Histopathological growth patterns of colorectal liver metastasis exhibit little heterogeneity and can be determined with a high diagnostic accuracy

Abstract

Colorectal liver metastases (CRLM) exhibit distinct histopathological growth patterns (HGPs) that are indicative of prognosis following surgical treatment. This study aims to assess the reliability and replicability of this histological biomarker. Within and between metastasis HGP concordance was analysed in patients who underwent surgery for CRLM. An independent cohort was used for external validation. Within metastasis concordance was assessed in CRLM with ≥ 2 tissue blocks. Similarly, concordance amongst multiple metastases was determined in patients with ≥ 2 resected CRLM. Diagnostic accuracy [expressed in area under the curve (AUC)] was compared by number of blocks and number of metastases scored. Interobserver agreement (Cohen’s k ) compared to the gold standard was determined for a pathologist and a PhD candidate without experience in HGP assessment after one and two training sessions. Both the within (95%, n = 825) and the between metastasis (90%, n = 363) HGP concordance was high. These results could be replicated in the external validation cohort with a within and between metastasis concordance of 97% and 94%, respectively. Diagnostic accuracy improved when scoring 2 versus 1 blocks(s) or CRLM (AUC = 95.9 vs. 97.7 [p = 0.039] and AUC = 96.5 vs. 93.3 [p = 0.026], respectively), but not when scoring 3 versus 2 blocks or CRLM (both p > 0.2). After two training sessions the interobserver agreement for both the pathologist and the PhD candidate were excellent ( k = 0.953 and k = 0.951, respectively). The histopathological growth patterns of colorectal liver metastasis exhibit little heterogeneity and can be determined with a high diagnostic accuracy, making them a reliable and replicable histological biomarker. Electronic supplementary material The online version of this article (10.1007/s10585-019-09975-0) contains supplementary material, which is available to authorized users.

Enrichment of the tumour immune microenvironment in patients with desmoplastic colorectal liver metastasis

“…This is likely of little relevance though, as interobserver reliability for HGP assessment, even for trained observers with limited histopathological experience, was found to be excellent. 48 Furthermore, within-and between-metastasis concordance of HGPs is especially high in chemo-naive patients. 48 Third, the semiquantitative IHC assessment in cohort A only incorporated grading of antibody expression and not antibody intensity compared to positive control.…”

“…48 Furthermore, within-and between-metastasis concordance of HGPs is especially high in chemo-naive patients. 48 Third, the semiquantitative IHC assessment in cohort A only incorporated grading of antibody expression and not antibody intensity compared to positive control. Previous studies have incorporated methods for scoring both antibody expression and antibody intensity.…”

Histopathological growth patterns as biomarker for adjuvant systemic chemotherapy in patients with resected colorectal liver metastases

“…Average HGP percentages were calculated per metastasis and per patient (in case of multiple CRLM). This method has been validated previously, demonstrating a 95% within CRLM concordance (in case of multiple H&E slides) and a 90% between metastases concordance (in case of multiple CRLM in one patient) [14]. Patients were classified in two groups: dHGP if all available slides showed a 100% desmoplastic interface and non-dHGP if a replacement or pushing type HGP was found on one or more slides [10].…”

“…vessel co-option) instead of angiogenesis [11,12]. Non-dHGP has been associated with a worse prognosis for patients undergoing resection of CRLM in multiple studies [10,13,14]. A large cohort study suggested that this effect was predominantly found in patients that were not pretreated with chemotherapy prior to CRLM resection [10] (Fig.…”

Diagnostics of metastasis: an increasing challenge with high clinical importance

“…There is a pressing need for clinical oncologists to include these developments in the standardized form of assessment and subsequent documentation of metastases. In this issue, Höppener et al [2] present attempts to achieve such standards for the pathological examination of metastatic lesions. Their effort to describe and classify heterogeneity within colorectal metastases should trigger further discussion and evaluation of these proposed standardizations.…”