A case of low-grade appendiceal mucinous neoplasm with infection treated with ileal resection

The 5th edition of the 2019 World Health Organization (WHO) classifies appendiceal epithelial lesions into low-grade appendiceal mucinous neoplasms (LAMN), high-grade appendiceal mucinous neoplasms (HAMN), and adenocarcinomas (mucinous adenocarcinoma, mucinous adenocarcinoma with signet ring cells, signet ring cell carcinoma, and non-mucinous adenocarcinoma colorectal type) [1]. Appendiceal mucinous neoplasms (LAMN and HAMN) are extremely rare, accounting for only 0.27% of appendectomy specimens [2]. Diagnosing LAMN is difficult as it can be misdiagnosed as appendicitis [3]. Previous studies have reported cases that were asymptomatic for long periods [4]. We treated a case of LAMN with an infection that required surgery after 14 years of no treatment. Given the rarity of this presentation, we report this case alongside a review of the relevant literature.

A 54-year-old woman with a five-day history of right abdominal pain and fever was admitted to our hospital. The patient presented with a solitary congenital kidney. She underwent surgery at approximately 20 years of age for a left ovarian cyst and bicornuate uterus, and bypass surgery at 28 years of age for adhesive bowel obstruction due to adhesions in the sigmoid colon. At 46 years, she underwent surgery for postoperative adhesive bowel obstruction, and at 52 years, she underwent a left axillary lipoma resection. Computed tomography (CT) performed 14 years previously indicated a cystic lesion that appeared contiguous with the appendix. Magnesium oxide, epinastine, tizanidine, diazepam, loxoprofen, sodium esomeprazole, and rizatriptan were administered. On arrival at our hospital, the patient’s temperature was 38.5 °C; all other vitals were stable. Mild tenderness was noted in the right lower abdomen; however, no signs of peritoneal irritation were observed. An initial hematological investigation revealed a white blood cell count of 7,370/mm³ with 79.0% neutrophils and elevated C-reactive protein (CRP) levels (10.95 mg/dL); there were no other major outliers. Abdominal CT revealed a cystic lesion, measuring 9 cm in diameter, extending from the tip of the appendix, accompanied by surrounding inflammation (Figure 1). Magnetic resonance imaging (MRI) revealed uniformity inside the cyst, which was attributed to fluid retention (Figure 2). Based on these findings, we diagnosed appendiceal mucinous neoplasm with infection and administered intravenous cefmetazole sodium. The patient was scheduled for surgery after the inflammation subsided; however, she did not respond to treatment and underwent ileocecal resection with D2 lymphadenectomy because of the possibility of malignancy on the 8th day of the hospitalization. Given the patient’s prior surgical history, the anticipated presence of adhesions to adjacent organs secondary to inflammation, and the substantial size of the tumor, a laparotomic approach was selected for resection. The tumor was located on the outer dorsal surface of the cecum and firmly attached to the cecum but was removed without damage. Histopathological examination revealed a LAMN with infection (Figure 3). The cyst wall was fibrotic and thickened with clusters of chronic inflammatory cells. The cyst lumen was almost devoid of epithelial cells. The remaining epithelium comprised a single layer of adenomatous columnar epithelium. A few atypical cells were observed. Mucus cytology revealed clusters of adenocytes with irregular nuclei.

The patient’s inflammatory response improved postoperatively. She experienced postoperative ileus; however, her symptoms improved with decompression through a nasogastric tube, and she was discharged on postoperative day 20.

The presence of low-grade cytologic atypia, together with one of the following, is defined as a LAMN: loss of the muscularis mucosa layer, submucosal fibrosis, pushing invasion, dissection with acellular mucin in the wall, undulating or stratified epithelial growth, appendiceal rupture, and the presence of extra-appendiceal mucin and/or cells. Mucinous neoplasms that display structural features similar to those of LAMN lack infiltrative invasion; however, cytologically high-grade atypia has also been identified as HAMN. Mucinous adenocarcinoma is used to describe mucinous tumors with infiltrative invasion [5]. Köhler et al. reported that the average age at diagnosis was 62 years, with 63% of patients being female, and the 5-year survival rate was approximately 80% [6]. An important complication of LAMN is pseudomyxoma peritonei (PMP), which is thought to be disseminated by the rupture of the tumor, causing mucus to disperse into the abdominal cavity [7]. In patients without perforation or PMP, appendectomy is performed; if mucus is disseminated into the abdominal cavity, hyperthermic intraperitoneal chemotherapy perfusion (HIPEC) is recommended in addition to tumor resection [8].

There is no consensus regarding the choice of technique (right hemicolectomy or appendectomy) or approach (laparoscopic or open surgery). With regard to the surgical technique, laparoscopic resection is perable if the appendix can be removed without perforation. In recent years, there have been increasing reports of laparoscopic resection [9]. Lymph node dissection is not necessary due to the low probability of lymph node metastasis in LAMN [10]. However, a biopsy carries the risk of intra-abdominal dissemination, and a preoperative diagnosis is often not made. Dissection is required when the tumor is malignant, such as in mucinous adenocarcinoma of the appendix. Theore, we selected a procedure similar to that for malignancy in consideration of the possibility of malignancy.

In this case, a cystic lesion was noted on CT 14 years prior and had been growing ever since; however, no surgical intervention was performed. Fortunately, there were no PMP and the tumor was removed without perforation. Because of the patient’s previous surgical history, expected adhesion to the surrounding organs due to inflammation, and the large size of the tumor, we chose to remove it via a laparotomy. Although the prognosis of LAMN is generally good, rupture, torsion [11], and infection have been reported in some cases, as in the present case. In addition, it is difficult to obtain a definitive diagnosis before surgery, and early surgical intervention is desirable for diagnostic purposes. In such cases, the surgical plan should be caully designed to avoid tumor damage.

The recurrence rate of LAMN was 2.7% [12]. Although there are no guidelines for postoperative surveillance, the most common surveillance method is imaging, and tumor markers are frequently used in combination [12]. Our hospital performs blood tests every six months and imaging tests every year for five years postoperatively. Furthermore, if R0 resection is performed for nonperforated LAMN, the risk of recurrence or postoperative PMP is extremely low, and surveillance may be omitted [13].

If LAMN can be resected without perforation, the risk of recurrence is low, and the prognosis is excellent; theore, early resection should be considered. It is important to caully plan surgery to avoid damaging the tumor.