% 33,35,36 . These results suggest that KRAS mutational analysis has lower sensitivity and specificity in detecting malignancy in biliary tract brushing compared with that in pancreatic solid or cystic lesion FNAs 24,33,34,38 .…”

“…KRAS mutation analysis has been used as an ancillary procedure for analysis of fine‐needle aspiration (FNA) of solid and cystic pancreatic masses, pancreas cystic lesions, and bile duct brushings 24,30‐34 . In pancreatic specimens, KRAS mutation has been identified in approximately 9% of benign conditions, including chronic pancreatitis, 10% of low‐grade dysplastic lesions, and 65% of invasive carcinomas 24,25,28,30,31‐38 . Therefore, KRAS mutations are not specific for invasive pancreatic carcinoma.…”