Appendiceal mucinous neoplasms (AMNs) are a unique and rare category of appendiceal tumors, accounting for approximately 1% of all gastrointestinal neoplasms. The diagnosis of AMN typically occurs through postoperative histopathological examination following surgical resection for suspected appendicitis. AMN is identified in around 0.2 − 0.3% of appendectomy specimens6–8 and is characterized by mucosal hyperplasia that can progress invasively through the appendiceal wall, leading to extensive mucinous deposition within the peritoneal cavity. This clinical manifestation is recognized as PMP,9 which carries a dismal prognosis once established and is predisposed to recurrence. Hence, prompt diagnosis and intervention prior to the onset of PMP are imperative for optimal patient outcomes.
AMN is most common in middle-aged and older women.10–13 The most common symptoms of AMN are acute or chronic abdominal pain in the lower right quadrant and a mass in the right iliac fossa. The nonspecific symptoms of AMN closely resemble those of appendicitis, with about a quarter of patients presenting without typical symptoms.7 Laboratory investigation may indicate elevated levels of CEA or CA199 levels in some patients.12,14,15 In the current case, CEA level were mildly elevated 3 years earlier at 12.3 ng/mL (normal: < 10 ng/mL). As the disease progressed, CEA, CA125, and CA199 levels showed significant elevation, suggesting the diagnostic significance of CEA as a serum tumour marker in AMN. Ultrasonography and abdominal CT scans play a crucial role in the diagnosis of AMN.13 Mucinous cysts typically appear hypoechoic on ultrasound with varying mucus density, and in some instances, calcification or nodules may be observed in the appendiceal wall.16 On CT imaging, AMN presents as an oval or tubular cystic mass within the appendix, characterized by cystic dilation of the appendiceal lumen exceeding 1.3 cm and calcification of the cystic wall.13,17 following the development of PMP, thickening of the peritoneum and omentum is observed, with the formation of "scalloped" indentations around the liver and spleen.13,18
In this particular case, the patient presented with abdominal pain and low-grade fever 3 years prior. Abdominal ultrasound suggested an appendiceal lumen size of 6.9 cm × 1.8 cm along with a periappendiceal abscess (Fig. 4B). Subsequent abdominal CT indicated significant thickening of the appendiceal lumen, obscuration of the surrounding fat pad, and an encapsulated fluid density shadow in the distal appendix (Fig. 4C-D). The diagnosis was acute appendicitis with periappendiceal abscess. Two months later, the patient was again hospitalized in the surgery department due to abdominal pain. Abdominal CT showed no substantial changes compared to previous examination, and the diagnoses of appendicitis and appendiceal abscess were reaffirmed. Given the lack of significant therapeutic response, the surgeon recommended abdominal exploration and potential appendectomy, which the patient declined. Consequently, the patient's condition deteriorated rapidly, culminating in the development of PMP.
During colonoscopy, AMN presents as a smooth submucosal elevated lesion near the appendiceal orifice 19–22 and may exhibit a crater-like appearance 7 with inflammatory exudate overflowing from the appendiceal orifice.22 In contrast to documented cases in the literature, the patient in question did not exhibit protrusion of the appendiceal orifice into the intestinal lumen and a large amount of viscous mucus in the appendiceal lumen. Observation through the appendiceal orifice revealed a characteristic undulating mucosa within the appendiceal lumen, with the presence of a white mucinous deposit. Upon retrospective examination of the patient's medical history, it was note that the patient had undergone two colonoscopies 3 years prior. During the initial colonoscopy, fecal matter obscured the appendiceal opening (Fig. 5A), and the endoscopist failed to adequately clear the area. Subsequent evaluation during the second colonoscopy four months later revealed persistent fecal coverage of the appendiceal orifice (Fig. 5B). However, significant swelling and stenosis of the appendiceal orifice was observed, the surrounding mucosa was stiff, and there was an overflow of a small amount of white mucus (Fig. 5C), of which the primarily liquid component was mucin.22 Pathology of the appendiceal orifice was suggestive of only chronic inflammation, likely attributed to the limited biopsied tissue obtained, consistent with findings documented in the literature.22 Previous studies have categorized LAMN into two subtypes, LAMN type 1, characterized by low mucin content confined to the appendiceal lumen, while LAMN type 2, distinguished by mucin infiltration into the submucosal or deeper layer, posing a higher risk of progression to PMP.11Klag et al 21firstly reported 3-year endoscopic follow-up of a patient with LAMN type 1 and concurrent ulcerative colitis. Despite an early misinterpretation of the lesion as fecal contamination during surveillance colonoscopy, the lesion exhibited no significant changes over the 3-year period, suggesting a benign course of the LAMN type 1. In our case, the rapid progression of the lesion over 3 years and the development of PMP suggested that the patient had LAMN type 2, demonstrating for the first time the rapidly progressive course of LAMN type 2 lesions. The alterations in the appendiceal orifice observed during the three-year period via colonoscopy revealed characteristic undulating epithelial changes. Additionaly, the extraction of a substantial volume of mucus and mucin casts from the appendiceal lumen represented a rare clinical occurrence.
Due to escalated mucus production, the appendiceal lumen gradually dilates, eventually leading to rupture of the appendix and spreading of the gelatinous material and tumour cells to the peritoneum, resulting in the development of PMP. The presence of a substantial quantify of mucin-laden mucus in the peritoneal cavity is commonly referred to as "jelly belly".6 In some cases, women may develop ovarian masses, while men are more prone to developing new hernias.23 LAMNs are precursor lesions of PMP, necessitating surgical intervention in all instances.24 When LAMN is confined to the appendiceal wall, the risk of disease recurrence after appendectomy is low.9 Care should be taken during the operation to completely remove the appendix to minimize the risk of iatrogenic rupture and peritoneal colonization. The 5-year survival rate is 79.52%.8 The prognosis of AMN hinges on the occurrence of progression to PMP. Following disease advancement, complete eradication of all tumor cells becomes unfeasible even with surgical intervention, owing to extensive peritoneal dissemination and organ infiltration. In such scenarios, a combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is essential to enhance long-term survival, diminish recurrence rates, and impede disease progression.11,25
AMN poses a rare clinical encounter and is often overlooked by clinicians and radiologists, rendering it susceptible to misdiagnosis and delayed diagnosis and treatment. AMN should be considered in cases with a long history of abdominal pain in the right lower quadrant, abdominal mass, recurrent appendicitis, elevated tumor markers, focal well-defined cystic mass on CT, and characteristic progression on enhanced CT.17 Such cases warrant detailed differential diagnosis and timely treatment. 26Particularly, AMN should be sontemplated in older women exhibiting nonspecific symptoms resembling those of appendicitis.10 Colonoscopic identification plays a crucial role in achieving an accurate diagnosis and guiding the management of AMN.27 It is important to note that due to the limited size of biopsy sample, pathology results often indicate inflammation but do not definitively rule out the presence of AMN.
While CT remains the primary modality for examination, colonoscopy holds the potential to identify alterations in the appendiceal orifice during the initial stages of the disease, even before the dilation of the appendiceal lumen becomes apparent. Endoscopic practitoners should exercise diligence in examining the appendiceal orifice. Given the unpredictable biological behavior of AMN, comprehending its features and facilitating early detection, timely diagnosis, and treatment are imperative to mitigate the incidence of PMP and enhance patient outcomes.