Multi-Institutional Study Evaluating the Role of Circulating Tumor DNA in the Management of Appendiceal Cancers.

PURPOSE: Conventional surveillance methods are poorly sensitive for monitoring appendiceal cancers (AC). This study investigated the utility of circulating tumor DNA (ctDNA) in evaluating systemic therapy response and recurrence after surgery for AC. METHODS: Patients from two specialized centers who underwent tumor-informed ctDNA testing (Signatera) were evaluated to determine the association between systemic therapy and ctDNA detection. In addition, the accuracy of ctDNA detection during surveillance for the diagnosis of recurrence after complete cytoreductive surgery (CRS) for grade 2-3 ACs with peritoneal metastases (PM) was investigated. RESULTS: In this cohort of 94 patients with AC, most had grade 2-3 tumors (84.0%) and PM (84.0%). Fifty patients completed the assay in the presence of identifiable disease, among which ctDNA was detected in 4 of 7 (57.1%), 10 of 16 (62.5%), and 19 of 27 (70.4%) patients with grade 1, 2, and 3 diseases, respectively. Patients who had recently received systemic chemotherapy had ctDNA detected less frequently (7 of 16 [43.8%] v 26 of 34 [76.5%]; odds ratio, 0.22 [95% CI, 0.06 to 0.82]; P = .02). Among 36 patients with complete CRS for grade 2-3 AC-PM, 16 (44.4%) developed recurrence (median follow-up, 19.6 months). ctDNA detection was associated with shorter recurrence-free survival (median 11.3 months v not reached; hazard ratio, 14.1 [95% CI, 1.7 to 113.8]; P = .01) and showed high accuracy for the detection of recurrence (sensitivity 93.8%, specificity 85.0%). ctDNA was more sensitive than carcinoembryonic antigen (62.5%), CA19-9 (25.0%), and CA125 (18.8%) and was the only elevated biomarker in four (25%) patients with recurrence. CONCLUSION: This study revealed a reduced ctDNA detection frequency after systemic therapy and accurate recurrence assessment after CRS. These findings underscore the role of ctDNA as a predictive and prognostic biomarker for grade 2-3 AC-PM management.

Peritoneal Microenvironment Promotes Appendiceal Adenocarcinoma Growth: A Multi-omics Approach Using Patient-Derived Xenografts.

Appendiceal adenocarcinoma (AA) is unique from other gastrointestinal malignancies in that it almost exclusively metastasizes to the peritoneal cavity. However, few studies have investigated the molecular interaction of the peritoneal microenvironment and AA. Here, we use a multi-omics approach with orthotopic and flank-implanted patient-derived xenografts (PDX) to study the effect of the peritoneal microenvironment on AA. AA tumors implanted in the peritoneal microenvironment tended to grow faster and displayed greater nuclear expression of Ki-67 relative to the same tumors implanted in the flank. Comparing the tumor-specific transcriptome (excluding stromal transcription), the peritoneal microenvironment relatively upregulated genes related to proliferation, including MKI67 and EXO1. Peritoneal tumors were also enriched for proliferative gene sets, including E2F and Myc Targets. Proteomic studies found a 2.5-fold increased ratio of active-to-inactive phosphoforms of the YAP oncoprotein in peritoneal tumors, indicating downregulation of Hippo signaling. IMPLICATIONS: The peritoneal microenvironment promotes growth of appendiceal tumors and expression of proliferative pathways in PDXs.

Taxane-Based Chemotherapy Is Effective in Metastatic Appendiceal Adenocarcinoma.

Appendiceal cancer is a rare, orphan disease with no therapies currently approved by the FDA for its treatment. Given the limited data regarding drug efficacy, these tumors have historically been treated with chemotherapy designed for colon cancer. However, an overwhelming body of molecular data has demonstrated that appendiceal adenocarcinoma is a distinct entity with key molecular differences from colon cancer, notably rare APC mutation. Recognizing that APC loss-of-function is thought to contribute to taxane resistance and that taxanes are effective in the treatment of other gastrointestinal tumors, including gastric, esophageal, and small bowel adenocarcinoma, we completed a single-center retrospective study to assess efficacy. In a cohort of 13 patients with metastatic appendiceal adenocarcinoma, treated with taxane chemotherapy the median overall survival was 8.8 months. Of 10 evaluable patients, we observed 3 responses, 4 patients with stable disease, and 3 with progression (30% response rate, 70% disease control rate). The results of this study showing activity of taxane-based chemotherapy in appendiceal adenocarcinoma support further clinical investigation of taxane therapy in this orphan disease.

The Promise of Epigenetics Research in the Treatment of Appendiceal Neoplasms.

Appendiceal cancers (AC) are a rare and heterogeneous group of malignancies. Historically, appendiceal neoplasms have been grouped with colorectal cancers (CRC), and treatment strategies have been modeled after CRC management guidelines due to their structural similarities and anatomical proximity. However, the two have marked differences in biological behavior and treatment response, and evidence suggests significant discrepancies in their respective genetic profiles. In addition, while the WHO classification for appendiceal cancers is currently based on traditional histopathological criteria, studies have demonstrated that histomorphology does not correlate with survival or treatment response in AC. Due to their rarity, appendiceal cancers have not been studied as extensively as other gastrointestinal cancers. However, their incidence has been increasing steadily over the past decade, making it crucial to identify new and more effective strategies for detection and treatment. Recent efforts to map and understand the molecular landscape of appendiceal cancers have unearthed a wealth of information that has made it evident that appendiceal cancers possess a unique molecular profile, distinct from other gastrointestinal cancers. This review focuses on the epigenetic landscape of epithelial appendiceal cancers and aims to provide a comprehensive overview of the current state of knowledge of epigenetic changes across different appendiceal cancer subtypes, highlighting the challenges as well as the promise of employing epigenetics in the quest for the detection of biomarkers, therapeutic targets, surveillance markers, and predictors of treatment response and survival in epithelial appendiceal neoplasms.

The Impact of Germline Alterations in Appendiceal Adenocarcinoma.

PURPOSE: More than 10% of assessed patients with appendiceal adenocarcinoma have a pathogenic (P) or likely pathogenic (LP) germline variant, including genes implicated in heritable gastrointestinal cancer syndromes, such as Lynch syndrome. We defined the clinical and molecular impact of heritable alterations in appendiceal adenocarcinoma to evaluate the need for dedicated appendiceal screening and prevention strategies in patients with LP/P germline variants. EXPERIMENTAL DESIGN: We performed an integrated germline and somatic molecular analysis for patients with confirmed appendiceal adenocarcinoma. Patients underwent paired tumor-normal sequencing for up to 90 hereditary cancer risk genes and 505 genes for somatic mutation profiling. We defined the cooccurrence of LP/P germline variants and second-hit pathogenic somatic alterations. The associations between germline variants and patient clinicopathologic features were also evaluated. RESULTS: Twenty-five of 237 patients (10.5%) carried pathogenic or likely pathogenic germline variants in cancer susceptibility genes. Clinicopathologic characteristics and appendiceal adenocarcinoma-specific survival were similar in patients with or without germline variants. Most (92%, N = 23/25) patients with germline variants demonstrated no second-hit somatic alterations, including loss of heterozygosity. Two patients with a germline APC I1307K low-penetrance founder variant exhibited secondary somatic pathogenic alterations in APC. However, only one patient tumor exhibited APC-mediated WNT signaling dysregulation: a plausible consequence of multiple somatic APC mutations with no germline variant contribution. Four patients had germline variants in PMS2 or MSH2 associated with Lynch syndrome, yet their cancers were microsatellite-stable. CONCLUSIONS: Germline variants are likely incidental without a contributory driver role in appendiceal adenocarcinoma. Appendiceal adenocarcinoma screening in patients with germline variants is not clearly merited.

Targeted Next-Generation Sequencing Improves the Prognostication of Patients with Disseminated Appendiceal Mucinous Neoplasms (Pseudomyxoma Peritonei).

BACKGROUND: Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients. METHODS: Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS). RESULTS: Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p < 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p < 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006). CONCLUSIONS: Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management.

A Novel Assessment of Metabolic Pathways in Peritoneal Metastases from Low-Grade Appendiceal Mucinous Neoplasms.

BACKGROUND: There is a paucity of targeted therapies for patients with pseudomyxoma peritonei (PMP) secondary to low-grade appendiceal mucinous neoplasms (LAMNs). Dysregulated metabolism has emerged as a hallmark of cancer, and the relationship of metabolomics and cancer is an area of active scientific exploration. We sought to characterize phenotypic differences found in peritoneal metastases (PM) derived from LAMN versus adenocarcinoma. METHODS: Tumors were washed with phosphate-buffered saline (PBS), microdissected, then dissociated in ice-cold methanol dried and reconstituted in pyridine. Samples were derivatized in tert-butyldimethylsilyl (TBDMS) and subjected to gas chromatography-coupled mass spectrometry. Metabolites were assessed based on a standard library. RNA sequencing was performed, with pathway and network analyses on differentially expressed genes. RESULTS: Eight peritoneal tumor samples were obtained and analyzed: LAMNs (4), and moderate to poorly differentiated adenocarcinoma (colon [1], appendix [3]). Decreases in pyroglutamate, fumarate, and cysteine in PM from LAMNs were found compared with adenocarcinoma. Analyses showed the differential gene expression was dominated by the prevalence of metabolic pathways, particularly lipid metabolism. The gene retinol saturase (RETSAT), downregulated by LAMN, was involved in the multiple metabolic pathways that involve lipids. Using network mapping, we found IL1B signaling to be a potential top-level modulation candidate. CONCLUSIONS: Distinct metabolic signatures may exist for PM from LAMN versus adenocarcinoma. A multitude of genes are differentially regulated, many of which are involved in metabolic pathways. Additional research is needed to identify the significance and applicability of targeting metabolic pathways in the potential development of novel therapeutics for these challenging tumors.

Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients With Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery.

OBJECTIVE: To investigate the role of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). BACKGROUND: Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in the detection of recurrence and initiation of further therapies. Plasma ctDNA has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection. METHODS: Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial postresection ctDNA assessments were included. Patients with rising postoperative ctDNA levels were compared with those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival, ctDNA sensitivity, lead time, and performance of ctDNA compared with carcinoembryonic antigen. RESULTS: One hundred thirty serial postresection ctDNA assessments [median 4, interquartile range (IQR), 3 to 5] were performed in 33 patients (n = 13 CRC, n = 20 HGA) who underwent completeness of cytoreduction-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n = 14, < 0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6 to 12) and not reached in the stable ( P = 0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI: 1.06-12.66, P = 0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead time was 3 months (IQR, 1 to 4). Carcinoembryonic antigen was less sensitive (50%) than ctDNA. CONCLUSIONS: This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.

The genetic profile and molecular subtypes of human pseudomyxoma peritonei and appendiceal mucinous neoplasms: a systematic review.

Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38-100%), GNAS (17-100%), and TP53 (5-23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.

The Prognostic Impact of Microsatellite Instability on the Outcome of Appendiceal Adenocarcinoma: a National Cancer Database Analysis.

BACKGROUND: Microsatellite instability (MSI) is recognized as a favorable outcome predictor in colorectal cancer. However, its impact on overall survival (OS) of appendiceal carcinoma has not been thoroughly studied. This study aimed to assess the impact of MSI on OS of patients with appendiceal adenocarcinoma, stratified by disease stage, tumor histology, and patients' demographics. METHODS: This was a retrospective cohort analysis of the colon cancer National Cancer Database (NCDB) between 2005 and 2019. Patients with appendiceal adenocarcinoma with known MSI status were included and subdivided according to MSI status into positive and negative. Primary outcome was OS stratified by MSI status. RESULTS: The study included 1681 (50.1% male) patients with a mean age of 58.9 ± 14.2 years; 211 (12.5%) had MSI-positive tumors (69 MSI low, 53 MSI high, and 89 not specified). Mean 5-year OS of patients with MSI-positive and MSI-negative carcinomas was similar (81.9 versus 78.6 months, p = 0.747). Patients with stage IV MSI-positive carcinomas had significantly longer OS than patients with MSI-negative carcinomas of the same stage (41.3 vs 26.5 months, p = 0.02). Differences in OS for patients with stages I-III were not statistically significant. Compared to MSI-negative/low carcinomas, MSI-high tumors had more advanced pathologic TNM stage (stage III: 23.9% vs 17.8%-stage IV: 41.3% vs 35.4%, p = 0.003), received more chemotherapy (56% vs 41%, p = 0.04), yet had similar OS (81.9 vs 78.9 months, p = 0.357). CONCLUSIONS: MSI status of appendiceal adenocarcinomas did not significantly impact survival, except for stage IV disease in which a survival benefit of MSI was noted.

Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis.

BACKGROUND AND OBJECTIVES: Published data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP). METHODS: CTP was performed, including next-generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB). RESULTS: One hundred thirty-six pAC and 348 pCRC samples underwent CTP. The cohorts' age and gender were similar. pCRC demonstrated increased pathogenic variants (PATHs) in APC (48% vs. 3%, p < 0.01), ARID1A (12% vs. 2%, p < 0.01), BRAF (12% vs. 2%, p < 0.01), FBXW7 (7% vs. 2%, p < 0.01), KRAS (52% vs. 41%, p < 0.05), PIK3CA (15% vs. 2%, p < 0.01), and TP53 (53% vs. 23%, p < 0.01), and decreased PATHs in GNAS (8% vs. 31%, p < 0.01). There was no difference in CNV, fusion rate, or MSI. Median TMB was higher in pCRC (5.8 vs. 5.0 mutations per megabase, p = 0.0007). Rates of TMB-high tumors were similar (pAC 2.1% vs. pCRC 9.0%, p = 0.1957). pCRC had significantly more TMB-high tumors at lower thresholds. CONCLUSIONS: Despite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.

Mutational profiles and prognostic impact in colorectal and high-grade appendiceal adenocarcinoma with peritoneal metastases.

BACKGROUND: Next-generation sequencing (NGS) personalizes cancer treatments. In this study, we analyze outcomes based on NGS testing for colorectal cancer (CRC) and high-grade appendiceal adenocarcinoma (HGA) with peritoneal metastases. METHODS: Retrospective review of genomic analyses and outcomes in patients with CRC or HGA with peritoneal metastases at a high-volume center from 2012 to 2019. RESULTS: Ninety-two patients (57 CRC, 35 HGA) were identified. Overall survival was longer for CRC (52.8 vs. 30.5 months, p = 0.03), though rates of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) were similar. Multiple genes were more frequently mutated in CRC, including KRAS (51% vs. 29%, p = 0.04), TP53 (47% vs. 20%, p < 0.01), and APC (46% vs. 6%, p < 0.01). For CRC, multivariate regression showed an increased hazard ratio (HR) with increasing peritoneal cancer index (1.06 [1.01-1.11], p = 0.02) and a decreased HR following CRS/HIPEC (0.30 [0.11-0.80], p = 0.02). PIK3CA mutation associated with significantly increased HR (3.62 [1.06-12.41], p = 0.04), though only in non-CRS/HIPEC patients. Multivariate analysis in the HGA group showed a benefit following CRS/HIPEC (0.18 [0.06-0.61], p = 0.01) and for mucinous disease (0.38 [0.15-0.96], p = 0.04), while there was an increased HR with TP53 mutation (6.89 [2.12-22.44], p < 0.01). CONCLUSION: CRC and HGA with peritoneal spread have distinct mutational profiles. PIK3CA and TP53 mutations are associated with survival for CRC or HGA with peritoneal metastases, respectively.

Practice patterns for reporting digestive system neuroendocrine neoplasms: results from a large, comprehensive international survey.

AIMS: Criteria for the interpretation of digestive system neuroendocrine neoplasms (NENs) continue to evolve. Although there are some literature recommendations regarding workup and diagnosis of these lesions, different practice patterns exist among pathologists when signing out these specimens. The aim of this study was to assess practice trends among pathologists worldwide when reporting these neoplasms. METHODS AND RESULTS: We created an online survey with multiple questions pertaining to digestive NENs. The results were analysed based on type of practice setting, years of sign-out experience, and practice location. Respondents included 384 practicing pathologists: 70% academic, 30% private practice; 63% gastrointestinal (GI) pathology-subspecialised, 37% not; 39% North American, 42% European, 19% others; 45% with ≤10 years in practice; 55% with >10 years. Some question responses were chosen by the majority (e.g. 85% use both mitotic count and Ki67 index for grading NENs, 82% complete a synoptic, and Ki67 stain even for small incidental appendiceal neuroendocrine tumours [NETs], and 96% utilize the diagnosis of grade 3 NET). However, some questions showed varying responses, including counting mitotic figures, Ki67 stain interpretation, and pancreatic grade 3 NEN workup. Pathologists also had some variability in interpreting regional metastatic foci of small bowel NETs and in choosing blocks for Ki67 staining in multifocal lesions. CONCLUSION: There existed scenarios wherein practice patterns varied despite recommendations in the literature, and there were also scenarios lacking clear guidelines wherein pathologists used varying judgement. This survey highlights current key grey areas in digestive system NEN evaluation, leading to variation in practice patterns.

Molecular Classification of Appendiceal Adenocarcinoma.

PURPOSE: Appendiceal adenocarcinomas (ACs) are rare, histologically diverse malignancies treated as colorectal cancers despite having distinct biology and clinical behavior. To guide clinical decision making, we defined molecular subtypes of AC associated with patient survival, metastatic burden, and chemotherapy response. PATIENTS AND METHODS: A comprehensive molecular analysis was performed in patients with AC to define molecular subtypes. Associations between molecular subtype and overall survival, intraoperative peritoneal cancer index, and first-line chemotherapy response were assessed adjusting for histopathologic and clinical variables using multivariable Cox proportional hazards, linear regression, and logistic regression models. RESULTS: We defined distinct molecular lineages of mucinous appendiceal adenocarcinoma (MAAP) from co-occurring mutations in GNAS, RAS, and TP53. Of 164 MAAP tumors, 24 were RAS-mutant (mut) predominant (RAS-mut/GNAS-wild-type [wt]/TP53-wt) with significantly decreased mutations and chromosomal alterations compared with tumors with GNAS mutations (GNAS-mut predominant) or TP53 mutations (TP53-mut predominant). No patient with RAS-mut predominant subtype metastatic MAAP died of cancer, and overall survival in this subgroup was significantly improved compared with patients with GNAS-mut (P = .05) and TP53-mut (P = .004) predominant subtypes. TP53-mut predominant subtypes were highly aneuploid; increased tumor aneuploidy was independently (P = .001) associated with poor prognosis. The findings retained significance in patients with any metastatic AC. RAS-mut predominant metastases exhibited reduced peritoneal tumor bulk (P = .04) and stromal invasion (P < .001) compared with GNAS-mut or TP53-mut predominant tumors, respectively. Patients with RAS-mut predominant MAAP responded more to first-line chemotherapy (50%) compared with patients with GNAS-mut predominant tumors (6%, P = .03). CONCLUSION: AC molecular patterns identify distinct molecular subtypes: a clinically indolent RAS-mut/GNAS-wt/TP53-wt subtype; a chemotherapy-resistant GNAS-mut predominant subtype; and an aggressive, highly aneuploid TP53-mut predominant subtype. Each subtype exhibits conserved clinical behavior irrespective of histopathology.

[A Case of Appendiceal Carcinoma with BRAF V600E Mutation and Microsatellite Instability-High].

A 75-year-old woman presented to our hospital with abdominal pain and melena. Colonoscopy revealed an ulcer at the appendiceal orifice. Histopathological examination of biopsy specimens revealed adenocarcinoma. Computed tomography showed an appendiceal mass of 11.8×6.7 cm in size involving the cecum and terminal ileum without any distant metastatic findings. Ileocecal resection with regional lymph node dissection to the root of the ileocolonic artery was performed. Histopathological examination of the specimen revealed appendiceal adenocarcinoma. Molecular subtype of the tumor was BRAF V600E mutation and microsatellite instability-high(MSI-H). The pathological stage was pT4bpN1bcM0, pStage ⅢC. She received 8 courses of CapeOX as adjuvant chemotherapy and no recurrence was noted 12 months following the surgery. The establishment of standard treatment strategies including surgery, chemotherapy, and immunotherapy for carcinoma of the appendix with BRAF V600E mutation and/or MSI-H is needed.