The most common symptom in both men and women with pseudomyxoma peritonei syndrome is a gradually increasing abdominal girth. In women, the second most common symptom is an ovarian mass, usually on the right side and frequently diagnosed during a routine gynecologic examination. In men, the second most common symptom is a new-onset hernia. The hernia sac is found to be filled by mucinous tumor. In both men and women, the third most common presenting feature is appendicitis. This is the clinical manifestation of rupture of an appendiceal mucocele that contains intestinal bacteria.

The most common varieties of epithelial malignancy within the appendix are mucinous adenomas or mucinous adenocarcinomas. Mucinous tumors from the appendix are many times more common than the intestinal type of adenocarcinoma. In contrast, only approximately 15% of colonic adenocarcinomas are of the mucinous variety. The preponderance of mucinous tumors is probably related to the high proportion of goblet cells within the appendiceal epithelium.

At the time of exploratory laparotomy or laparoscopy, it may be difficult or impossible to distinguish a mucinous tumor of the appendix from a benign mucocele. Both benign and malignant tumors of the appendix are likely to cause symptoms, and there may be mucin collections within the right lower quadrant or throughout the abdominopelvic space. Two features should be sought that will histopathologically separate tumors that are inconsequential with complete removal from those capable of causing death from progressive pseudomyxoma peritonei syndrome. The first is invasion through the appendiceal wall by neoplastic glands. The second is atypical epithelial cells found within the extra-appendiceal mucin collection. If these clinical features occur, the diagnosis of pseudomyxoma peritonei syndrome is made and aggressive treatments are required.