Comparison of World Health Organization 2000/2004 and World Health Organization 2010 classifications for gastrointestinal and pancreatic neuroendocrine tumors

Paşaoğlu, Esra; Dursun, Nevra; Özyalvaçlı, Gülzade; Hacıhasanoğlu, Ezgi; Behzatoğlu, Kemal; Calay, Ozden

doi:10.1016/j.anndiagpath.2015.01.001

Cited by 34 publications

(27 citation statements)

References 21 publications

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“…Our results showed that a higher Ki-67 PI was associated with more advanced disease such as larger tumor size, deeper tumor invasion, and lymph node or distant metastasis in gastric WDNET, which is consistent with previous studies [10][11][12]. Prognostic value of WHO 2010 grading system based on Ki-67 PI has been validated in GI neuroendocrine neoplasms by others [6,7].…”

Section: Discussionsupporting

confidence: 93%

“…However, Ki-67 PI in the clinical subtypes of gastric WDNET has not been evaluated in detail. Also, only a few studies have reported correlation between Ki-67 PI and clinicopathologic factors of gastric WDNET [10][11][12]. We aimed to evaluate clinicopathologic characteristics and Ki-67 PI status in the clinical subtypes of gastric WDNET in detail.…”

Section: Introductionmentioning

confidence: 99%

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Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index

et al. 2016

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Well-differentiated neuroendocrine tumor (WDNET) of the stomach can arise in three distinct clinical settings: (1) in association with autoimmune atrophic gastritis, (2) in association with multiple neuroendocrine neoplasia type I (MEN I) or Zollinger-Ellison syndrome (ZES), or (3) sporadic. The Ki-67 proliferative index (PI) in gastric WDNETs in these three distinct clinical settings has not been evaluated in detail. Forty-five gastric WNETs underwent polypectomy (n = 4), endoscopic mucosal resection (n = 12), and surgical resection (n = 29) between 1994 and 2015 were included. H&E slides from each case were reviewed, and Ki-67 immunostain was performed on one representative tumor block. Ki-67 PI was determined by quantitative Aperio image analysis software in areas of strongest nuclear labeling ("hot spots"), and correlated with underlying clinical and pathological features. Twenty-one patients were male and 24 female with a median age of 57 years (range, 30-80 years). Tumors were classified as type I (n = 17), type II (n = 6), and type III (n = 22) WDNETs. Types II and III showed more advanced TNM stage compared to type I (p = 0.02, overall). WHO grade based on Ki-67 PI was higher in type III WDNETs [grade 1 (G1), n = 3; grade 2 (G2), n = 15; and grade 3 (G3), n = 4] than in type I WDNETs [G1, n = 5; G2, n = 12] and in type II WDNETs [G1, n = 2; G2, n = 4] (p = 0.050, overall). Ki-67 PI was significantly higher in type III WDNETs (mean ± SD = 13.0 ± 13.3 %) than in non-sporadic (type I and II) WDNETs (mean ± SD = 5.3 ± 3.3 %; p = 0.015). There was no difference in Ki-67 PI between type I WDNETs (mean ± SD = 5.2 ± 3.5 %) and type II WDNETs (mean ± SD = 5.6 ± 3.1%; p = 0.817). Higher Ki-67 PI was associated with higher tumor T stage (p = 0.003) and also tended to be associated with lymph node metastasis (p = 0.071). In the Kaplan-Meier survival analysis, type I was associated with a significantly longer disease-free survival (DFS) time compared to type II (p = 0.018) or III (0.010). Also, the WHO G3 group had a significantly shorter DFS time than the WHO G1 (p = 0.020) or G2 (p = 0.007) group. Gastric WDNET is a heterogeneous disease entity encompassing three clinical subtypes-type I, type II, and type III-having their own distinct clinicopathologic characteristics and prognosis. Our results showed that sporadic (type III) WDNET had a significantly higher Ki-67 PI than non-sporadic cases (type I or II); increased PI was associated with higher tumor stage. We also described four type III cases of morphologically WD gastric NET with WHO grade 3 on the basis of Ki-67 PI.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index

et al. 2016

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“…In our series of GEP-NENs, the proportions of G1/G2/G3 were 63.3/16.3/20.4 %, respectively. These are very comparable to the results of other reports that classify their cases as proportions of G1/G2/G3; these are 64.9-73.2/6.3-10.5/16.3-24.7 %, respectively [18][19][20]. The most common type of lung NEN is reported to be SCC, which accounts for 60-80 % of pulmonary NENs and, together with another highly malignant NEN, LCNEC, represents over 80 %; in comparison, two lung NENs with low-to intermediate-grade malignancy (typical and atypical carcinoids) represent less than 20 % [21][22][23].…”

Section: Discussionsupporting

confidence: 93%

Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin

et al. 2016

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Neuroendocrine neoplasms (NENs) are derived from endocrine cells in various organs and share common morphological features. This study aimed to clarify whether NENs of different organs are comparable at the molecular pathologic level. We retrospectively collected 99 cases of NENs from gastro-entero-pancreatic, lung, and other organs and reclassified these according to identical criteria. Grade, site, and molecular expression profile including NE markers, Ki-67, p53, somatostatin receptor type 2A (SSTR2A), and phosphatase and tensin homolog (PTEN) were compared. PTEN immunoreactivity was also compared with genomic copy number by fluorescence in situ hybridization (FISH) and droplet digital polymerase chain reaction (ddPCR). No significant differences were observed in the immunoreactivities of NE markers, p53, SSTR2A, or PTEN expression in NENs between the different organ sites. PTEN and p53 functional inactivation along with the loss of membranous SSTR2A expression appeared to be commonly involved in high-grade NEN. FISH results were significantly correlated with the level of PTEN immunoreactivity and with the findings of ddPCR analyses. The demonstration that these tumors are comparable at the molecular level will likely contribute to the broadening of therapeutic options such as the use of somatostatin analogues and mTOR inhibitors against NENs regardless of the affected organ, whereas molecular characterization of tumor grade will be useful for determining treatment strategy.

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“…A possible solution to this problem would be to eliminate the term 'malignant' (Tischler 2008b) and replace it with a diagnostic classification based on multi-parameter risk stratification (Eisenhofer et al 2012). A precedent for this type of approach has already been set for low-grade neuroendocrine tumors of the gastro-entero-pancreatic axis (Klöppel 2011), which have many similarities to pheochromocytoma/paraganglioma and are currently all considered to have the potential to metastasize (Pasaoglu et al 2015).…”

Section: Thematic Reviewmentioning

confidence: 99%

15 YEARS OF PARAGANGLIOMA: Pathology of pheochromocytoma and paraganglioma

Tischler¹,

deKrijger²

2015

Endocrine-Related Cancer

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Pathologists using their routine diagnostic tools can contribute both to the care of patients with pheochromocytoma/paraganglioma and to understanding the pathobiology of the tumors. They can document details of tissue organization and cytology that are accessible only by microscopy and can characterize admixtures of cell types that are morphologically distinct or show differential expression of immunohistochemical markers. Current roles and challenges for pathologists include differential diagnosis, identifying clues to the presence of hereditary disease, and effective communication of pathology information for clinical and research purposes. Future roles will increasingly involve risk stratification, identification of actionable targets for personalized therapies, and aiding the interpretation of molecular tests by helping characterize genetic variants of unknown significance. It remains to be determined to what extent the need for pathology input will be overshadowed by the availability of genetic testing and other molecular analyses at ever-decreasing cost, together with very effective clinical paradigms for risk stratification and patient care.

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Comparison of World Health Organization 2000/2004 and World Health Organization 2010 classifications for gastrointestinal and pancreatic neuroendocrine tumors

Cited by 34 publications

References 21 publications

Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index

Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index

Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin

15 YEARS OF PARAGANGLIOMA: Pathology of pheochromocytoma and paraganglioma

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