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Surgical Pathology Clinics Jun 2022This review provides an overview of the pathology of selected benign and malignant lesions of the female peritoneum and their often-encountered differential diagnoses.... (Review)
Review
This review provides an overview of the pathology of selected benign and malignant lesions of the female peritoneum and their often-encountered differential diagnoses. It includes endometriosis and its related lesions, endosalpingiosis, pseudomyxoma peritonei (PMP) and related ovarian/appendiceal pathology, and malignant and benign mesothelial tumors. The current terminology associated with PMP is also discussed.
Topics: Appendiceal Neoplasms; Female; Humans; Ovarian Neoplasms; Peritoneal Neoplasms; Peritoneum; Pseudomyxoma Peritonei
PubMed: 35715161
DOI: 10.1016/j.path.2022.02.005 -
European Journal of Surgical Oncology :... Jul 2022The metastasizing potential of pseudomyxoma peritonei (PMP) is largely unknown. We assessed incidence, impact on prognosis, treatments, and outcomes of systemic...
BACKGROUND
The metastasizing potential of pseudomyxoma peritonei (PMP) is largely unknown. We assessed incidence, impact on prognosis, treatments, and outcomes of systemic metastases after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).
METHODS
A prospective database of 327 patients undergoing CRS/HIPEC for PMP of appendiceal origin was reviewed. PMP was graded according to the Peritoneal Surface Oncology Group International (PSOGI) classification. Haematogenous metastases, and non-regional lymph-node involvement were considered as systemic metastases.
RESULTS
After a median follow-up of 74.8 months (95% confidence interval [CI] = 68.0-94.8), systemic metastases occurred in 21 patients. Eleven patients were affected by low-grade PMP, and ten by high-grade PMP. Metastatic disease involved the lung (n = 12), bone (n = 1), liver (n = 4), distant nodes (n = 3), both lung and distant nodes (n = 1). Systemic metastases independently correlated with PSOGI histological subtypes (P = 0.001), and incomplete cytoreduction (P = 0.026). Median OS was 139.0 months (95%CI = 56.6-161.9) for patients who experienced systemic metastases, and 213.8 months (95%CI = 148.7-not reached) for those who did not (P = 0.159). Eight of eleven patients who had curative-intent surgery are presently alive at a median of 52.5 months (range 2.0-112.7). Seven are disease-free at a median of 27.4 months (range 2.0-110.4). At multivariate analysis, PSOGI histological subtypes (P = 0.001), completeness of cytoreduction (P = 0.001), and preoperative systemic chemotherapy (P = 0.020) correlated with poorer survival. Systemic metastases did not (P = 0.861).
CONCLUSIONS
After CRS/HIPEC, systemic metastases occur in a small but clinically relevant number of patients, and the risk increases with incomplete cytoreduction and aggressive histology. In selected patients, surgical resection of metastatic disease can result in long survival.
Topics: Appendiceal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Humans; Hyperthermia, Induced; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Retrospective Studies; Survival Rate
PubMed: 35090796
DOI: 10.1016/j.ejso.2022.01.010 -
Journal of Cancer Research and Clinical... Sep 2020Pseudomyxoma peritonei (PMP) is a rare clinical malignancy syndrome characterized by the uncontrollable accumulation of copious mucinous ascites in the peritoneal... (Review)
Review
PURPOSE
Pseudomyxoma peritonei (PMP) is a rare clinical malignancy syndrome characterized by the uncontrollable accumulation of copious mucinous ascites in the peritoneal cavity, resulting in "jelly belly". The mechanism of tumor progression and mucin hypersecretion remains largely unknown, but GNAS mutation is a promising contributor. This review is to systemically summarize the biological background and variant features of GNAS, as well as the impacts of GNAS mutations on mucin expression, tumor cell proliferation, clinical-pathological characteristics, and prognosis of PMP.
METHODS
NCBI PubMed database (in English) and WAN FANG DATA (in Chinese) were used for literature search. And NCBI Gene and Protein databases, Ensembl Genome Browser, COSMIC, UniProt, and RCSB PDB database were used for gene and protein review.
RESULTS
GNAS encodes guanine nucleotide-binding protein α subunit (Gsα). The mutation sites of GNAS mutation in PMP are relatively stable, usually at Chr20: 57,484,420 (base pair: C-G) and Chr20: 57,484,421 (base pair: G-C). Typical GNAS mutation results in the reduction of GTP enzyme activity in Gsα, causing failure to hydrolyze GTP and release phosphoric acid, and eventually the continuous binding of GTP to Gsα. The activated Gsα could thus continuously promote mucin secretion through stimulating the cAMP-PKA signaling pathway, which is a possible mechanism leading to elevated mucin secretion in PMP.
CONCLUSION
GNAS mutation is one of the most important molecular biological features in PMP, with major functions to promote mucin hypersecretion.
Topics: Biomarkers, Tumor; Cell Proliferation; Chromogranins; GTP-Binding Protein alpha Subunits, Gs; Humans; Mucins; Mutation; Peritoneal Neoplasms; Prognosis; Pseudomyxoma Peritonei; Signal Transduction
PubMed: 32700107
DOI: 10.1007/s00432-020-03321-8 -
International Journal of Cancer Apr 2021Pseudomyxoma peritonei (PMP) is a rare disorder with unique pathological and genetic changes. Although several studies have reported the clinical features and mutational...
Pseudomyxoma peritonei (PMP) is a rare disorder with unique pathological and genetic changes. Although several studies have reported the clinical features and mutational changes of PMP that originates from the appendix, few studies on PMP originating from the ovary have been reported due to its extreme rarity. In order to characterize the somatic mutational landscape and to investigate the prognosis predicting factors of ovary-originating PMP, we examined 830 cases of PMP and identified 16 patients with PMP that originated from the ovary. Whole-exome sequencing (WES) was performed on 12 cases using formalin-fixed, paraffin-embedded (FFPE) tissue samples. We found that 25% (3/12) of the patients carried mutations in cancer driver genes, including TP53, ATM and SETD2, and 16.7% (2/12) of the patients carried mutations in cancer driver genes, including ATRX, EP300, FGFR2, KRAS, NOCR1 and RB1. The MUC16 (58.33%), BSN (41.67%), PCNT (41.67%), PPP2R5A (41.67%), PRSS36 (41.67%), PTPRK (41.67%) and SBF1 (41.67%) genes presented the highest mutational frequencies. The PI3K-Akt signaling pathway, human papillomavirus infection pathway, cell skeleton, cell adhesion, and extracellular matrix and membrane proteins were the major pathways or functions that were affected. Patients were followed up to 174 months (median: 48.26 months). The 5-year OS rate for all patients was 71.2% and the median OS was not reached. PTPRK mutations, presurgical CA199 level, completeness of cytoreduction (CCR) and peritoneal cancer index (PCI) were identified as potential predictive factors for patient survival. In conclusion, the mutational landscape for ovary-originating PMP was revealed and exhibited unique features distinct from appendix-originating PMP. PTPRK, CA199, CCR and PCI may predict patient survival.
Topics: Adult; Aged; Ataxia Telangiectasia Mutated Proteins; Female; Genetic Predisposition to Disease; Histone-Lysine N-Methyltransferase; Humans; Kaplan-Meier Estimate; Middle Aged; Mutation; Ovary; Peritoneal Neoplasms; Prognosis; Pseudomyxoma Peritonei; Retinoblastoma Binding Proteins; Retrospective Studies; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases; Exome Sequencing
PubMed: 33403690
DOI: 10.1002/ijc.33460 -
Current Oncology (Toronto, Ont.) May 2022Pseudomyxoma peritonei (PMP) is a rare clinical syndrome. It originates from neoplasms of the appendix and leads to the formation of peritoneal implants and the... (Review)
Review
Pseudomyxoma peritonei (PMP) is a rare clinical syndrome. It originates from neoplasms of the appendix and leads to the formation of peritoneal implants and the accumulation of mucinous ascites. PMP represents a spectrum of low to high-grade disease. Despite aggressive management, many PMP patients recur, leading to debilitating symptoms and few treatment options. Therefore, scientists have continued to look for ways to improve treatment and further understand disease pathogenesis. Microorganisms were previously hypothesized to play a role in PMP progression and development. Hence, antibacterial treatment was suggested by some authors, but the data were limited. In this paper, we review the current data on the role of bacteria in PMP, discuss the significance, and suggest possible solutions to the inherent challenges in these studies. Given the limitations of the discussed studies, we remain skeptical about introducing novel antibacterial treatment into clinical practice at this time; however, the available data are valuable and indicate that more research into the molecular mechanisms of PMP is needed.
Topics: Appendiceal Neoplasms; Appendix; Humans; Neoplasm Recurrence, Local; Peritoneal Neoplasms; Pseudomyxoma Peritonei
PubMed: 35621679
DOI: 10.3390/curroncol29050289 -
The American Journal of Surgical... Jan 2022Appendiceal mucinous neoplasms show a range of morphologic features and biological risk. At one end of the spectrum, high-grade adenocarcinomas are cytologically... (Review)
Review
Appendiceal mucinous neoplasms show a range of morphologic features and biological risk. At one end of the spectrum, high-grade adenocarcinomas are cytologically malignant with infiltrative invasion, lymph node metastases, and behavior similar to that of extra-appendiceal mucinous adenocarcinomas. At the other end, mucinous neoplasms confined to the mucosa are uniformly benign. Some cases lying between these extremes have potential risk to metastasize within the abdomen despite a lack of malignant histologic features. They show "diverticulum-like," pushing invasion of mostly low-grade epithelium through the appendix with, or without, concomitant organizing intra-abdominal mucin. The latter condition, widely termed "pseudomyxoma peritonei," tends to pursue a relentless course punctuated by multiple recurrences despite cytoreductive therapy, culminating in death for many patients. The combination of bland histologic features and protracted behavior of peritoneal disease has led some authors to question whether these metastatic tumors even represent malignancies. The World Health Organization and its cadre of experts widely promote usage of "low-grade appendiceal mucinous neoplasm" as an umbrella term to encompass benign and malignant conditions, as well as those that have uncertain biological potential. Although this practice greatly simplifies tumor classification, it causes confusion and consternation among pathologists, clinical colleagues, and patients. It also increases the likelihood that at least some patients will undergo unnecessary surveillance for, and treatment of, benign neoplasms and non-neoplastic conditions. The purpose of this review is to critically evaluate the relevant literature and discuss a practical approach to classifying appendiceal mucinous neoplasms that more closely approximates their biological risk.
Topics: Appendiceal Neoplasms; Appendix; Biomarkers, Tumor; Biopsy; Clinical Decision-Making; Humans; Neoplasm Grading; Neoplasms, Cystic, Mucinous, and Serous; Predictive Value of Tests; Pseudomyxoma Peritonei; Risk Assessment; Risk Factors
PubMed: 33417324
DOI: 10.1097/PAS.0000000000001662 -
International Journal of Dermatology Jul 2022
Topics: Female; Humans; Ovarian Neoplasms; Peritoneal Neoplasms; Pseudomyxoma Peritonei
PubMed: 34714931
DOI: 10.1111/ijd.15952 -
Journal of Cancer Research and... Jan 2024Pseudomyxoma peritonei (PMP) is an unusual clinical condition typically presenting with widespread mucinous neoplastic lesions within the peritoneum resulting in gelatin...
BACKGROUND
Pseudomyxoma peritonei (PMP) is an unusual clinical condition typically presenting with widespread mucinous neoplastic lesions within the peritoneum resulting in gelatin material-rich ascites. It was first described by Werth in 1884. Ever since, its clinical presentation, definition, site of origin, and prognosis have been a subject of debate. However, many histopathologic, immunohistochemical, and genetic studies have attempted to locate the primary lesion in the appendix in both genders.
OBJECTIVES
To analyze the histological origin and survival outcomes of pseudomyxoma peritonei in patients treated at a regional cancer center.
MATERIALS AND METHODS
Fifteen cases of PMP were diagnosed during the five-year study period. The demographic and clinicopathological details were retrieved; the slides were reviewed and histological parameters reassessed. Descriptive statistics were used to express proportions. Continuous variables were recorded as mean (SD) or median (IQR). Kaplan-Meier (KM) curve was used to estimate overall survival.
RESULTS
Mean age for PMP was found to be 47.5 years for low grade Mucinous Carcinoma Peritonei (MCP), 54.2 years for high grade MCP, and 58 years for high grade MCP with signet ring cells. Most common overall presentation was abdominal distension in 53.3% (8/15) of cases, followed by acute appendicitis in 20% (3/15) cases. PMP was detected synchronous with the primary tumor in 9/15 cases (60%). Primary lesion in the appendix was grossly identified in 7/15 cases, while it was not explored in the remaining eight cases. Yet, by combined clinical, radiological, histopathological, and immunohistochemical analysis, we identified that most of the cases (14/15) had an appendiceal origin (93.3%). The overall survival for 12 months was 50% and for 18 months was 37%.
CONCLUSION
The surgeon and radiologist may well bear in mind the most common possibility of an appendiceal origin for PMP and resect the appendix, irrespective of the presence of a grossly or radiologically detectable lesions. We emphasize that immunohistochemistry helped to detect the site of origin even when the primary was occult.
PubMed: 38261429
DOI: 10.4103/jcrt.jcrt_191_23 -
Frontiers in Oncology 2023Pseudomyxoma peritonei (PMP) is a rare malignant disease characterized by a massive multifocal accumulation of mucin within the peritoneal cavity. The current treatment...
INTRODUCTION
Pseudomyxoma peritonei (PMP) is a rare malignant disease characterized by a massive multifocal accumulation of mucin within the peritoneal cavity. The current treatment option is based on complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. However, the recurrence is frequent with subsequent progression and death. To date, most of the studies published in PMP are related to histological and genomic analyses. Thus, the need for further studies unveiling the underlying PMP molecular mechanisms is urgent. In this regard, hypoxia and oxidative stress have been extensively related to tumoral pathologies, although their contribution to PMP has not been elucidated.
METHODS
In this manuscript, we have evaluated, for the first time, the intratumoral real-time oxygen microtension (pO2mt) in the tumor (soft and hard mucin) and surrounding healthy tissue from five PMP patients during surgery. In addition, we measured hypoxia (Hypoxia Inducible Factor-1a; HIF-1α) and oxidative stress (catalase; CAT) markers in soft and hard mucin from the same five PMP patient samples and in five control samples.
RESULTS
The results showed low intratumoral oxygen levels, which were associated with increased HIF-1α protein levels, suggesting the presence of a hypoxic environment in these tumors. We also found a significant reduction in CAT activity levels in soft and hard mucin compared with healthy tissue samples.
DISCUSSION
In conclusion, our study provides the first evidence of low intratumoral oxygen levels in PMP patients associated with hypoxia and oxidative stress markers. However, further investigation is required to understand the potential role of oxidative stress in PMP in order to find new therapeutic strategies.
PubMed: 36776312
DOI: 10.3389/fonc.2023.1076500 -
Frontiers in Oncology 2021To describe the clinicopathological characteristics of mucinous ovarian cancer (MOC)-derived pseudomyxoma peritonei (PMP) and identify prognostic factors for survival.
OBJECTIVE
To describe the clinicopathological characteristics of mucinous ovarian cancer (MOC)-derived pseudomyxoma peritonei (PMP) and identify prognostic factors for survival.
METHODS
Medical records from patients with MOC-derived PMP who attended the Aerospace Center Hospital, Beijing, China between January 2009, and December 2019 were retrospectively reviewed. Survival analysis was performed with the Kaplan-Meier method, the log-rank test, and a Cox proportional hazards model.
RESULTS
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for PMP originating from MOC were performed on 22 patients, who had a median age of 52 years at the time of surgery. At the last follow-up in June 2020, 9 (41%) patients were still alive. Median OS was 12 months (range, 1 to 102 months), and the 2-, 3-, and 5-year survival rates were 23, 9, and 5%, respectively.
CONCLUSION
Histopathologic subtype and PCI may be applied as predictors of prognosis in patients with MOC-derived PMP. Patients with high-grade disease could benefit from completeness of cytoreduction (CCR) 0/1.
PubMed: 33968739
DOI: 10.3389/fonc.2021.641053