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Predictable Factors of Histologic Discrepancy of Gastric Cancer between the Endoscopic Forceps Biopsy and Endoscopic Treatment Specimen

Background/Aims: Recently, variable gastrointestinal track tumors including early stage malignancies are treated by endoscopic procedure. However, the discrepancy of histologic diagnosis may sometimes exist between the pretreatment forceps biopsy results and those of post treatment specimen. So the prediction of malignant lesion is important in the aspect of treatment selection. In this study, we investigated the predictable factors of the histologic discrepancy through the clinical, endoscopic features of the lesion diagnosed as adenocarcinoma in the post-endoscopic treatment specimen after the adenoma was diagnosed by the endoscopic forceps biopsy. Methods: From March 2005 to April 2009, 129 gastric tumor lesions (129 patients) which were not diagnosed as malignancy and treated with endoscopic procedure were enrolled retrospectively. We compared the pretreatment endoscopic forceps biopsy results and post-treatment specimen biopsy results, then, analyzed the tumor characteristics. Results: Twenty-one cases (16.3%) were diagnosed as malignancy after endoscopic treatment. Especially, discrepancy occurred more frequently in depressed lesions than in flat or elevated lesions (41.7% vs. 13.7%, p=0.012), and in lesions diagnosed as high grade adenomas than low or moderate grade adenomas (33.3% vs. 11.1%. p=0.004). Conclusions: In cases of depressed type lesions in the pretreatment endoscopy or those diagnosed as high grade adenoma in the pretreatment forceps biopsy, we should consider combined malignant lesion. Therefore, treatment modalities ensuring accurate diagnosis and potentially curative resection, should be carefully selected and performed in cases which have these features. (Korean J Gastroenterol 2012;59:354-359)


INTRODUCTION
Gastric adenoma is defined as a raised lesion composed of dysplastic epithelium that is flat-topped, villiform, or forms a pedunculated polyp. 1 Adenomas are reportedly associated with synchronous gastric carcinomas with varying frequen-cies, ranging from 8% to 59%. The reported incidence of carcinoma arising within adenomas also varies considerably, from 4% to 60%. 2 In 1963, early gastric cancer (EGC) was defined as adenocarcinoma confined to the mucosa or submucosa, irrespective of lymph node involvement. 1 Surgical resection was once considered to be the only curative stand-ard procedure for gastric cancer. 3 However, EGC that is smaller than 2 cm and limited to the mucosal layer rarely involves lymph node metastasis. 4  To this end, we retrospectively reviewed patients whose lesions were diagnosed as non-malignant by forceps biopsies and were subsequently treated with EMR or ESD. We then investigated the factors predictive of a histologic discrepancy between forceps-biopsied and post-endoscopic treatment specimens. We analyzed the cases that were diagnosed as adenoma using specimens obtained by forceps biopsy, but as adenocarcinomas by using endoscopically resected specimens.  Hypertonic saline mixed with epinephrine (5-30 mL) was injected into the submucosal layer to produce a mucosal bleb.

SUBJECTS AND METHODS
The lesion was incised (precut) along the outer border of the marked lesion using a needle knife. EMR/ESD was carried   In other words, the depressed type lesions might have a higher risk of containing malignant components even in cases diagnosed as premalignant lesions before treatment ( Table 2).
Most of the lesions were located in the lower third of the stomach (120 lesions, 93.0%). Two (1.6%) and 7 (5.4%) cases were located in the upper and mid-third of the stomach, respectively. Histologic discrepancies were more frequent in the group with lesions in the lower third (20/120, 16.7%) than in the group with lesions in the mid-third of the stomach (1/7, 14.3%). None of the lesions in the upper third showed histologic discrepancies. There was no statistical difference between the groups (p=0.810) ( Table 2).

Correlation between grade of dysplasia in pre-treatment diagnosis and histologic discrepancies
Using forceps-biopsied specimens, pre-treatment diagnosis classified 99 lesions (76.7%) as adenoma with a low or moderate grade and 30 lesions (23.3%) as adenoma with high grade dysplasia (Table 1). Histologic discrepancies were more frequent in lesions diagnosed as adenoma with high grade dysplasia (10/30, 33.3%) than in lesions diagnosed as low or moderate grade dysplasia (11/99, 11.1%; p=0.004) (Tables 2, 3).

Multivariate analysis of predictive factors
On multivariate analysis, depressed type lesions (OR, 5.873; p=0.023) and a pretreatment histologic finding of high grade dysplasia (OR, 4.734; p=0.007) were also found to be meaningful predictive factors (Table 4). In short, lesion type and grade of dysplasia as determined by pretreatment forceps biopsy were factors predictive of histologic discrepancies between pre-and post-treatment diagnosis. Surgical resection had been considered to be the only curative, standard procedure for gastric cancer. After EMR and ESD were introduced in Japan, its use rapidly expanded to neighboring countries because of its safety, diagnostic and therapeutic efficacy, and minimal invasiveness. 13,17,18 Currently, EMR and ESD are performed worldwide and are accepted as a treatment option for gastroesophageal mucosal lesions. 18 The EMR/ESD procedure cannot be performed during a routine diagnostic endoscopy due to the relatively long length of the procedure and potential complication risks. Patients with cardiac and pulmonary compromise and those taking anticoagulants are at high risk for complications. [19][20][21] Therefore, the risks and benefits must be considered before performing EMR/ESD in those cases. Clinicians can decide to perform the procedure based on the results of endoscopy and forceps biopsy results. 22 However, it is well known that endoscopic mucosal biopsies obtained with standard biopsy forceps can yield false-negative results, especially if the transmural epithelial layer is not involved in the pathological process. Hidden foci of malignancy can be missed by forceps biopsy, also leading to false-negative results.
According to the results of several studies, 23-26 the discrepancy rates between endoscopic forceps biopsied samples and post-treatment resected specimens are 10-25%. The concordance rate between endoscopic forceps biopsied samples and entirely resected specimens after ESD are re-ported to be low as 65-76% in Japan. 9,27 EMR and ESD involve en bloc resection of the entire lesion, the histological examination of which is clearly more reliable than forceps biopsy.
However, EMR and ESD are not frequently used for diagnostic purposes in developed countries. 28 There are few studies on the factors predictive of this histologic discrepancy, especially regarding the diagnosis of malignancy. We therefore planned this study to determine whether there were factors predictive of this histologic discrepancy and to thus improve the management of gastric adenomatous lesions.
Of the 129 cases included in our retrospective study, 21 (16.3%) had histologic discrepancies between forceps biopsy samples and post-EMR/ESD specimens. In other words, some of the tumor lesions were misdiagnosed before treatment. Our study showed that the rate of histologic discrepancies was higher in depressed-type lesions and in those that involved high grade dysplasia. These results indicate that when gastric adenoma is found in combination with these features, treatment modalities assuring en bloc resection should be considered.
Our study has the following limitation. The possibility of selection bias resulted from the fact that consecutive cases were not analyzed, as this study was performed retrospectively. As such, a further large-scale prospective study is necessary to overcome this limitation.
In conclusion, our study suggests that depressed-type tumor morphology and high grade dysplasia are factors predictive of a histologic discrepancy between diagnostic forceps biopsy results and post-treatment specimen diagnosis of gastric adenomatous lesions in terms of malignancy.
Therefore, treatment modalities ensuring accurate diagnosis and potentially curative resection, such as ESD, should be carefully selected and performed in cases that involve these features.