Morphologic Criteria of Invasive Colonic Adenocarcinoma on Biopsy Specimens

摘要

The World Health Organization (WHO) defines an invasive colonic adenocarcinoma as a tumor that invades through the muscularis mucosa, into or beyond the submucosa. This feature may not be easily distinguishable in scant colonoscopic biopsy specimens. Our objective is to identify additional morphologic criteria to aide in the diagnosis of invasive colonic adenocarcinoma on scant biopsy material. We evaluated six additional morphologic criteria in a retrospective observational study of 55 consecutive malignant and 16 benign colonic biopsy specimens whose final diagnoses were confirmed by concordant colonic resection. Statistic analysis shows that desmoplasia, cribiform pattern, intraluminal necrosis and high-grade nuclear atypia are independent factors that are highly associated with invasive adenocarcinoma (p < 0.05). Both desmoplasia and cribiform pattern demonstrate 100% specificity and high sensitivity with 83.6% and 89.1% respectively in diagnosing invasive colonic adenocarcinoma. Intraluminal necrosis and high-grade nuclear atypia also showed high sensitivity (92.7% and 90.9%) and high specificity (93.8% and 87.5%). The presence of any of the following four histologic features: stromal desmoplasia, cribriform pattern, intraluminal necrosis and high-grade nuclear atypia in the biopsy specimen, should warrant consideration of a complete resection. Introduction Colonic adenocarcinoma is the third most common cause of cancer mortality in the United States.1 As such, screening colonoscopies are utilized to detect colon cancer at its earliest and potentially curable stage, resulting in a surge in the number of colon biopsies submitted to pathology departments. On biopsy specimens, the diagnostic criteria for colonic adenocarcinoma are different between Japanese and Western pathologists.2 According to the WHO definition, colonic adenocarcinoma is diagnosed when neoplastic glands invade submucosa and beyond.3 However, biopsy specimens have a propensity to be small and poorly oriented, causing difficulty in the demonstration of invasion to the submucosa. Other than invasion to the submucosa, many pathologists rely on the presence of desmoplasia as an additional criterion to diagnose invasive adenocarcinoma. An invasive adenocarcinoma consistently induces a desmoplastic reaction4 and desmoplasia was noted to be highly associated recurrent cancer in patients with endoscopic resection of submucosal invasive adenocarcinoma (pT1).5 We attest there are a group of additional morphologic features that can aide in the diagnosis of invasive colonic adenocarcinoma in biopsy material and that these evidence based features should be considered as additions to the current criteria. Materials and Methods This study is a retrospective observational analysis of colon biopsy specimens and their subsequent resections that occurred at a community hospital in 2008. A total of 71 cases were recruited including, 16 benign and 55 malignant cases based on the resection results. It was key that each biopsy evaluated have a subsequent resection in order to decrease the effect of sampling error on the data. Each specimen had the following demographic information gathered: age, sex, and site. The biopsy specimens had the following evaluated: the volume of biopsy, and six morphologic features including the presence/absence of desmoplastic stromal response (Figure 1), the presence/absence of a cribriform pattern, the presence /absence of atypical glands penetrating the muscularis mucosa (Figure 2), the presence/absence of atypical glands next to the normal mucosa (Figure 3), the presence/absence of intraluminal necrosis (Figure 4) and the presence/absence of high grade nuclear atypia. Cribriform pattern is defined as gland within gland and/or back-to-back arrangement without stroma in between (Figure 3). High-grade nuclear atypia is defined as rounded or pleomorphic nuclei with prominent nucleoli and high nuclear to cytoplasmic ratio as well as loss of the nucle