TY - JOUR
T1 - Infiltration pattern predicts metastasis and progression better than the T-stage and grade in pancreatic neuroendocrine tumors
T2 - a proposal for a novel infiltration-based morphologic grading
AU - Taskin, Orhun Cig
AU - Reid, Michelle D.
AU - Bagci, Pelin
AU - Balci, Serdar
AU - Armutlu, Ayse
AU - Demirtas, Deniz
AU - Pehlivanoglu, Burcin
AU - Saka, Burcu
AU - Memis, Bahar
AU - Bozkurtlar, Emine
AU - Leblebici, Can Berk
AU - Birceanu, Adelina
AU - Xue, Yue
AU - Erkan, Mert
AU - Kapran, Yersu
AU - Baygul, Arzu
AU - Sokmensuer, Cenk
AU - Scarpa, Aldo
AU - Luchini, Claudio
AU - Basturk, Olca
AU - Adsay, Volkan
N1 - Funding Information:
This study was presented in part at the 110th annual meeting of the United States and Canadian Academy of Pathology in March 2021.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
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U2 - 10.1038/s41379-021-00995-4
DO - 10.1038/s41379-021-00995-4
M3 - Article
C2 - 34969955
AN - SCOPUS:85122086326
SN - 0893-3952
VL - 35
SP - 777
EP - 785
JO - Modern Pathology
JF - Modern Pathology
IS - 6
ER -