Unusual findings in 68 cases of appendiceal diverticulum: Accompanying neoplastic lesion should be kept in mind

Unusual findings in 68 cases of appendiceal diverticulum: Accompanying neoplastic lesion should be kept in mind | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Unusual findings in 68 cases of appendiceal diverticulum: Accompanying neoplastic lesion should be kept in mind Nese Ekinci, Eylul Gun This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2245915/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Congenital and acquired diverticula of the appendix are very rare and may be associated with a variety of lesions. In this study, we aimed to evaluate the cases of the appendiceal diverticulum (AD) in terms of histopathological features and accompanying neoplastic and non-neoplastic lesions. Methods: A retrospective analysis of the appendectomy specimens between January 2007 and June 2022 was performed. All of the cases with AD were reviewed and slides of all cases were re-examined by two pathologists, one of whom was highly experienced in gastrointestinal pathology. The cases were evaluated in terms of age, gender, histopathological features, accompanying neoplastic and non-neoplastic lesions, presence of periappendicular mucin, and misdiagnosis. Results: There were a total of 68 AD cases with 32 (47%) males and 36 (53%) females. The mean age was 54,1 years (24-93). Diverticulitis was seen in 44 cases (64,7%). In 28 (41,1%) cases ADs were accompanied by other lesions such as low-grade appendiceal mucinous neoplasm (LAMN, n=13), endometriosis (n=4), well-differentiated neuroendocrine tumor (n=3), sessile serrated adenoma (SSA, n=3), adenocarcinoma (n=2), LAMN and WD-NET (n=1), granular cell tumor (n=1), and hyperplastic polyp with inflammatory fibroid polyp (n=1). Periappendiceal acellular mucin deposition was seen in 23 (33,8%) cases with associated diverticulitis in 12 of them. In 7 of the 13 cases of LAMN there was mucin accumulation. AD was incidentally found in 15 appendectomies performed during other surgeries. Although defined macroscopically in 8 cases, the diagnosis of AD was missed during the microscopical examination. Conclusion: The probability of detecting a neoplastic lesion in cases with AD is quite high as proven in our study. Therefore, the entire appendix can be sampled in these cases. It is important to pay attention to macroscopic definitions in order not to miss a possible diverticulum in all cases with microscopic perforation and dense inflammation. The close association between LAMN and AD should be kept in mind. Appendix diverticulum diverticulosis appendiceal neoplasms Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Firstly described in the literature in 1893, appendiceal diverticulum (AD) is a rare lesion that is defined as the herniation or outpouching of the mucosa through the muscularis propria or vascular hiatus of low resistance in the wall of the appendix. If the intraluminal pressure increases as a result of a tumor, fecalith, or voluminous mucus deposition, obstruction of the lumen occurs which then causes the formation of the diverticula [ 1 ]. It may be congenital or acquired, and while reported incidence rates vary between appendectomy series and autopsy studies, it is reported to be 0,014 and 0,20% to approximately 2%, respectively [ 2 – 6 ]. Acquired AD is often asymptomatic but sometimes may produce symptoms if diverticulitis or perforation occurs. They may be associated with many conditions such as cystic fibrosis as well as with benign and malignant neoplasms including well-differentiated neuroendocrine tumors, low-grade mucinous neoplasm, and adenocarcinoma [ 6 – 8 ]. It is also reported to carry a higher risk of perforation than acute appendicitis due to the lack of muscularis propria [ 9 ]. The mucin accumulation caused by the perforation may sometimes mimic mucinous neoplasms [ 10 ]. Recent literature emphasizes that AD may be considered as a marker of local and regional neoplasms, therefore thorough histopathological examination carries great importance [ 11 – 12 ]. AD usually goes unnoticed in clinical practice and may sometimes be overlooked in the macroscopical examination. Pathological examination is essential in defining the diverticular disease of the appendix as it is hard to distinguish from acute appendicitis both clinically and radiologically. Therefore, the primary objective of this study is to assess the pathological findings of AD and particularly highlight its coexistence not only with organ-specific neoplastic lesions but also with regional organs’ neoplasms. Materials And Methods A retrospective analysis of the appendectomy specimens with a morphology code for AD in the files of the pathology department of Izmir Katip Celebi University Ataturk Training and Research Hospital located in western Türkiye between January 2007 and June 2022 was conducted. The computerized database revealed appendectomies resected for clinical suspicion of appendicitis and incidental appendectomies that were performed during other surgeries, such as right hemicolectomy and total abdominal hysterectomy with bilateral salpingooferectomy. The histopathology reports were examined for demographic data, clinical presentation, and gross characteristics, and cases with AD diagnosis were segregated for review. Two pathologists re-evaluated all routine hematoxyline-eosine and immunohistochemically stained slides, with one of them being a highly experienced gastrointestinal pathologist. The presence of appendiceal inflammation/diverticulitis, localized peritonitis, perforation of the diverticula, and accumulation of periappendiceal mucin were recorded. Coexistent morphologies such as endometriosis and benign or malignant neoplastic lesions were recorded and renamed according to current nomenclature. The primary pathology of other organs of the incidental appendectomies was also evaluated. The age and gender of all patients were recorded. This study was performed in line with the principles of the Declaration of Helsinki and approval was granted by the Ethics Committee of Izmir Katip Celebi University approved the study numbered 2022-GOKAE-0531. Results There were a total of 2602 appendectomies performed in a period of 15,5 years. Of these appendectomies, 53 were found to have AD (2%). Additionally, 15 ADs were encountered as incidental findings of other surgeries in the database search making the total count of AD as 68. The mean age of the patients was 54,1 years (24–93) with 32 (47%) males and 36 (53%) females. Diverticulitis was observed in 44 cases (64,7%) and coincided with localized peritonitis in 37 (54,5%) of them. ADs were accompanied by different lesions in 28 (41,1%) of the cases in the appendix. The most common accompanying lesion was detected to be a low-grade appendiceal mucinous neoplasm (LAMN) in 13 (19,1%) cases ( Fig. 1 ) followed by endometriosis in 4 (5,8%), well-differentiated neuroendocrine tumor (NET) also known as a carcinoid tumor in 3 (4,4%) ( Fig. 2 ) , and sessile serrated adenoma (SSA) in 3 (4,4%) cases ( Fig. 3 ) . One (1,4%) case had both LAMN and NET as a collision tumor next to the AD. A pT3 adenocarcinoma was encountered in 2 (2,9%) cases with one of them arising from a LAMN and a granular cell tumor was seen in 1 (1,4%) case ( Fig. 4 ) . Another interesting case was an AD with a hyperplastic polyp accompanied by an inflammatory fibroid polyp (IFP) (1,4%) ( Fig. 5 ). The female-to-male ratio of these lesions was 21/6. Table 1 depicts the accompanying lesions to the ADs. When endometriosis cases were excluded, the number of coexistent neoplasia with AD was found to be 23 (33,8%). Table 1 Accompanying lesions to the appendiceal diverticula Accompanying lesion Number (n) Overall percentage (%) F/M LAMN 13 19,1% 11/2 Endometriosis 4 5,8% 4/0 NET 3 4,4% 2/1 Sessile serrated adenoma 3 4,4% 2/1 Adenocarcinoma 2 2,9% 1/1 LAMN + NET 1 1,4% 0/1 Granular cell tumor 1 1,4% 1/0 HP + IFP 1 1,4% 1/0 TOTAL 28 41,1% 21/7 LAMN: Low-grade mucinous neoplasm, NET: Neuroendocrine tumor, HP: Hyperplastic polyp, IFP: Inflammatory fibroid polyp Periappendicular acellular mucin accumulation was another common finding in ADs. A total of 23 (33,8%) cases had this feature; of these only 3 had AD alone (Fig.s 4 and 6) . There was associated diverticulitis in 12 of these cases, with 3 of them having LAMN and 1 of them having endometriosis at the same time. Seven of the 13 cases with LAMN showed mucin deposition. The cases with mucin accumulation and their coexisting pathologies are listed in Table 2 . Table 2 Coexisting pathologies of the cases with mucin accumulation Coexisting pathology Number (n) Overall percentage (%) Diverticula only 3 4,4% Diverticulitis only 8 11,7% LAMN 4 5,8% Diverticulitis + LAMN 3 4,4% NET 1 1,4% Endometriosis 1 1,4% Diverticulitis + Endometriosis 1 1,4% Granular cell tumor 1 1,4% Adenocarcinoma 1 1,4% TOTAL 23 33,8 (%) LAMN: Low-grade mucinous neoplasm, NET: Neuroendocrine tumor In 15 cases in which AD was incidentally found, 2 of them were along with LAMN, 1 with SSA, and 1 with diverticulitis. Other pathologies of these incidental cases included malignant lesions such as carcinomas of the colon and ovaries and benign pathologies such as uterine leiomyoma, ovarian endometriotic cyst, colonic perforation due to ischemic changes, and ulcerations. One of the most striking findings of this study was the misdiagnosis of ADs in the microscopical examination in 8 (12,5%) cases. Even though the diverticular features were described during the macroscopical examination, the diverticula were not diagnosed due to excessive inflammation and suppuration around the appendiceal wall and were recognized during the re-examination of the slides during this study. Discussion AD has been described more than a century ago but remains to be an underdiagnosed and poorly understood pathological entity [ 1 ]. A higher incidence rate of AD in autopsy studies has been reported compared to appendectomies ranging from 0,014 to 2%. Hospital records for a 15,5-year period revealed a high number of appendectomies in our study. However, the incidence rate of AD among these specimens was only 2% proving the rarity of AD. This rate is on the higher end compared to other studies in the literature that were conducted with appendectomies. Male gender, age over 30 years, Hirschsprung’s disease, and cystic fibrosis are reported as risk factors for the development of AD [ 6 , 13 , 14 ]. In the study by Marcacuzco et al, which is one of the studies with the highest number of AD cases in the literature, 42 cases of AD in 7044 appendectomies were reported with an F/M ratio of 15/27 and a mean age of 46 [ 15 ]. Chia et al. reported a median age of 29 years and a 55% male incidence [ 13 ]. The mean age was 54,1 years in our study and in contrast to the literature, there was a female predominance of 53%. The high mean age can be explained by the absence of children in our population as our hospital does not have a pediatric surgery department. Two types of AD have been identified as congenital (including all four layers of the bowel wall) and acquired (including the mucosa and submucosa of the bowel wall without the muscular layer) which is also known as a pseudo-diverticulum. Congenital diverticula are much rarer than acquired ones and are known to be more resistant to perforation because of the muscular layer that they comprise [ 6 , 13 ]. All the cases in our study were acquired AD. An increased intraluminal pressure plays role in the formation of AD. The anatomical structure of the appendix enables the lumen to be obstructed easily and the obstruction may be caused by a tumor, fecalith, or voluminous mucus deposition [ 8 ]. The diagnosis of AD is usually made when there is an obstruction of the appendiceal lumen. Mucin accumulation is one of the main reasons for the obstruction and may be a result of many pathologies. It is also described with the term “mucocele” based on the macroscopic appearance by the clinicians [ 16 ]. In our study, 33,8% of the cases showed mucin accumulation with almost half of them having diverticulitis. The causes of mucin accumulation also include benign and/or malignant epithelial proliferations such as appendiceal mucinous neoplasia and adenocarcinoma and other neoplastic lesions of the appendix such as NET or SSAs. Seven cases with mucin accumulation within the appendiceal lumen had LAMN in our study with 3 of them having concurrent diverticulitis. Diverticulitis occurs as a common complication of AD, is difficult to distinguish from acute appendicitis clinically and radiologically, and is usually diagnosed histopathologically [ 17 ]. The literature indicates that acute or chronic diverticulitis will eventually develop in almost two-thirds of AD cases. Perforation is more prevalent than cases of acute appendicitis without AD owing to the absence of a muscular layer. In most cases, the mesoappendix surrounds the perforation and the AD is mesenteric which results in localized peritonitis [ 6 ]. Yardimci et al. reported a 70% perforation rate in their study with 24 cases of acute appendiceal diverticulitis [ 18 ]. Among 68 cases of AD, 44 of them had diverticulitis (64,7%) and 37 (54,5%) of these cases showed perforation and localized peritonitis. The rate of diverticulitis was found to be consistent with the literature findings. The coexistence of neoplastic lesions and AD has not been fully evaluated in the literature, only a couple of studies pointed out this association to date with varying incidence rates from 17,5–48% [ 8 , 11 , 12 , 19 , 20 , 21 ]. Dupre et al. reported a 48% rate of appendiceal neoplasia in cases with AD. They found that the most common appendiceal neoplasia associated with AD was NET followed by mucinous adenomas and adenocarcinomas [ 8 ]. Similarly, Medlicott et al. reported the most common neoplasm associated with AD to be NET [ 21 ]. In another study, this rate was found to be 18,1% with the majority of them being LAMNs followed by SSA and NET [ 11 ]. Kallenbach et al. reported a 43,6% rate of coexistent neoplasms and stated the LAMN to be the most common AD-associated mass lesion [ 12 ]. This rate was 35,2% in our study with 24 neoplastic lesions. Consistent with the literature, the most common was LAMN (n = 13), followed by NET (n = 3), SSA (n = 3), adenocarcinoma (n = 2), granular cell tumor (n = 1), hyperplastic polyp accompanied by an IFP (n = 1) and a collision tumor of LAMN and NET within multiple AD which we reported recently [ 22 ]. Although the most common neoplasm of the appendix is known to be a NET, because of their typical localization in the distal tip of the appendix they do not always cause luminal obstruction [ 23 ]. LAMN on the other hand is characterized by abundant mucin production and acellular mucin dissection in the appendiceal wall. The development of LAMN within an AD may be explained by the thinning of the muscularis propria by the increased intraluminal pressure and prolapse of the mucinous epithelium from the weak points of the wall. The mucin accumulation in 7 cases of 13 LAMNs in our study supports this theory. This also indicates the role of AD in the pathogenesis of pseudomyxoma peritonei. Appendiceal endometriosis is very rare and constitutes 1% of all endometriotic lesions [ 24 ]. The only reported case of the combination of AD and endometriosis in the literature belongs to our institution [ 25 ]. In the following years, 3 more cases of endometriosis were diagnosed as accompanying lesions to the AD. With a total of 4 cases, the incidence of endometriosis with AD was 5,8% in this study. IFPs are rare, benign, mesenchymal submucosal lesions of the gastrointestinal tract. Appendiceal IFPs accont for < 1% of all [ 26 ]. Even though there are a couple of case studies about appendiceal IFPs in the literature, our AD case that harbors both an IFP and a hyperplastic polyp is unique with the coexistence of both lesions. A thorough sampling of the appendectomy specimen and a careful macroscopic microscopic evaluation is crucial to overcome the underdiagnosis of AD and the accompanying lesions. As described in the study by Li et al. some important neoplastic lesions of the appendix including AD, SSA, and LAMN may be underestimated because of insufficient macroscopic sampling [ 27 ]. Sampling the entire appendix does not seem cost-effective and will more likely increase the workload, however, underdiagnosing or misdiagnosing a neoplastic entity will also bring its own problems. A thoughtful histopathological approach to suspicious cases might be a good solution. This study represents a high number of detected ADs in the literature with 68 cases. Other strengths include the detailed demographic features and histopathological evaluation of the cases. One limitation of our study was the absence of pediatric cases since the hospital does not specialize in pediatric surgery. Because the study was designed from a histopathological approach, the clinical signs and symptoms of the cases before undergoing operation were not included. In conclusion, the real incidence rates of AD may be higher than reported in the literature and this can be achieved by a detailed macroscopic and microscopic examination. Our study results revealed that ADs are accompanied by neoplastic lesions at a rate of 35,2%. Thus, it is important for surgeons and pathologists to be aware of AD and the coexisting pathologies they may harbor. When processing the appendectomy specimen in the pathology laboratory, if there is a pre-diagnosis or suspicion of AD and/or if there is apparent mucin accumulation it may be important to take more samples than usual not to miss any underlying neoplasms. The close association between LAMN and AD should be kept in mind when assessing the appendix. Declarations Author Contributions: Author Nese Ekinci and author Eylul Gun contributed equally. Conceptualization: Nese Ekinci, Eylul Gun; Methodology: Nese Ekinci, Eylul Gun; Formal analysis and investigation: Nese Ekinci; Writing - original draft preparation: Eylul Gun; Writing - review and editing: Nese Ekinci; Resources: Eylul Gun; Supervision: Nese Ekinci. Acknowledgments: The preliminary results of this study were presented as a poster at the 30 th Turkish Congress of Pathology which was held virtually on 20-23 May 2021. Conflict of interest: None. Funding: The authors have no relevant financial or non-financial interests to disclose and no funds, grants, or other support was received. References Kelynack TN. A contribution to the pathology of the vermiform appendix. London: HK Lewis, 1893, p.60. Delikaris P, Stubbe Teglbjaerg P, Fisker-Sorensen P, Balslev I. Diverticula of the vermiform appendix. Alternatives of the clinical presentation and significance. Dis Colon Rectum. 1983;26:374–376. Everts-Suare EA, Noteboom B. 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Inflammatory fibroid polyps of the appendix: different presentation and literature review. J Surg Case Rep . 2018;2018(8):rjy200. Published 2018 Aug 20. doi: 10.1093/jscr/rjy200 Li F, Lu Y, Hou F, Ma R, Wang D, Qi C. Significance of the Entire Appendiceal Evaluation in the Diagnosis of Serrated Lesions, Low-Grade Appendiceal Mucinous Neoplasm, and Appendiceal Diverticulosis Disease. Front Oncol. 2022;11:812794. Published 2022 Jan 18. doi: 10.3389/fonc.2021.812794 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2245915","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":151177828,"identity":"b4115529-6343-4c14-bd8d-003df5004aa0","order_by":0,"name":"Nese Ekinci","email":"","orcid":"","institution":"Izmir Kâtip Çelebi University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nese","middleName":"","lastName":"Ekinci","suffix":""},{"id":151177829,"identity":"5f97d97e-a106-41ce-af52-5ddb6497b0d4","order_by":1,"name":"Eylul 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2","display":"","copyAsset":false,"role":"figure","size":1318733,"visible":true,"origin":"","legend":"\u003cp\u003eNeuroendocrine tumor and appendiceal diverticulum (H\u0026amp;E 20x)\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-2245915/v1/ec1371752aa507ba2d2f1260.png"},{"id":29035998,"identity":"7d8f0761-3d87-4603-aa09-f5a557621a33","added_by":"auto","created_at":"2022-11-14 16:02:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1269307,"visible":true,"origin":"","legend":"\u003cp\u003eSessile serrated adenoma within appendiceal diverticulum (H\u0026amp;E 20x, Inset H\u0026amp;E 100x)\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-2245915/v1/c2135c8735d3d1bc640e882b.png"},{"id":29035997,"identity":"1a015654-b0a0-4b3e-85ed-cd324cc8dfd8","added_by":"auto","created_at":"2022-11-14 16:02:43","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1074047,"visible":true,"origin":"","legend":"\u003cp\u003eAppendiceal diverticulum with periappendicular mucin accumulation and granular cell tumor (H\u0026amp;E 20x, Inset: Granular cell tumor H\u0026amp;E 100x)\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-2245915/v1/2df7fbb5751a7f7b1767ae9b.png"},{"id":29036001,"identity":"a4aacea6-c514-426a-8669-78f57f41e7b1","added_by":"auto","created_at":"2022-11-14 16:02:43","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1183103,"visible":true,"origin":"","legend":"\u003cp\u003eInflammatory fibroid polyp in the appendiceal wall (H\u0026amp;E 40x, Inset CD34 stain)\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-2245915/v1/2f5af591e7a93ac53cef9b73.png"},{"id":29036002,"identity":"dd10924d-e28e-4ae8-a06f-7a279f24957b","added_by":"auto","created_at":"2022-11-14 16:02:43","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1344282,"visible":true,"origin":"","legend":"\u003cp\u003eAppendiceal diverticulum with periappendiceal mucin accumulation (H\u0026amp;E 20x)\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-2245915/v1/ab3fb7acf68260e8199e5bc0.png"},{"id":29285471,"identity":"f9c18452-10e0-4f9b-a029-d68c9c89ef68","added_by":"auto","created_at":"2022-11-19 19:44:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7065429,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2245915/v1/a9f2a6fe-2935-4051-bc41-fa871d669a11.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Unusual findings in 68 cases of appendiceal diverticulum: Accompanying neoplastic lesion should be kept in mind","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFirstly described in the literature in 1893, appendiceal diverticulum (AD) is a rare lesion that is defined as the herniation or outpouching of the mucosa through the muscularis propria or vascular hiatus of low resistance in the wall of the appendix. If the intraluminal pressure increases as a result of a tumor, fecalith, or voluminous mucus deposition, obstruction of the lumen occurs which then causes the formation of the diverticula [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It may be congenital or acquired, and while reported incidence rates vary between appendectomy series and autopsy studies, it is reported to be 0,014 and 0,20% to approximately 2%, respectively [\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAcquired AD is often asymptomatic but sometimes may produce symptoms if diverticulitis or perforation occurs. They may be associated with many conditions such as cystic fibrosis as well as with benign and malignant neoplasms including well-differentiated neuroendocrine tumors, low-grade mucinous neoplasm, and adenocarcinoma [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It is also reported to carry a higher risk of perforation than acute appendicitis due to the lack of muscularis propria [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The mucin accumulation caused by the perforation may sometimes mimic mucinous neoplasms [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Recent literature emphasizes that AD may be considered as a marker of local and regional neoplasms, therefore thorough histopathological examination carries great importance [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAD usually goes unnoticed in clinical practice and may sometimes be overlooked in the macroscopical examination. Pathological examination is essential in defining the diverticular disease of the appendix as it is hard to distinguish from acute appendicitis both clinically and radiologically. Therefore, the primary objective of this study is to assess the pathological findings of AD and particularly highlight its coexistence not only with organ-specific neoplastic lesions but also with regional organs\u0026rsquo; neoplasms.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eA retrospective analysis of the appendectomy specimens with a morphology code for AD in the files of the pathology department of Izmir Katip Celebi University Ataturk Training and Research Hospital located in western T\u0026uuml;rkiye between January 2007 and June 2022 was conducted. The computerized database revealed appendectomies resected for clinical suspicion of appendicitis and incidental appendectomies that were performed during other surgeries, such as right hemicolectomy and total abdominal hysterectomy with bilateral salpingooferectomy.\u003c/p\u003e \u003cp\u003e The histopathology reports were examined for demographic data, clinical presentation, and gross characteristics, and cases with AD diagnosis were segregated for review. Two pathologists re-evaluated all routine hematoxyline-eosine and immunohistochemically stained slides, with one of them being a highly experienced gastrointestinal pathologist. The presence of appendiceal inflammation/diverticulitis, localized peritonitis, perforation of the diverticula, and accumulation of periappendiceal mucin were recorded. Coexistent morphologies such as endometriosis and benign or malignant neoplastic lesions were recorded and renamed according to current nomenclature. The primary pathology of other organs of the incidental appendectomies was also evaluated. The age and gender of all patients were recorded. This study was performed in line with the principles of the Declaration of Helsinki and approval was granted by the Ethics Committee of Izmir Katip Celebi University approved the study numbered 2022-GOKAE-0531.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThere were a total of 2602 appendectomies performed in a period of 15,5 years. Of these appendectomies, 53 were found to have AD (2%). Additionally, 15 ADs were encountered as incidental findings of other surgeries in the database search making the total count of AD as 68. The mean age of the patients was 54,1 years (24\u0026ndash;93) with 32 (47%) males and 36 (53%) females.\u003c/p\u003e\n\u003cp\u003eDiverticulitis was observed in 44 cases (64,7%) and coincided with localized peritonitis in 37 (54,5%) of them. ADs were accompanied by different lesions in 28 (41,1%) of the cases in the appendix. The most common accompanying lesion was detected to be a low-grade appendiceal mucinous neoplasm (LAMN) in 13 (19,1%) cases \u003cstrong\u003e(\u003c/strong\u003eFig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e followed by endometriosis in 4 (5,8%), well-differentiated neuroendocrine tumor (NET) also known as a carcinoid tumor in 3 (4,4%) \u003cstrong\u003e(\u003c/strong\u003eFig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e, and sessile serrated adenoma (SSA) in 3 (4,4%) cases \u003cstrong\u003e(\u003c/strong\u003eFig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e. One (1,4%) case had both LAMN and NET as a collision tumor next to the AD. A pT3 adenocarcinoma was encountered in 2 (2,9%) cases with one of them arising from a LAMN and a granular cell tumor was seen in 1 (1,4%) case \u003cstrong\u003e(\u003c/strong\u003eFig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e. Another interesting case was an AD with a hyperplastic polyp accompanied by an inflammatory fibroid polyp (IFP) (1,4%) \u003cstrong\u003e(\u003c/strong\u003eFig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cstrong\u003e).\u003c/strong\u003e The female-to-male ratio of these lesions was 21/6. Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e depicts the accompanying lesions to the ADs. When endometriosis cases were excluded, the number of coexistent neoplasia with AD was found to be 23 (33,8%).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAccompanying lesions to the appendiceal diverticula\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cspan class=\"Underline\" name=\"Emphasis\" type=\"Underline\"\u003eAccompanying lesion\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cspan class=\"Underline\" name=\"Emphasis\" type=\"Underline\"\u003eNumber (n)\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cspan class=\"Underline\" name=\"Emphasis\" type=\"Underline\"\u003eOverall percentage (%)\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cspan class=\"Underline\" name=\"Emphasis\" type=\"Underline\"\u003eF/M\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLAMN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19,1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11/2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEndometriosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSessile serrated adenoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdenocarcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLAMN\u0026thinsp;+\u0026thinsp;NET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGranular cell tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHP\u0026thinsp;+\u0026thinsp;IFP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTOTAL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e28\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e41,1%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e21/7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eLAMN: Low-grade mucinous neoplasm, NET: Neuroendocrine tumor, HP: Hyperplastic polyp, IFP: Inflammatory fibroid polyp\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003ePeriappendicular acellular mucin accumulation was another common finding in ADs. A total of 23 (33,8%) cases had this feature; of these only 3 had AD alone \u003cstrong\u003e(Fig.s 4 and 6)\u003c/strong\u003e. There was associated diverticulitis in 12 of these cases, with 3 of them having LAMN and 1 of them having endometriosis at the same time. Seven of the 13 cases with LAMN showed mucin deposition. The cases with mucin accumulation and their coexisting pathologies are listed in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCoexisting pathologies of the cases with mucin accumulation\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCoexisting pathology\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumber (n)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOverall percentage (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiverticula only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiverticulitis only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11,7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLAMN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiverticulitis\u0026thinsp;+\u0026thinsp;LAMN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEndometriosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiverticulitis\u0026thinsp;+\u0026thinsp;Endometriosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGranular cell tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdenocarcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTOTAL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e23\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e33,8 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003eLAMN: Low-grade mucinous neoplasm, NET: Neuroendocrine tumor\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eIn 15 cases in which AD was incidentally found, 2 of them were along with LAMN, 1 with SSA, and 1 with diverticulitis. Other pathologies of these incidental cases included malignant lesions such as carcinomas of the colon and ovaries and benign pathologies such as uterine leiomyoma, ovarian endometriotic cyst, colonic perforation due to ischemic changes, and ulcerations.\u003c/p\u003e\n\u003cp\u003eOne of the most striking findings of this study was the misdiagnosis of ADs in the microscopical examination in 8 (12,5%) cases. Even though the diverticular features were described during the macroscopical examination, the diverticula were not diagnosed due to excessive inflammation and suppuration around the appendiceal wall and were recognized during the re-examination of the slides during this study.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAD has been described more than a century ago but remains to be an underdiagnosed and poorly understood pathological entity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. A higher incidence rate of AD in autopsy studies has been reported compared to appendectomies ranging from 0,014 to 2%. Hospital records for a 15,5-year period revealed a high number of appendectomies in our study. However, the incidence rate of AD among these specimens was only 2% proving the rarity of AD. This rate is on the higher end compared to other studies in the literature that were conducted with appendectomies.\u003c/p\u003e \u003cp\u003eMale gender, age over 30 years, Hirschsprung\u0026rsquo;s disease, and cystic fibrosis are reported as risk factors for the development of AD [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In the study by Marcacuzco et al, which is one of the studies with the highest number of AD cases in the literature, 42 cases of AD in 7044 appendectomies were reported with an F/M ratio of 15/27 and a mean age of 46 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Chia et al. reported a median age of 29 years and a 55% male incidence [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The mean age was 54,1 years in our study and in contrast to the literature, there was a female predominance of 53%. The high mean age can be explained by the absence of children in our population as our hospital does not have a pediatric surgery department.\u003c/p\u003e \u003cp\u003eTwo types of AD have been identified as congenital (including all four layers of the bowel wall) and acquired (including the mucosa and submucosa of the bowel wall without the muscular layer) which is also known as a pseudo-diverticulum. Congenital diverticula are much rarer than acquired ones and are known to be more resistant to perforation because of the muscular layer that they comprise [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. All the cases in our study were acquired AD. An increased intraluminal pressure plays role in the formation of AD. The anatomical structure of the appendix enables the lumen to be obstructed easily and the obstruction may be caused by a tumor, fecalith, or voluminous mucus deposition [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The diagnosis of AD is usually made when there is an obstruction of the appendiceal lumen. Mucin accumulation is one of the main reasons for the obstruction and may be a result of many pathologies. It is also described with the term \u0026ldquo;mucocele\u0026rdquo; based on the macroscopic appearance by the clinicians [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In our study, 33,8% of the cases showed mucin accumulation with almost half of them having diverticulitis. The causes of mucin accumulation also include benign and/or malignant epithelial proliferations such as appendiceal mucinous neoplasia and adenocarcinoma and other neoplastic lesions of the appendix such as NET or SSAs. Seven cases with mucin accumulation within the appendiceal lumen had LAMN in our study with 3 of them having concurrent diverticulitis.\u003c/p\u003e \u003cp\u003eDiverticulitis occurs as a common complication of AD, is difficult to distinguish from acute appendicitis clinically and radiologically, and is usually diagnosed histopathologically [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The literature indicates that acute or chronic diverticulitis will eventually develop in almost two-thirds of AD cases. Perforation is more prevalent than cases of acute appendicitis without AD owing to the absence of a muscular layer. In most cases, the mesoappendix surrounds the perforation and the AD is mesenteric which results in localized peritonitis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Yardimci et al. reported a 70% perforation rate in their study with 24 cases of acute appendiceal diverticulitis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Among 68 cases of AD, 44 of them had diverticulitis (64,7%) and 37 (54,5%) of these cases showed perforation and localized peritonitis. The rate of diverticulitis was found to be consistent with the literature findings.\u003c/p\u003e \u003cp\u003eThe coexistence of neoplastic lesions and AD has not been fully evaluated in the literature, only a couple of studies pointed out this association to date with varying incidence rates from 17,5\u0026ndash;48% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Dupre et al. reported a 48% rate of appendiceal neoplasia in cases with AD. They found that the most common appendiceal neoplasia associated with AD was NET followed by mucinous adenomas and adenocarcinomas [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Similarly, Medlicott et al. reported the most common neoplasm associated with AD to be NET [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In another study, this rate was found to be 18,1% with the majority of them being LAMNs followed by SSA and NET [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Kallenbach et al. reported a 43,6% rate of coexistent neoplasms and stated the LAMN to be the most common AD-associated mass lesion [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This rate was 35,2% in our study with 24 neoplastic lesions. Consistent with the literature, the most common was LAMN (n\u0026thinsp;=\u0026thinsp;13), followed by NET (n\u0026thinsp;=\u0026thinsp;3), SSA (n\u0026thinsp;=\u0026thinsp;3), adenocarcinoma (n\u0026thinsp;=\u0026thinsp;2), granular cell tumor (n\u0026thinsp;=\u0026thinsp;1), hyperplastic polyp accompanied by an IFP (n\u0026thinsp;=\u0026thinsp;1) and a collision tumor of LAMN and NET within multiple AD which we reported recently [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough the most common neoplasm of the appendix is known to be a NET, because of their typical localization in the distal tip of the appendix they do not always cause luminal obstruction [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. LAMN on the other hand is characterized by abundant mucin production and acellular mucin dissection in the appendiceal wall. The development of LAMN within an AD may be explained by the thinning of the muscularis propria by the increased intraluminal pressure and prolapse of the mucinous epithelium from the weak points of the wall. The mucin accumulation in 7 cases of 13 LAMNs in our study supports this theory. This also indicates the role of AD in the pathogenesis of pseudomyxoma peritonei.\u003c/p\u003e \u003cp\u003eAppendiceal endometriosis is very rare and constitutes 1% of all endometriotic lesions [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The only reported case of the combination of AD and endometriosis in the literature belongs to our institution [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In the following years, 3 more cases of endometriosis were diagnosed as accompanying lesions to the AD. With a total of 4 cases, the incidence of endometriosis with AD was 5,8% in this study.\u003c/p\u003e \u003cp\u003eIFPs are rare, benign, mesenchymal submucosal lesions of the gastrointestinal tract. Appendiceal IFPs accont for \u0026lt;\u0026thinsp;1% of all [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Even though there are a couple of case studies about appendiceal IFPs in the literature, our AD case that harbors both an IFP and a hyperplastic polyp is unique with the coexistence of both lesions.\u003c/p\u003e \u003cp\u003eA thorough sampling of the appendectomy specimen and a careful macroscopic microscopic evaluation is crucial to overcome the underdiagnosis of AD and the accompanying lesions. As described in the study by Li et al. some important neoplastic lesions of the appendix including AD, SSA, and LAMN may be underestimated because of insufficient macroscopic sampling [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Sampling the entire appendix does not seem cost-effective and will more likely increase the workload, however, underdiagnosing or misdiagnosing a neoplastic entity will also bring its own problems. A thoughtful histopathological approach to suspicious cases might be a good solution.\u003c/p\u003e \u003cp\u003eThis study represents a high number of detected ADs in the literature with 68 cases. Other strengths include the detailed demographic features and histopathological evaluation of the cases. One limitation of our study was the absence of pediatric cases since the hospital does not specialize in pediatric surgery. Because the study was designed from a histopathological approach, the clinical signs and symptoms of the cases before undergoing operation were not included.\u003c/p\u003e \u003cp\u003eIn conclusion, the real incidence rates of AD may be higher than reported in the literature and this can be achieved by a detailed macroscopic and microscopic examination. Our study results revealed that ADs are accompanied by neoplastic lesions at a rate of 35,2%.\u003c/p\u003e \u003cp\u003eThus, it is important for surgeons and pathologists to be aware of AD and the coexisting pathologies they may harbor. When processing the appendectomy specimen in the pathology laboratory, if there is a pre-diagnosis or suspicion of AD and/or if there is apparent mucin accumulation it may be important to take more samples than usual not to miss any underlying neoplasms. The close association between LAMN and AD should be kept in mind when assessing the appendix.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e Author Nese Ekinci and author Eylul Gun contributed equally.\u003c/p\u003e\n\u003cp\u003eConceptualization: Nese Ekinci, Eylul Gun; Methodology: Nese Ekinci, Eylul Gun; Formal analysis and investigation: Nese Ekinci; Writing - original draft preparation: Eylul Gun; Writing - review and editing: Nese Ekinci; Resources: Eylul Gun; Supervision: Nese Ekinci.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e The preliminary results of this study were presented as a poster at the 30\u003csup\u003eth\u003c/sup\u003e Turkish Congress of Pathology which was held virtually on 20-23 May 2021.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThe authors have no relevant financial or non-financial interests to disclose and no funds, grants, or other support was received.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eKelynack TN. A contribution to the pathology of the vermiform appendix. London: HK Lewis, 1893, p.60.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eDelikaris P, Stubbe Teglbjaerg P, Fisker-Sorensen P, Balslev I. Diverticula of the vermiform appendix. Alternatives of the clinical presentation and significance. Dis Colon Rectum. 1983;26:374\u0026ndash;376.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eEverts-Suare EA, Noteboom B. Congenital diverticula of the appendix: review of the world\u0026rsquo;s literature and report of a case. Penn Med J 1961; 64: 1454\u0026ndash;1458.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eCollins DC. A study of 50,000 specimens of the human vermiform appendix. Surg Gynecol Obstet. 1955;101: 437\u0026ndash;445.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMarudanayagam R, Williams GT, Rees BI. Review of the pathological results of 2660 appendicectomy specimens. 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GE Port J Gastroenterol. 2021;28(4):236\u0026ndash;242. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000511822\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAl-Brahim N, Al-Kandari I, Munahai M, Sharma P. Clinicopathological study of 25 cases of diverticular disease of the appendix: experience from farwaniya hospital. Patholog Res Int. 2013;2013:404308. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2013/404308\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMarcacuzco AA, Manrique A, Calvo J, et al. Clinical implications of diverticular disease of the appendix. Experience over the past 10 years. Cir Esp. 2016;94(1):44\u0026ndash;47. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ciresp.2014.05.003\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLouis TH, Felter DF. Mucocele of the appendix. Proc (Bayl Univ Med Cent). 2014 Jan;27(1):33\u0026ndash;4. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/08998280.2014.11929046\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eOsada H, Ohno H, Saiga K, Watanabe W, Okada T, Honda N. Appendiceal diverticulitis: multidetector CT features. Jpn J Radiol. 2012;30(3):242\u0026ndash;248. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11604-011-0039-2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eYardimci AH, Bektas CT, Pasaoglu E, et al. 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The coexistence of low-grade mucinous neoplasms of the appendix and appendiceal diverticula: A possible role in the pathogenesis of pseudomyxoma peritonei. Mod Pathol 2000;13:495\u0026ndash;501\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMedlicott SAC, Urbanski SJ. Acquired Diverticulosis of the Vermiform Appendix: A Disease of Multiple Etiologies: A Retrospective Analysis and Review of the Literature. International Journal of Surgical Pathology. 1998;6(1):23\u0026ndash;27. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/106689699800600106\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eEkinci N, G\u0026uuml;n E, Avcı A, Er A. Coexistence of low-grade mucinous neoplasm and carcinoid (collision tumor) within multiple appendiceal diverticula: A case report. Turk J Surg. 2021;37(3):303\u0026ndash;306. Published 2021 Sep 28. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.47717/turkjsurg.2021.3877\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHines JJ, Paek GK, Lee P, Wu L, Katz DS. Beyond appendicitis; radiologic review of unusual and rare pathology of the appendix. Abdom Radiol (NY). 2016;41(3):568\u0026ndash;581. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00261-015-0600-z\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAkbulut S, Dursun P, Kocbiyik A, Harman A, Sevmis S. Appendiceal endometriosis presenting as perforated appendicitis: report of a case and review of the literature. Arch Gynecol Obstet. 2009;280(3):495\u0026ndash;497. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00404-008-0922-y\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eEkinci N, Altindag SD, Avci A, Gur E. Diverticular disease and endometriosis of the vermiform appendix: A unique combination. Ege Tip Dergisi. 2019; 58 (4): 412\u0026ndash;414.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAlbabtain I, Arishi H, Albaghli S, Aljahani J. Inflammatory fibroid polyps of the appendix: different presentation and literature review. \u003cem\u003eJ Surg Case Rep\u003c/em\u003e. 2018;2018(8):rjy200. Published 2018 Aug 20. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/jscr/rjy200\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLi F, Lu Y, Hou F, Ma R, Wang D, Qi C. Significance of the Entire Appendiceal Evaluation in the Diagnosis of Serrated Lesions, Low-Grade Appendiceal Mucinous Neoplasm, and Appendiceal Diverticulosis Disease. Front Oncol. 2022;11:812794. Published 2022 Jan 18. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fonc.2021.812794\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Appendix, diverticulum, diverticulosis, appendiceal neoplasms","lastPublishedDoi":"10.21203/rs.3.rs-2245915/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2245915/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eCongenital and acquired diverticula of the appendix are very rare and may be associated with a variety of lesions. In this study, we aimed to evaluate the cases of the appendiceal diverticulum (AD) in terms of histopathological features and accompanying neoplastic and non-neoplastic lesions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A retrospective analysis of the appendectomy specimens between January 2007 and June 2022 was performed. All of the cases with AD were reviewed and slides of all cases were re-examined by two pathologists, one of whom was highly experienced in gastrointestinal pathology. The cases were evaluated in terms of age, gender, histopathological features, accompanying neoplastic and non-neoplastic lesions, presence of periappendicular mucin, and misdiagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThere were a total of 68 AD cases with 32 (47%) males and 36 (53%) females. The mean age was 54,1 years (24-93). Diverticulitis was seen in 44 cases (64,7%). In 28 (41,1%) cases ADs were accompanied by other lesions such as low-grade appendiceal mucinous neoplasm (LAMN, n=13), endometriosis (n=4), well-differentiated neuroendocrine tumor (n=3), sessile serrated adenoma (SSA, n=3), adenocarcinoma (n=2), LAMN and WD-NET (n=1), granular cell tumor (n=1), and hyperplastic polyp with inflammatory fibroid polyp (n=1). Periappendiceal acellular mucin deposition was seen in 23 (33,8%) cases with associated diverticulitis in 12 of them. In 7 of the 13 cases of LAMN there was mucin accumulation. AD was incidentally found in 15 appendectomies performed during other surgeries. Although defined macroscopically in 8 cases, the diagnosis of AD was missed during the microscopical examination.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe probability of detecting a neoplastic lesion in cases with AD is quite high as proven in our study. Therefore, the entire appendix can be sampled in these cases. It is important to pay attention to macroscopic definitions in order not to miss a possible diverticulum in all cases with microscopic perforation and dense inflammation. The close association between LAMN and AD should be kept in mind.\u003c/p\u003e","manuscriptTitle":"Unusual findings in 68 cases of appendiceal diverticulum: Accompanying neoplastic lesion should be kept in mind","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-11-14 16:02:38","doi":"10.21203/rs.3.rs-2245915/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4deeed8e-5d24-4c0a-ab11-872cf3aac0c1","owner":[],"postedDate":"November 14th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-11-19T19:44:15+00:00","versionOfRecord":[],"versionCreatedAt":"2022-11-14 16:02:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2245915","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2245915","identity":"rs-2245915","version":["v1"]},"buildId":"ehx78VzkSd0WSzXnipQa-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}