Indirect Clinical Validation of a Programmed Death-Ligand 1 Laboratory-Developed Test for Gastric/Gastroesophageal Junction Adenocarcinoma with 22C3 Antibody Concentrate.

BACKGROUND: The PD-L1 IHC 22C3 pharmDx used on the Dako Autostainer Link 48 (ASL48) staining platform is an established method for assessing programmed death-ligand 1 (PD-L1) expression in tumor tissue and determining patient eligibility for pembrolizumab treatment; however, the availability of this platform is limited in Europe and Asia. OBJECTIVES: The aims of this study were to develop and optimize protocols for the PD-L1 22C3 antibody concentrate with multiple immunohistochemistry staining platforms and to validate these protocols using PD-L1 combined positive score (CPS) with a cut-off of ≥ 1 in gastric or gastroesophageal junction adenocarcinoma. DESIGN: The 22C3 antibody concentrate was tested and optimized protocols were developed for use with three staining platforms: Dako ASL48, Ventana BenchMark ULTRA, and Leica BOND-MAX. Tumor specimens (N = 120) from patients with gastric or gastroesophageal junction adenocarcinoma were used for the validation study; these specimens were evaluated independently by three pathologists for PD-L1 CPS as a continuous variable and using a cut-off of ≥ 1. PD-L1 IHC 22C3 pharmDx used on the Dako ASL48 platform served as the reference or gold standard. RESULTS: The intraclass correlation coefficient of CPS as a continuous variable between the gold standard and each staining platform assessed was 0.910-0.989. When CPS was dichotomized based on a cut-off of ≥ 1, depending on the pathologist and the platform used, positive percentage agreement was 81-99% and negative percentage agreement was 90-100%. Interobserver agreement using the gold standard showed substantial agreement (κ = 0.779). CONCLUSION: The PD-L1 22C3 antibody concentrate can potentially be used with the laboratory-developed test on three commercially available immunohistochemistry staining platforms to determine PD-L1 expression in tumor samples from patients with gastric or gastroesophageal junction adenocarcinoma.

Long-term Prognosis of Localized Lymphoid Hyperplasia of the Rectum.

Background/Aims: Although localized lymphoid hyperplasia (LLH) of the rectum is occasionally observed, its clinical implications are unclear. This study aimed to investigate the clinical course and significance of LLH of the rectum. Methods: We identified 65 patients diagnosed with LLH of the rectum using a histopathologic examination and who received follow-up endoscopies between January 2009 and June 2015. Patients with a history of inflammatory bowel disease, lymphoma, familial adenomatous polyposis, or uncontrolled malignancy and patients who underwent scar biopsy after endoscopic resection or surgery were excluded. Endoscopic findings and clinical courses were analyzed. Results: During the median follow-up of 31 months (interquartile range, 19 to 40 months), 81.5% (53/65) of LLHs of the rectum were resolved. Clinically significant diseases, including ulcerative colitis (UC, n=5) and mucosa-associated lymphoid tissue (MALT) lymphoma (n=1), were diagnosed in 9.2% of patients (6/65). The other six patients showed no significant changes in the lesion (n=3) or a waxing and waning appearance (n=3). According to endoscopic findings, all of the 47 polypoid types showed resolution or waxing and waning patterns. Five of the 11 nodular types (45.5%) developed into UC. One of the seven submucosal tumor (SMT)-like types (14.3%) developed into MALT lymphoma. Conclusions: LLH of the rectum with persistent symptoms or the endoscopic appearance of the nodular or SMT-like type may lead to clinically significant disease. Risk stratification according to endoscopic findings and careful surveillance are required for these lesions.

Small-cell neuroendocrine carcinoma of the ileum: case report and literature review.

BACKGROUND: Poorly differentiated neuroendocrine carcinomas (NECs) originating from the gastrointestinal (GI) tract are rare and very highly malignant disease with a poor prognosis. Poorly differentiated NECs most commonly arise in the esophagus and the large bowel; however, they may occur within virtually any portion of the GI tract. It is known, however, that they do not typically occur in the small intestine. CASE REPORT: A 21-year-old woman visited an emergency room with acute abdominal pain that commenced 2 days prior to her presentation. Thereafter, a computed tomography (CT) scan was notable for a small-intestine perforation, and huge masses were observed in the small intestine and the mesentery. The mass that was located at the ileum site is approximately 100 cm above the ileocecal (IC) valve, and while it is located on the anti-mesenteric border and it seems that luminal narrowing had occurred, an obstruction is absent. Also, a same-nature mass is on the mesentery. The pathologic reports confirmed a small-cell-type NEC with a mass size of 7.5 × 6.5 cm. The mitotic count is up to 24/10 high-power fields (HPFs), the results of the immunohistochemical stain are positive for CD56 and synaptophysin, and the Ki-67 level is 50%. %. After the operation, she was treated with Etoposide-Cisplatin (EP) chemotheraphy. Stable disease was seen during Etoposide-Cisplatin chemotheraphy. Liver metastasis was also confirmed after chemotheraphy. Additionally, Irinotecan and cisplatin were used for 3 cycles, but progression of disease, neutropenic fever, thrombocytopenia, general weakness persisted. Eventually, she died 1 year and 6 months after surgery. CONCLUSION: Ileum-located NECs are diagnosed very rarely. The most common locations for these tumors along the GI tract are the esophagus and the large intestine, but they can arise anywhere. The prognosis for NECs is poor due to the metastatic disease of most patients at the time of diagnosis. The role of adjuvant treatment requires further evaluation for the attainment of a better understanding of the overall treatment effect.