Appendiceal pseudomyxoma peritonei: unmasking the indolent invader

Appendiceal mucinous neoplasms are rare, but have significant clinical consequences. This is because in the setting of a ruptured appendix, these proliferating mucus-secreting epithelia will seed the peritoneal lining and eventually develop into pseudomyxoma peritonei (PMP), characterized by presence of intra-abdominal mucin with gelatinous ascites. There is a spectrum of clinical presentation with appendiceal mucinous neoplasm, from an incidental radiological finding of an appendiceal mucocele to extensive PMP including what has been described as ‘scalloping’ of the spleen and liver. The most common clinical situation is a provisional diagnosis of acute appendicitis, often with evidence of perforation on a CT scan. However, intra-operative findings clearly show mucin in the intra-peritoneal cavity suspicious for evolving PMP. In such a situation, tissue sampling is required to confirm the diagnosis and stratify the patient’s prognosis including the appropriateness of cytoreductive surgery, the extent of colonic resection and hyperthermic intraperitoneal chemotherapy (HIPEC). According to the 2020 Peritoneal Surface Oncology Group International (PSOGI) classification, primary appendiceal neoplasm can be classified as following; (a) low grade appendiceal mucinous neoplasm (LAMN), (b) high grade appendiceal mucinous neoplasm (HAMN), (c) mucinous adenocarcinoma signet ring cells, and (d) mucinous goblet cell carcinoma. A LAMN does not routinely require a right hemicolectomy given the exceptionally negligible to no risk of lymph node metastasis. Moreover, a right hemicolectomy in an index operation in the absence of intraperitoneal chemotherapy, has the risk of tumour cells disseminating onto newly exposed retroperitoneal planes. This can enable deeper, retroperitoneal implantation of mucinous disease (see Fig. 1) and compromise definitive cytoreductive surgery, potentially worsening survival outcomes. On the other end of spectrum, features such as signet ring cells or mucinous goblet cell carcinoma have negative prognostic implications. Their pre-operative laparoscopic staging is key in determining the treatment algorithm, with consideration of neoadjuvant chemotherapy such as 5-fluorouracil and oxalipatin. Hence, if PMP is suspected on the index operation, the preference is to gain a tissue diagnosis without breaching the normal anatomical planes. This would include an appendicectomy, oophorectomy and/or peritoneal nodule excision. A thorough examination of the remainder of the peritoneal cavity should be sought, with documentation on the location of peritoneal disease including photographs on each quadrant and extent of small intestinal involvement. The priority is still controlling sepsis, finding a healthy base after an appendicectomy and if a caecectomy is required, that would be the preference followed by a right hemicolectomy in situations where a minimal resection is not possible. Once appropriate staging has been performed, cytoreductive surgery and HIPEC remain the mainstay of treatment for patients with PMP. A review of 2298 patients from 16 centres affiliated with PSOGI reported an overall survival post CRS and HIPEC of 64% at 10 years and 59% at 15 years. In addition, of the patients that developed peritoneal recurrence post CRS and HIPEC, those who underwent iterative CRS and HIPEC had a 100% 5-year survival. In a 10-year cohort study, postoperative grade III/IV complications were occurred in 20.6% of patients, with 0.0% mortality. In conclusion, appendiceal mucinous neoplasm and PMP is a rare disease entity. An appreciation of the variety of pathologies and the differences in their malignant potential dictate differing treatment algorithm after tissue diagnosis has been obtained. At index operation, it is key to obtain adequate tissue samples without violating unnecessary tissue planes that may enable deep invasion of tumour cells, in the absence of HIPEC. CRS and HIPEC remain the mainstay of treatment for PMP, with improved overall survival and an acceptable safety profile. Hence, it is pertinent to approach the appendix au fait to avoid undue worsening of survival outcomes in an otherwise treatable disease. Fig. 1. Illustrates an example of retroperitoneal seeding adjacent to the psoas muscle 2 months after a patient underwent index right hemicolectomy for a node-negative, perforated Grade I, pT4a LAMN with acellular mucin involving the local peritoneal surface.