Faculty Bibliography

OBJECTIVES/OBJECTIVE:This study compares the progression of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs) to unifocal (UF) lesions. METHODS:We performed a retrospective review of demographics, risk factors, and cyst characteristics of a prospectively maintained database of 999 patients with pancreatic cysts. Patients included had IPMN under surveillance for 12 months or more. Those with high-risk stigmata were excluded. Cyst size progression and development of worrisome features were compared between MF and UF cohorts. We evaluated whether the dominant cyst in MF-IPMN had more significant growth than did the other cysts. RESULTS:Seventy-seven patients with MF-IPMN and 54 patients with UF-IPMN, with mean follow-up of 27 and 34 months, met the criteria. There were no significant differences between demographics, risk factors, or initial cyst sizes. Fifty-seven percent of MF dominant cysts and 48% of UF cysts increased in size (P = 0.31). Progression in MF was more likely in the dominant cyst (P < 0.05). There were no significant differences in the development of mural nodules or increase in cyst size to more than 3 cm. CONCLUSIONS:Demographics of both cohorts were similar, as was the overall incidence of worrisome features. Because meaningful size progression primarily occurred in the dominant cyst, our findings support surveillance based on the dominant cyst in MF disease.

BACKGROUND:Brush cytology is the initial intervention when evaluating biliary strictures. Biliary brush cytology is known for its low sensitivity (but high specificity) and may be accompanied by biopsies and/or fluorescent in situ hybridization (FISH) to improve diagnostic yield. This study aimed to identify features to enhance cytological sensitivity, and assess which sampling method(s) improve identification of pancreatobiliary adenocarcinomas (PBCa). METHODS:Seventy-three biliary stricture cases were retrieved (38 PBCa and 35 control benign strictures). Biliary brushings, FISH, and biopsies were reviewed. Cytology specimens were evaluated for cellularity and presence of drunken honeycomb (DH), loosely cohesive clusters of round cells (LCCRC), large atypical cells with foamy cytoplasm (LACF), and single vacuolated malignant cells (SCs). Biopsies were examined for the presence of stromal invasion (SI). RESULTS:Biliary brushings were scantly cellular in 47.4% of PBCa and 51.4% of controls, resulting in 69.6% nondiagnostic/false-negative cytology diagnoses. DH, LACF, and SCs were significantly associated with adenocarcinoma (P < .00001, .0033, and .00002, respectively). By univariate analysis, SCs and LACF were predictors of malignancy in brushings (P = .0002 and .05). By multivariate analysis, only SCs were predictive of malignancy (P = .002). SI facilitated the diagnosis in 9 biopsies. Sensitivity/specificity of brush cytology, FISH, and biopsy were 39.5%/94.3%, 63.9%/94.3%, and 84.2%/100%, respectively. CONCLUSIONS:The low sensitivity of biliary brushings results from limited cellularity. Identification of LACF, DH, and SCs improves sensitivity. Sampling of stromal tissue may facilitate PBCa diagnosis. Concurrent biopsies and FISH are helpful in enhancing the diagnostic yield of PBCa.

CONTEXT/BACKGROUND:Molecular analysis of pancreatic cyst fluid obtained by EUS-FNA may increase diagnostic accuracy. We evaluated the utility of cyst-fluid molecular analysis, including mutational analysis of K-ras, loss of heterozygosity (LOH) at tumor suppressor loci, and DNA content in the diagnoses and surveillance of pancreatic cysts. METHODS:We retrospectively reviewed the Columbia University Pancreas Center database for all patients who underwent EUS/FNA for the evaluation of pancreatic cystic lesions followed by surgical resection or surveillance between 2006-2011. We compared accuracy of molecular analysis for mucinous etiology and malignant behavior to cyst-fluid CEA and cytology and surgical pathology in resected tumors. We recorded changes in molecular features over serial encounters in tumors under surveillance. Differences across groups were compared using Student's t or the Mann-Whitney U test for continuous variables and the Fisher's exact test for binary variables. RESULTS:Among 40 resected cysts with intermediate-risk features, molecular characteristics increased the diagnostic yield of EUS-FNA (n=11) but identified mucinous cysts less accurately than cyst fluid CEA (P=0.21 vs. 0.03). The combination of a K-ras mutation and ≥2 loss of heterozygosity was highly specific (96%) but insensitive for malignant behavior (50%). Initial data on surveillance (n=16) suggests that molecular changes occur frequently, and do not correlate with changes in cyst size, morphology, or CEA. CONCLUSIONS:In intermediate-risk pancreatic cysts, the presence of a K-ras mutation or loss of heterozygosity suggests mucinous etiology. K-ras mutation plus ≥2 loss of heterozygosity is strongly associated with malignancy, but sensitivity is low; while the presence of these mutations may be helpful, negative findings are uninformative. Molecular changes are observed in the course of cyst surveillance, which may be significant in long-term follow-up.

BACKGROUND:The diagnosis of serous cystadenoma (SCA), a rare benign pancreatic neoplasm, can alter the management of patients with pancreatic masses. Although characteristic imaging findings and fluid chemical analysis have been described, SCAs are not always recognized preoperatively. Furthermore, scant cellular yield on fine-needle aspiration (FNA) often leads to a nondiagnostic or nonspecific benign diagnosis. α-Inhibin (AI), a sensitive marker for SCA, is infrequently required for diagnosis in surgical specimens due to their characteristic histologic appearance. The objective of the current study was to determine whether AI staining can improve SCA diagnosis on FNA specimens. METHODS:Fifteen confirmed cases of SCA with prior FNA specimens were selected for this study. FNAs were evaluated for cellularity, cellular arrangement, and cytomorphology. Resection specimens were reviewed. RESULTS:Of the 15 FNA cases, approximately 75% demonstrated scant cellularity (11 of 15 cases). On smears, the cells were arranged as flat sheets, corresponding to strips of cells on cell block sections. The cells were small and round to cuboidal, with clear cytoplasm; occasional plasmacytoid cells and oncocytic cells were identified. Flattened cells, corresponding to attenuated epithelial cells lining macrocysts on the resections, were also noted. Stromal fragments were present in 5 FNAs and correlated with the hyalinized stroma in the resection specimens. AI immunostaining was positive in 88% of cases (7 of 8 of cases), thereby supporting the diagnosis of SCA. CONCLUSIONS:The results of the current study indicate that low cellularity and bland cytology are inherent to SCAs. Performing cell blocks and AI staining on FNA specimens is useful for establishing the diagnosis of SCA. An immunohistochemical panel including AI, chromogranin, and synaptophysin may enhance the diagnostic accuracy of pancreatic FNA specimens.