Cytology Adds Value to Imaging Studies for Risk Assessment of Malignancy in Pancreatic Mucinous Cysts

Abstract

Objective Evaluate the value of cytology relative to imaging features in risk assessment for malignancy as defined in the Sendai Guidelines. Background The Sendai Guidelines list symptoms, cyst size > 30mm, dilated main pancreatic duct (MPD) > 6mm, mural nodule (MN) and “positive” cytology as high risk stigmata for malignancy warranting surgical triage. Methods We reviewed clinical, radiological and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas evaluated in a single tertiary medical center. Cytology slides were blindly re-reviewed and epithelial cells grouped as either benign or high grade atypia (HGA) [≥ high grade dysplasia]. Histologically, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (in-situ and invasive carcinoma). Performance characteristics of cytology relative to other risk factors were evaluated. Results Dilated MPD, MN and HGA were independent predictors of malignancy (p<0.0001), but not symptoms (p=.29) or cyst size > 30 mm (p=.51). HGA was the most sensitive predictor of malignancy in all cysts (72%) and in small (≤ 30 mm) branch-duct IPMN (67%) while also being specific (85 and 88% respectively). MN and dilated MPD were highly specific (>90%), but insensitive (39–44%). Cytology detected 30% more cancers in small cysts than dilated MPD or MN and half of the cancers without either of these high risk imaging features. Conclusions Cytology adds value to the radiological assessment of predicting malignancy in mucinous cysts, particularly in small branch-duct IPMN.

mAb Das-1 is specific for high-risk and malignant intraductal papillary mucinous neoplasm (IPMN)

“…Unfortunately, pre-operative evaluation of cytology in lesional fluid was not available in the majority of our cohort. While highly specific in the hands of an experienced GI cytopathologist, 43 studies have brought into question its utility when acellular material is aspirated and expert interpretation is not available. 44 In our study, cyst fluid samples from IPMN were assayed with high reliability for mAb Das-1 using standard techniques.…”

Revised international consensus guidelines for the management of patients with mucinous cysts

“…Likewise, the absence of high-grade atypia has been shown to provide a negative predictive value of > 90% for malignancy in the context of the absence of the high-risk imaging features of a dilated MPD and mural nodule, a so-called triple-negative test. 30 Our ability to preoperatively diagnose and manage patients with pancreatic mucinous cysts continues to evolve as we gain experience in all disciplines. The 2012 guidelines offer an improved algorithm for patient management that attempts to balance the risk of malignancy with the risk of surgery (Fig.…”

“…21 A cytological diagnosis of ''positive'' or ''malignant'' is generally 100% specific but very insensitive for detecting highgrade dysplasia. 30,31 Aspirating the contents of the cyst is really a screening test for the detection of dysplastic cells, akin to a Papanicolaou test. There is no directed biopsy of the cyst lining; the cells that are collected are those floating in the cyst cavity and adjoining ducts and abraded from the cyst wall with the aspiration needle.…”

Pancreatic Mucinous Lesions: How Dangerous are they?

“…The prevalence of incidental pancreatic cystic lesions found on Multidetector Computed Tomography (MDCT) has been reported to be as high as 2.6% [1]. Retrospective reviews of Magnetic Resonance Imaging (MRI) have shown an even higher prevalence of pancreatic cysts, from 13.5% to 19.6% [2,3]. Mucinous cystic neoplasm (MCN) and Intraductal Papillary Mucinous Neoplasm (IPMN) comprise up to half of all resected pancreatic cysts that are incidentally discovered [4,5].…”

“…Cyst fluid Carcinoembryonic Antigen (CEA) level ≥192-200 ng/mL is close to 80% accurate for the diagnosis of a mucinous cyst, but the CEA level has no use in distinguishing benign from malignant cysts [7,18]. The addition of cytology in one study detected 30% more malignant lesions in small (<3 cm) BD-IPMN [19]. Molecular analyses of cyst fluid, notably KRAS and GNAS mutations, also offer promise in the diagnosis of malignancy [20,21].…”