Need for normalization: the non-standard reference standard for microvascular invasion diagnosis in hepatocellular carcinoma

Abstract

BackgroundPreoperative microvascular invasion (MVI) assessment in hepatocellular carcinoma (HCC) is one of the current research focuses, with studies reporting controversial results regarding MVI-associated risk factors. As a possible source of bias, reported MVI rate (percentage of MVI-positive patients) varies a lot among studies. Pathological examination should have been the golden criteria of MVI diagnosis, but no standard and generally adopted pathological examination protocol exists.Methods and resultsIt is highly possible that underestimated pathological diagnosis of MVI exists. We present two likely examples to stress the problem and indicate the root of the problem partially being an unreliable pathological examination. Results of studies basing on unreliable reference standard can be less convincing and even misleading, which is the most basic and fundamental problem in this research field.ConclusionThere is an urgent need to settle the disputes regarding pathological sampling, microscopy, and reporting, in order to promote future academic exchange and consensus development on MVI assessment. Several concerns about pathological MVI assessment should be focused on in the future research as we put up in the review.

Mass‐forming intrahepatic cholangiocarcinoma: Can diffusion‐weighted imaging predict microvascular invasion?

“…The ancillary findings including bile duct invasion, perineural invasion, and tumor grade were also recorded. Pathological samples were collected using a 7‐point baseline sample collection protocol . However, for IMCC that manifested as a solitary tumor with a maximum diameter of ≤3 cm, the whole tumor should be sampled .…”

“…Pathological samples were collected using a 7‐point baseline sample collection protocol . However, for IMCC that manifested as a solitary tumor with a maximum diameter of ≤3 cm, the whole tumor should be sampled . MVI was defined as a tumor within a vascular space lined by endothelium that was visible only at microscopy.…”

“…23,24 However, for IMCC that manifested as a solitary tumor with a maximum diameter of ≤3 cm, the whole tumor should be sampled. 24 MVI was defined as a tumor within a vascular space lined by endothelium that was visible only at microscopy. ICC tumor grade was evaluated by using the following criteria: G1: well differentiated; G2: moderately differentiated; G3: poorly differentiated.…”

Innovative Synoptic Reporting With Seven-Point Sampling Protocol to Improve Detection Rate of Microvascular Invasion in Hepatocellular Carcinoma

“…Currently, many studies have indicated adjuvant transarterial chemotherapy after hepatic resection could help to improve long-term survival in MVIpositive patients (4)(5)(6)(7)(8). However, previous studies showed the MVI positive rate after hepatectomy in pathology report varied substantially, from 7.8 to 57.1% (9). Thus, an accurate and standardized report of MVI is needed for precise patient stratification and consequent individualized treatments.…”

“…Traditionally, HCC sampling focuses on confirmation of the histological features of HCC, completeness of surgical excision, and cirrhosis condition ( 20 , 21 ). Given that MVI is unevenly distributed in the adjacent liver parenchyma around HCC ( 2 ), traditional sampling method usually resulted in false-negative detection ( 9 ). The MVI rate under traditional sampling was reported varied from 7.8 to 28.4% ( 22 , 23 ).…”