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

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.

Vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti‐angiogenic therapies

“…Histopathology scoring of the growth patterns was performed using the consensus guidelines [15]. All slides were scanned at 403 magnification using the Aperio AT Turbo system.…”

“…They have been designated (1) the desmoplastic HGP (DHGP) characterized by a desmoplastic stroma at the interface of the metastases and liver parenchyma and no direct contact between the tumour cells and the hepatocytes; (2) the pushing HGP (PHGP) where liver cell plates are pushed aside by the growing tumour and run in parallel with the circumference of the metastases at the tumour-liver parenchyma interface and (3) the replacement HGP (RHGP) where tumour cells are replacing parenchymal cells in the liver plates. These HGPs can be assessed reproducibly on an H&E section according to international guidelines [15]. Although these HGPs have been identified as early as 1987 and infiltrative tumours were shown to have a worse prognosis [16], the biological explanation for the existence of the different HGPs remains unknown although some hypotheses have been put forward [15,17,18].…”

“…These HGPs can be assessed reproducibly on an H&E section according to international guidelines [15]. Although these HGPs have been identified as early as 1987 and infiltrative tumours were shown to have a worse prognosis [16], the biological explanation for the existence of the different HGPs remains unknown although some hypotheses have been put forward [15,17,18]. We have recently reported [12] in CRCLMs resected from patients that: (a) vessel cooption was the predominant mechanism of vascularization in approximately 40% of the lesions we examined, (b) metastases that utilize vessel co-option responded poorly to chemotherapy 1 bevacizumab, (c) vessel co-option was more prevalent in patients who progressed following treatment with chemotherapy 1 bevacizumab, and (d) patients with metastases that utilized vessel co-option obtained less clinical benefit from chemotherapy 1 bevacizumab in terms of OS.…”

Replacement and desmoplastic histopathological growth patterns: A pilot study of prediction of outcome in patients with uveal melanoma liver metastases

“…Conversely, the liver is a frequent site of metastasis for tumours originating from the gastrointestinal tract, pancreas, breast, and lung but also not uncommonly from renal cell carcinoma, various sarcomas, and cutaneous melanoma [17][18][19][20][21]. Liver metastases from colon and breast cancers have been extensively studied and show distinctive 'histopathological growth patterns' (HGPs) [19][20][21]. In brief, these HGPs are: 'replacement', 'desmoplastic', 'pushing', and two rare variantsthe 'sinusoidal' and 'portal' HGPs.…”

Critical considerations for targeting colorectal liver metastases with nanotechnology

“…Hence, NPs whose actions solely rely on the abnormal vasculature may be impaired and any strategies to normalize the tumor vasculature through antiangiogenic therapies may be hindered by drug resistance, as seen from previous studies (Emblem & Jain, 2016;Frentzas et al, 2016;Qian, 2013). More recently, it was highlighted that approximately two-thirds of patients presented with mixed growth patterns (mixed phenotype of co-opted vessels and angiogenesis) (van Dam et al, 2017). Therapeutic approaches that can suppress both angiogenesis and vessel co-option may therefore be justified.…”