Original articleMicroscopic venous invasion in patients with pancreatic neuroendocrine tumor as a potential predictor of postoperative recurrence☆
Introduction
Pancreatic neuroendocrine tumor (PNET) is a rare form of epithelial neoplasm with histologic evidence of neuroendocrine differentiation. This unique neoplasm has been increasingly diagnosed in Japan and other countries [1], [2]. PNETs are classified into two groups based on histopathological findings. Well differentiated PNETs are characterized by relatively uniform, less dysplastic tumor cells arranged in a solid or trabecular pattern, while poorly differentiated PNETs are pancreatic equivalents of lung small cell carcinomas or large cell neuroendocrine carcinomas [3]. As mitotic counts and Ki-67 indices on tissue are currently the only reproducible prognostic factors for patients with PNET, these microscopic findings are currently endorsed for tumor grading by the World Health Organization (WHO) [4]. In the 2010 WHO classification, PNETs are graded on a three-tiered system [2], [5]. Although grade 3 (G3) PNETs are highly malignant neoplasms with aggressive clinical behavior, it is generally difficult to predict the prognosis of patients with G1/2 PNET. Identification of additional prognostic factors that can be used together with WHO grading will assist in the stratification of patients for the risk of tumor recurrence.
Lymphatic and venous drainage are primary routes of tumor dissemination from a primary tumor site to regional lymph nodes and distant organs. The presence of microscopic venous invasion is believed to be a histologic indicator of aggressive tumor behavior, and has been determined as an independent factor for poor prognosis for various cancers [6], [7], [8]. Previous studies on neuroendocrine tumors (NETs) of the lung has shown that microscopic venous and lymphatic invasion is significantly correlated with WHO histologic grades, tumor sizes, recurrence, and patients' survival [9]. However, this correlation remains controversial for PNETs. In the current study, we examined microscopic venous and lymphatic invasion in patients with resectable well differentiated PNET using immunohistochemistry for CD31 and D2-40, and correlated the results with other clinicopathologic parameters including recurrence-free survival.
Section snippets
Patient selection
The study protocol was approved by the Ethics Committee at Kobe University, and written informed consents were obtained from all patients. During the study period from January 2008 to April 2014, 33 patients with PNET underwent surgical resection at our institute. One patient was excluded from this study due to the presence of multiple small metastatic nodules in the liver found during surgery that lead to incomplete resection. The remaining 32 patients who had complete resection were included
Clinical features
The study cohort consisted of 18 men and 14 women with a median age of 64 years (range: 29–87 years). The tumor sizes ranged from 10 to 156 mm (median 16 mm). Three patients had another primary NET in an extrapancreatic organ (the lung, duodenum, and stomach). Two patients had a history of von Hippel-Lindau disease, and another patient had multiple endocrine neoplasia type 1.
Based on WHO grading, 16 cases were graded as G1, and 13 were G2. The remaining three showed well differentiated
Discussion
The WHO grading scheme has been widely accepted as a good prognostic indicator for patients with PNET. In agreement with other studies, the current study also supports the prognostic value of the WHO system [12], [13]. Recently, however, some experts have argued that tumors categorized in each grade are heterogeneous in tumor biology and clinical behavior [14]. Therefore, it is likely that there are some other factors that can be used together with histologic grades for prognosis. This clinical
Acknowledgments
The authors declare that they have no conflict of interest.
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Cited by (32)
Venous invasion and lymphatic invasion are correlated with the postoperative prognosis of pancreatic neuroendocrine neoplasm
2023, Surgery (United States)Citation Excerpt :Previous research, especially outside Japan, has analyzed LVI as a prognostic factor in patients with PNENs (Supplementary Table S1). In Japan, it is customary to use immunostaining to distinguish between venous invasion and lymphatic invasion,27–29 and the current study especially emphasized that these 2 factors should be separately evaluated when estimating the prognosis of patients with PNENs. To support this, the 5-year cumulative liver and lymph node metastasis rates in the LVI 2 group were 33.3% and 70.0%, respectively, which were both higher than those in the LVI 1 group (15.8% and 23.1%, respectively).
Prognostic factors for relapse in resected gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis
2021, Cancer Treatment ReviewsCitation Excerpt :The included studies (n = 63) [7,9,13-16,18-75] include 64 datasets (one study [54] provided separate analyses for a cohort of patients with pancreatic NENs and a cohort of patients with duodenal NENs within the same article) and 13,715 patients. Of these 64 datasets, 56 reported on pancreatic NENs only [9,14,16,19-21,23-31,33-60,62-64,66-70,72-75] (12,418 patients), 3 reported on duodenal NENs (155 patients)[18,54,61] and 5 reported on mixed primary sites including pancreatic, gastroduodenal, gastric and small bowel NENs (1,142 patients) [7,15,32,65,71]. Of the 64 datasets included, 24 reported on grade 1–2 tumours only [9,15,16,21,22,29,32,38,40,45,46,48,49,53,54,57,61,64,65,69-71,74] (4,735 patients) and 40 included grade 1–3 tumours [7,13,14,18,19,21-24,27-32,34,35,37-41,43,45-48,51,54-56,59,60,62-64,66,67,69-71,75] (8,980 patients).
Prediction of lymph node metastasis in pancreatic neuroendocrine tumors by contrast enhancement characteristics
2017, PancreatologyCitation Excerpt :The presence of microscopic tumor invasion into the adjacent pancreatic parenchyma, lymphovascular invasion, LN metastasis, and tumor grade were analyzed for pathological evaluation. Lymphovascular invasion was assessed by visualizing microvascular and lymphatic vessels via immunostaining for CD31 and D2-40 as previously described [10]. Tumor grades were evaluated according to the World Health Organization (WHO) 2010 classification, which is based on mitotic counts and Ki-67 indices (G1: mitotic count < 2 per 10 high-power fields [HPFs] and/or Ki-67 ≤ 2%; G2: mitotic count 2–20 per 10 HPFs and/or Ki-67 3–20%; and G3: mitotic count > 20 per 10 HPFs and/or Ki-67 > 20%) [11].
The Usefulness of Elastin Staining to Detect Vascular Invasion in Cancer
2023, International Journal of Molecular SciencesVenous Invasion in Pancreatic Neuroendocrine Tumors Is Independently Associated With Disease-free Survival and Overall Survival
2023, American Journal of Surgical Pathology
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Institute where the work was conducted: Kobe University Hospital.