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DEVELOPMENT OF CONFOCAL ENDOMICROSCOPY CRITERIA FOR EARLY SIGNET-RING CELL CARCINOMA INPATIENTS WITH HEREDITARY DIFFUSE GASTRIC CANCER SYNDROME

Presentation Number: Su585

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AuthorBlock: Nastazja Dagny Pilonis2,1, Maria O'Donovan3, Sue Richardson2, Rebecca C. Fitzgerald2, Massimiliano Di Pietro2
1Department of Gastroenterological Oncology, Maria-Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland, Warsaw, Poland; 2MRC Cancer Unit, Cambridge, United Kingdom; 3Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK,, Cambridge, United Kingdom;

Abstract Body
Background: Hereditary diffuse gastric cancer (HDGC) syndrome, linked to germline CDH1pathogenic variants (PV), confers a 70% lifetime risk of gastric cancer. Prophylactic gastrectomy is the mainstay of management for patients with a confirmed CDH1 PV, however endoscopic surveillance is recommended for those without a known genetic cause and in CDH1 PV carriers who prefer to delay gastrectomy. Foci of signet-ring cell carcinoma (SRCC) can appear as subtle pale areas or can be inconspicuous when neoplastic cells lie underneath normal mucosa. Currently, it is not known if probe-based confocal laser endomicroscopy (pCLE) which provides a magnified, cellular level view of gastrointestinal epithelia can help diagnose early SRCC. The aim of this study was to develop pCLE diagnostic criteria for early SRCC in HDGC individuals undergoing surveillance endoscopy.
Methods: This was a prospective study on HDGC patients undergoing endoscopic surveillance. Up to 4 pale areas and one negative control region were identified by white-light endoscopy or narrow band imaging, marked by diathermy coagulation and then assessed by pCLE after intravenous fluorescein injection. Targeted biopsies were taken for histologic assessment. In the first phase of the study, two investigators assessed 113 video sequences off-line to identify pCLE features related to SRCC diagnosis. Corresponding histological slides from the biopsies were used as a reference for pCLE. During the valdation phase of the study, pCLE diagnostic criteria were retrospectively reviewed in an independent video set (n = 38) by an endoscopist experienced in pCLE and gastrointestinal pathologist with interest in HDGC, who were blinded to the histologic diagnosis. Sensitivity, specificity, accuracy, negative and positive predictive values, and interobserver agreement were calculated.
Results: The first phase included from 50 endoscopic locations from 16 HDGC patients. Four pCLE features characteristic of SRCC were identified: (A) glands with attenuated margins, (B) glands with spiculated or irregular shape, (C) heterogenous granular stroma with sparse glands, (D) enlarged vessels with tortuous shape and tubular flow (Figure 1). In the second phase, an independent set of video sequences (n=39) derived from 23 patients was assessed. Criteria A and B and C had the highest diagnostic accuracy. The interobserver agreement ranged from 0.153 to 0.565. Using a minimum of two criteria, selected from A, B and C, for a diagnosis of SRCC, the panel has a sensitivity of 67% and a specificity of 83%.
Conclusions: We have generated and validated pCLE criteria for early SRCC. The low sensitivity likely relates to the millimetric size of SRCC foci in most cases. Real-time validation of the criteria and assessment of reproducibility by multiple endoscopists are required prior to routine use of pCLE in HDGC endoscopic surveillance.