Fine‐needle aspiration biopsy of pancreatic neuroendocrine tumors: Correlation between Ki‐67 index in cytological samples and clinical behavior

Arco, Cristina Díaz del; López-Jamar, José Miguel Esteban; Ortega, Luís; Pérez, José Ángel Díaz; Fernández-Aceñero, María Jesús

doi:10.1002/dc.23635

Cited by 21 publications

(11 citation statements)

References 35 publications

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“…However, similar to previous studies, intermediate-grade tumors had a lower concordance rate between Ki67 grading on EUS-FNA cytology and surgical resection histology. 8,25,27 The lower Ki67 concordance rate in our intermediate-grade NF-PNETs could be due to several causes including the following: (1) intratumoral heterogeneity that is reported to be higher in intermediate-grade surgical Ki67 tumors than in low-grade surgical Ki67 tumors; 25 (2) increased tumor size, which may contribute to increased intratumoral heterogeneity; 27 or (3) lower cell count from EUS-FNA sampling, as Hasegawa et al noted increased Ki67 concordance rates from 77.8% to 90% when patients with <2,000 tumor cells were excluded. 8 Overall, our Ki67 concordance rate was consistent with prior studies considering both functioning and NF-PNETs, but on the lower end of the range of previously reported concordance rates.…”

Section: Discussion Concordancementioning

confidence: 99%

“…Numerous studies investigating NF-PNETs have found tumor diameter, Ki67 proliferative index >2%, and/or presence of lymph node disease to be predictive of malignant potential and worse outcomes. 1,5,7,9,[19][20][21][22][23][24][25] Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a validated method used to identify, measure, sample, and risk-stratify all PNETs according to these prognostic factors. 23,26,27 Prior studies have evaluated the concordance between Ki67 indices obtained from EUS-FNA cytology and from surgical pathology specimens in all (functioning and nonfunctioning) PNETs.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Endoscopic Ultrasound-Guided Ki67 in the Management of Non-Functioning Pancreatic Neuroendocrine Tumors

et al. 2020

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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-stratify PNETs. 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; concordance was 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), tumor size >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 with intermediate-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. Clin Endosc 2020;53:213-220

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Section: Discussion Concordancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Role of Endoscopic Ultrasound-Guided Ki67 in the Management of Non-Functioning Pancreatic Neuroendocrine Tumors

et al. 2020

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“…Traditionally, endoscopic ultrasound (EUS)‐guided tissue sampling has been carried out using a thin and flexible fine‐needle aspiration (FNA) needle, which mainly yields individual cells (cytology) rather than histologically intact tissue fragments. Although diagnostic accuracy rates of FNA are fair, intact tissue fragments are preferred to enable identification of tumor invasion and allow for ancillary immunological and molecular testing; for example, in submucosal and neuroendocrine tumors . Furthermore, histology enables genetic profiling and a patient‐tailored approach, which is becoming increasingly relevant in this era of personalized medicine .…”

Section: Introductionmentioning

confidence: 99%

“…Although diagnostic accuracy rates of FNA are fair, intact tissue fragments are preferred to enable identification of tumor invasion and allow for ancillary immunological and molecular testing; for example, in submucosal and neuroendocrine tumors. [1][2][3][4][5][6][7][8][9] Furthermore, histology enables genetic profiling and a patient-tailored approach, which is becoming increasingly relevant in this era of personalized medicine. [10][11][12][13][14] The growing need for histology resulted in the introduction of fine-needle biopsy (FNB) needles.…”

Section: Introductionmentioning

confidence: 99%

Agreement on endoscopic ultrasonography‐guided tissue specimens: Comparing a 20‐G fine‐needle biopsy to a 25‐G fine‐needle aspiration needle among academic and non‐academic pathologists

Riet

Cahen

Biermann

et al. 2019

Digestive Endoscopy

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Background and Aim A recently carried out randomized controlled trial showed the benefit of a novel 20‐G fine‐needle biopsy (FNB) over a 25‐G fine‐needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non‐academic pathologists. Methods This study was a side‐study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re‐reviewed by five expert academic and five non‐academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non‐academic pathologists, target lesions, and cytology versus histological specimens. Results Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P < 0.001) and classification according to Bethesda (ĸ = 0.45 vs ĸ = 0.61, P < 0.001). This equally applied for expert academic and non‐academic pathologists and for pancreatic and lymph node specimens. Sample quality was also rated higher for FNB, but agreement ranged from poor (ĸ = 0.04) to fair (ĸ = 0.55). Histology provided better agreement than cytology, but only when a core specimen was obtained with FNB (P = 0.004 vs P = 0.432). Conclusion This study shows that the 20‐G FNB outperforms the 25‐G FNA needle in terms of diagnostic agreement, independent of the background and experience of the pathologist. This endorses use of the 20‐G FNB needle in both expert and lower volume EUS centers.

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“…Current prognostic parameters and systems, such as tumor size and World Health Organization (WHO) grade, are susceptible to interpretation errors, sampling issues and, in a subset of PanNETs, do not accurately reflect the clinical behavior of these neoplasms. 1–4 Hence, additional markers are needed to improve the prognostic classification of PanNETs.…”

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confidence: 99%

Loss of Chromatin-Remodeling Proteins and/or CDKN2A Associates With Metastasis of Pancreatic Neuroendocrine Tumors and Reduced Patient Survival Times

et al. 2018

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Despite prognostic grading and staging systems, it is a challenge to predict outcomes for patients with pancreatic neuroendocrine tumors (PanNETs). Sequencing studies of PanNETs have identified alterations in death domain-associated protein (DAXX) and ATRX chromatin remodeler (ATRX). In tumors, mutations in DAXX or ATRX and corresponding loss of protein expression correlate with shorter times of disease-free survival and disease-specific survival of patients. However, DAXX or ATRX proteins were lost in only 50% of distant metastases analyzed. We performed whole-exome sequencing analyses of 20 distant metastases from 20 patients with a single non-syndrome, non-functional PanNET. We found distant metastases contained alterations in MEN1 (n=8), ATRX (n=5), DAXX (n=5), TSC2 (n=3), and DEPDC5 (n=3). We found copy number loss of CDKN2A in 15 metastases (75%) and alterations in genes that regulate chromatin remodeling including SETD2 (n=4), ARID1A (n=2), CHD8 (n=2), and DNMT1 (n=2). In a separate analysis of 347 primary PanNETs, we found loss or deletion of DAXX and ATRX, disruption of SETD2 function (based on loss of H3K36me3), loss of ARID1A expression or deletions in CDKN2A in 81% of primary PanNETs with distant metastases. Among patients with loss or deletion of at least 1 of these proteins or genes, 39% survived disease free for 5 years and 44% had disease-specific survival times of 10 years. Among patients without any of these alterations, 98% survived disease free for 5 years and 95% had disease-specific survival times of 10 years. Therefore, primary PanNETs with loss of DAXX, ATRX, H3K36me3, ARID1A, and/or CDKN2A associate with shorter survival times of patients. Our findings indicate that alterations in chromatin remodeling genes and CDKN2A contribute to metastasis of PanNETs.

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Fine‐needle aspiration biopsy of pancreatic neuroendocrine tumors: Correlation between Ki‐67 index in cytological samples and clinical behavior

Abstract: Higher Ki-67 index in cytology specimens portends a worse outcome, although some G1 tumors may progress or cause death. Diagn. Cytopathol. 2017;45:29-35. © 2016 Wiley Periodicals, Inc.

Cited by 21 publications

References 35 publications

The Role of Endoscopic Ultrasound-Guided Ki67 in the Management of Non-Functioning Pancreatic Neuroendocrine Tumors

The Role of Endoscopic Ultrasound-Guided Ki67 in the Management of Non-Functioning Pancreatic Neuroendocrine Tumors

Agreement on endoscopic ultrasonography‐guided tissue specimens: Comparing a 20‐G fine‐needle biopsy to a 25‐G fine‐needle aspiration needle among academic and non‐academic pathologists

Loss of Chromatin-Remodeling Proteins and/or CDKN2A Associates With Metastasis of Pancreatic Neuroendocrine Tumors and Reduced Patient Survival Times

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