恶性肿瘤质地松散（PCCs）是一种以单个细胞或类似线条的基质浸润为主的质地不佳的生长方式来定义的肿瘤。与传统的小肠腺癌相比，小肠PCC（SB-PCCs）具有独特的临床病理学和预后特征，但是SB-PCCs的遗传基因谱仍未知，我们的目的是分析SB-PCC的分子景观。对15个非泌管性SB-PCC系列采用 Trusight Oncology 500 进行下一代测序分析。最常见的基因突变是TP53 (53%)和RHOA (13%)突变和KRAS扩增(13%)，而未发现KRAS、BRAF和PIK3CA的突变。大多数SB-PCCs(80%)与克罗恩病相关，包括RHOA突变的SB-PCCs，其特点是非SRC型组织学，并且具有一种奇特的阑尾型低级别粘液细胞腺瘤(GCA)-样成分。偶尔，SB-PCCs表现出高微卫星不稳定性、IDH1和ERBB2基因的突变或FGFR2扩增（每种情况仅有一例），而这些都是这种侵袭性癌症已确立的或有前景的治疗靶点。SB-PCCs可能携带RHOA突变，这与胃癌或阑尾GCA的弥散亚型类似，而KRAS和PIK3CA突变通常涉及结肠和小肠腺癌，却不是这种癌症的典型特征。©2023年美国临床病理学会。

Poorly cohesive carcinomas (PCCs) are neoplasms defined by a predominantly dyshesive growth pattern with single cell or cord-like stromal infiltration. The -distinctive clinicopathologic and prognostic features of small bowel PCCs (SB-PCCs) in comparison with conventional-type small intestinal adenocarcinomas have only recently been characterized. However, as SB-PCCs' genetic profile is still unknown, we aimed to analyze the molecular landscape of SB-PCCs.A next-generation sequencing analysis through Trusight Oncology 500 on a series of 15 nonampullary SB-PCCs was performed.The most frequently found gene alterations were TP53 (53%) and RHOA (13%) mutations and KRAS amplification (13%), whereas KRAS, BRAF, and PIK3CA mutations were not identified. Most SB-PCCs (80%) were associated with Crohn disease, including both RHOA-mutated SB-PCCs, which featured a non-SRC-type histology, and showed a peculiar appendiceal-type, low-grade goblet cell adenocarcinoma (GCA)-like component. Rarely, SB-PCCs showed high microsatellite instability, mutations in IDH1 and ERBB2 genes, or FGFR2 amplification (one case each), which are established or promising therapeutic targets in such aggressive cancers.SB-PCCs may harbor RHOA mutations, which are reminiscent of the diffuse subtype of gastric cancers or appendiceal GCAs, while KRAS and PIK3CA mutations, commonly involved in colorectal and small bowel adenocarcinomas, are not typical of such cancers.© American Society for Clinical Pathology, 2023.