Appendiceal adenocarcinoma arising from serrated lesions: A case report

Abstract

BACKGROUND

The association between serrated lesions of the appendix and the development of appendiceal adenocarcinoma has been inadequately characterized in the existing literature. Moreover, the feasibility and safety of endoscopic resection for such malignancies remain underexplored. To our best knowledge, this case report firstly provides evidence that appendiceal adenocarcinoma can arise secondary to serrated lesions and demonstrates successful complete endoscopic resection.

CASE SUMMARY

A 70-year-old male patient with a medical history significant for hypertension was incidentally identified to have a polypoid lesion located in the appendiceal fossa during a routine physical examination. Subsequent outpatient colonoscopy revealed a polypoid protrusion accompanied by thickening of the surface glandular ducts. Histological analysis of biopsy specimens demonstrated mucinous epithelium with mild atypical hyperplasia, without evidence of invasive growth. Contrast-enhanced abdominal computed tomography imaging showed an elongated and thickened appendix. Endoscopic ultrasound examination revealed heterogeneous hypoechoic alterations. The patient underwent an endoscopic transcecal appendectomy, involving full-thickness resection performed with an insulated-tip electrosurgical knife. Hemostasis was successfully achieved via electrocoagulation, and the resultant full-thickness defect was closed using metal clips reinforced with nylon sutures. The postoperative course was uneventful, and the patient was discharged on postoperative day seven. Histopathological evaluation confirmed the presence of differentiated adenocarcinoma with mucinous components, invading the muscularis propria and focally extending to the serosal layer, without evidence of neural or vascular invasion, and with negative resection margins; lymph node assessment revealed no metastasis (0/1). Immunohistochemical analysis demonstrated asymmetric Ki-67 expression and diffuse cytokeratin 20 positivity, consistent with adenocarcinoma arising from a serrated lesion. The patient subsequently underwent additional surgical intervention (right hemicolectomy), which revealed no residual tumor.

CONCLUSION

Appendiceal adenocarcinoma can arise secondary to serrated lesions, and complete endoscopic resection via transcecal appendectomy appears technically feasible and safe in this selected case. Comprehensive endoscopic assessment and en bloc resection are recommended to achieve accurate pathological staging and exclude occult malignancy. However, larger studies are needed to establish the definitive role of this approach.

Key Words: Appendiceal neoplasms; Serrated lesions; Adenocarcinoma; Endoscopic mucosal resection; Transcecal appendectomy; Case report

Core Tip: To our best knowledge, this is the first reported case of appendiceal adenocarcinoma arising from serrated lesions that was successfully treated by endoscopic transcecal appendectomy. The technique avoids abdominal incision, reduces postoperative complications, and allows precise pathological staging. Immunohistochemistry (Ki-67 asymmetry, cytokeratin 20 positivity) was pivotal in confirming the serrated origin. This case highlights the need for complete resection of serrated lesions at the appendiceal orifice.

INTRODUCTION

Serrated lesions of the appendix are rare, and their potential for malignancy remains inadequately defined. In contrast to serrated lesions of the colorectum, which are well-established precursors to adenocarcinoma, the role of appendiceal serrated lesions within the carcinogenic pathway has not been conclusively determined. As a result, the optimal therapeutic approach for these lesions is yet to be clearly delineated[1,2].

Endoscopic resection of appendiceal lesions has traditionally posed significant challenges, primarily due to risks such as incomplete excision, perforation, and damage to the appendiceal artery. While conventional appendectomy performed via laparoscopy or laparotomy is commonly favored, it is associated with complications including incisional hernia, stump inflammation, and prolonged recovery periods[3]. In 2018, Liu et al[4] introduced endoscopic transcecal appendectomy (ETA), a novel technique that facilitates full-thickness resection of the appendix through the cecal lumen, thereby obviating the need for abdominal incisions.

In this report, we present a case of appendiceal adenocarcinoma originating from a serrated lesion that was successfully managed using ETA. To the best of our knowledge, this represents the first documented instance of such a pathological association and its endoscopic treatment.

CASE PRESENTATION

Chief complaints

A 70-year-old male was admitted to the hospital in 2025 following the incidental detection of a polypoid lesion in the appendiceal fossa during a routine physical examination.

History of present illness

The patient was asymptomatic, with no abdominal pain, changes in bowel habits, weight loss, or gastrointestinal bleeding. The lesion was discovered on screening colonoscopy.

History of past illness

The patient had a history of hypertension, for which he was on regular medication. No prior abdominal surgeries or malignancies were reported.

Personal and family history

No family history of colorectal or appendiceal cancer. No history of smoking or excessive alcohol use.

Physical examination

Upon admission, physical examination demonstrated a flat and soft abdomen without tenderness, rebound tenderness, palpable masses, or lymphadenopathy. No tenderness or rebound tenderness was noted at McBurney’s point.

Laboratory examinations

Laboratory investigations, including complete blood count, liver and renal function tests, and tumor markers (carcinoembryonic antigen 19-9), were within normal limits.

Imaging examinations

Contrast-enhanced abdominal computed tomography (CT) revealed an elongated and thickened appendix without obvious lymphadenopathy or distant metastases (Figure 1). Endoscopic ultrasound colonoscopy revealed heterogeneous hypoechoic alterations emanating from the appendiceal orifice, accompanied by thickening of the superficial glandular ducts (Figure 2).

Figure 1 Contrast-enhanced abdominal computed tomography findings. Computed tomography scan showing an elongated and thickened appendix without obvious lymphadenopathy or distant metastases.

Figure 2 Endoscopic ultrasound showing a mixed hypoechoic lesion at the appendiceal orifice. A: White-light endoscopy; B: Endoscopic ultrasound image.

FINAL DIAGNOSIS

Based on the histopathological and immunohistochemical findings of the resected specimen, the final diagnosis was differentiated adenocarcinoma of the appendix (including areas of mucinous adenocarcinoma) arising from a serrated lesion. Pathological staging: PT3NxMx.

TREATMENT

The presence of malignancy was not identified prior to the ETA. Preoperative biopsy results indicated only “mucous epithelium without invasion, exhibiting mild atypical hyperplasia”, as reported in the original manuscript. Endoscopic evaluation suggested that the lesion was likely a serrated lesion with potential low-grade dysplasia, leading to the decision to perform ETA as both a diagnostic and therapeutic intervention aimed at complete resection of the appendiceal lesion. The diagnosis of pT3 adenocarcinoma was an unexpected outcome revealed by the final histopathological analysis of the excised specimen. Subsequent to the pathological confirmation of invasive adenocarcinoma (pT3), the patient was referred for right hemicolectomy in accordance with established oncological treatment protocols. Following detailed discussion with the patient, an endoscopic appendectomy via the cecum (ETA) was proposed. Preoperative preparation included a one-day liquid diet and bowel cleansing using compound polyethylene glycol powder.

The procedure was performed under general anesthesia with tracheal intubation, with the patient in the left lateral decubitus position. Intraoperatively, a mucosal elevation approximately 2.0 cm in size was observed at the appendiceal orifice. Submucosal injection was administered at the raised margin, followed by mucosal incision using an electrosurgical knife. Full-thickness resection of the appendiceal lesion was achieved employing an insulated-tip electrosurgical knife along the lesion’s periphery, with careful dissection of the appendix external to the lumen. Hemostasis was secured by electrocoagulation of appendiceal vessels using hemostatic forceps. The appendix and associated mass were completely excised. After ensuring hemostasis, the full-thickness defect was closed with metal clips, reinforced with nylon sutures at the clip base. Abdominal puncture and decompression were performed intraoperatively. The resected specimen was extracted transrectally. Gross examination of the appendiceal stump revealed mucinous changes. Prophylactic antibiotics were administered perioperatively (Figure 3).

Figure 3 Intraoperative endoscopic images. A and B: Full-thickness resection; C and D: Closure of defect with metal clips; E and F: Excised specimen.

OUTCOME AND FOLLOW-UP

Postoperatively, the patient was maintained fasting for three days without fever or abdominal pain. Upon resumption of normal bowel function and passage of flatus, oral intake was gradually reintroduced. The patient was discharged on postoperative day seven. Subsequent to discharge, the patient underwent additional surgical intervention (right hemicolectomy) as per oncological guidelines, with postoperative pathology revealing no residual tumor. Specifically, the surgical pathology report documented that 15 regional lymph nodes were examined, all of which were negative for malignancy (0/15). The appendiceal resection margins and the cecal resection margins were also negative for residual tumor. The peritoneal surfaces showed no evidence of tumor implants.

Histopathological examination of the endoscopic resection specimen confirmed a differentiated adenocarcinoma with mucinous components, invading the muscularis propria and focally extending to the serosal layer (pT3), without lymphovascular or perineural invasion, and with negative resection margins. The tumor exhibited crypt branching, serrated architecture, cytoplasmic eosinophilia, and surface goblet cells -features suggestive of a serrated precursor. Immunohistochemistry revealed asymmetric Ki-67 expression (confined to the basal crypt regions) and diffuse cytokeratin 20 (CK20) positivity, confirming the diagnosis of adenocarcinoma arising from a serrated lesion (Figure 4).

Figure 4 Histopathology and immunohistochemistry. A: Hematoxylin and eosin stain showing crypt branching and serrated morphology (× 40); B: Diffuse cytokeratin 20 positivity (× 40); C: Asymmetric Ki-67 expression (× 40); D: Hematoxylin and eosin stain showing crypt branching and serrated morphology (× 100); E: Diffuse cytokeratin 20 positivity (× 100); F: Asymmetric Ki-67 expression (× 100).

The patient was followed up at 3 months and 6 months post-discharge with colonoscopy and CT, showing no evidence of recurrence.

DISCUSSION

To our best knowledge, this report provides the first documented evidence that appendiceal adenocarcinoma can originate from serrated lesions and be effectively managed through endoscopic ETA. This observation offers significant clinical insights into the treatment of this rare pathological condition. While the serrated pathway is a well-recognized mechanism in colorectal carcinogenesis, its involvement in appendiceal neoplasia has remained ambiguous. Appendiceal serrated lesions encompass hyperplastic polyps, sessile serrated lesions, and traditional serrated adenomas[5,6]. In the present case, histopathological examination revealed features characteristic of serrated lesions, including crypt branching, eosinophilic cytoplasm, and the presence of goblet cells on the mucosal surface. Immunohistochemical analysis demonstrated an asymmetric Ki-67 proliferation index and diffuse CK20 expression, corroborating the diagnosis of adenocarcinoma arising from a serrated precursor lesion. These findings extend the applicability of the serrated pathway to appendiceal tumors and highlight the critical importance of accurate identification and complete resection of such lesions. Although patients with sporadic sessile serrated lesions (SSLs) are known to be at risk for malignant transformation[7], the precise oncogenic potential of appendiceal serrated lesions remains unclear due to their rarity. pT3 staging was assigned based on tumor invasion into the subserosa without definitive penetration of the visceral peritoneum, according to the AJCC 8th edition criteria. Nevertheless, the presence of deep tumor invasion (pT3) in this case suggests that appendiceal serrated lesions may exhibit comparable or even heightened neoplastic potential, potentially attributable to the anatomical thinness of the appendiceal wall and delays in diagnosis. Although ETA achieved complete local resection with negative margins, the presence of pT3 invasion warrants consideration of the risk of lymphatic dissemination. Right hemicolectomy remains the standard of care for accurate nodal staging and to exclude occult metastases, as endorsed by current guidelines.

ETA, initially described by Liu et al[4] in 2018, enables full-thickness resection of the appendix via the cecal lumen, thereby obviating the need for an abdominal incision. This minimally invasive approach reduces the risk of postoperative complications commonly associated with conventional appendectomy, such as incisional hernia and stump inflammation. Although endoscopic management of the appendiceal artery has traditionally been considered challenging, intraoperative endoscopic visualization facilitates clear identification of the vessel, and the use of hemostatic forceps allows for precise electrocoagulation and vessel cauterization. The present case confirms the safety and technical feasibility of ETA even in the context of malignant lesions. Since its initial introduction, several small case series have reported successful application of ETA for benign appendiceal lesions, including low-grade appendiceal mucinous neoplasms[8,9]. However, to our knowledge, this is the first report documenting the use of ETA for invasive adenocarcinoma arising from a serrated lesion. The technical success achieved in this case - including full-thickness resection, effective hemostasis, and defect closure reinforced with metal clips - demonstrates that ETA can accomplish R0 resection even for pT3 tumors. Furthermore, the adjunctive use of nylon sutures to reinforce clip closure may mitigate the risk of delayed perforation, a recognized concern associated with large full-thickness defects[10]. In this case, intraoperative challenges include: (1) Intraoperative endoscopic visualization facilitates clear identification, and hemostatic forceps allow precise electrocoagulation; (2) Achieving complete full-thickness resection while avoiding injury to surrounding structures; (3) Managing the risk of perforation during dissection; and (4) We employed metal clips reinforced with nylon sutures at the clip base to reduce the risk of delayed perforation.

The extent of tumor invasion (pT3) observed in this case warrants particular attention. Despite the tumor penetrating the serosal layer, a complete endoscopic resection with clear margins was successfully accomplished. Subsequent right hemicolectomy revealed no residual neoplastic tissue, thereby demonstrating the oncological adequacy of the initial endoscopic procedure. This finding implies that, for carefully selected patients with localized appendiceal adenocarcinoma, endoscopic full-thickness resection may function not only as a diagnostic tool but also as a potentially curative intervention, potentially obviating the need for more extensive surgical approaches in low-risk scenarios. Nevertheless, prevailing clinical guidelines typically advocate for right hemicolectomy in cases of appendiceal adenocarcinoma exhibiting deep submucosal invasion (≥ pT2), due to the associated risk of lymphatic dissemination[11]. In the present case, adherence to these guidelines led to the performance of right hemicolectomy. ETA may serve as a diagnostic and potentially therapeutic procedure for carefully selected patients, but that right hemicolectomy remains the standard of care for invasive appendiceal adenocarcinoma with deep submucosal invasion.

From a pathological standpoint, the diagnosis of a serrated lesion origin was substantiated through a combination of morphological assessment and immunohistochemical analysis. Features such as crypt branching, serrated architectural patterns, and eosinophilic cytoplasm are characteristic of sessile serrated lesions[5]. The observed asymmetric Ki-67 expression, confined to the basal crypt regions, contrasts with the diffuse Ki-67 staining typically observed in conventional adenomas, while widespread CK20 positivity corroborates colonic-type differentiation[6,12]. These immunohistochemical markers are particularly valuable when serrated morphology is obscured by high-grade dysplasia or invasive carcinoma. It is recommended that pathologists routinely evaluate these features in appendiceal adenocarcinomas to identify tumors arising from serrated precursors, as this distinction may carry prognostic significance. Some studies have indicated that serrated pathway carcinomas possess a distinct molecular profile - such as BRAF mutations and the CpG island methylator phenotype - and may exhibit differential responses to chemotherapeutic regimens[13].

Based on the current World Health Organization classification of digestive system tumors (5^th edition), serrated lesions of the appendix encompass hyperplastic polyps, SSLs, and traditional serrated adenomas. In our case, the precursor lesion exhibited the following features: (1) Crypt branching with serrated architectural patterns; (2) Eosinophilic cytoplasm; (3) Goblet cells on the mucosal surface; (4) Asymmetric Ki-67 expression confined to the basal crypt regions; and (5) Diffuse CK20 positivity. These findings are most consistent with a SSL according to World Health Organization criteria[14].

We recommend that patients presenting with serrated lesions at the appendiceal orifice, as identified through endoscopic examination, undergo thorough lesion evaluation, including endoscopic ultrasound and advanced imaging modalities. When clinically appropriate, complete en bloc resection should be performed to facilitate precise pathological staging and to exclude occult malignancy. Furthermore, considering the potential for synchronous or metachronous serrated lesions elsewhere in the colorectum, patients with appendiceal serrated lesions may benefit from surveillance colonoscopy at intervals analogous to those advised for high-risk serrated polyps, such as every three years[15].

This study has limitations. It is a single case report without long-term follow-up. Larger series are needed to confirm the safety and efficacy of ETA for appendiceal adenocarcinoma and to establish the true incidence of malignant transformation of appendiceal serrated lesions. Additionally, the optimal surveillance strategy after endoscopic resection of appendiceal adenocarcinoma remains undefined. What is more, the follow-up duration of only 6 months is insufficient to establish long-term oncologic outcomes. Extended surveillance is ongoing, and the patient is scheduled for colonoscopy and CT at 12 months, 24 months, and 36 months postoperatively. Longer-term follow-up results will be reported in future communications. Finally, in our case, molecular testing for BRAF mutation and CpG island methylator phenotype was not performed on the resected specimen. Future prospective registries and multicenter collaborations will be essential to address these knowledge gaps.

CONCLUSION

In conclusion, this case represents the initial documentation demonstrating that appendiceal adenocarcinoma can originate from serrated lesions. Furthermore, it establishes that complete endoscopic resection through ETA is both technically achievable and safe in this selected case. This approach facilitates precise pathological staging and has the potential to obviate the need for unnecessary abdominal surgery. It is imperative for endoscopists to recognize the malignant potential inherent in appendiceal serrated lesions and to contemplate full-thickness resection as a definitive therapeutic strategy.

ACKNOWLEDGEMENTS

We thank the participant of this case.