Molecular and clinicopathological features of appendiceal mucinous neoplasms

Yanai, Yuka; Saito, Tsuyoshi; Hayashi, Takuo; Akazawa, Yoichi; Yatagai, Noboru; Tsuyama, Sho; Tomita, Shigeki; Hirai, Shu; Ogura, K.; Matsumoto, Takeshi; Wada, Ryo; Yao, Takashi

doi:10.1007/s00428-020-02906-5

Cited by 17 publications

(18 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some studies have shown that the pathway differs in appendiceal lesions in that the KRAS mutation is present but the BRAF mutation is less commonly found ( 7 ). Interestingly, several studies have revealed that the LAMNs are more likely to be associated with high-frequency mutation of KRAS ( 13 – 15 ). In the present study, we found four incidental LAMNs with a background of serrated lesions.…”

Section: Discussionmentioning

confidence: 99%

Significance of the Entire Appendiceal Evaluation in the Diagnosis of Serrated Lesions, Low-Grade Appendiceal Mucinous Neoplasm, and Appendiceal Diverticulosis Disease

Fang

Hou

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

ObjectiveThis study was conducted in order to investigate the significance of the entire appendiceal evaluation in the pathological diagnosis of appendiceal serrated lesions, low-grade appendiceal mucinous neoplasm (LAMN), and appendiceal diverticulosis disease (ADD).MethodsA total of 702 appendectomy specimens diagnosed from 2017 to 2020 were reviewed retrospectively. The specimens were divided into two groups according to the different sampling procedures. In group 1, the vast majority of 337 specimens were partially submitted by routine sampling within 18 months from October 2017 to March 2019. In group 2, 365 of specimens were entirely submitted and examined within 18 months from April 2019 to October 2020. The incidence and pathological features of serrated lesions, LAMN, and ADD in the two groups were compared and analyzed. The clinicopathological characteristics between different entities were also studied.ResultsForty appendiceal serrated lesions, 8 LAMNs, and 21 diverticula were accidentally detected in 702 appendectomy specimens. As compared with group 1, the incidence of appendiceal serrated lesions in group 2 was significantly increased (9.3% vs. 1.8%, P < 0.01), especially for the serrated lesions without dysplasia (7.4% vs. 1.2%, P < 0.01). The entire sampling revealed that loss of lamina propria and replacement with dysplastic mucinous epithelium were statistically significantly associated with LAMN rather than serrated lesions and ADD (P < 0.01 and P < 0.01, respectively). Mural mucin deposition and fibrosis were useful features to distinguish LAMN from simple serrated lesions (P < 0.01 and P < 0.05, respectively), but mucin deposition was useless for the distinction between LAMN and ADD (P > 0.05) or serrated lesions combined with ADD.ConclusionOur study highlights the importance and necessity of careful gross assessment and histologic examination of the entire appendectomy specimen, since the association with unexpected appendiceal lesions is significant and cannot be ignored. The entirely submitted appendix is more sensitive for the detection of appendiceal serrated lesions. In addition, thorough examination and evaluation are essential to distinguish the key pathological features between appendiceal serrated lesions, LAMN, and ADD.

show abstract

Section: Discussionmentioning

confidence: 99%

Significance of the Entire Appendiceal Evaluation in the Diagnosis of Serrated Lesions, Low-Grade Appendiceal Mucinous Neoplasm, and Appendiceal Diverticulosis Disease

Fang

Hou

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…According to cytology, AMN is classified into low-grade and high-grade by the WHO Classification of Tumors of the Digestive System (2019), which is defined as a tumor with appendiceal mucinous epithelial hyperplasia, accompanied by extracellular mucus and “pushing” tumor border ( 6 ). Some studies demonstrated that KRAS and GNAS gene mutations occurred in LAMN ( 22 , 23 ), and patients with high-grade AMN manifested mutations of KRAS and GNAS, along with TP53, as well as ATM ( 24 ). The pathogenesis needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Characteristics of Primary Appendiceal Mucinous Neoplasm and Recurrence After Radical Resection

et al. 2022

View full text Add to dashboard Cite

ObjectiveAppendiceal mucinous neoplasm (AMN) is a rare obstructive dilatation of the appendix caused by an intraluminal accumulation of mucoid material, showing an insidious onset and few specific clinical manifestations. The purpose of the study is to analyze clinicopathological characteristics of primary AMN and recurrence after radical resection.MethodsA total of 50 patients were included in the retrospective cohort study of AMN. Patient data, such as demographics, tumor characteristics, surgical management, preoperative serum carcinoembryonic antigen (CEA), and carcinoembryonic antigen 19-9 (CA19-9) levels, were collected. All patients were followed-up with interval CT scans until the end of December 2021, with overall survival (OS) and progression-free survival (PFS) being calculated.ResultsAll patients were confirmed as AMN by pathological diagnosis after surgery, including 28 cases (56.00%) of low-grade AMN (LAMN) and 22 cases (44.00%) of non-LAMN. Among 50 patients with AMN, there were 12 cases (24.00%) complicated with pseudomyxoma peritonei (PMP). Higher proportions of patients with pTis, pT3, pT4a, ruptured at presentation, and PMP were found in patients with non-LAMN patients than LAMN (p < 0.05). There was a remarkable difference about preoperative serum CA19-9 levels between patients with LAMN and non-LAMN (p = 0.044). Patients complicated with PMP had a higher proportion of patients with ruptured at presentation than those who were not (p < 0.001). The patients with PMP had increased tumor size compared with those without PMP (p = 0.031). Remarkable differences were observed in terms of preoperative serum CA19-9 (p = 0.009) levels between patients with PMP and without PMP. We performed a multivariate analysis of the presence or absence of PMP and found that ruptured at presentation was found to be a risk factor for PMP in patients with AMN (p = 0.003). The PFS in the patients with PMP and those without was 33.33% (4/12) and 2.63% (1/38), showing a significant difference (P = 0.002).ConclusionThe study demonstrates that ruptured at presentation and PMP may influence the prognosis and survival of patients with AMN.

show abstract

“…Several studies (Valasek and Pai 2018;Nummela et al 2015) have identified abnormal TP53 expression in a significant fraction (30%) of high-grade mucinous adenocarcinoma. Considering that only 7% of low-grade tumours show this characteristic, TP53 status appears to be the only marker associated with the acquisition of an aggressive phenotype in tumours with PMP.…”

Section: Discussionmentioning

confidence: 99%

“…KRAS mutations (preferentially observed in exon 2) seem to have a pivotal role in the development of appendiceal mucinous neoplasms (Kabbani et al 2002 ; Borazanci et al 2017 ). KRAS is mutated in 41–100% of appendiceal mucinous adenomas (Szych et al 1999 ; Zauber et al 2011 ; Yantiss et al 2007 ; Tsai et al 2019 ; Liao et al 2020 ; Yanai et al 2020 ). Pai et al ( 2014 ) analysed a series of 132 appendiceal lesions, revealing that serrated lesions of the appendix often harbour KRAS mutations and only infrequently display BRAF mutations.…”

Section: Discussionmentioning

confidence: 99%

“…This seem to be in agreement with previously published data, since alterations of RNF43 affect both up-stream (Koo et al 2012 ) and down-stream (Loregger et al 2015 ) activation of Frizzled and consequently of Wnt/beta-catenin pathway (Borowsky et al 2018 ; Hao et al 2016 ). Yanai and colleagues (Yanai et al 2020 ) recently suggested RNF43 mutations may occur at a later stage of mucinous adenocarcinoma development and may not be associated with PMP. The significance of RNF43 mutation in appendiceal tumours has not been clarified yet, but its role has been better characterized in IPMN (Lee et al 2016 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular profiling of appendiceal serrated lesions, polyps and mucinous neoplasms: a single-centre experience

Munari

Businello

Mattiolo

et al. 2021

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Purpose Non-neuroendocrine neoplasms of the appendix are a phenotypically heterogeneous group of lesions; a comprehensive molecular characterization of these tumors is still lacking. Methods A total of 52 samples taken from 49 patients was evaluated: 18 sessile serrated lesions (SSL; 3 with dysplasia), 2 high-grade tubular adenomas, 1 tubulo-villous adenoma,1 hyperplastic polyp, 18 low-grade appendiceal mucinous neoplasms (LAMN), 3 high-grade appendiceal mucinous neoplasms (HAMN) and 9 mucinous adenocarcinomas. Hotspot mutational profiling of the RNF43, SMAD4, KRAS, NRAS, BRAF and PIK3CA genes was performed. Expression of p53, MLH1, PMS2, MSH2, and MSH6 was evaluated by immunohistochemistry. Results KRAS was the most frequently mutated gene (53.9% of cases), followed by RNF43 (15.4%), and BRAF (13.5%). In particular: KRAS was mutated in 44.4% of adenocarcinomas, 66.7% of HAMNs, 61.1% of LAMNs, 53.3% of SSL without dysplasia and in 66.7% of SSL with dysplasia; RNF43 was mutated in 33.3% of adenocarcinomas, 66.7% of HAMNs, 11.1% of LAMNs and in 6.7% of SSL without dysplasia; BRAF was mutated in 11.1% of adenocarcinomas, 26.7% of SSL without dysplasia and in 5.6% of LAMNs. Only a case of high-grade tubular adenoma showed mismatch repair deficiency, while immunohistochemical expression of p53 was altered in 21.1% of cases. Conclusions The histological phenotypic similarities between appendicular mucinous lesions and serrated colon lesions do not reflect a similar genetic landscape. Mismatch repair deficiency is a rare event during appendiceal mucinous carcinogenesis.

show abstract

Molecular and clinicopathological features of appendiceal mucinous neoplasms

Cited by 17 publications

References 33 publications

Significance of the Entire Appendiceal Evaluation in the Diagnosis of Serrated Lesions, Low-Grade Appendiceal Mucinous Neoplasm, and Appendiceal Diverticulosis Disease

Significance of the Entire Appendiceal Evaluation in the Diagnosis of Serrated Lesions, Low-Grade Appendiceal Mucinous Neoplasm, and Appendiceal Diverticulosis Disease

Clinicopathological Characteristics of Primary Appendiceal Mucinous Neoplasm and Recurrence After Radical Resection

Molecular profiling of appendiceal serrated lesions, polyps and mucinous neoplasms: a single-centre experience

Contact Info

Product

Resources

About