A rare multiple primary sarcomatoid carcinoma (SCA) of small intestine harboring driver gene mutations: a case report and a literature review

Abstract

Primary sarcomatoid carcinoma (SCA) is a type of rare tumor consisting of both malignant epithelial and mesenchymal components. Only 32 cases of SCA of the small bowel have been reported in the literature to date. Due to its rarity and complexity, this cancer has not been genetically studied and its diagnosis and treatment remain difficult. Here we report a 54-year-old male underwent emergency surgical resection in the small intestine due to severe obstruction and was diagnosed with multiple SCA based on postoperative pathological examination. Over 100 polypoid tumors scattered along his whole jejunum and proximal ileum. Chemotherapy (IFO+Epirubicin) was performed after surgery while the patient died two months after the surgery due to severe malnutrition. Whole-exome sequencing was performed for the tumor tissue with normal tissue as the control. Important cancer-related gene mutations, including KRAS (c.37G>T, p.G13C), TP53 (c.871A>T, p.K291*), EGFR (c.1351C>T, p.R451C), and CDKN2A (c.104_138del, p.G35fs), were found among 286 nonsynonymous somatic mutations (SNV and Indel). Copy-number amplified genes mainly gathered in chromosome 6, 7, 16 and 20. Mutation clustering analysis showed that main genetic abnormalities included DNA methylation, DNA alkylation, cellular homeostasis, and shared similarities with melanoma, glioma, prostate cancer, bladder cancer, non-small cell lung cancer, and pancreatic cancer. In summary, the genomic features of the small intestine SCA were explored at whole-exome level for the first time, and over 200 somatic mutations were identified in the tumor tissue. Key tumor driver gene mutations were revealed, as well as several aberrant functional pathways. These results contribute to further understanding of the pathogenesis and molecular mechanism of this rare tumor.

Multiple sarcomatoid carcinomas in the small intestine with perforation: A case report and literature review

“…Its occurrence may be related to prolonged regional inflammation. [ 6 ] According to statistics, [ 7 , 8 ] there have been just over 30 reported cases to date, predominantly affecting middle-aged and elderly males, with a higher incidence in men than in women, and most cases are solitary tumors, with a higher occurrence in the jejunum than in the ileum. In this case, the patient was an elderly male with multiple lesions, and the tumors were mostly located in the jejunum, which is in line with the statistical data.…”

“…According to domestic and foreign reports, [ 8 ] the current radiotherapy and chemotherapy regimens are ineffective for small intestine sarcomatoid carcinoma. Radical resection with regional lymph node clearance can improve prognosis to some extent, but it is difficult to alter the overall outcome.…”

“…In recent years, there have been reports of specific expression of the programmed death ligand 1 (PD-L1) protein in small intestine sarcomatoid carcinoma, suggesting that PD-L1-targeted immunotherapy might be effective, [ 9 , 17 ] and further verification and trials are warranted. Additionally, the genomic characteristics of small intestine sarcomatoid carcinoma have been identified in some studies, [ 8 ] and further research may reveal its molecular pathogenesis and help discover new treatment approaches.…”

Molecular Anatomy of Prostate Cancer and Its Implications in Active Surveillance and Early Intervention Strategies

“…Cribriform patterns can be further classified based on the proportion of cancer cells exhibiting PTEN-loss and PD-L1 overexpression [128]. Genes such as AR, ERG, FOXA1/2, MUC16, RB1, CDH1, BRCA2, and TP53 have also been involved in different variants of prostate cancer [129][130][131]. However, the molecular mechanisms underlying these rare variants are still poorly understood despite extensive research.…”