Ki-67 labeling index of neuroendocrine tumors of the lung has a high level of correspondence between biopsy samples and surgical specimens when strict counting guidelines are applied.

Alessandra Fabbri, Mara Cossa, Angelica Sonzogni, Mauro Papotti, Luisella Righi, Gaia Gatti, Patrick Maisonneuve, Barbara Valeri, Ugo Pastorino, Giuseppe Pelosi

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Abstract

Optimal histopathological analysis of biopsies from metastases of neuroendocrine tumor (NET) of the lung requires more than morphology only. Additional parameters such as Ki-67 labeling index are required for adequate diagnosis, but few studies have compared reproducibility of different counting protocols and modalities of reporting on biopsies of lung NET. We compared the results of four different manual counting techniques to establish Ki-67 LI. On 47 paired biopsies and surgical specimens from 22 typical carcinoids (TCs), 14 atypical carcinoids (ACs), six large cell neuroendocrine carcinomas (LCNECs), and five small cell carcinomas (SCCs) immunohistochemical staining of Ki-67 antigen was performed. We counted, in regions of highest nuclear staining (HSR), a full x40-high-power field (diameter = 0.55 mm), 500 or 2000 cells, or 2 mm2 surface area, including the HSR or the entire biopsy fragment(s). Mitoses and necrosis were evaluated in an area of 2 mm2 or the entire biopsy fragment(s). Between the four counting methods, no differences in Ki-67 LI were observed. However, a Ki-67 LI higher than 5% was found in only four cases when in an HSR, 500 cells were counted (18, five (23 when in an HSR 2000 cells were counted, four (18 when 2 mm2 were counted, and one (5 TC case when the entire biopsy was counted. A 20% cutoff distinguished TC and AC from LCNEC and SCC with 100% specificity and sensitivity, while mitoses and necrosis failed to a large extent. Ki-67 LI in biopsy samples was concordant with that in resection specimens when 2000 cells, 2 mm2, or the entire biopsy fragment(s) were counted. Our results are important for clinical management of patients with metastases of a lung NET.
Original languageUndefined/Unknown
Pages (from-to)153-164
Number of pages12
JournalVirchows Archiv - A Pathological Anatomy and Histopathology
Volume470
Issue number2
DOIs
Publication statusPublished - Feb 1 2017

Keywords

  • Adult, Aged, Aged, 80 and over, Atypical, Biopsy, Carcinoid, carcinoma, Cell, Female, Humans, Immunohistochemistry, KI-67 antigen, Ki-67 Antigen/*metabolism, Large, Lung, Lung/*metabolism/*pathology/surgery, Lung Neoplasms/*metabolism/*pathology/surgery, Male, Methodology, Middle Aged, Necrosis, Neuroendocrine, Neuroendocrine Tumors/*metabolism/*pathology/surgery, Practice Guidelines as Topic, Reproducibility of Results, Retrospective Studies, Small, Tumors, Typical

Cite this

@article{62e04700cafa4283bd55d84198eb9c9c,
title = "Ki-67 labeling index of neuroendocrine tumors of the lung has a high level of correspondence between biopsy samples and surgical specimens when strict counting guidelines are applied.",
abstract = "Optimal histopathological analysis of biopsies from metastases of neuroendocrine tumor (NET) of the lung requires more than morphology only. Additional parameters such as Ki-67 labeling index are required for adequate diagnosis, but few studies have compared reproducibility of different counting protocols and modalities of reporting on biopsies of lung NET. We compared the results of four different manual counting techniques to establish Ki-67 LI. On 47 paired biopsies and surgical specimens from 22 typical carcinoids (TCs), 14 atypical carcinoids (ACs), six large cell neuroendocrine carcinomas (LCNECs), and five small cell carcinomas (SCCs) immunohistochemical staining of Ki-67 antigen was performed. We counted, in regions of highest nuclear staining (HSR), a full x40-high-power field (diameter = 0.55 mm), 500 or 2000 cells, or 2 mm2 surface area, including the HSR or the entire biopsy fragment(s). Mitoses and necrosis were evaluated in an area of 2 mm2 or the entire biopsy fragment(s). Between the four counting methods, no differences in Ki-67 LI were observed. However, a Ki-67 LI higher than 5{\%} was found in only four cases when in an HSR, 500 cells were counted (18, five (23 when in an HSR 2000 cells were counted, four (18 when 2 mm2 were counted, and one (5 TC case when the entire biopsy was counted. A 20{\%} cutoff distinguished TC and AC from LCNEC and SCC with 100{\%} specificity and sensitivity, while mitoses and necrosis failed to a large extent. Ki-67 LI in biopsy samples was concordant with that in resection specimens when 2000 cells, 2 mm2, or the entire biopsy fragment(s) were counted. Our results are important for clinical management of patients with metastases of a lung NET.",
keywords = "Adult, Aged, Aged, 80 and over, Atypical, Biopsy, Carcinoid, carcinoma, Cell, Female, Humans, Immunohistochemistry, KI-67 antigen, Ki-67 Antigen/*metabolism, Large, Lung, Lung/*metabolism/*pathology/surgery, Lung Neoplasms/*metabolism/*pathology/surgery, Male, Methodology, Middle Aged, Necrosis, Neuroendocrine, Neuroendocrine Tumors/*metabolism/*pathology/surgery, Practice Guidelines as Topic, Reproducibility of Results, Retrospective Studies, Small, Tumors, Typical",
author = "Alessandra Fabbri and Mara Cossa and Angelica Sonzogni and Mauro Papotti and Luisella Righi and Gaia Gatti and Patrick Maisonneuve and Barbara Valeri and Ugo Pastorino and Giuseppe Pelosi",
year = "2017",
month = "2",
day = "1",
doi = "10.1007/s00428-016-2062-2",
language = "Non definita",
volume = "470",
pages = "153--164",
journal = "Virchows Archiv - A Pathological Anatomy and Histopathology",
issn = "0945-6317",
publisher = "Springer Verlag",
number = "2",

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TY - JOUR

T1 - Ki-67 labeling index of neuroendocrine tumors of the lung has a high level of correspondence between biopsy samples and surgical specimens when strict counting guidelines are applied.

AU - Fabbri, Alessandra

AU - Cossa, Mara

AU - Sonzogni, Angelica

AU - Papotti, Mauro

AU - Righi, Luisella

AU - Gatti, Gaia

AU - Maisonneuve, Patrick

AU - Valeri, Barbara

AU - Pastorino, Ugo

AU - Pelosi, Giuseppe

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Optimal histopathological analysis of biopsies from metastases of neuroendocrine tumor (NET) of the lung requires more than morphology only. Additional parameters such as Ki-67 labeling index are required for adequate diagnosis, but few studies have compared reproducibility of different counting protocols and modalities of reporting on biopsies of lung NET. We compared the results of four different manual counting techniques to establish Ki-67 LI. On 47 paired biopsies and surgical specimens from 22 typical carcinoids (TCs), 14 atypical carcinoids (ACs), six large cell neuroendocrine carcinomas (LCNECs), and five small cell carcinomas (SCCs) immunohistochemical staining of Ki-67 antigen was performed. We counted, in regions of highest nuclear staining (HSR), a full x40-high-power field (diameter = 0.55 mm), 500 or 2000 cells, or 2 mm2 surface area, including the HSR or the entire biopsy fragment(s). Mitoses and necrosis were evaluated in an area of 2 mm2 or the entire biopsy fragment(s). Between the four counting methods, no differences in Ki-67 LI were observed. However, a Ki-67 LI higher than 5% was found in only four cases when in an HSR, 500 cells were counted (18, five (23 when in an HSR 2000 cells were counted, four (18 when 2 mm2 were counted, and one (5 TC case when the entire biopsy was counted. A 20% cutoff distinguished TC and AC from LCNEC and SCC with 100% specificity and sensitivity, while mitoses and necrosis failed to a large extent. Ki-67 LI in biopsy samples was concordant with that in resection specimens when 2000 cells, 2 mm2, or the entire biopsy fragment(s) were counted. Our results are important for clinical management of patients with metastases of a lung NET.

AB - Optimal histopathological analysis of biopsies from metastases of neuroendocrine tumor (NET) of the lung requires more than morphology only. Additional parameters such as Ki-67 labeling index are required for adequate diagnosis, but few studies have compared reproducibility of different counting protocols and modalities of reporting on biopsies of lung NET. We compared the results of four different manual counting techniques to establish Ki-67 LI. On 47 paired biopsies and surgical specimens from 22 typical carcinoids (TCs), 14 atypical carcinoids (ACs), six large cell neuroendocrine carcinomas (LCNECs), and five small cell carcinomas (SCCs) immunohistochemical staining of Ki-67 antigen was performed. We counted, in regions of highest nuclear staining (HSR), a full x40-high-power field (diameter = 0.55 mm), 500 or 2000 cells, or 2 mm2 surface area, including the HSR or the entire biopsy fragment(s). Mitoses and necrosis were evaluated in an area of 2 mm2 or the entire biopsy fragment(s). Between the four counting methods, no differences in Ki-67 LI were observed. However, a Ki-67 LI higher than 5% was found in only four cases when in an HSR, 500 cells were counted (18, five (23 when in an HSR 2000 cells were counted, four (18 when 2 mm2 were counted, and one (5 TC case when the entire biopsy was counted. A 20% cutoff distinguished TC and AC from LCNEC and SCC with 100% specificity and sensitivity, while mitoses and necrosis failed to a large extent. Ki-67 LI in biopsy samples was concordant with that in resection specimens when 2000 cells, 2 mm2, or the entire biopsy fragment(s) were counted. Our results are important for clinical management of patients with metastases of a lung NET.

KW - Adult, Aged, Aged, 80 and over, Atypical, Biopsy, Carcinoid, carcinoma, Cell, Female, Humans, Immunohistochemistry, KI-67 antigen, Ki-67 Antigen/metabolism, Large, Lung, Lung/metabolism/pathology/surgery, Lung Neoplasms/metabolism/pathology/surgery, Male,

U2 - 10.1007/s00428-016-2062-2

DO - 10.1007/s00428-016-2062-2

M3 - Articolo

VL - 470

SP - 153

EP - 164

JO - Virchows Archiv - A Pathological Anatomy and Histopathology

JF - Virchows Archiv - A Pathological Anatomy and Histopathology

SN - 0945-6317

IS - 2

ER -