Elsevier

Human Pathology

Volume 45, Issue 2, February 2014, Pages 268-275
Human Pathology

Original contribution
Histologic grading based on counting poorly differentiated clusters in preoperative biopsy predicts nodal involvement and pTNM stage in colorectal cancer patients

https://doi.org/10.1016/j.humpath.2013.07.046Get rights and content

Summary

Histologic grading is commonly assessed in colorectal cancer preoperative biopsies. Nevertheless, its clinical impact is limited by low interobserver reproducibility and poor concordance with grading found in the final resection specimen. In the present study, we aimed to investigate the reproducibility, accuracy, and predictive value on lymph node status or pTNM stage of a novel grading system based on the number of poorly differentiated clusters in colorectal cancer preoperative endoscopic biopsies. Grading based on counting poorly differentiated clusters was assessed in 163 colorectal cancer endoscopic biopsies and corresponding surgical specimens. With this system, 152 biopsies could be graded with good interobserver agreement (κ = 0.735). In comparison with the surgical specimens, 75% of colorectal cancers were correctly graded in the biopsy, and 81% of poorly differentiated colorectal cancers were identified at initial biopsy. High poorly differentiated clusters grade in the biopsy was significantly associated with nodal metastasis, high pTNM stage (P < .0001), or histologic features suggestive of more aggressive behavior (tumor budding, perineural invasion, vascular invasion, and infiltrating tumor border) in the surgical specimen. Furthermore, this system identified colorectal cancer with nodal involvement or high pTNM stage with a 78% positive predictive value and 71% and 69% negative predictive values, respectively. Our findings suggest that a grading system based on the quantification of poorly differentiated clusters is feasible in most colorectal cancer endoscopic biopsies. In view of its good reproducibility, accuracy, and predictive value on the anatomical extent of the disease, it may be taken into account for decision-making in colorectal cancer treatment.

Introduction

Colorectal carcinoma (CRC) is one of the most common malignancies in Western countries. At present, the pathologic (p) TNM stage, established in accordance to the International Union Against Cancer [1] and the American Joint Committee on Cancer [2] staging classifications, is regarded as the main predictor of outcome of this tumor [3] and is taken into account as a basis for therapeutic management. Nonetheless, several other histologic features have received attention as prognostic factors for this neoplasia [4]. Among these, tumor histologic grading is commonly described in the pathologic report of surgically resected tumors, due to its supposed prognostic value on the clinical course of CRC [5], [6], [7].

According to the World Health Organization (WHO) classification of tumors of the digestive system [8], [9], histologic grade of CRC is defined by considering the percentage of the tumor showing formation of gland-like structures: well-differentiated (grade 1) CRCs exhibit glandular structures in more than 95% of the tumor; moderately differentiated (grade 2), in 50% to 95%; poorly differentiated (grade 3), in 5% to 50%; and undifferentiated (grade 4), in less than 5% [8]. In addition, in the fourth edition of the WHO classification [9], it has been proposed to group grades 1 and 2 as “low-grade” and grades 3 and 4 as “high-grade” CRCs. Although widely used, this grading system suffers from a significant degree of interobserver variability [10], [11], [12], which limits its utility for prognostic purposes [12], due to the lack an objective method to assess the amount of glandular component.

With the need to standardize the criteria for histologic grading of CRC, a novel grading system based on the count of cancer clusters composed of greater than or equal to 5 cancer cells and lacking a gland-like structure (poorly differentiated clusters) was recently proposed [13]. There is evidence that grading based on poorly differentiated clusters (PDCs) is more reproducible and provides more significant prognostic information than grading assessed by the percentage of glandular component in CRC surgical specimens [13], [14].

In routine practice, histologic grading is also assessed on preoperative endoscopic biopsies of CRC. Nevertheless, serious concerns exist about the clinical relevance of presurgical grading [11], [15], [16], due to its low interobserver reproducibility and poor concordance with grading found in the final resection specimen [11], [17]. In a recent Letter to the Editor [18], we suggested that the histologic grading based on the PDC count may also be performed on CRC endoscopic biopsy. Hence, in the present study, we aimed to investigate the interobserver reproducibility of this grading system in preoperative endoscopic biopsy and its agreement with grading assessed in the final resection specimen as well as its clinical relevance in terms of predictive value on lymph node status or pTNM stage of the tumor.

Section snippets

Materials and methods

All procedures were performed in compliance with relevant laws and institutional guideline and approved by the local institutional committee of Policlinic G. Martino, Messina, Italy.

The design and main findings of the study are illustrated in Fig. 1. In detail, 163 consecutive endoscopic preoperative biopsies and corresponding surgical specimens of CRC (74 male and 89 female patients; age range, 43-90 years; mean age, 71.42 years) were initially selected from the files of our institutions and

Results

The clinicopathologic characteristics of the cases included in the study are shown in Table 1. In the preoperative biopsies, the PDC count ranged between 0 and 7 (median, 0). According to our cutoff values, 96 CRCs were classified as G1, 35 as grade G2, and 21 as G3 (Fig. 3). In the surgical specimens, the number of PDCs ranged between 0 and 13 (median, 4), and we identified 85 G1, 43 G2, and 24 G3 CRCs. The interobserver agreement in the assessment of grading was good in the biopsies (κ =

Discussion

The prognostic value of preoperative histologic grading performed on CRC endoscopic biopsy was first suggested in 1929 by Stewart and Spies [20], who stated also that small biopsy specimens are sufficient for grading assessment. Then, in 1953 in an article entitled “Is histologic grading of colon carcinoma a valid procedure?” [21], Qualheim and Gall concluded that there is no basis for using histologic grade as a means for determining CRC prognosis, as most biopsy samples would not be

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    Disclosure: We have no conflict of interest or funding to disclose.

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