ENDOSCOPIC ULTRASOUND GUIDED-FINE NEEDLE ASPIRATION CYTOLOGY OF PANCREAS Khalid Amin M.D. Assistant Professor Department of Laboratory Medicine and Pathology University of Minnesota Outline Pancreatic EUS-FNA general aspects Cytomorphologic features of solid neoplasms/lesions of the pancreas Cystic lesions - diagnostic approach, role of tumor and molecular markers and cytomorphologic features Performance of Pancreatic EUS-FNA in Detecting Malignancy Malignant Diagnosis Sensitivity: 85% (95% CI:84-86%) Specificity: 98% (95% CI:97-99%) Suspicious or Atypical Diagnosis Sensitivity: 91% (95% CI:90-92%) Specificity: 94% (95% CI:93-96%) PPV: 99% NPV: 64% Sensitivity of EUS-FNA in detecting malignancy is decreased in presence of chronic pancreatitis GASTROINTEST ENDOSC. 2012 Feb;75(2):319-31 1
Diagnostic performance of rapid on-site evaluation by a cytopathologist/cytotechnician in the evaluation of solid pancreatic masses Studies Year With No. of cases Without With Accuracy Without P value Klapman et al 2003 108 87 78% 52% 0.001 Alsohaibani et al 2009 47 60 77% 53% 0.001 Iglesias-Garcia et al 2011 95 987 96.80% 86.20% 0.013 Collins et al 2013 379 377 97.10% 94.10% N.S. : Rapid on-site evaluation. Repeat rate: 2.9 % 5.8% 0.02 WORLD J GASTROENTEROL. 2014 Jul 28;20(28): 9451-9457 PROPOSED PANCREATOBILIARY TERMINOLOGY CLASSIFICATION SCHEME I - Non-diagnostic II- Negative (for malignancy) Benign pancreatobiliary tissue in the setting of vague fullness and no discrete mass Acute pancreatitis Chronic pancreatitis Autoimmune pancreatitis Pseudocyst Lymphoepithelial cyst Splenule/accessory spleen III- Atypical IV- Neoplastic: Neoplastic: Benign Neoplastic: Other (SFT, PancNET, IPMN, MCN) V- Suspicious (for malignancy) VI-Positive/malignant DIAGN CYTOPATHOL. 2014 Apr;42(4):338-50. NORMAL EPITHELIAL COMPONENTS - DUCTAL Normally present but sparse 2-dimensional cohesive orderly honeycomb sheets Uniform cuboidal to columnar cells Smooth nuclei with fine chromatin, small nucleoli Delicate, pale finely vacuolated cytoplasm 2
NORMAL EPITHELIAL COMPONENTS - ACINAR Two-dimensional microacinar clusters or three-dimensional grape-like clusters Polygonal or pyramidal cell outlines with indistinct borders Round and uniform eccentric nuclei with granular and evenly distributed chromatin, prominent nucleolus Abundant, coarsely granular cytoplasm CONTAMINANTS - INTESTINAL EPITHELIUM Cohesive uniform forming large sheets with starry sky appearance due to interspersed goblet cells Apical cytoplasmic thickening striated border Occasionally papillary-like aggregates mimicking IPMN Seen in FNA of head and uncinate process lesions CONTAMINANTS - GASTRIC EPITHELIUM Cohesive uniform flat sheets of orderly cells in honeycomb arrangement with well-defined borders Single cells often present Round smooth uniform nuclei Gastric foveolar cells can be difficult to distinguish from lowgrade IPMN Parietal (oxyphilic) and chief (granular basophilic) cells uncommon Seen in FNA of body and tail lesions 3
SOLID LESIONS/NEOPLASMS CHRONIC PANCREATITIS FNA performed to exclude malignancy rather that diagnose chronic pancreatitis Non-specific findings Diagnostic sensitivity of EUS-FNA in diagnosing cancer decreased in setting of chronic pancreatitis due to difficulties in imaging Distinguishing well-differentiated pancreatic adenocarcinoma from chronic pancreatitis can be a diagnostic dilemma - made worse as both coexist CHRONIC PANCREATITIS -More ductal than acinar cells -Overall low cellularity -Cohesive, honeycomb sheets, some crowding -Stromal fragments -Debris and calcified material -Fat necrosis -Atrophic acini -Stromal fibrosis with chronic inflammation 4
AUTOIMMUNE PANCREATITIS (AIP) Definitive diagnosis challenging if not impossible on EUS-FNA Improved prospects of AIP Dx with newer EUS needles Cytologic Features More stromal fragments Inflammatory cells within stromal fragments Increased cellularity of stromal fragments Fragments of fibrous tissue with atrophic acini Acinar and Centroacinar/Ductular Cells with mild to moderate cytologic atypia Histology and cytology of AIP: Cytologic Features of Autoimmune pancreatitis A, Single lymphocytes in background with a single small stromal fragment B, Autoimmune pancreatitis with characteristic periductal lymphocytic cuffing and stromal fibroblastic proliferation C, Cellular stromal fragment (stromal cellularity 3+) with spindled cells (fibroblasts) and small lymphocytes D, Corresponding pancreatectomy demonstrating cellular stroma infiltrated by lymphocytes E, Prominent centroacinar cells in AIP reminiscent of solid-pseudopapillary tumor. F, Corresponding histology The American Journal of Surgical Pathology Issue: Volume 29(11), November 2005, pp 1464-1471 Neoplastic pancreatic tumor diagnoses via endoscopic ultrasound-guided fine needle aspiration within our institution from January 1 st, 2006 to July 1 st, 2016 Diagnosis Incidence (% total cases) Metastatic lesions to the pancreas 25 (4.2) Metastatic renal cell carcinoma 10 (1.7) Metastatic colorectal adenocarcinoma 3 (0.5) Metastatic ovarian high-grade serous carcinoma 2 (0.3) Metastatic lung small cell carcinoma 2 (0.3) Metastatic ovarian carcinosarcoma 1 (0.2) Metastatic breast ductal carcinoma 1 (0.2) Metastatic vulvar squamous cell carcinoma 1 (0.2) Metastatic maxillary sinus melanoma 1 (0.2) Metastatic oral squamous cell carcinoma 1 (0.2) Metastatic esophageal adenocarcinoma 1 (0.2) Metastatic colonic large cell neuroendocrine carcinoma 1 (0.2) Metastatic leiomyosarcoma 1 (0.2) Adenocarcinoma 449 (75.6) Acinar cell carcinoma 2 (0.3) IPMN with associated invasive carcinoma 2 (0.3) Benign mucinous neoplasmsa 28 (4.7) Solid-pseudopapillary neoplasm 4 (0.7) Serous cystadenoma 4 (0.7) Neuroendocrine neoplasm 71 (12.0) Hematolymphoid processes 7 (1.2) Diffuse large B-cell lymphoma 4 (0.7) Follicular lymphoma 2 (0.3) Plasma cell neoplasm 1 (0.2) Mesenchymal tumors 2 (0.3) Liposarcoma 1 (0.2) Solitary fibrous tumor 1 (0.2) TOTAL 594 DIAGN CYTOPATHOL. 2017 May;45(5):418-425 5
WELL-DIFFERENTIATED ADENOCARCINOMA -Cellular smears dominated by ductal cells -Variably sized cluster, large sheets plus single intact cells -Abnormal architectural arrangements - Crowded, disorderly sheets, tight wads with nuclear overlap and loss of polarity -Loose sheets of irregularly spaced cell drunken honeycomb WELL-DIFFERENTIATED ADENOCARCINOMA -Irregular nuclear membranes Nuclear membrane irregularities (folds, clefts, grooves) -Prominent cherry red nucleoli WELL-DIFFERENTIATED ADENOCARCINOMA -Anisonucleosis (4:1) -Hyper or hypochromasia (chromatin clearing) -Cells with mucin vacuoles -Careful search will yield obviously malignant cells in small clusters or isolated 6
MODERATELY-DIFFERENTIATED ADENOCARCINOMA -Highly pleomorphic cell groups -Necrosis and obvious nuclear atypia -Single highly atypical cells Tombstone Cell Comparison of Cytologic Features of Confirmed Pancreatic Well-Differentiated Adenocarcinoma and Benign Lesions Criteria Cytologic feature WDA (n = 74) (%) Suspicious (n = 6) (%) False negative (n = 4) (%) Benign (n = 23) (%) 1 Anisonucleosis (greater than four times) 97 100 75 0 2 Nuclear membrane irregularity 97 83 50 4 3 Nuclear crowding/overlapping/threedimensionality 92 67 50 17 4 Nuclear enlargement (> 2 RBC) 99 83 100 17 5 Gap vs. confluent cell spacing 38 16 25 4 6 Hyperchromasia 36 0 25 7 7 Macronucleoli 14 0 0 0 8 Mitosis 22 0 25 7 9 Chromatin clearing 14 33 0 4 10 Necrosis 7 0 0 0 Cancer Cytopathology Volume 99, Issue 1, pages 44-50, 12 Dec 2002 Cytologic Features of Well-differentiated Adenocarcinoma Well differentiated adenocarcinoma of the pancreas, misdiagnosed cytologically as benign Cancer Cytopathology Volume 99, Issue 1, pages 44-50, 12 Dec 2002 7