Original article Clinical endoscopy| Volume 90, ISSUE 5, P784-792.e4, November 2019

Interobserver agreement among expert pathologists on through-the-needle microforceps biopsy samples for evaluation of pancreatic cystic lesions

      Background and Aims

      The recent development of microforceps for EUS through-the-needle biopsy (TTNB) sampling of the wall of pancreatic cystic lesions (PCLs) allows the collection of histologic specimens never handled and evaluated before by pathologists. We aimed to estimate the interobserver agreement among pathologists in evaluating such samples.


      TTNB specimen slides from 40 PCLs with worrisome features were retrieved and independently evaluated for specimen adequacy, presence of lining epithelium, grade of epithelial dysplasia, presence of ovarian type stroma, and specific diagnosis by 6 expert pathologists from 6 different tertiary care centers. The Gwet’s AC1 was used to assess interobserver agreement.


      An almost perfect agreement was observed for specimen adequacy (AC1, .82; 95% confidence interval [CI], .79-.98), presence of lesional epithelium (AC1, .90; 95% CI, .86-.92), epithelial dysplasia (AC1, .97; 95% CI, .95-.99), and ovarian-like stroma (AC1, .90; 95% CI, .86-.93). When considering all diagnoses separately, a moderate to substantial agreement was observed (AC1, .62; 95% CI, .57-.67), similarly to mucinous cysts versus serous adenoma versus other diagnoses (AC1, .65; 95% CI, .59-.70) and for mucinous cysts versus all other diagnoses (AC1,.74; 95% CI, .68-.84). The agreement for diagnosis of mucinous cystic neoplasm versus intraductal mucinous papillary neoplasm was almost perfect (AC1, .88; 95% CI, .81-.95).


      Interobserver agreement between expert pathologists in the evaluation of TTNB samples from PCLs with worrisome features was close to perfection for all evaluated parameters, except definitive diagnosis. When mucinous cystic lesions were compared versus all other diagnoses, the agreement became substantial, thus indicating that TTNB specimens can provide important information for PCL management decisions.

      Graphical abstract


      IPMN (intraductal papillary mucinous neoplasm), MCN (mucinous cystic neoplasm), PCL (pancreatic cystic lesion), SCA (serous cyst adenoma), TTNB (through-the-needle biopsy)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Gastrointestinal Endoscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Brugge W.R.
        Diagnosis and management of cystic lesions of the pancreas.
        J Gastrointest Oncol. 2015; 6: 375-388
        • Tanaka M.
        • Fernández-Del Castillo C.
        • Kamisawa T.
        • et al.
        Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas.
        Pancreatology. 2017; 17: 738-753
        • Dumonceau J.M.
        • Deprez P.H.
        • Jenssen C.
        • et al.
        Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline—updated January 2017.
        Endoscopy. 2017; 49: 695-714
        • The European Study Group on Cystic Tumours of the Pancreas
        European evidence-based guidelines on pancreatic cystic neoplasms.
        Gut. 2018; 67: 789-804
        • Brugge W.R.
        • Lewandrowski K.
        • Lee-Lewandrowski E.
        • et al.
        Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study.
        Gastroenterology. 2004; 126: 1330-1336
        • de Jong K.
        • Poley J.W.
        • van Hooft J.E.
        • et al.
        Endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesions provides inadequate material for cytology and laboratory analysis: initial results from a prospective study.
        Endoscopy. 2011; 43: 585-590
        • DiMaio C.J.
        Current guideline controversies in the management of pancreatic cystic neoplasms.
        Gastrointest Endosc Clin North Am. 2018; 28: 529-547
        • Salvia R.
        • Malleo G.
        • Marchegiani G.
        • et al.
        Pancreatic resections for cystic neoplasms: from the surgeon's presumption to the pathologist's reality.
        Surgery. 2012; 152: S135-S142
        • de Pretis N.
        • Mukewar S.
        • Aryal-Khanal A.
        • et al.
        Pancreatic cysts: diagnostic accuracy and risk of inappropriate resections.
        Pancreatology. 2017; 17: 267-272
        • Mittal C.
        • Obuch J.C.
        • Hammad H.
        • et al.
        Technical feasibility, diagnostic yield, and safety of microforceps biopsies during EUS evaluation of pancreatic cystic lesions (with video).
        Gastrointest Endosc. 2018; 87: 1263-1269
        • Basar O.
        • Yuksel O.
        • Yang D.J.
        • et al.
        Feasibility and safety of microforceps biopsy in the diagnosis of pancreatic cysts.
        Gastrointest Endosc. 2018; 88: 79-86
        • Barresi L.
        • Crinò S.F.
        • Fabbri C.
        • et al.
        Endoscopic ultrasound-through-the-needle biopsy in pancreatic cystic lesions: a multicenter study.
        Dig Endosc. 2018; 30: 760-770
        • Kovacevic B.
        • Klausen P.
        • Hasselby J.P.
        • et al.
        A novel endoscopic ultrasound-guided through-the-needle microbiopsy procedure improves diagnosis of pancreatic cystic lesions.
        Endoscopy. 2018; 50: 1105-1111
        • Kovacevic B.
        • Karstensen J.G.
        • Havre R.F.
        • et al.
        Initial experience with EUS-guided microbiopsy forceps in diagnosing pancreatic cystic lesions: a multicenter feasibility study (with video).
        Endosc Ultrasound. 2018; 7: 383-388
        • Yang D.
        • Samarasena J.B.
        • Jamil L.H.
        • et al.
        Endoscopic ultrasound-guided through-the-needle microforceps biopsy in the evaluation of pancreatic cystic lesions: a multicenter study.
        Endosc Int Open. 2018; 6: E1423-E1430
        • Yang D.
        • Trindade A.J.
        • Yachimski P.
        • et al.
        Histologic analysis of endoscopic ultrasound-guided through the needle microforceps biopsies accurately identifies mucinous pancreas cysts.
        Clin Gastroenterol Hepatol. 2019; 17: 1587-1596
        • Gwet K.L.
        Computing inter-rater reliability and its variance in the presence of high agreement.
        Br J Math Stat Psychol. 2008; 61: 29-48
        • Feinstein A.R.
        • Cicchetti D.V.
        High agreement but low kappa. I. The problems of two paradoxes.
        J Clin Epidemiol. 1990; 43: 543-549
        • Byrt T.
        • Bishop J.
        • Carlin J.B.
        Bias, prevalence and kappa.
        J Clin Epidemiol. 1993; 46: 423-429
        • Sahai A.V.
        The role of EUS for diagnosis of pancreatic cysts: observe, needle, or brush?.
        Endoscopy. 2010; 42: 153-154
        • Pausawasdi N.
        • Ratanachu-Ek T.
        Endoscopic ultrasonography evaluation for pancreatic cysts: necessity or overkill?.
        Dig Endosc. 2017; 29: 444-454
        • Crinò S.F.
        • Bernardoni L.
        • Brozzi L.
        • et al.
        Association between macroscopically visible tissue samples and diagnostic accuracy of EUS-guided through-the-needle microforceps biopsy of pancreatic cystic lesions.
        Gastrointest Endosc. Epub 2019 May 14;
        • Tarantino I.
        • Fabbri C.
        • Di Mitri R.
        • et al.
        Complications of endoscopic ultrasound fine needle aspiration on pancreatic cystic lesions: final results from a large prospective multicenter study.
        Dig Liver Dis. 2014; 46: 41-44
        • Lee L.S.
        • Saltzman J.R.
        • Bounds B.C.
        • et al.
        EUS-guided fine needle aspiration of pancreatic cysts: a retrospective analysis of complications and their predictors.
        Clin Gastroenterol Hepatol. 2005; 3: 231-236
        • Zhang M.L.
        • Arpin R.N.
        • Brugge W.R.
        • et al.
        Moray micro forceps biopsy improves the diagnosis of specific pancreatic cysts.
        Cancer Cytopathol. 2018; 126: 414-420