Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms.
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ABSTRACT:
SUBMITTER: Kang DW
PROVIDER: S-EPMC8353140 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The molecular basis for the development of appendiceal mucinous tumours, which can be a cause of pseudomyxoma peritonei, remains largely unknown.Thirty-five appendiceal mucinous neoplasms were analysed for GNAS and KRAS mutations. A functional analysis of mutant GNAS was performed using a colorectal cancer cell line.A mutational analysis identified activating GNAS mutations in 16 of 32 low-grade appendiceal mucinous neoplasms (LAMNs) but in none of three mucinous adenocarcinomas (MACs). KRAS mutations were found in 30 LAMNs and in all MACs. We additionally analysed a total of 186 extra-appendiceal mucinous tumours and found that GNAS mutations were highly prevalent in intraductal papillary mucinous tumours of the pancreas (88%) but were rare or absent in mucinous tumours of the colorectum, ovary, lung and breast (0-9%). The prevalence of KRAS mutations was quite variable among the tumours. The introduction of the mutant GNAS into a colorectal cancer cell line markedly induced MUC2 and MUC5AC expression, but did not promote cell growth either in vitro or in vivo.Activating GNAS mutations are a frequent and characteristic genetic abnormality of LAMN. Mutant GNAS might play a direct role in the prominent mucin production that is a hallmark of LAMN.
| S-EPMC3590682 | biostudies-other
Project description:BACKGROUND:Occasionally, low-grade appendiceal mucinous neoplasms (LAMN) present with mucinous peritoneal deposits (MPD) localized to periappendiceal tissue or diffused throughout the peritoneum. OBJECTIVE:This study was aimed at evaluating the relevance of mucin cellularity for predicting outcomes of LAMN with remote MPD. METHODS:The records of patients with LAMN and remote MPD who underwent initial assessment at a comprehensive cancer center from 1990 to 2015 were reviewed, and diagnostic procedures, treatments, and outcomes were analyzed. RESULTS:Of 48 patients included in the analysis, 19 had cellular MPD (CMPD) and 29 had acellular MPD. Of 33 patients who underwent cytoreductive surgery, 30 had a complete cytoreduction; the 3 patients with an incomplete cytoreduction had CMPD. In the follow-up period (median, 4 years), 6 patients died of the disease, all of whom had CMPD. Of 11 patients who had progression of disease, 10 had CMPD. CONCLUSION:Cellularity of remote MPD is an important determinant of disease outcome in LAMN. Approaches such as active surveillance may have a role in selected patients with LAMN and AMPD.
| S-EPMC6339600 | biostudies-literature
Project description:OBJECTIVES:It is challenging to distinguish between primary ovarian mucinous tumors and metastatic mucinous neoplasms from the lower gastrointestinal tract, including appendiceal tumors. A combination of PAX8 and SATB2 immunohistochemical stains can be used as a diagnostic tool to distinguish between these cases. RESULTS:Immunostaining for SATB2, PAX8, CK7, CK20 and CDX2 was performed on 50 ovarian mucinous neoplasms (OMN) (39 cystadenomas, 4 borderline and 7 adenocarcinomas), 63 mucinous colorectal carcinoma (CRC), and 9 appendiceal mucinous neoplasms (AMN) [8 low grade appendiceal mucinous neoplasms (LAMN) and 1 adenocarcinoma]. PAX8 was positive in 32% of OMN and negative in all CRC and AMN cases. SATB2 was expressed in 2.0% of OMN, 77.8% of AMN, and 49.2% of CRC cases. CK7 was positive in 78.0% of OMN, 33.3% of AMN, and 9.5% of CRC cases. CK20 was expressed in 24.0% of OMN, 88.9% of OMN, and 87.3% of CRC cases. CDX2 was positive in 14.0% of OMN, 100% of AMN, and 90.5% of CRC cases. PAX8 can differentiate between OMN and AMN with high specificity but low sensitivity. CDX2 is the most sensitive marker for CRC and AMN, whereas SATB2 has better specificity.
| S-EPMC6880435 | biostudies-literature
Project description:BackgroundAppendiceal mucinous neoplasm (AMN) with peritoneal metastasis is a rare but deadly disease with few prognostic or therapy-predictive biomarkers to guide treatment decisions. Here, we investigated the prognostic and biological attributes of gene expression-based AMN molecular subtypes.MethodsAMN specimens (n = 138) derived from a population-based subseries of patients treated at our institution with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 05/2000 and 05/2013 were analyzed for gene expression using a custom-designed NanoString 148-gene panel. Signed non-negative matrix factorization (sNMF) was used to define a gene signature capable of delineating robustly-classified AMN molecular subtypes. The sNMF class assignments were evaluated by topology learning, reverse-graph embedding and cross-cohort performance analysis.ResultsThree molecular subtypes of AMN were discerned by the expression patterns of 17 genes with roles in cancer progression or anti-tumor immunity. Tumor subtype assignments were confirmed by topology learning. AMN subtypes were termed immune-enriched (IE), oncogene-enriched (OE) and mixed (M) as evidenced by their gene expression patterns, and exhibited significantly different post-treatment survival outcomes. Genes with specialized immune functions, including markers of T-cells, natural killer cells, B-cells, and cytolytic activity showed increased expression in the low-risk IE subtype, while genes implicated in the promotion of cancer growth and progression were more highly expressed in the high-risk OE subtype. In multivariate analysis, the subtypes demonstrated independent prediction power for post-treatment survival.ConclusionsOur findings suggest a greater role for the immune system in AMN than previously recognized. AMN subtypes may have clinical utility for predicting CRS/HIPEC treatment outcomes.
| S-EPMC7147286 | biostudies-literature
Project description:BackgroundLow-grade appendiceal mucinous neoplasm (LAMN) with peritoneal involvement is a common indication for cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC). With peritoneal recurrence, patients are increasingly being offered repeat CRS/HIPECs, however optimal timing for a second CRS/HIPEC remains unknown.MethodsA prospectively maintained 30-year database at our high-volume HIPEC center was analyzed retrospectively for patients with LAMNs and peritoneal recurrence receiving one or two CRS/HIPECs. Kaplan-Meier survival analysis, linear regression modeling, and Cox proportional hazards regression analyses were performed.ResultsOverall, 143 patients with LAMNs who underwent CRS/HIPECs had confirmed postoperative peritoneal recurrence. Of these patients, 85 underwent one CRS/HIPEC and 58 underwent two CRS/HIPECs. The groups had significant differences in age, with younger patients more likely to undergo a second CRS/HIPEC (48.5 vs. 58.0 years; p < 0.001). The median overall survival (OS) for the group undergoing two CRS/HIPECs was approximately four times longer compared with the group undergoing one CRS/HIPEC (227.1 vs. 54.5 months; p < 0.0001). The time from recurrence to the second CRS/HIPEC was not significantly associated with OS from the time of the first operation. Instead, a shorter time between the first CRS/HIPEC and recurrence was significantly associated with shorter OS from the time of the first operation (p = 0.037).ConclusionIn peritoneal LAMNs with recurrence, receiving two CRS/HIPECs was associated with better OS compared with receiving one CRS/HIPEC. Longer time to recurrence was a good prognostic factor. Delay between recurrence and second CRS/HIPEC had no apparent impact on OS from the first CRS/HIPEC; thus, immediate or delayed reoperative intervention are both reasonable approaches.
| S-EPMC10085001 | biostudies-literature
Project description:Introduction The prevalence of appendiceal mucinous neoplasms (AMN) is about 0.2%–0.3% in the specimens of the appendix. The LAMN may appear unremarkable or can present as mucin-filled, crystally dilated tissues. The diagnosis of early-stage AMN is mostly incidental. It is of vital importance to know the features of LAMN for a timely diagnosis Case presentation A 46-year-old male came with the complaint of right iliac fossa swelling along with severe intensity pain and a single episode of vomiting. A 4 × 4cm tender, soft, cystic, mobile swelling was found upon the examination. Contrast-enhanced Computerized tomography (CT) scan of the abdomen revealed the appendix diameter of 10mm well-circumscribed cystic measuring 2.1 × 2 cm. Therefore, an open resection surgery was performed. The histopathological report revealed an intraepithelial lesion composed of flat mucinous epithelial cells having eosinophilic cytoplasm and low-grade nuclear atypia. Case discussion The AMNs are very rare neoplasms. The imaging modalities that can be diagnostic methods are abdominal and transvaginal ultrasonography (US), and abdominal computed tomography (CT). The low-grade features of the appendiceal mucinous neoplasms have the possibility of recurrence. The CT-scan findings of appendiceal lump>1.3cm along with cystic dilation and the calcification of the wall are the suggestive features of AMN. There is a high chance of dissemination and port site seeding in case of pneumoperitoneum. Conclusion This rare case suggests the significance of adding AMNs as a differential diagnosis in patients with abdominal pain and choosing the right approach to treat such patients to avoid complications. Highlights • The incidence of low-grade appendiceal mucinous neoplasms (LAMN) is quite low.• The diagnosis of the LAMN is incidental and should be included in the differentials for abdominal pain.• There should be proper examination along with appropriate investigations for patients presenting with abdominal pain.• The timely diagnosis and the appropriate management allow better outcomes.• Laparoscopy is preferred as compared to open resection.
| S-EPMC9793229 | biostudies-literature
Project description: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.
2024-05-01 | GSE266352 | GEO
Project description: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.
| S-EPMC10014681 | biostudies-literature
Project description:BackgroundNon-operative management has been suggested as a therapy for uncomplicated appendicitis. Notwithstanding, the risk of missing an appendiceal tumor must be considered, being the surgical piece crucial to rule out neoplasms. Therefore, we aim to determine the incidence of appendiceal neoplasms in patients with acute appendicitis, tumor types and the importance of the anatomopathological study of the surgical piece.Study designRetrospective study in which we described patients who underwent emergent appendectomy with histopathological findings of appendiceal neoplasms from January 2012 to September 2018. Descriptive analysis included demographic variables, diagnostic methods, and surgical techniques.Results2993 patients diagnosed with acute appendicitis who underwent an emergency appendectomy. 64 neoplasms of the appendix were found with an incidence of 2,14%. 67.2% were women, the mean age was 46,4 years (± 19.5). The most frequent appendiceal neoplasms were neuroendocrine tumors (42,2%), followed by appendiceal mucinous neoplasms (35,9%), sessile serrated adenomas (18,8%), and adenocarcinomas (3,1%). In 89,1% of the cases, acute appendicitis was determined by imaging, and 14% of cases were suspected intraoperatively. Appendectomy was performed in 78,1% without additional procedures.ConclusionsAppendiceal tumors are rare and must be ruled out in patients with suspected acute appendicitis. The incidence of incidental neoplasms is higher in this study than in the previously reported series. This information must be included in decision-making when considering treatment options for acute appendicitis.
| S-EPMC10512515 | biostudies-literature
Project description:Aim:Appendiceal mucinous neoplasms are rare, and thus the literature is sparse with regard to histological types, staging, and prognosis. In particular, it is unclear how long-term outcome may differ between mucinous adenocarcinomas and other adenocarcinomas. In the present study, we aimed to investigate the histological types and stages of appendiceal neoplasms, and to evaluate the prognostic impacts of these factors in patients with mucinous adenocarcinomas and non-mucinous adenocarcinomas. Methods:Patients with appendiceal tumors diagnosed between 2007 and 2016 were retrospectively identified from the databases of 19 institutions in the Clinical Study Group of Osaka University, Colorectal Group. Results:A total of 266 patients with appendiceal tumors were identified, of whom 130 had pathologically diagnosed adenocarcinomas, including 57 with mucinous adenocarcinomas and 73 with non-mucinous adenocarcinomas. Five-year overall survival (OS) rates were 64.5% for mucinous adenocarcinomas, and 49.0% for non-mucinous adenocarcinomas. OS was significantly shorter among patients with non-mucinous adenocarcinomas compared to mucinous adenocarcinomas. Among patients with mucinous adenocarcinomas, 5-year OS rates were 53.6% for stage 0/I, 82.6% for II/III, and 48.4% for IV. Among patients with non-mucinous adenocarcinomas, 5-year OS rates were 90.9% for stage 0/I, 68.8% for II/III, and 7.1% for IV. Analysis of patients with stage IV disease revealed significantly shorter OS among patients with non-mucinous adenocarcinomas compared to mucinous adenocarcinomas. Conclusion:Our present findings showed a better prognosis in patients with mucinous adenocarcinomas compared to non-mucinous adenocarcinomas. In this setting, Union for International Cancer Control staging was associated with prognosis for non-mucinous adenocarcinomas, but not for mucinous adenocarcinomas.
| S-EPMC6524118 | biostudies-literature