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Archives of Pathology & Laboratory... Nov 2010The appendix gives rise to an array of epithelial neoplasms showing glandular or neuroendocrine differentiation, and some tumors with elements of both cell types.... (Review)
Review
CONTEXT
The appendix gives rise to an array of epithelial neoplasms showing glandular or neuroendocrine differentiation, and some tumors with elements of both cell types. Although some appendiceal neoplasms resemble their counterparts in the small and large intestines (conventional adenocarcinoma and carcinoid tumor), the appendix also gives rise to relatively unique entities including mucinous neoplasms and goblet cell carcinoid tumors, which present a challenge in pathologic classification and clinical management.
OBJECTIVE
To review clinical and diagnostic issues for 3 pathologic types of epithelial neoplasms of the appendix: (1) adenocarcinoma, with specific focus on mucinous neoplasm; (2) goblet cell carcinoid tumor and associated adenocarcinoma; and (3) typical carcinoid tumor.
DATA SOURCES
Case-derived material and literature review.
CONCLUSIONS
The most important issue in pathologic assessment of epithelial tumors of the appendix is to understand the clinical implications inherent in the diagnosis.
Topics: Adenocarcinoma; Appendiceal Neoplasms; Appendix; Carcinoid Tumor; Humans
PubMed: 21043814
DOI: 10.5858/2010-0073-CCR.1 -
Cells Jul 2023Appendiceal cancers (AC) are a rare and heterogeneous group of malignancies. Historically, appendiceal neoplasms have been grouped with colorectal cancers (CRC), and... (Review)
Review
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.
Topics: Humans; Appendiceal Neoplasms; Incidence
PubMed: 37566041
DOI: 10.3390/cells12151962 -
Indian Journal of Cancer 2023Neoplastic lesions of the vermiform appendix are still considered to be rare, some studies suggest that appendix cancer may be on the rise, with an estimated incidence...
BACKGROUND
Neoplastic lesions of the vermiform appendix are still considered to be rare, some studies suggest that appendix cancer may be on the rise, with an estimated incidence of 0.08-0.1% of all appendiceal specimens. The lifetime incidence of malignant appendiceal tumors ranges from 0.2 to 0.5%.
PATIENTS AND METHODS
Our study is applied at the Department of General Surgery at tertiary training and research hospital; 14 patients who had appendectomy or right hemicolectomy between December 2015 and April 2020 were evaluated.
RESULTS
The mean age of the patients was 52.3 ± 15.1 (range, 26-79) years. Gender of the patients were: five (35.7%) men and nine (64.3%) women. The clinical diagnosis was appendicitis without suspected findings in 11 (78.6%), appendicitis with suspected findings (appendiceal mass, etc.) in three (21.4%) of the patients, and there is no patient with asymptomatic or other rare findings. Surgeries applied for the patients were: nine (64.3%) underwent open appendectomy, four (28.6%) underwent laparoscopic appendectomy, and one (7.1%) underwent open right hemicolectomy. Histopathologic results were as follows: five (35.7%) neuroendocrine neoplasm, eight (57.1%), noninvasive mucinous neoplasm, and one (7.1%) adenocarcinoma.
CONCLUSION
While diagnosis and management of appendiceal pathology, surgeons should be familiar with suspected findings of appendiceal tumors and discuss them with patients to the possibility of histopathologic results.
Topics: Male; Humans; Female; Adult; Middle Aged; Aged; Appendiceal Neoplasms; Appendicitis; Appendix; Appendectomy; Adenocarcinoma; Retrospective Studies
PubMed: 36861689
DOI: 10.4103/ijc.IJC_1121_20 -
Indian Journal of Pathology &... 2022Low-grade appendiceal mucinous neoplasms (LAMN) of the appendix have bland cytological features and well-differentiated morphology. Despite this, they may cause a...
BACKGROUND
Low-grade appendiceal mucinous neoplasms (LAMN) of the appendix have bland cytological features and well-differentiated morphology. Despite this, they may cause a pseudomyxoma peritonei (PMP) disease characterized by mucinous deposits in the peritoneal cavity and may exhibit malignant behavior.
AIMS AND OBJECTIVES
In this study, we evaluated the clinical course and histopathological findings of LAMN. The rate of progression to PMP, factors affecting its development, and the clinical course of cases with PMP were investigated.
MATERIALS AND METHODS
Twelve thousand and forty-seven cases who underwent appendectomy were reviewed, and 71 mucinous lesions cases whose slides are in our archive were included in the study. Histopathological findings were re-evaluated. Morphological findings that guide the differential diagnosis, the clinical course of the patients, and factors affecting PMP development were determined.
RESULTS
The cases were divided into group 1 non-neoplastic (9.9%), group 2 benign (18.3%), group 3 LAMN (60.6), and group 4 malignant neoplasms (11.3%). Age, gender, appendix diameter, gross appearance, epithelial characteristics, and presence of microcalcification were significantly different between the patient groups. The presence of mucin in the ileocecal region was found to be significant in the development of PMP. It was observed that the additional procedure performed after the appendectomy did not prevent a recurrence.
CONCLUSION
LAMNs are lesions with characteristic findings and different behaviors. The only method to distinguish from the lesions included in the differential diagnosis is to interpret the histopathological findings correctly. Additional operations after appendectomy do not contribute to preventing recurrence.
Topics: Appendiceal Neoplasms; Diagnosis, Differential; Humans; Neoplasms, Glandular and Epithelial; Peritoneal Neoplasms; Prognosis; Pseudomyxoma Peritonei
PubMed: 35900483
DOI: 10.4103/ijpm.ijpm_827_21 -
Evaluation of appendiceal mucinous neoplasms with a new classification system and literature review.The Turkish Journal of Gastroenterology... Sep 2018Appendiceal mucinous neoplasms constitute a diagnostic spectrum ranging from adenoma to mucinous adenocarcinoma. To date, many classification systems have been proposed... (Review)
Review
Appendiceal mucinous neoplasms constitute a diagnostic spectrum ranging from adenoma to mucinous adenocarcinoma. To date, many classification systems have been proposed to reflect the histomorphological diversity of neoplasms in this range and their clinical correspondence, and also to form a common terminology between the pathologist and clinicians. The aim of this review is to provide an updated perspective on the pathological features of appendiceal mucinous neoplasms. Using the 2016 Modified Delphi Consensus Protocol (Delphi) and the Eighth Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 19 cases presented from June 2011 to December 2016 were evaluated and diagnosed with appendiceal mucinous neoplasia. According to the Delphi, non-carcinoid epithelial tumours of the appendix were categorized in eight histomorphological architectural groups. These groups are adenoma, serrated polyp, low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm, mucinous adenocarcinoma, poorly-differentiated adenocarcinoma with signet-ring, signet-ring cell carcinoma and adenocarcinoma. The most common symptom was right lower quadrant pain. The median age of these cases was 60±15 years. There was a preponderance of females (F/M: 15/4). In our re-evaluation, six cases were diagnosed as serrated polyp. There were 11 cases in the LAMN group and two cases in the mucinous adenocarcinoma group. Using the Delphi and the AJCC manual, there were many changes in the classification, evaluation and treatment of appendiceal mucinous neoplasms. These classification systems have facilitated the compatibility and communication of clinicians and pathologists and have guided clinicians on treatment methods.
Topics: Aged; Appendiceal Neoplasms; Clinical Protocols; Consensus; Delphi Technique; Female; Humans; Male; Middle Aged; Neoplasm Staging; Neoplasms, Cystic, Mucinous, and Serous
PubMed: 30260774
DOI: 10.5152/tjg.2018.17605 -
Molecular Cancer Therapeutics Dec 2020Goblet cell carcinoid (GCC) is a distinct subtype of appendiceal neoplasm that exhibits unique clinical and pathologic features. We aimed to reveal the molecular...
Goblet cell carcinoid (GCC) is a distinct subtype of appendiceal neoplasm that exhibits unique clinical and pathologic features. We aimed to reveal the molecular profiles of GCC compared with other appendiceal tumors, such as adenocarcinomas and neuroendocrine tumors. A total of 495 appendiceal tumor samples (53 GCCs, 428 adenocarcinomas, and 14 neuroendocrine tumors) were tested with next-generation sequencing (NGS) on a 592-gene panel and IHC. Microsatellite instability (MSI)/mismatch repair (MMR) status was tested with a combination of NGS, IHC, and fragment analyses. Tumor mutational burden (TMB) was evaluated by NGS, and PD-L1 expression was tested by IHC (SP142). The most prevalent mutated genes within GCCs were (24.0%), (15.4%), (9.4%), and (7.5%). Pathway-specific alterations were dominantly observed in cell cycle, MAPK, epigenetic, and TGFβ signaling pathways. GCCs as compared with adenocarcinomas exhibited significantly lower mutation rates in , and , and significantly higher mutation rates in , and GCCs as compared with neuroendocrine tumors showed significantly lower mutation rates in , and In GCCs, MSI high/MMR deficient, TMB high (≥17 mutations/Mb), and PD-L1 expression were seen in 0.0%, 0.0%, and 2.0% of tumors, respectively. No significant differences were observed in any immunotherapy-related markers examined when compared with adenocarcinomas and neuroendocrine tumors. In conclusion, GCCs had considerably distinct mutational profiles compared with appendiceal adenocarcinomas and neuroendocrine tumors. Understanding these molecular characteristics may be critical for the development of novel and more effective treatment strategies for GCC.
Topics: Adult; Aged; Alleles; Appendiceal Neoplasms; Biomarkers, Tumor; Carcinoid Tumor; Disease Susceptibility; Female; Gene Expression Profiling; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Male; Middle Aged; Mutation; Mutation Rate; Neuroendocrine Tumors
PubMed: 33037134
DOI: 10.1158/1535-7163.MCT-20-0318 -
Archives of Pathology & Laboratory... Jun 2010Low grade appendiceal mucinous neoplasms can spread to the peritoneum as pseudomyxoma peritonei even though they are not obviously invasive in the appendix. During the... (Review)
Review
Low grade appendiceal mucinous neoplasms can spread to the peritoneum as pseudomyxoma peritonei even though they are not obviously invasive in the appendix. During the past several decades, several problematic issues surrounding this enigmatic tumor have been debated in the literature, including appropriate nomenclature for the appendiceal tumors and their peritoneal metastases. In this article, the most contentious issues in the area of appendiceal mucinous tumors are examined. First, the classification systems that have been proposed for these tumors are compared in the context of whether the appendiceal mucinous tumors are ruptured adenomas or invasive carcinomas. The controversy about the nature of pseudomyxoma peritonei and its classification systems is discussed in the following section. A brief discussion follows that examines the issue of localized pseudomyxoma peritonei and its clinical significance. Next reviewed is the largely resolved controversy about whether ovarian mucinous tumors in this setting are separate primaries or are metastases from the appendiceal tumor. Finally, the controversy about the most effective treatment of patients with pseudomyxoma peritonei is discussed.
Topics: Adenocarcinoma, Mucinous; Appendiceal Neoplasms; Diagnosis, Differential; Female; Humans; Ovarian Neoplasms; Peritoneal Neoplasms; Pseudomyxoma Peritonei
PubMed: 20524864
DOI: 10.5858/134.6.864 -
Archives of Pathology & Laboratory... Dec 2022High-grade appendiceal mucinous neoplasm (HAMN) is a relatively recently introduced term describing a rare epithelial neoplasm of the appendix that demonstrates...
CONTEXT.—
High-grade appendiceal mucinous neoplasm (HAMN) is a relatively recently introduced term describing a rare epithelial neoplasm of the appendix that demonstrates pushing-type invasion but high-grade cytologic atypia. It remains understudied.
OBJECTIVE.—
To describe clinicopathologic features of HAMNs.
DESIGN.—
We identified 35 HAMNs in a multi-institutional retrospective study. Clinical and histologic features were reviewed in all cases, as well as molecular features in 8 cases.
RESULTS.—
Patients were 57 years of age on average and most commonly presented with abdominal/pelvic pain. Histologically, 57% of the tumors showed widespread high-grade features. Architectural patterns in high-grade areas included flat, undulating, or villous growth, and occasionally micropapillary, cribriform, or multilayered growth. Thirteen cases had intact serosa, and the remaining 22 perforated the serosa, including 7 with peritoneal acellular mucin beyond appendiceal serosa and 10 with grade 2 pseudomyxoma peritonei. Molecular abnormalities included KRAS mutations in 7 cases and TP53 mutations in 4. No tumor confined to the appendix recurred. Two patients without pseudomyxoma peritonei at initial presentation developed pseudomyxoma on follow-up. Among 11 patients who presented with pseudomyxoma peritonei, 5 died of disease and 3 were alive with disease at last follow-up.
CONCLUSIONS.—
HAMNs have a similar presentation to low-grade appendiceal mucinous neoplasm, and similar stage-based prognosis. When they spread to the peritoneum, they typically produce grade 2 pseudomyxoma peritonei, which may be associated with a worse prognosis than classical grade 1 pseudomyxoma peritonei.
Topics: Humans; Pseudomyxoma Peritonei; Retrospective Studies; Peritoneal Neoplasms; Neoplasm Recurrence, Local; Appendiceal Neoplasms
PubMed: 35472721
DOI: 10.5858/arpa.2021-0430-OA -
Modern Pathology : An Official Journal... May 2020Post-inflammatory mucosal hyperplasia and appendiceal diverticulosis simulate mucinous neoplasms, causing diagnostic confusion. Distinction between neoplasia and its...
Post-inflammatory mucosal hyperplasia and appendiceal diverticulosis simulate mucinous neoplasms, causing diagnostic confusion. Distinction between neoplasia and its mimics is particularly important since many authorities now consider all appendiceal mucinous neoplasms to be potentially malignant. The purpose of this study was to identify clinicopathologic and molecular features that may distinguish appendiceal mucinous neoplasms from non-neoplastic mimics. We retrospectively identified 92 mucinous lesions confined to the right lower quadrant, including 55 non-neoplastic examples of mucosal hyperplasia and/or diverticulosis and 37 low-grade neoplasms. Presenting symptoms, radiographic findings, appendiceal diameter, appearances of the lamina propria, non-neoplastic crypts, and epithelium, as well as mural changes were recorded. Twenty non-neoplastic lesions were subjected to KRAS mutational testing. Non-neoplastic appendices were smaller (p < 0.05) and more likely to present with symptoms of appendicitis (p < 0.05) than neoplasms. While post-inflammatory mucosal hyperplasia and diverticula often showed goblet cell-rich epithelium, extruded mucin pools, and patchy mural alterations with fibrosis, they always contained non-neoplastic crypts lined by mixed epithelial cell types and separated by lamina propria with predominantly preserved wall architecture. On the other hand, mucinous neoplasms lacked normal crypts (p < 0.05) and showed decreased lamina propria (p < 0.05) with diffusely thickened muscularis mucosae and lymphoid atrophy. Six (30%) non-neoplastic lesions contained KRAS mutations, particularly those containing goblet cell-rich hyperplastic epithelium. We conclude that distinction between neoplastic and non-neoplastic mucinous appendiceal lesions requires recognition of key morphologic features; KRAS mutational testing is an unreliable biomarker that cannot be used to assess biologic risk or confirm a diagnosis of neoplasia.
Topics: Adenocarcinoma, Mucinous; Adult; Aged; Appendiceal Neoplasms; Appendicitis; Appendix; Cecal Diseases; Diagnosis, Differential; Diverticulum; Female; Humans; Hyperplasia; Male; Middle Aged; Retrospective Studies
PubMed: 31857681
DOI: 10.1038/s41379-019-0435-1 -
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