The study was approved by the institutional review board of Tokai University Hachioji Hospital (Hachioji, Japan; approval no. R14-242). Informed consent for the appendectomy was obtained from the patients and/or family members.

Radical appendectomies/ileocecal resections were performed without attempting conservative therapies, including antimicrobial agents, if an abdominal CT or ultrasound identified an appendiceal lesion. By reviewing the pathological database of the appendectomy specimens from patients who underwent an appendectomy between March 2002 and September 2014 at Hachioji hospital, a total of 803 patients were identified, among whom 752 had appendiceal disease. For clinicopathological analysis, appendiceal neoplasms were primarily classified according to the 2010 World Health Organization (WHO) classification (12). A total of 55 patients were excluded, including 11 with metastatic carcinoma or tumor invasion from adjacent organs, and 44 patients with a normal appendix who underwent an incidental or prophylactic appendectomy during surgery for other diseases, such as hemicolectomy/ileocecal resection for cecal cancer, diverticular disease or at the patient's request. Also, single center cases of material from The Tokai University Hachioji Hospital (Tokyo, Japan) were investigated.

The resected appendiceal lesions were routinely fixed with 10% neutral buffered formalin, embedded in paraffin, and cut into 3-µm thick sections that were stained with hematoxylin and eosin. For the present study, 2 expert pathologists and a clinician reviewed the slides. Appendiceal neoplasms (1–22 slides per case) were classified as benign (adenoma, dysplasia or mesenchymal tumor) or malignant [G1-G3 neuroendocrine tumor (NET), adenocarcinoma, mucinous adenocarcinoma, mixed adenoneuroendocrine carcinoma (MANEC) arising from pre-existing goblet cell carcinoid (13,14) or low-grade appendiceal mucinous neoplasm (LAMN)]. As mucinous adenocarcinomas exhibit infiltration or invasion with fibrous desmoplasia, tumors that featured complex epithelial proliferation (complex papillary fronds and cribriform glandular spaces) or high-grade cytological atypia (full-thickness nuclear stratification, vesicular/prominent nuclei, and mitotic activity) and infiltration with fibrous desmoplasia were classified as mucinous adenocarcinomas (Fig. 1).

Conversely, tumors that exhibited minimal architectural complexity (villiform, flat epithelial proliferation and focal papillary excrescences) and low-grade cytologic atypia (mild nuclear enlargement, nuclear stratification, rare mitotic figures and single cell necrosis) were classified as LAMN (Fig. 2A). LAMN may be a precursor to low-grade pseudomyxoma peritonei (12), although its biological behavior is ambiguous; therefore, these tumors were classified separately according to the Japanese Society for Cancer of the Colon and Rectum classification, although they were also included as adenocarcinomas based on the 2010 WHO classification (12,13,15).

Pseudomyxoma peritonei accompanying mucinous adenocarcinoma or LAMN were also identified. Peritoneal tumors composed of atypical glands in desmoplastic stroma or tumors with high cellularity and cytological atypia containing pools of mucin were classified as mucinous adenocarcinoma-associated pseudomyxoma peritonei (high-grade; Fig. 1C) (12), whereas tumors composed of mucinous epithelium with low-grade atypia and containing mucin pools were classified as LAMN-associated pseudomyxoma peritonei (low-grade; Fig. 2B) (12). Acellular mucinosis were not categorized as an appendiceal neoplasms, but rather as a secondary lesion as mucocele is a descriptive term, according to the 2010 WHO classification (12).

The variables for evaluation included the age and sex of the 752 patients, the initial surgical findings (neoplasm or inflammation), and the age and sex of the patients grouped according to the 2 basic lesion types. The present study focused on the pathological characteristics of the appendiceal neoplasms and the clinical characteristics of the patients with these neoplasms. In this group of patients, the presenting symptoms, imaging diagnosis, preoperative diagnosis, and the types and incidence of appendiceal lesions determined by postoperative pathological examination were also reviewed. Special note was made of the intramucosal lesion types.

Patients with appendiceal neoplasms were divided into two groups aged <60 and ≥60 years, and the difference in the incidence of appendiceal neoplasms was analyzed by the Mann-Whitney U and χ² tests. All statistical analyses were performed with SPSS 21.1 (IBM Corp., Armonk, NY, USA). P<0.05 was considered to indicate a statistically significant difference.

The 752 patients ranged in age from 2 to 89 years, with a mean age of 34.2 years. There were 431 males and 321 females. The surgical diagnosis was inflammation (appendicitis) in 735 patients (97.7%), and appendiceal neoplasm in 17 patients (2.3%).

The profiles of the 17 patients with appendiceal neoplasms are included in Table I, whereas the age-specific distribution of the histologic diagnoses are included in Table II. The 17 patients ranged in age from 36 to 86 years, with a mean age of 77.0 years. There were 10 men and 7 women. The majority of the appendiceal neoplasms were identified in patients aged ≥60 years (14/17, 82.3%), and there was a significant difference in incidence between patients aged ≥60 years and those aged <60 years (P<0.001). The chief presenting symptom of the majority of patients with an appendiceal neoplasm was right lower quadrant pain (n=11, 64.7%). A total of 2 patients (11.7%) presented with an abdominal mass, 1 patient (5.88%) had generalized abdominal discomfort, and 3 patients (17.6%) had no symptoms. In these 3 patients, the appendiceal neoplasm was identified with the investigation of elevated serum tumor markers, such as carcinoembryonic antigen, or incidentally by PET/CT or preoperative workup for gastric cancer. The tumor was benign in 3 patients (17.6%) and malignant in 14 patients (82.3%). In the 3 patients with benign disease, the preoperative clinical diagnosis was appendiceal tumor, appendiceal cancer, and secondary appendicitis caused by ileus strangulation, respectively. In the 14 patients with malignancy, the preoperative clinical diagnosis was appendicitis (n=8, 57.1%), perforated appendiceal diverticulitis (n=1, 5.88%) or appendiceal neoplasm (n=5, 35.3%).

The 3 benign neoplasms included 1 tubular adenoma, 1 tubulovillous adenoma, and 1 mesenchymal schwannoma (Fig. 3). The 14 malignant neoplasms included 6 adenocarcinomas (4 mucinous adenocarcinomas, 1 papillary adenocarcinoma and 1 moderately differentiated adenocarcinoma), 1 MANEC (Fig. 4), 1 neuroendocrine tumor (G1), and 6 LAMNs (1 with low-grade pseudomyxoma peritonei). One malignant tumor was associated with high-grade pseudomyxoma peritonei. None of the cases were considered discordant, i.e., there were no low-grade appendiceal tumors combined with high-grade peritoneal tumors. A total of 4 (23.5%) of the lesions were intramucosal neoplasms, including adenomas and in situ carcinomas (patients 1, 2, 7, and 8).

The 735 patients with appendicitis ranged in age from 2 to 89 years, with a mean age of 28.0 years. They included 421 males and 314 females. Appendicitis was catarrhal in 80 patients (10.9%), phlegmonous in 352 patients (47.9%), and gangrenous in 268 patients (36.5%). A total of 26 patients (3.5%) had chronic inflammatory appendicitis that had not resolved with antibiotic treatment, 8 patients (1.1%) had appendiceal diverticulitis and 1 patient (0.1%) had an underlying Entamoeba histolytica infection. Almost half (43.1%) of the patients with appendicitis were <10 years old. Seven of these young patients had gangrenous appendicitis, and 6 (85.5%) of those 7 patients were under 4 years of age. More than half (63.7%) of the patients with gangrenous appendicitis were over 60 years old.