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Practice Guideline
. 2017 Nov 7;117(10):1427-1441.
doi: 10.1038/bjc.2017.334. Epub 2017 Oct 5.

International consensus guidelines for scoring the histopathological growth patterns of liver metastasis

Pieter-Jan van Dam  1 , Eric P van der Stok  2 , Laure-Anne Teuwen  1 , Gert G Van den Eynden  1 , Martin Illemann  3 , Sophia Frentzas  4 , Ali W Majeed  5 , Rikke L Eefsen  6 , Robert R J Coebergh van den Braak  2 , Anthoula Lazaris  7 , Maria Celia Fernandez  8 , Boris Galjart  2 , Ole Didrik Laerum  9 , Roni Rayes  8 , Dirk J Grünhagen  2 , Michelle Van de Paer  1   10 , Yves Sucaet  11   12 , Hardeep Singh Mudhar  13 , Michael Schvimer  14 , Hanna Nyström  15 , Mark Kockx  10 , Nigel C Bird  16 , Fernando Vidal-Vanaclocha  17 , Peter Metrakos  7 , Eve Simoneau  7 , Cornelis Verhoef  2 , Luc Y Dirix  1 , Steven Van Laere  1 , Zu-Hua Gao  18 , Pnina Brodt  8 , Andrew R Reynolds  4   19 , Peter B Vermeulen  1   4   10
Affiliations
Practice Guideline

International consensus guidelines for scoring the histopathological growth patterns of liver metastasis

Pieter-Jan van Dam et al. Br J Cancer. .

Abstract

Background: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs.

Methods: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined.

Results: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006).

Conclusions: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Decision tree to assess the growth patterns of liver metastases based on the key histopathological characteristics.
Figure 2
Figure 2
H&E images of the desmoplastic histopathological growth pattern. (A–C) Low magnification images of the desmoplastic histopathological growth pattern. (D) Higher magnification image of the desmoplastic histopathological growth pattern. (E) Desmoplastic histopathological growth pattern with ductular proliferation (also known as ductular reaction) and dense lymphocyte infiltrate. (F) Portal tracts at the tumour–liver interface. D, desmoplastic rim; DP, ductular proliferation; L, lymphocyte infiltrate; N, normal liver parenchyma; PT, portal tract; T, vital tumour tissue. Scale bar=1000 μm (A–C and F), 100 μm (D and E).
Figure 3
Figure 3
H&E images of the pushing histopathological growth pattern. (A) Low magnification image of the pushing histopathological growth pattern. (B and C) Higher magnification images of the pushing histopathological growth pattern. N, normal liver parenchyma; T, vital tumour tissue. Scale bar=500 μm (A), 100 μm (B), 50 μm (C).
Figure 4
Figure 4
H&E images of the replacement histopathological growth pattern. (A) Low magnification image of the replacement histopathological growth pattern. (B and C) Higher magnification images of the type 1 replacement histopathological growth pattern. (D and E) Higher magnification images of the type 2 replacement histopathological growth pattern. N, normal liver parenchyma; T, vital tumour tissue. Scale bar=2000 μm (A), 100 μm (B, D and E), 50 μm (C).
Figure 5
Figure 5
H&E image of the sinusoidal histopathological growth pattern. Arrowheads indicate tumour cell emboli present within the lumen of liver sinusoidal vessels. N, normal liver parenchyma. Scale bar=100 μm.
Figure 6
Figure 6
Analytical validation of the guidelines. Heat map of the unsupervised hierarchical clustering of the colour-coded mean intraclass correlation coefficients of each growth pattern for all observers (n=12 observers).
Figure 7
Figure 7
Clinical validation of the guidelines. Kaplan–Meier curves depicting overall survival of patients with colorectal liver metastases, stratified by predominant (>50%) HGP (n=370 patients).
See this image and copyright information in PMC

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