Grading pancreatic neuroendocrine neoplasms by Ki-67 staining on cytology cell blocks: manual count and digital image analysis of 58 cases

Jin, Ming; Roth, Rachel; Gayetsky, Vera; Niederberger, Nicholas; Lehman, Amy; Wakely, Paul E.

doi:10.1016/j.jasc.2016.03.002

Cited by 20 publications

(24 citation statements)

References 21 publications

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“…G3 tumours tend also to be larger at diagnosis, which influences the overall area punctured by FNA, and furthermore, they dilute the hotspot areas. Over-grading has also been described in the literature [9,20] and can be explained by the fact that some pNETs are contaminated by proliferating inflammatory cells, mostly lymphocytes or endothelial cells, which can sometimes be confounding on FNA material.…”

Section: Progression-free Survivalmentioning

confidence: 91%

“…Secondly, different counting methods have been described, including eyeballing, cell count via the microscope or on digitalized and printed slides as well as automated methods. Two recent papers compared all or some of these methods on resection specimens [8] and EUS-FNA [9]. Both reached the same conclusion: manual count on a digitalized and printed document is the most accurate way to determine the Ki67-LI.…”

Section: Introductionmentioning

confidence: 91%

“…Since 2014 and the publication of our first paper [17], a few groups have done comparative studies between the Ki67-LI obtained on FNA and the corresponding resection specimens [2,9,15,16,[20][21][22][23][24]. Our study represents the largest to date, not only in terms of comparison of grading, but also in terms of Ki67-LI absolute values, between cytology and corresponding resection specimens, studying the influence of tumour size, the number of counted cells on FNA and overall and progression-free survival.…”

Section: Progression-free Survivalmentioning

confidence: 99%

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Accuracy of Pancreatic Neuroendocrine Tumour Grading by Endoscopic Ultrasound-Guided Fine Needle Aspiration: Analysis of a Large Cohort and Perspectives for Improvement

Boutsen¹,

Jouret‐Mourin²,

Borbath

et al. 2017

Neuroendocrinology

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Introduction: Since the WHO Classification of Tumours of the Digestive System has been published in 2010, resected pancreatic neuroendocrine tumours (pNETs) are graded as grade 1 (G1), grade 2 (G2) or grade 3 (G3) using the Ki67 labelling index (Ki67-LI). Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is often used for diagnosis, but few studies have assessed its value for grading. Aims: The aims of this study were to compare the Ki67-LI obtained by cytological grading (cG) with that obtained by histological grading (hG) and to assess (1) the influence of tumour size and the number of counted cells on FNA grading as well as (2) the overall survival (OS) and progression-free survival based on cG. Materials and Methods: EUS-FNA was performed for 102 pNETs (57 resected). cG (200 cells counted) was done on all FNAs. For 29 FNAs, >2,000 cells were counted (14 resected). A comparison was made between hG and cG for the 57 resected patients. Patients were followed up until June 2016. Results: cG was consistent with hG in 39 of 57 patients with a concordance rate of 72% using a Ki67-LI cut-off of 5% for G1/G2. For Ki67-LI absolute values, the correlation was r = 0.443 and increased to r = 0.824 (p < 0.001) when only FNAs with >2,000 cells were counted. Twenty-one of 22 pNETs <2 cm had the same grading on cG and hG, whereas grading was discordant for 15 of 16 pNETs >2 cm. Thirty-eight patients died after 70.5 months of follow-up. OS for the whole cohort was 235 months and differed between cG1 (235 months), cG2 (36.3 months) and cG3 (10.9 months). Conclusion: cG of pNETs is more accurate when tumours measure <2 cm and more cells are counted on FNA. Discrepancies are seen between G2 tumours which are often considered G1 on FNA due to tumour heterogeneity. EUS-FNA is valuable to distinguish between patients with good (cG1) and poor (cG3) prognosis.

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Section: Progression-free Survivalmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 91%

Section: Progression-free Survivalmentioning

confidence: 99%

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Accuracy of Pancreatic Neuroendocrine Tumour Grading by Endoscopic Ultrasound-Guided Fine Needle Aspiration: Analysis of a Large Cohort and Perspectives for Improvement

Boutsen¹,

Jouret‐Mourin²,

Borbath

et al. 2017

Neuroendocrinology

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“…After confirmation of neuroendocrine and epithelial differentiation, the next step pertains to differentiating a well‐differentiated NET (WDNET) from a poorly differentiated NEC . While tumor cytomorphology, including mitotic activity, may be sufficient in making this distinction, the concurrent use of a proliferative biomarker (Ki‐67/MIB‐1) is generally advised . The classification of NET is site‐ and grade‐dependent, requiring careful evaluation of cytomorphology along with proliferative features of the tumor .…”

Section: Introductionmentioning

confidence: 99%

“…The real challenge arises when distinguishing between low‐grade versus intermediate‐grade NETs. The proliferation index in fine‐needle aspiration cell blocks should be interpreted with caution . Because neuroendocrine neoplasms can be quite heterogeneous with respect to their proliferative activity, small biopsy specimens often fail to meet the minimum requirements for formal grading .…”

Section: Introductionmentioning

confidence: 99%

Algorithmic approach to neuroendocrine tumors in targeted biopsies: Practical applications of immunohistochemical markers

Duan

Mete

2016

Cancer Cytopathology

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Neuroendocrine tumors (NETs) constitute a heterogeneous group of neoplasms with distinct biological behaviors, depending on the site of origin and the degree of tumor proliferation. Although advances in biochemical and radiological modalities have enhanced the ability to detect NETs, tissue diagnosis remains the gold standard to assess tumor characteristics for treatment decision making. In an era with growing demands for precision diagnostics based on smaller tissue samples, immunohistochemistry has become an indispensable tool in the pathologist's repertoire. In conjunction with clinical findings and cytomorphology, complementary use of 1) markers of neuroendocrine differentiation, 2) markers confirming epithelial nature, 3) markers of cellular proliferation, 4) transcription factors and hormonal markers, as well as 5) predictive and prognostic markers may be necessary to guide patient management in NETs. The current review summarizes common applications of these immunohistochemical markers when confronted with a potential neuroendocrine neoplasm, and proposes a stepwise algorithmic approach to avoid diagnostic errors in targeted biopsies. Cancer Cytopathol 2016;124:871-84. V C 2016 American Cancer Society.

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Advances in the cytologic diagnosis of gastroenteropancreatic neuroendocrine neoplasms

Sigel

2018

Cancer Cytopathology

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Two‐thirds of neuroendocrine neoplasms arising in the human body originate from the gastrointestinal system or pancreas. Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous, comprising both well differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The clinical presentation, molecular characteristics, and behavior are distinct for NETs and NECs. Fine‐needle aspiration is an important modality for the primary diagnosis and staging of these neoplasms and can provide information of prognostic and therapeutic significance. Our evolving understanding of neuroendocrine neoplasm biology has led to several iterations of classification. In this review, new concepts and issues most relevant to cytology diagnosis of gastroenteropancreatic neuroendocrine neoplasms are discussed, such as newer detection methods that aid in diagnosis and staging, recent changes in World Health Organization classification, practical issues related to grading these neoplasms on cytology, guidelines for diagnostic reporting, and panels of immunohistochemical stains for the diagnosis of metastasis. The current understanding of genetic and epigenetic events related to tumor development and potential applications for cytology also are presented as they relate to prognostication and recent therapeutic advances.

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Grading pancreatic neuroendocrine neoplasms by Ki-67 staining on cytology cell blocks: manual count and digital image analysis of 58 cases

Cited by 20 publications

References 21 publications

Accuracy of Pancreatic Neuroendocrine Tumour Grading by Endoscopic Ultrasound-Guided Fine Needle Aspiration: Analysis of a Large Cohort and Perspectives for Improvement

Accuracy of Pancreatic Neuroendocrine Tumour Grading by Endoscopic Ultrasound-Guided Fine Needle Aspiration: Analysis of a Large Cohort and Perspectives for Improvement

Algorithmic approach to neuroendocrine tumors in targeted biopsies: Practical applications of immunohistochemical markers

Advances in the cytologic diagnosis of gastroenteropancreatic neuroendocrine neoplasms

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