Interobserver, intraobserver, and interlaboratory variability in reporting pT4a colon cancer

Abstract

Clinical significance of the pT4 category in colon cancer is increasing with several therapeutic implications. The aim of this study was to evaluate variability in diagnosing pT4a colon cancer. Twelve pathologists classified 66 preselected scanned Hematoxylin/Eosin-stained slides with tumor cells at a distance of 25-1500 μm (n = 22), 0-25 μm (n = 22), or on (n = 22) the peritoneal surface. Inter- and intraobserver variability were calculated using Kappa statistics. For interlaboratory variability, pathology reports of pT3 and pT4a colon cancer were extracted from the Dutch Pathology Registry between 2012 and 2015. The proportion of pT4a (pT4a/(pT3+pT4a)) was compared between 33 laboratories. Potential risk of understaging was assessed by determining the average number of blocks taken from pT3 and pT4a N0-2M0 tumors with metachronous peritoneal metastasis. Interobserver variability among 12 pathologists was 0.50 (95%CI 0.41-0.60; moderate agreement). Intraobserver variability (8 pathologists) was 0.71 (substantial agreement). A total of 7745 reports with pT3 or pT4aN0-2M0 colon cancer from 33 laboratories were included for interlaboratory analysis. Median percentage of pT4a was 15.5% (range 3.2-24.6%). After adjustment for case mix, 8 labs diagnosed pT4a significantly less or more frequently than the median lab. Metachronous peritoneal metastases were histologically verified in 170 of 6629 pT3 and in 129 of 1116 pT4a tumors, with a mean number of blocks of 4.03(SD 1.51) and 4.78 (SD 1.76) taken from the primary tumors, respectively (p < 0.001). A substantial variability in diagnosing pT4a colon cancer exists, both at pathologist and laboratory level. Diagnosis of pT4a stage appears to be challenging and there is a need for standardizing assessment of this pathological entity.

Keywords: Interobserver variability; T4 colon cancer, peritoneal tumor involvement.

Fig. 1

a, b Colon carcinomas with tumor cells “on” the peritoneal surface (H&E stains, × 20) that could be regarded as LPI4 (category 3). In both cases, consensus (> 80%) of pT4a was reached. However, in each case, 1 or 2 pathologists preferred pT3

Fig. 2

Colon carcinomas with tumor cells close to the peritoneal surface (distance to peritoneal surface, 60–200 μm (category 1); H&E stains, × 20) that could be regarded LPI2. In all cases, consensus (> 80%) of pT3 was reached; however, in all cases, still 1 or 2 pathologists preferred pT4a

Fig. 3

a–d Colon carcinomas with tumor cells very close to or “at” the peritoneal surface (H&E stains, × 20) that could be regarded LPI3 (distance of tumor cells to the peritoneal surface measured 25 μm or less (category 2)). No consensus was reached in cases a, b, c, and d (classified as pT4a by 4/12, 5/12, 5/12, and 9/12 pathologists, respectively). Although similar to the other cases in Fig. 3, consensus of pT3 was reached for cases e and f (considered as pT4a by 2/12 and 1/12 pathologists, respectively)

Fig. 4

a–f Examples of cases with tumor cells or mucin close to or at the peritoneal surface with and without reactive changes (H&E stains, × 10 and × 20). In case a (classified pT4a by 2/12 pathologists), the lack of reactive changes was mentioned by some as the reason for preferring pT3. No consensus was reached in case b. Some pathologists mentioned the presence of serosal reaction, while others contradictorily described the lack of serosal reaction in this case, indicating that serosal reaction is a subjective parameter. In case c, consensus of pT3 was reached. Still, one pathologist chose T4a based on the reactive changes with the lack of a clear mesothelial lining. For other pathologists, the amount of tissue between the tumor cells and the surface was used as an argument for pT3. These cases demonstrate inconsistency in applying reactive changes when distinguishing between pT3 and pT4a

Fig. 5

Colon carcinomas with tumor cells close to the peritoneal surface (H&E stains). Case a, presence of subsurface hemorrhage (× 4 and × 20) (classified pT4a by 10/12 pathologists). Case b, groups of tumor cells in a cleft (classified pT4a by 5/12 pathologists). By some, this was considered as a (potential) artifact. Also, case b shows ink on the surface which was mentioned as obscuring some of the morphological details, thus hindering assessment. Case c (× 10), reactive mesothelial cells in a cleft (arrow) resembling sheets of tumor cells that are in the vicinity (arrowhead) (classified pT4a by 3/12 pathologists). Cases d and e demonstrate peritoneal involvement that is likely to have been missed. Case d, peritoneal cleft buried inside the slide (arrows), focally (arrowhead) showing full penetration of tumor cells (inlet photo) (classified pT4a by 3/12 pathologists). Case e, most of the pathologists assessed only the peritoneal surface in front of the tumor (arrowhead) and missed the flat peritoneal surface on the side of the slide (arrow) showing tumor cells very close to the surface (classified pT4a by 2/12 pathologists)

Fig. 6

Proportion of pT4a diagnoses per laboratory for pT3-4aN0-2M0 colorectal carcinomas

Fig. 7

Adjusted OR’s per laboratory. Laboratory 0 is the reference laboratory based on the median. Asterisk indicates laboratories that significantly differed from the reference laboratory. Total, total numbers of pT3-4aN0-2M0 specimens evaluated in each laboratory