Assessment of Likelihood of Submucosal Invasion in Non-Polypoid Colorectal Neoplasms

Although of lower prevalence compared with polypoid neoplasms, the non-polypoid neoplasms, especially the depressed type, are important to diagnose because they belong to a distinct biologically aggressive subset, given the high rate of intramucosal or submucosal cancers. The detection and diagnosis of the non-polypoid colorectal neoplasm presents a challenge and an opportunity. Above all, characteristic colonoscopic findings obtained by a combination of conventional colonoscopy and magnifying chromoendoscopy are useful for determination of the invasion depth of non-polypoid colorectal cancers, an essential factor in selecting a treatment modality.

Endoscopic mucosal resection (EMR) is indicated to treat intramucosal colorectal carcinoma because the risk of lymph node metastasis is nil. Surgery is indicated to treat submucosal invasive cancers (cancer cells invading through the muscularis mucosa into the submucosal layer but not extending into the muscularis propria) because of the 6% to 12% risk of lymph node metastasis. However, there is increasing evidence to suggest that lesions with submucosal invasion lower than 1000 μm, without lymphovascular invasion and without poor differentiation, also have a minimal risk of lymph node metastasis and can be cured by EMR alone. It is therefore important to be able to distinguish neoplasms that are candidates for EMR from those that will require surgery, because EMR of lesions containing massive submucosal invasive cancer is associated with the risk of bleeding and perforation and is unlikely to be curative.

Current endoscopes have high-resolution imaging that provides clear, vivid, and detailed features of the detected lesions. When combined with image enhancement, high-magnification endoscopy can provide a detailed analysis of the morphologic architecture of mucosal crypt orifices (ie, pit pattern) in a simple and quick manner. As such, magnifying chromoendoscopy has been shown to be effective for the differential diagnosis between colorectal neoplastic and non-neoplastic lesions and determination of the depth invasion of colorectal cancers. The authors highlight methods to assess depth of invasion of non-polypoid colorectal cancers based on a review of the literature and our experience at National Cancer Center Hospital in Japan.

Importance of estimation of submucosal invasion

In Japan, findings of deep submucosal invasion (≥1000 μm), and/or lymphovascular invasion, and/or poorly differentiated adenocarcinoma in the histopathology of an EMR specimen would lead to consideration for surgery. Though lymphovascular invasion and poorly differentiated adenocarcinoma components are impossible to predict before resection, the vertical depth of invasion of submucosal cancers can be estimated based on the morphologic appearance at the time of endoscopy.

However, estimation of submucosal invasion requires more than the measurement of the lesion size. Small colorectal neoplasms are historically believed to have a lower malignancy potential than large ones, and several authors have reported that the malignant potential of early colorectal cancer increases with size. Although this observation may be true for adenomatous lesions, the data for submucosally invasive carcinomas are conflicting. In the authors’ own large study involving 583 lesions, they found that that small submucosal cancers (≤10 mm, n = 120) had a similarly aggressive behavior and malignant potential as the larger ones (>10mm, n = 463); the risks of lymph node metastasis were similar (small: 11.2%, large: 12.1%, P = .85), lymphovascular invasion (small: 21.7%, large: 27%, P = .23), and poorly differentiated adenocarcinoma components (small: 10%, large: 17.1%, P = .06). They also described that small submucosal cancers were more likely to have non-polypoid growth (NPG) type than the larger lesions (68.3% vs 46.0%, P <.0001). In this retrospective study, the rate of EMR used as an initial treatment was 33.4% (195/583). EMR was more often used to resect the small lesion rather than the large lesion group (51.6% vs 28.7%, P <.0001). However, they were surprised to find that there were no differences in the positive rate of cut margins in both groups (17.7% vs 19.5%, P = .81). This result implies that EMR should not be easily applied to small colorectal lesions when they appear to be submucosally invasive because of its risk of complication and the concept of no-touch isolation.

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