👤 Levente Kuthi

The clinicopathologic and molecular features of serrated lesions with dysplasia in inflammatory bowel disease (IBD) remain poorly understood. We examined a total of 2396 patients treated for IBD at the University of Szeged between 2011 and 2023. Among them, 177 (7%) patients were diagnosed with colorectal neoplasia, of which only 11 (6%) had serrated dysplasia (n = 13). Of the 13 lesions, 5 (38%) showed features of sessile serrated lesion (SSL)-like dysplasia; 1 (8%) exhibited characteristics of traditional serrated adenoma (TSA)-like dysplasia; 6 (46%) were classified as serrated dysplasia, not otherwise specified (NOS); and 1 (8%) displayed mixed features of SSL-like and TSA-like dysplasias. At the time of the serrated dysplasia diagnosis, the mean age of the patients was 56 years. Ten (91%) patients had ulcerative colitis, and one (9%) had Crohn's disease. Pancolitis was observed in seven (64%) patients. The mean duration of IBD at the time of the serrated dysplasia diagnosis was 26 years. Most lesions (n = 9; 69%) were found in the left colon, including SSL-like dysplasia (3/5; 60%) and serrated dysplasia NOS (5/6, 83%). Eleven (85%) lesions had a polypoid endoscopic appearance. The mean size of the serrated dysplasia was 0.8 cm. Most lesions (n = 8; 62%) showed low-grade dysplasia. Serrated dysplasia was often associated with conventional (n = 3; 27%) or nonconventional dysplasia (n = 3; 27%). During the follow-up, 5 (45%) of the 11 patients developed colorectal cancer, including 3 patients with serrated dysplasia NOS, 1 with SSL-like dysplasia, and 1 with TSA-like dysplasia. Whole-exome sequencing revealed that the SSL-like dysplasia harbored mutations in Show less

Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare entity with worse prognosis compared to conventional gastric adenocarcinomas. Its histological characteristics are fetal gut-like architecture and tumor cells with cytoplasmic clearing, as well as positive immunohistochemical reaction to at least one of the enteroblastic markers. Hereby, we present a case of GAED with neuroendocrine marker positivity, with whole-exome sequencing (WES), and an updated literature review. A 68-year-old woman presented at the general practitioner with abdominal pain. Abdominal ultrasound described gastric wall thickening raising suspicion of gastric cancer; thus, gastroscopy was performed, and biopsy samples were taken, which confirmed malignancy. Neoadjuvant systemic chemotherapy was initiated, and total gastrectomy was performed. Microscopically, pleomorphic polygonal cells were visible with clear cytoplasm and high-grade cellular atypia. Alcian blue and PAS stains demonstrated positivity for acidic and neutral mucins. P53 IHC was negative, indicative of null-phenotype, while Syntaxin-1 and Chromogranin showed focal positivity. SALL4 and Glypican 3 were positive; however, AFP displayed only minimal, uncertain positivity. The Ki67 labeling index was 70%. Due to the morphological and immunohistochemical characteristics, the tumor was concluded as GAED with neuroendocrine marker positivity. WES was carried out revealing 4 pathogenic, including TP53, KLHL7, RAPSN, and ACTA1, and 3 likely pathogenic mutations, encompassing PNKP, HNF1A, and ADNP. GAED is a rare subtype of gastric adenocarcinomas, representing 0.3-5.4% of all cases, and has an unclarified etiology. Our WES results identified new pathogenic and likely pathogenic mutations. From a differential diagnostic point of view, hepatoid adenocarcinoma and the possibility of metastatic origin have to be excluded. Show less