Introduction

Appendiceal mucinous neoplasm (AMN) was described in 1842 by Rokitansky as a luminal dilation of the appendix caused by accumulation of mucus secretion^1,2.

Non-carcinoid appendiceal neoplasms have an incidence of about 0.9 per 100,000 per year; thus, AMNs represent 0.2-0.7% of all appendectomies^1,3,4, while 25% correspond to adenocarcinomas.

These tumors are more prevalent in women (female-to-male ratio 4:1) with mean age of 55 years⁵.

Incidental finding is the most common clinical presentation, but they may present as chronic pain in the right iliac fossa or be found in appendectomy specimens sent for pathological examination^3,5,6. The diagnosis should be suspected in patients with chronic pain in the right iliac fossa^1,7.

Non-carcinoid appendiceal neoplasms include adenoma (similar to colorectal adenoma), serrated lesion (polyp), low-grade appendiceal mucinous neoplasms (LAMN), high-grade appendiceal mucinous neoplasms (HAMN), mucinous adenocarcinoma, nonmucinous appendiceal adenocarcinoma ^4,8-10.

The World Health Organization (WHO) classifies LAMNs as non-invasive tumors⁷. High-grade appendiceal neoplasms share some histological features with LAMNs but exhibit more aggressive cytologic atypia and are less prevalent^8,10. Both LAMNs and HAMNs are considered benign neoplasms as they do not produce infiltrative invasion like mucinous adenocarcinoma⁴. These tumors have malignant potential as they may perforate and spread throughout the peritoneal cavity. Perforation may be spontaneous or iatrogenic, and when it includes abundant mucin production, the term pseudomyxoma peritonei (PMP) is used. This serious complication may cause mucinous ascites and peritoneal implants^2,4,6,9.

KRAS mutation is common but microsatellite instability or BRAF mutation are rare^6,8,10,11.

Appendicular mucocele is a descriptive term used to encompass benign or malignant conditions that can produce cystic dilatation of the appendix^3,6; or may just be a retention cyst (inflammatory mucocele)³. Lesions > 20 mm are more likely to be mucinous neoplasms, especially in the absence of obstruction^5,6. Mucoceles < 20 mm are rarely malignant, but those > 60 mm have high probability of malignancy and spontaneous perforation^1,12.

Preoperative diagnosis is difficult in the absence of luminal dilation, but it should be suspected if the intraluminal diameter of the appendix is > 13 mm or if there are mural calcifications or intraluminal contents^3,14.

Accurate diagnosis of AMN and PMP is clinically relevant as management may include prolonged follow-up or radical treatment such as cytoreductive surgery with intraperitoneal chemotherapy^6,8.

Therefore, appendectomy is the treatment of choice for AMN to preserve the integrity of the surgical specimen. Management in case of positive margins with cells or mucin is controversial. Some authors suggest extending the resection while others state that follow-up is safe even in case of perforation¹⁵. Right hemicolectomy does not offer any additional benefit over appendectomy alone for patients with LAMN^8,10. Unnecessary incisions in the entire wall of the appendix should not be made during surgery to prevent dissemination of mucus or neoplastic cells into the peritoneal cavity^13,16.

There is little evidence about the postoperative management and follow-up of neoplasms of the appendix. A reasonable strategy includes contrast-enhanced computed tomography (CT) scan of the abdomen and tumor markers (CEA, CA 125, CA19.9) one year after the resection, decreasing the frequency in case of normal results⁴, discontinuing follow-up after 5 years^6,9,13,17,18.

Colonoscopy is recommended to rule out synchronous neoplasms^4,6,20.

Objectives

The aim of this study was to present four case reports of patients admitted in the emergency department of Sanatorio Parque (Centro de Emergencia Rosario) with acute appendicitis who underwent appendectomy at the Department of General Surgery during 2019 and had a histopathological diagnosis of NMA.

Case reports

We describe four case reports. The demographic and laboratory data are described in Table 1.

Table 1 Demographic and laboratory data of each patient 

All the patients underwent contrast-enhanced multislice CT scan of the abdomen and pelvis to rule out other diagnoses of acute abdomen. The history of iodinated contrast media adverse reactions and kidney function were evaluated before the procedure and beta subunit was determined in all women of childbearing age before exposure to radiation.

Case #1

A 56-year-old female patient without significant history sought medical care due to periumbilical abdominal pain that had started five days before and radiated to the right iliac fossa, accompanied by fever within the past 24 hours. On physical examination, she presented pain in the right iliac fossa and hypogastrium with guarding. A CT scan of the abdomen and pelvis was performed (Fig. 1A).

Laparoscopic surgery was decided. During surgery, an appendiceal mass was found and appendectomy was performed.

The pathology report of the surgical specimen informed acute purulent appendicitis with periappendicitis and mesoappendicitis associated with mucinous neoplasm, low-grade dysplasia and irregular pools of mucinous material in the appendiceal wall (Fig. 1.B). Positive margin with foci of mucin within the wall.

On postoperative day 30, a new CT scan of the abdomen and laboratory tests were performed on an outpatient basis, with normal results. The patient underwent video-assisted colonoscopy. There were no lesions in the fundus of the cecum (Fig. 1.C). A biopsy sample obtained from the ostium of the appendix showed normal mucosa.

Figure 1 A: CT scan with intravenous contrast in the portal venous phase, axial section, showing vermiform appendix with a maximal diameter of 12 mm and cystic dilation within the appendiceal lumen (arrow). A collection with well- defined walls associated with changes in the surrounding fat planes (arrowhead) is observed in the tip of the appendix. B: Microscopic examination of the surgical specimen; hematoxylin and eosin stain (HE X10) shows low-grade appendiceal mucinous neoplasm associated with inflammation of the wall. A pushing like image is observed, without infiltration (arrow). C: Video-assisted colonoscopy. The fundus of the cecum is normal. 

Case #2

A 39-year-old male patient without significant history asked for medical advice due to abdominal pain which had started 9 days before in the epigastric region and then migrated to the right iliac fossa, without accompanying symptoms. A CT scan of the abdomen and pelvis was performed (Fig. 2.A).

The patient underwent laparoscopic surgery. The vermiform appendix was enlarged, and a tumor was visualized, The appendix was resected.

The pathology report informed the presence of a distal cyst in the vermiform appendix, LNMA and clear margins (Fig. 2.B).

Figure 2 A: CT scan with intravenous contrast in the portal venous phase, coronal view showing vermiform appendix with a maximal diameter of 10 mm (arrow). The surrounding fat planes are preserved. B: Microscopic examination of the surgical specimen; hematoxylin and eosin stain (HE x4) shows luminal dilation and intraluminal accumulation of mucus occupied by mucinous material (arrow) and lining of the mucosa by low grade villous type epithelium (arrowhead). 

Case #3

A male patient aged 47 years without significant past history complaint of diffuse abdominal pain that had started 72 hours before and migrated to the right iliac fossa within the past 12 hours, accompanied by decreased appetite and fever. A CT scan of the abdomen and pelvis was performed (Fig. 3.A).

Figure 3 A: CT scan with intravenous contrast in the portal venous phase, axial view, showing vermiform appendix with a maximal diameter of 11 mm (arrow), inflammatory changes in the surrounding fat and thickening of the distal ileum walls (arrowhead). B. Histology of surgical specimen (hematoxylin-eosin, magnification x4), showing replacement of normal epithelium by mucinous epithelium with signs of low grade atypia (arrow). No underlying lymphoid tissue is observed. 

Case #4

A 77-year-old male patient with a history of benign prostatic hyperplasia and hypertension was admitted with lower abdominal pain and fever. The pain had started in the periumbilical region 24 hours before. A CT scan of the abdomen and pelvis was performed (Fig. 4.A). During laparoscocopy, appendicular peritonitis and an appendiceal mass were found. The pathology report informed LAMN associated with acute appendicitis, with mucinous lakes in the muscular layer in the distal end (Fig. 4.B).

Figure 4 A: CT scan with intravenous contrast in the portal venous phase, coronal view, showing vermiform appendix with a maximal diameter of 11 mm (arrow) associated with changes in the surrounding fat and thickening of the distal ileum walls (arrowhead). B. Histology of surgical specimen (hematoxylin-eosin, magnification x4) showing mucinous lakes in the wall of the appendix (arrow). The patient underwent video-assisted laparoscopy during which appendicular peritonitis was observed with an appendiceal mass in the right iliac fossa. The pathology report informed LAMN associated with acute purulent appendicitis (Fig. 3.B). 

Discussion

In 2019, 303 appendectomies were performed in our hospital. The postoperative diagnosis of AMN was made with the pathology report in 4 of these patients.

As this condition is very rare, we considered that this number is very significant, and thus we decided to present this paper.

In our experience, all the patients presented acute symptoms suggestive of acute appendicitis. The most common sign was abdominal pain in the right iliac fossa with localized guarding, absence of signs of peritonitis, and sequence of Murphy.

The CT scan images were not suggestive of AMN and the diagnosis was always retrospective. Although the prevalence is higher in women with a female-to-male ratio of 4:1, we observed that 75% of our patients were men. This can be explained by a bias due to the low number of patients in our population, so we cannot draw a conclusion about the demographic characteristics of this disease.

Conclusion

In the presence of chronic pain in the right iliac fossa with acute abdomen due to an acute appendicitis with a luminal diameter > 13 mm or wall calcifications in imaging tests, the diagnosis of AMN should be suspected^2,3.

In these cases, extreme care must be taken during surgery to avoid perforation of the appendicular wall and the subsequent dissemination of neoplastic cells or mucus into the peritoneum^13,16.

One of the most dreadful complication of AMN is PMP; thus, postoperative follow-up is crucial in these patients².