The Role of Endoscopic Ultrasound-Guided Ki67 in the Management of Non-Functioning Pancreatic Neuroendocrine Tumors
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Background/Aims: The management of small, incidentally discovered nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs)has been a matter of debate. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a tool used to identify and risk-stratifyPNETs. This study investigates the concordance rate of Ki67 grading between EUS-FNA and surgical pathology specimens in NF-PNETs and whether certain NF-PNET characteristics are associated with disease recurrence and disease-related death. Methods: We retrospectively reviewed the clinical history, imaging, endoscopic findings, and pathology records of 37 cases of NF-PNETs that underwent pre-operative EUS-FNA and surgical resection at a single academic medical center. Results: There was 73% concordance between Ki67 obtained from EUS-FNA cytology and surgical pathology specimens; concordancewas the highest for low- and high-grade NF-PNETs. High-grade Ki67 NF-PNETs based on cytology (p=0.028) and histology (p=0.028)were associated with disease recurrence and disease-related death. Additionally, tumors with high-grade mitotic rate (p=0.005), tumorsize >22.5 mm (p=0.104), and lymphovascular invasion (p=0.103) were more likely to have poor prognosis. Conclusions: NF-PNETs with high-grade Ki67 on EUS-FNA have poor prognosis despite surgical resection. NF-PNETs withintermediate-grade Ki67 on EUS-FNA should be strongly considered for surgical resection. NF-PNETs with low-grade Ki67 on EUS-FNA can be monitored without surgical intervention, up to tumor size 20 mm.
Abstract
Background/Aims: The management of small, incidentally discovered nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs)has been a matter of debate. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a tool used to identify and risk-stratifyPNETs. This study investigates the concordance rate of Ki67 grading between EUS-FNA and surgical pathology specimens in NF-PNETs and whether certain NF-PNET characteristics are associated with disease recurrence and disease-related death. Methods: We retrospectively reviewed the clinical history, imaging, endoscopic findings, and pathology records of 37 cases of NF-PNETs that underwent pre-operative EUS-FNA and surgical resection at a single academic medical center. Results: There was 73% concordance between Ki67 obtained from EUS-FNA cytology and surgical pathology specimens; concordancewas the highest for low- and high-grade NF-PNETs. High-grade Ki67 NF-PNETs based on cytology (p=0.028) and histology (p=0.028)were associated with disease recurrence and disease-related death. Additionally, tumors with high-grade mitotic rate (p=0.005), tumorsize >22.5 mm (p=0.104), and lymphovascular invasion (p=0.103) were more likely to have poor prognosis. Conclusions: NF-PNETs with high-grade Ki67 on EUS-FNA have poor prognosis despite surgical resection. NF-PNETs withintermediate-grade Ki67 on EUS-FNA should be strongly considered for surgical resection. NF-PNETs with low-grade Ki67 on EUS-FNA can be monitored without surgical intervention, up to tumor size 20 mm.
참고문헌 (34)
- Halfdanarson TR, "Pancreatic endocrine neoplasms : epidemiology and prognosis of pancreatic endocrine tumors", Endocr Relat Cancer, 15, pp.409~427 (2008)
- Metz DC, "Gastrointestinal neuroendocrine tumors : pancreatic endocrine tumors", Gastroenterology, 135, pp.1469~1492 (2008)
- Grimelius L, "Cytological differentiation of asymptomatic pancreatic islet cell tumours in autopsy material", Virchows Arch A Pathol Anat Histol, 365, pp.275~288 (1975)
- Kimura W, "Clinical pathology of endocrine tumors of the pancreas. Analysis of autopsy cases", Dig Dis Sci, 36, pp.933~942 (1991)
- Halfdanarson TR, "Pancreatic neuroendocrine tumors(PNETs) : incidence, prognosis and recent trend toward improved survival", Ann Oncol, 19, pp.1727~1733 (2008)
- Fitzgerald TL, "Changing incidence of pancreatic neoplasms : a 16-year review of statewide tumor registry", Pancreas, 37, pp.134~138 (2008)
- Kuo EJ, "Population-level analysis of pancreatic neuroendocrine tumors 2 cm or less in size", Ann Surg Oncol, 20, pp.2815~2821 (2013)
- Hasegawa T, "Evaluation of Ki-67 index in EUS-FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors", Endoscopy, 46, pp.32~38 (2014)
- Gullo L, "Nonfunctioning pancreatic endocrine tumors : a multicenter clinical study", Am J Gastroenterol, 98, pp.2435~2439 (2003)
- Hill JS, "Pancreatic neuroendocrine tumors : the impact of surgical resection on survival", Cancer, 115, pp.741~751 (2009)
- Franko J, "Non-functional neuroendocrine carcinoma of the pancreas : incidence, tumor biology, and outcomes in 2, 158 patients", J Gastrointest Surg, 14, pp.541~548 (2010)
- Bettini R, "Tumor size correlates with malignancy in nonfunctioning pancreatic endocrine tumor", Surgery, 150, pp.75~82 (2011)
- Lee LC, "Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors(PNETs) : role for nonoperative management", Surgery, 152, pp.965~974 (2012)
- Kishi Y, "Basing treatment strategy for non-functional pancreatic neuroendocrine tumors on tumor size", Ann Surg Oncol, 21, pp.2882~2888 (2014)
- Zhang IY, "Operative versus nonoperative management of nonfunctioning pancreatic neuroendocrine tumors", J Gastrointest Surg, 20, pp.277~283 (2016)
- Regenet N, "Is the 2-cm size cutoff relevant for small nonfunctioning pancreatic neuroendocrine tumors : a French multicenter study", Surgery, 159, pp.901~907 (2016)
- "NCCN clinical practice guidelines in oncology neuroendocrine and adrenal tumors (United States)" (2019)[URL]
- Falconi M, "ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors", Neuroendocrinology, 103, pp.153~171 (2016)
- La Rosa S, "Prognostic criteria in nonfunctioning pancreatic endocrine tumours", Virchows Arch, 429, pp.323~333 (1996)
- Bettini R, "Prognostic factors at diagnosis and value of WHO classification in a mono-institutional series of 180 non-functioning pancreatic endocrine tumours", Ann Oncol, 19, pp.903~908 (2008)
- Alexiev BA, "Proliferative rate in endoscopic ultrasound fine-needle aspiration of pancreatic endocrine tumors : correlation with clinical behavior", Cancer, 117, pp.40~45 (2009)
- Hamilton NA, "Ki-67 predicts disease recurrence and poor prognosis in pancreatic neuroendocrine neoplasms", Surgery, 152, pp.107~113 (2012)
- Unno J, "The usefulness of endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of pancreatic neuroendocrine tumors based on the World Health Organization classification", Scand J Gastroenterol, 49, pp.1367~1374 (2014)
- Cherenfant J, "Comparison of tumor markers for predicting outcomes after resection of nonfunctioning pancreatic neuroendocrine tumors", Surgery, 156, pp.1504~1510 (2014)
- Díaz Del Arco C, "Fine-needle aspiration biopsy of pancreatic neuroendocrine tumors : correlation between Ki-67 index in cytological samples and clinical behavior", Diagn Cytopathol, 45, pp.29~35 (2017)
- McLean AM, "Endoscopic ultrasound in the localisation of pancreatic islet cell tumours", Best Pract Res Clin Endocrinol Metab, 19, pp.177~193 (2005)
- Fujimori N, "Efficacy of endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors", Scand J Gastroenterol, 51, pp.245~252 (2016)
- Piani C, "Cytological Ki-67 in pancreatic endocrine tumours : an opportunity for pre-operative grading", Endocr Relat Cancer, 15, pp.175~181 (2008)
- Larghi A, "Ki-67 grading of nonfunctioning pancreatic neuroendocrine tumors on histologic samples obtained by EUS-guided fine-needle tissue acquisition : a prospective study", Gastrointest Endosc, 76, pp.570~577 (2012)
- Carlinfante G, "Ki-67 cytological index can distinguish well-differentiated from poorly differentiated pancreatic neuroendocrine tumors : a comparative cytohistological study of 53 cases", Virchows Arch, 465, pp.49~55 (2014)
- Farrell JM, "Pancreatic neuroendocrine tumors : accurate grading with Ki-67 index on fine-needle aspiration specimens using the WHO 2010", ENETS criteria, 2014, pp.122, 770~778
- Weynand B, "Pancreatic neuroendocrine tumour grading on endoscopic ultrasound-guided fine needle aspiration : high reproducibility and inter-observer agreement of the Ki-67 labelling index", Cytopathology, 25, pp.389~395 (2014)
- Rebours V, "Can pancreatic neuroendocrine tumour biopsy accurately determine pathological characteristics?", Dig Liver Dis, 47, pp.973~977 (2015)
- Boutsen L, "Accuracy of pancreatic neuroendocrine tumour grading by endoscopic ultrasound-guided fine needle aspiration : analysis of a large cohort and perspectives for improvement", Neuroendocrinology, 106, pp.158~166 (2018)