Low-grade appendiceal mucinous neoplasms combined with incidental gallbladder cancer: a case report

Introduction

Low-grade appendiceal mucinous neoplasm (LAMN) represents an uncommon tumor arising from the appendix, categorized within the realm of appendiceal mucinous cysts that exhibit malignant potential or are classified as low-grade. A defining feature of LAMN is the abundant accumulation of mucinous material within the appendiceal lumen, coupled with mild to moderate dysplastic changes in the epithelial cells. Despite its relatively indolent biological nature, some instances of LAMN may evolve into pseudomyxoma peritonei (PMP), resulting in extensive abdominal dissemination and consequently having a profound impact on patients’ quality of life and survival prospects (1). Incidental gallbladder cancer (IGBC) pertains to cases where gallbladder cancer (GBC) is incidentally detected during cholecystectomy procedures conducted for benign gallbladder conditions, such as gallstones and cholecystitis. While its incidence is not elevated, the preoperative diagnosis rate remains exceptionally low due to its nonspecific early symptoms, leading to a situation where the majority of patients are diagnosed only upon postoperative pathological examination. The prognosis of IGBC is intimately tied to the tumor’s stage; patients with lymph node metastasis or distant metastasis, in particular, face a relatively grim outlook. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-285/rc).

Case presentation

A 73-year-old man experienced intermittent abdominal pain and discomfort in the lower right abdomen without any obvious cause 2 days ago. The patient denied nausea, vomiting, acid reflux, abdominal distension, diarrhea, vomiting of blood, chills, rigors, or aversion to cold. The patient came to our hospital for further diagnosis and treatment. After an outpatient examination, the patient was admitted to the hospital with “acute appendicitis”. The patient expressed “feeling overwhelmed and filled with fear for the future” when he had known two primary cancers simultaneously. After discussing the indolent characteristics of LAMN and IGBC, the patient stated, “I trust the team’s decision-making, and there is a basis for closely monitoring and avoiding unnecessary secondary surgery.” During regular follow-ups, the patient felt reassured by his communication with the treatment team and hoped that sharing his experience would provide support for others facing similar complex decisions. We have incorporated a detailed chronological table (Table 1), including corresponding dates and clinical significance, ensuring both intuitive visualization and precise documentation of the patient’s process. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This case report was approved by the Medical Ethics Committee of The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People’s Hospital (No. 2025-054-01). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Abdominal computed tomography (CT) diagnosis showed that the wall of the appendix is slightly thickened (Figure 1A,1B). Abdominal ultrasound diagnosis showed that a blind tube-like structure measuring 5.1 cm × 1.4 cm in size can be seen in the appendix area of the lower right abdomen, with a thickened tube wall, peripheral omentum accumulation, enhanced echo, and an “Onion Skin” sign in the transverse section. A hypoechoic area approximately 1.6 cm deep can be seen in the lower right abdomen (Figure 1C). Meanwhile, gallbladder enlargement with multiple nodular high-density lesions visible within the gallbladder, with larger ones measuring approximately 15 mm in length (Figure 1D,1E), in abdominal CT. Abdominal ultrasound diagnosis showed that the size of the gallbladder is about 14.3 cm × 5.1 cm, and multiple strong echoes can be seen in the gallbladder cavity, with a range of about 7.6 cm × 2.2 cm, accompanied by acoustic shadows. Multiple slightly strong echoes can be seen on the gallbladder wall, with larger ones measuring about 0.4 cm × 0.3 cm, inactive and without shadows (Figure 1F).

Figure 1 Patient’s imaging of abdominal CT and ultrasound diagnosis. (A,B) CT scan showed a slight thickening of the appendix wall, with a mass at the root of the appendix filled with mucus. (C) Abdominal ultrasound showing a blind tube-like structure can be seen in the appendix, with a thickened tube wall, peripheral omentum accumulation, enhanced echo, and an “Onion Skin” sign in the transverse section. (D,E) CT scans showing gallbladder enlargement with multiple nodular high-density lesions visible within the gallbladder. (F) Abdominal ultrasound showed multiple strong echoes that can be seen in the gallbladder cavity, accompanied by acoustic shadows. Multiple slightly strong echoes can be seen on the gallbladder wall, inactive and without shadows. CT, computed tomography.

The patient underwent laparoscopic cholecystectomy and appendectomy. Pathological examination revealed that the appendix measured 4 cm × 3 cm in size (Figure 2A), and the gallbladder measured 11 cm × 7 cm × 3 cm, with a smooth inner wall and a wall thickness of 0.2 cm (Figure 2B).

Figure 2 Surgical images and pathological diagnosis of the patient. (A) The screen showed a tumor visible at the root of the appendix, with dilated lumen and no obvious signs of enlarged lymph nodes or peritoneal spread around it. (B) The screen showed that the overall volume of the gallbladder increased, with slightly thicker walls and a gourd-shaped appearance. No obvious tumors or metastases were observed in the serosal layer of the gallbladder. (C) Acute exacerbation of chronic appendicitis accompanied by peripheral inflammation, with tumor cells containing mucus arranged in the appendix cavity, showing slight proliferation. The tumor mucus has infiltrated the intrinsic muscle layer and subserosal tissue of the appendix but has not broken through the appendix serosal layer (H&E staining; ×200). (D) High-grade dysplasia and local carcinogenesis of some glands in the gallbladder, involving the lamina propria of the mucosa, with no tumor found at the resection margin (H&E staining; ×200). H&E, hematoxylin and eosin.

Pathological diagnosis

(I) Acute exacerbation of chronic appendicitis with peripheral inflammation, consistent with LAMN, involving the subserosal layer, and no tumor found at the root margin (Figure 2C); (II) High grade dysplasia and local carcinogenesis of some glands in the gallbladder, involving the lamina propria of the mucosa, with no tumor found at the resection margin (Figure 2D).

Postoperative follow-up

Due to being in the early stage of LAMN TNM stage (pT3N0M0) and IGBC TNM stage (pT1aN0M0), the patient did not undergo intra-abdominal chemotherapy or radical surgery for GBC.

Discussion

LAMN belong to the family of appendiceal mucinous tumors, which are borderline or low-grade malignant tumors, accounting for about 0.4–1% of all gastrointestinal malignancies and about 70% of appendiceal epithelial tumors (2,3). They are essentially a type of histologically well-differentiated adenoma but can proliferate outside the appendix in a malignant tumor growth pattern, causing accumulation of appendiceal mucus, and leading to appendiceal perforation and abdominal dissemination (4). When a large amount of mucus is produced in the abdominal dissemination site, it is defined as PMP. Due to the easy recurrence of PMP after treatment and a 10-year overall survival rate of approximately 63%, PMP can be defined as a malignant disease, and the number of cells in the mucus is closely related to the patient’s prognosis. The diagnosis of LAMN mainly relies on the following three aspects: (I) Serum tumor markers CEA, CA19-9, and CA125 can be used for the diagnosis and evaluation of LAMN. The normal expression of tumor markers in this case before surgery usually indicates a good prognosis. (II) Imaging examination CT can evaluate LAMN and metastatic lesions (5). Magnetic resonance imaging (MRI) can detect the mucus outside the appendix cavity, predict the peritoneal cancer index (PCI) before surgery, and can be used for follow-up monitoring of tumor recurrence after surgery. (III) Pathological examination can observe the abnormal accumulation of a large amount of mucus in the appendix cavity of LAMN, leading to the dilation of the appendix cavity.

The best treatment for LAMN is still surgical treatment. Typically, LAMN is diagnosed by pathology after appendectomy (6). In cases where the surgical margin is negative and there is no appendiceal perforation or peritoneal involvement, simple appendectomy is safe and has a low postoperative recurrence rate. During the appendectomy process in this case, there was no iatrogenic cause of the appendiceal rupture, and the pathological specimen bag was removed to ensure the safety of the surgery. On the contrary, one should choose to switch to open surgery, locally remove the affected peritoneum, and avoid the transfer of puncture holes. There are also studies suggesting that when LAMN is accompanied by histological manifestations of neuroendocrine tumors or epithelial adenocarcinoma, right hemicolectomy should be performed.

The therapeutic effect of systemic chemotherapy on LAMN is limited, but due to the inertness of LAMN and peritoneal metastasis, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are often feasible. For LAMN patients with peritoneal metastasis, simple right hemicolectomy is often not sufficient, and HIPEC chemotherapy should be received after surgery (7,8). Mitomycin C or platinum-based drugs are the most commonly used chemotherapy drugs. When female LAMN is accompanied by peritoneal metastasis, ovarian metastasis usually occurs. Due to the rapid progression of ovarian tumors and insensitivity to systemic chemotherapy, bilateral oophorectomy and salpingectomy are recommended.

A previous study has shown that serum tumor markers CEA, CA19-9, and CA125 have no definite effect on predicting the recurrence of LAMN (9). We should also use them in follow-up patients and combine them with imaging examinations to better monitor tumor recurrence. Since LAMN patients rarely progress to PMP after simple appendectomy, MRI and tumor marker examinations should be performed every 6 months for localized LAMN patients for 2 years. For LAMN patients with peritoneal metastasis, history of right hemicolectomy or lymph node metastasis, abdominal CT or MRI should be performed every 4–6 months for the first 2 years after surgery to monitor tumor recurrence; if there is no evidence of recurrence within 2 years, the follow-up will be reviewed once a year, and the total follow-up time will not be less than 5 years. Due to the indolent nature of PMP, some authoritative guidelines do suggest extending surveillance to 10 years for pT3 disease to capture late recurrences. It shows that our recommendation is made with awareness of the broader guidelines, thereby providing readers with a more comprehensive and valuable perspective on managing this condition, emphasizing the principle of individualized, shared decision-making in determining follow-up plans.

GBC is the most common type of malignant tumor in the biliary system. The incidence rate of GBC is low in North America. The incidence rate of GBC is relatively high in Chile, India, Japan, and other countries. The incidence rate of GBC in China is about (1.00~1.30)/100,000. Due to the absence of clinical symptoms in patients with GBC, when they experience “cholecystitis” symptoms, GBC is often in a late stage. Although salvage surgeries such as lymph node dissection or liver resection are performed, the recurrence and mortality rates are also high. According to research, the 5-year survival rate for advanced GBC is less than 5%, with a median survival time of 6 months. Despite the poor prognosis, radical surgery remains the only possible cure for GBC patients (10,11).

According to the 8th edition of American Joint Committee on Cancer (AJCC) staging, the surgical treatment methods and approaches for GBC can be roughly classified into the following categories. (I) For Tis and T1a stage GBC, simple cholecystectomy can achieve tumor radical effect, but when dealing with the gallbladder, it is important to avoid tumor dissemination caused by gallbladder rupture. (II) For T1b stage GBC, perform liver wedge resection and regional lymph node dissection at a distance of more than 2cm from the gallbladder bed (12). (III) For T2 stage GBC, according to the AJCC 8th edition tumor location staging, it is divided into the peritoneal side (T2a) and hepatic side (T2b). (IV) T2a is separated from the liver, and it is recommended to perform a combined wedge resection of liver tissue and regional lymph node dissection at a distance of more than 2 cm from the gallbladder bed. (V) The proportion of T2b stage GBC with vascular and nerve invasion and lymph node metastasis is high. It is recommended to perform a wedge resection of the liver or resection of liver 4b+5 segments + regional lymph node dissection (13). However, for T1b, T2a, and T2b stage GBC, intraoperative frozen pathology often makes it difficult to determine the depth of invasion accurately. Therefore, if preoperative imaging or intraoperative exploration suggests suspected invasion of the gallbladder bed, it is recommended to perform liver 4b+5 segment resection combined with regional lymph node dissection, rather than simple wedge resection. This strategy can reduce the risk of positive margins. If it is clear during the operation that there is no deep infiltration, wedge resection (margin ≥2 cm) can be used as an alternative option. (VI) For GBC in the T3 stage, it is recommended to perform liver resection at 4b+5 segments and regional lymph node dissection (14). For the T3N1 stage, it is recommended to perform the right hemihepatectomy or hepatic trisegmentectomy. If some T3 stage involves extrahepatic organs, combined organ resection should be performed. Extended right hepatectomy in T3N1 GBC aims to achieve R0 resection by addressing direct hepatic invasion and adjacent structure involvement. It enhances local control and may improve survival in select patients with resectable nodal (N1) disease, particularly when combined with lymphadenectomy. However, its use must balance morbidity risks and requires multidisciplinary evaluation to optimize outcomes. (VII) For T4 stage GBC, the lymph node metastasis rate is relatively high, reaching over 75%. In addition, GBC has more distant metastasis, so the prognosis of patients is poor. Multi-center data show that the average survival time of T4-stage patients is only 8.2 months, with a median survival time of 6.3 months. The surgical plan is determined based on the degree of invasion, usually involving right hemihepatectomy or hepatic trisegmentectomy. If multiple organs are involved, combined multi-organ resection or chemotherapy is required. Multiorgan resection in locally advanced GBC is indicated when tumors invade adjacent organs (e.g., liver, bile duct, colon, or duodenum), aiming to achieve R0 margins. It improves survival in carefully selected patients by addressing locoregional spread, though morbidity risks (e.g., bile leakage, infection) are significant. Preoperative imaging and multidisciplinary assessment are critical to evaluate resectability and optimize patient selection. Studies suggest survival benefits in node-negative or limited N1 disease, but outcomes depend on tumor biology and adjuvant therapy integration. (VIII) For IGBC, frozen pathology is highly suspected during surgery, and the surgical scope should be determined based on the staging. If postoperative pathology reveals Tis or T1a stage, follow-up will be conducted, and if T1b or above stage is detected, GBC radical surgery will be performed according to the above method.

IGBC refers to GBC diagnosed pathologically during or after cholecystectomy. It is the most common malignant tumor of the biliary tract, with different incidence rates around the world (15). With the wide application of laparoscopy, the incidence rate of IGBC has increased year by year, about 0.2–2.8%. Meanwhile, it was found that 45% to 60% of IGBC patients still have residual lesions after cholecystectomy. IGBC is often in an early stage, and for patients with local cancer, simple cholecystectomy can usually achieve a cured state. However, for patients with bile leakage, positive margins, poor tumor differentiation, or a high risk of metastasis during surgery, laparoscopic exploration is often necessary again (16). Radical cholecystectomy, liver lobectomy, and regional lymph node dissection are the best treatment options for IGBC, and postoperative adjuvant chemotherapy may improve prognosis (17). Retrospective analysis shows that the patient in this case had IGBC and localized cancer. The gallbladder was completely removed after being fitted with a specimen retrieval bag, and there was no bile leakage or contact with the puncture hole during the process. Therefore, simple removal of the gallbladder is sufficient. Routine re-exploration or port-site excision is not indicated for T1a disease. The prophylactic “no-touch” technique, embodied by the use of a retrieval bag, is not merely a technical detail but the paramount surgical lesson emanating from this unique case of synchronous tumors. Through this approach, we can completely avoid the catastrophic risk of peritoneal inoculation in the event of iatrogenic rupture of LAMN and GBC. Even if there is a risk of trocar hole metastasis after the first cholecystectomy of IGBC, it is not recommended to perform trocar hole tissue resection again because it cannot improve the patient’s prognosis and may also pose a risk of incisional hernia.

This case reports a rare case of LAMN combined with IGBC. For pT1a GBC, we cite the National Comprehensive Cancer Network (NCCN) guideline to support that a simple cholecystectomy is curative and that extended resection increases morbidity without survival benefit (18). For margin-negative LAMN, we cite the PSOGI consensus to justify that appendectomy alone is sufficient and that right hemicolectomy is not indicated (19). This allows us to reframe the approach not as “conservative”, but as the precisely indicated and guideline-endorsed optimal surgical strategy for each specific stage of disease. At present, the patient’s condition is stable and recovering well after surgery. They have been discharged and are still under follow-up.

Conclusions

This first reported case of concurrent LAMN and IGBC highlights that despite their rarity, rigorous no-touch techniques, for example, intraoperative specimen bag use, and tailored surveillance can optimize outcomes in such complex dual malignancies. These findings underscore the importance of meticulous surgical and follow-up strategies in managing synchronous rare tumors, offering novel insights for multidisciplinary approaches to multiprimary cancers.

Acknowledgments

The author would like to thank the pathologists from Yichang Central People’s Hospital for their assistance.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-285/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-285/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-285/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This case report was approved by the Medical Ethics Committee of The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People’s Hospital (No. 2025-054-01). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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