Cytohistological diagnosis of pancreatic serous cystadenoma: a multimodal approach

Abstract

<jats:sec><jats:title>Aims</jats:title><jats:p>Serous cystadenomata (SCAs) are benign pancreatic cystic neoplasms that present a diagnostic challenge despite many investigational approaches. Notwithstanding the promise of molecular diagnostics, these tests have limited accessibility in day-to-day surgical pathology practices. We aim to corroborate and build on recent evidence which suggests that positive α-inhibin immunohistochemistry (IHC) is a helpful adjunct in the biopsy confirmation of pancreatic SCA.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We retrospectively reviewed 22 fine-needle aspirates/biopsies from 14 patients (mean age 65 years, 47–83 years) with pancreatic multicystic lesions radiologically suspicious for SCA (location: 6 body, 2 head, 4 tail, 1 neck, 1 uncinate; cyst size: mean 3.7 cm, 2.0–7.6 cm), as well as an additional 10 pancreatic resection specimens with confirmed SCA; α-inhibin IHC was performed on all cell blocks, biopsy slides and representative resection specimen sections. Where available, associated cyst fluid was analysed for correlative vascular endothelial growth factor A (VEGF-A) and carcinoembryonic antigen levels.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>An α-inhibin IHC sensitivity of 80% was observed in the cases with resection confirmed SCA. Of the fine-needle aspirate/biopsy specimens, 59% (13/22) contained epithelial cells strongly positive for α-inhibin. When selecting for specimens that exhibited distinct strips of epithelium, the α-inhibin strong positivity rate increased to 73% (8/11). VEGF-A values were supportive of false-negative α-inhibin IHC in three cases and true-negative α-inhibin IHC in one case.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study postulates a diagnostic algorithm to confirm pancreatic SCA which may help to decrease unnecessary follow-up endoscopy/surgical resection and would decrease the associated morbidity, mortality and financial costs in patients with this otherwise benign condition.</jats:p></jats:sec>

My approach to endoscopic ultrasound-guided fine-needle aspiration biopsy specimens of the pancreas

“…The author’s experience that SCAs consistently yield hypocellular EUS-FNAB specimens has also been reported elsewhere 21. Indeed, this contrast with the usually hypercellular specimens from NET is a first way to exclude what the author feels is the closest, most common morphological mimic of SCA.…”

Calponin and MUC6 complement inhibin as diagnostic immunomarkers of serous cystadenoma in endoscopic ultrasound‐guided aspiration/biopsy specimens

“…4,6,9 In one of the latter studies, two of 11 (18%) EUS-FNAB samples reported as morphologically suggestive of SCA still did not show inhibin positivity. 9 Further, in a study where SCA was diagnosed from resected specimens but their pre-operative FNA specimens were more often reported as nondiagnostic or suggesting NET, one of eight (13%) SCAs lacked inhibin expression. 6 Finally, these proportions are similar to the 10% 9 and 18% 8 of resected SCAs reported to lack inhibin positivity.…”

“…9 Further, in a study where SCA was diagnosed from resected specimens but their pre-operative FNA specimens were more often reported as nondiagnostic or suggesting NET, one of eight (13%) SCAs lacked inhibin expression. 6 Finally, these proportions are similar to the 10% 9 and 18% 8 of resected SCAs reported to lack inhibin positivity. In a similar fashion to sensitivity, specificity of inhibin as a SCA marker has also been questioned.…”

Molecular markers contribute to the clinical diagnosis for pancreatic cystic neoplasms

“…[36] SCAs can be identified on the basis of a biochemical profile of carcinoembryonic antigen (CEA) levels <5 ng/mL (sensitivity of 50% and specificity of 95% for SCAs/ pseudocyst) and amylase levels <250 U/L (sensitivity of 44% and specificity of 98% for SCA, mucinous cystadenoma, and mucinous cystadenocarcinoma). [37] Most SCAs (89%-100%) have tumor suppressor gene VHL mutations, including loss of heterozygosity and chromosome 3p aneuploidy. [38] When the cut-off is >5000 pg/mL, elevated levels of vascular endothelial growth factor A (VEGF-A) have a sensitivity of 100% and specificity of 83.7% for differentiating between SCNs and other cystic lesions.…”

“…[39] Furthermore, expression of a-inhibin on immunohistochemistry has a sensitivity of 80% for identifying SCAs. [37] SPNs SPNs are rare and are often observed in relatively young women (average age <35 years), usually in the pancreatic body and tail. Resected SPNs show a large single tumor (5-10 cm) with cystic and solid components.…”