Infiltration pattern predicts metastasis and progression better than the T-stage and grade in pancreatic neuroendocrine tumors: a proposal for a novel infiltration-based morphologic grading.
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
14
06
2021
accepted:
11
12
2021
revised:
06
12
2021
pubmed:
1
1
2022
medline:
10
6
2022
entrez:
31
12
2021
Statut:
ppublish
Résumé
The advancing edge profile is a powerful determinant of tumor behavior in many organs. In this study, a grading system assessing the tumor-host interface was developed and tested in 181 pancreatic neuroendocrine tumors (PanNETs), 63 of which were <=2 cm. Three tumor slides representative of the spectrum (least, medium, and most) of invasiveness at the advancing edge of the tumor were selected, and then each slide was scored as follows. Well-demarcated/encapsulated, 1 point; Mildly irregular borders and/or minimal infiltration into adjacent tissue, 2 points; Infiltrative edges with several clusters beyond the main tumor but still relatively close, and/or satellite demarcated nodules, 3 points; No demarcation, several cellular clusters away from the tumor, 4 points; Exuberantly infiltrative pattern, scirrhous growth, dissecting the normal parenchymal elements, 5 points. The sum of the rankings on the three slides was obtained. Cases with scores of 3-6 were defined as "non/minimally infiltrative" (NI; n = 77), 7-9 as "moderately infiltrative" (MI; n = 68), and 10-15 as "highly infiltrative" (HI; n = 36). In addition to showing a statistically significant correlation with all the established signs of aggressiveness (grade, size, T-stage), this grading system was found to be the most significant predictor of adverse outcomes (metastasis, progression, and death) on multivariate analysis, more strongly than T-stage, while Ki-67 index did not stand the multivariate test. As importantly, cases <=2 cm were also stratified by this grading system rendering it applicable also to this group that is currently placed in "watchful waiting" protocols. In conclusion, the proposed grading system has a strong, independent prognostic value and therefore should be considered for integration into routine pathology practice after being evaluated in validation studies with larger series.
Identifiants
pubmed: 34969955
doi: 10.1038/s41379-021-00995-4
pii: S0893-3952(22)00052-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
777-785Informations de copyright
© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
Références
Li, C., Xiang, J. & Wang, Y. Risk factors for predicting lymph nodes posterior to right recurrent laryngeal nerve (Ln-PRRLN) metastasis in thyroid papillary carcinoma: a meta-analysis. Int. J. Endocrinol. 2019, 7064328 (2019).
pubmed: 31049063
pmcid: 6462345
Jung, C. K. et al. Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma. Mod. Pathol. 23, 1201–1208 (2010).
doi: 10.1038/modpathol.2010.116
pubmed: 20543822
Taşkın, O. et al. Tumor border pattern and size help predict lymph node status in papillary microcarcinoma: a clinicopathologic study. Ann. Diagn. Pathol. 48, 151592 (2020).
doi: 10.1016/j.anndiagpath.2020.151592
pubmed: 32871504
Lloyd, R., Osamura, R., Klöppel, G. & Rosai, J. WHO classification of tumours of the endocrine organs, 4th edn. (International Agency for Research on Cancer, 2017).
Gulluoglu, M. et al. Tumor budding is independently predictive for lymph node involvement in early gastric cancer. Int. J. Surg. Pathol. 23, 349–358 (2015).
doi: 10.1177/1066896915581200
pubmed: 25911564
Ohike, N. et al. Tumor budding as a strong prognostic indicator in invasive ampullary Adenocarcinomas. Am. J. Surg. Pathol. 34, 1417–1424 (2010).
doi: 10.1097/PAS.0b013e3181f0b05a
pubmed: 20871215
pmcid: 3163902
Ito, T. et al. High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection. BMC Cancer https://doi.org/10.1186/s12885-020-6695-9 (2020).
Lugli, A. et al. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod. Pathol. 30, 1299–1311 (2017).
doi: 10.1038/modpathol.2017.46
pubmed: 28548122
Lawlor, R. T. et al. Prognostic role of high-grade tumor budding in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis with a focus on epithelial to mesenchymal transition. Cancers (Basel) 11, 113 https://doi.org/10.3390/cancers11010113 (2019).
Losi, L. et al. Prognostic significance of histological features and biological parameters in stage I (pT1 and pT2) colorectal adenocarcinoma. Pathol. Res. Pract. 202, 663–670 (2006).
Shih, A. R. & Mino‐Kenudson, M. Updates on spread through air spaces (STAS) in lung cancer. Histopathology 77, 173–180 (2020).
doi: 10.1111/his.14062
pubmed: 31943337
Amin, M. B. et al. AJCC Cancer Staging Manual, 8th edn. (Springer International Publishing, American Joint Commission on Cancer, 2017).
Japan Pancreas Society. in Classification of Pancreatic Carcinoma, 4th English Edn., 70–101 (Kanehara & Co., Ltd, 2017).
Zhang, L. et al. KIT is an independent prognostic marker for pancreatic endocrine tumors: a finding derived from analysis of islet cell differentiation markers. Am. J. Surg. Pathol. 33, 1562–1569 (2009).
doi: 10.1097/PAS.0b013e3181ac675b
pubmed: 19574886
Chatterjee, D. et al. Intratumoral fibrosis and tumor growth pattern as prognostic factors in optimally resected pancreatic neuroendocrine neoplasms: an analysis of 168 cases. Pancreas 49, 255–260 (2020).
doi: 10.1097/MPA.0000000000001478
pubmed: 32011527
pmcid: 7021221
Shi, H., Zhang, Q., Han, C., Zhen, D. & Lin, R. Variability of the Ki-67 proliferation index in gastroenteropancreatic neuroendocrine neoplasms—a single-center retrospective study. BMC Endocr. Disord. 18, 51 https://doi.org/10.1186/s12902-018-0274-y (2018).
Nuñez‐Valdovinos, B. et al. Neuroendocrine tumor heterogeneity adds uncertainty to the World Health Organization 2010 Classification: real‐world data from the Spanish Tumor Registry (R‐GETNE). Oncologist 23, 422–432 (2018).
doi: 10.1634/theoncologist.2017-0364
pubmed: 29330208
pmcid: 5896708
Liszka, Ł. Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas. Pol. J. Pathol. 67, 318–331 (2016).
doi: 10.5114/pjp.2016.65864
pubmed: 28547959
Pea, A. et al. Genetic analysis of small well-differentiated pancreatic neuroendocrine tumors identifies subgroups with differing risks of liver metastases. Ann. Surg. 271, 566–573 (2020).
doi: 10.1097/SLA.0000000000003022
pubmed: 30339629
Koelzer, V. H. & Lugli, A. The tumor border configuration of colorectal cancer as a histomorphological prognostic indicator. Front. Oncol. 4, 29 (2014).
pubmed: 24600585
pmcid: 3927120
Karamitopoulou, E. et al. Tumour border configuration in colorectal cancer: proposal for an alternative scoring system based on the percentage of infiltrating margin. Histopathology 67, 464–473 (2015).
doi: 10.1111/his.12665
pubmed: 25648412
Xue, Y. et al. Growth pattern of invasive ampullary carcinomas as demarcated versus infitlrative has significant prognostic correlation: a clinicopathologic analysis of 257 cases. United States & Canadian Academy of Pathology Annual Meeting Abstracts. Mod. Pathol. 31, 313 (2018).
Reid, M. D. et al. Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies. Mod. Pathol. 28, 686–694 (2015).
doi: 10.1038/modpathol.2014.156
pubmed: 25412850
Gaujoux, S. et al. Observational study of natural history of small sporadic nonfunctioning pancreatic neuroendocrine tumors. J. Clin. Endocrinol. Metab. 98, 4784–4789 (2013).
doi: 10.1210/jc.2013-2604
pubmed: 24057286
Pavlakis, K. et al. MELF invasion in endometrial cancer as a risk factor for lymph node metastasis. Histopathology 58, 966–973 (2011).
doi: 10.1111/j.1365-2559.2011.03802.x
pubmed: 21438907
Mccall, C. M. et al. Serotonin expression in pancreatic neuroendocrine tumors correlates with a trabecular histologic pattern and large duct involvement. Hum. Pathol. 43, 1169–1176 (2012).
doi: 10.1016/j.humpath.2011.09.014
pubmed: 22221702
pmcid: 3323730
Chou, A. et al. ATRX loss is an independent predictor of poor survival in pancreatic neuroendocrine tumors. Hum. Pathol. 82, 249–257 (2018).
doi: 10.1016/j.humpath.2018.07.032
pubmed: 30081149
Roy, S. et al. Loss of chromatin-remodeling proteins and/or CDKN2A associates with metastasis of pancreatic neuroendocrine tumors and reduced patient survival times. Gastroenterology 154, 2060–2063.e8 (2018).
doi: 10.1053/j.gastro.2018.02.026
pubmed: 29486199
Hackeng, W. M. et al. Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size. Gut https://doi.org/10.1136/gutjnl-2020-322595 (2021).
Jiao, Y. et al. DAXX/ATRX, MEN1 and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331, 1199–1203 (2011).
doi: 10.1126/science.1200609
pubmed: 21252315
pmcid: 3144496
Ishida, H. & Lam, A. K. Y. Pancreatic neuroendocrine neoplasms: the latest surgical and medical treatment strategies based on the current World Health Organization classification. Crit. Rev. Oncol. Hematol. 145, 102835 https://doi.org/10.1016/j.critrevonc.2019.102835 (2020).
Lopez-Aguiar, A. G. et al. The conundrum of <2-cm pancreatic neuroendocrine tumors: a preoperative risk score to predict lymph node metastases and guide surgical management. Surgery 166, 15–21 (2019).
doi: 10.1016/j.surg.2019.03.008
pubmed: 31072670
Melia, J. et al. A UK-based investigation of inter- and intra-observer reproducibility of Gleason grading of prostatic biopsies. Histopathology 48, 644–654 (2006).
doi: 10.1111/j.1365-2559.2006.02393.x
pubmed: 16681679
Montironi, R. et al. Gleason grading of prostate cancer in needle biopsies or radical prostatectomy specimens: Contemporary approach, current clinical significance and sources of pathology discrepancies. BJU Int. 95, 1146–1152 (2005).
doi: 10.1111/j.1464-410X.2005.05540.x
pubmed: 15877724
Rabe, K. et al. Interobserver variability in breast carcinoma grading results in prognostic stage differences. Hum. Pathol. 94, 51–57 (2019).
doi: 10.1016/j.humpath.2019.09.006
pubmed: 31655171
Meyer, J. S. et al. Breast carcinoma malignancy grading by Bloom-Richardson system vs proliferation index: Reproducibility of grade and advantages of proliferation index. Mod. Pathol. 18, 1067–1078 (2005).
doi: 10.1038/modpathol.3800388
pubmed: 15920556
Mahajan, D. et al. Reproducibility of the villous component and high-grade dysplasia in colorectal adenomas <1 cm: Implications for endoscopic surveillance. Am. J. Surg. Pathol. 37, 427–433 (2013).
doi: 10.1097/PAS.0b013e31826cf50f
pubmed: 23348206
Vennalaganti, P. et al. Discordance among pathologists in the United States and Europe in diagnosis of low-grade dysplasia for patients with Barrett’s esophagus. Gastroenterology 152, 564–570.e4 (2017).
doi: 10.1053/j.gastro.2016.10.041
pubmed: 27818167
Downs-Kelly, E. et al. Poor interobserver agreement in the distinction of high-grade dysplasia and adenocarcinoma in pretreatment Barrett’s esophagus biopsies. Am. J. Gastroenterol. 103, 2333–2340 (2008).
doi: 10.1111/j.1572-0241.2008.02020.x
pubmed: 18671819
Kerkhof, M. et al. Grading of dysplasia in Barrett’s oesophagus: substantial interobserver variation between general and gastrointestinal pathologists. Histopathology 50, 920–927 (2007).
doi: 10.1111/j.1365-2559.2007.02706.x
pubmed: 17543082
Dano, H. et al. Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study. Mod. Pathol. 33, 354–366 (2020).
doi: 10.1038/s41379-019-0367-9
pubmed: 31534203