The classification of appendiceal mucinous neoplasms has been controversial, largely focused on a particular subset of low-grade mucinous tumors that, despite their innocuous appearance, can disseminate to the peritoneal cavity as pseudomyxoma peritonei (PMP). Recent WHO classification of these tumors as low-grade appendiceal mucinous neoplasms acknowledges their unique morphologic appearance and biologic behavior. Still, debate about the use of this term and its parameters continues to impede the adoption of consensus classification for appendiceal mucinous neoplasms. The classification of PMP has also been the subject of debate, with international authorities advocating for the use of malignant terminology to describe all grades of PMP, even though some authorities consider low-grade PMP to be dissemination of adenomatous epithelium in the peritoneum. Recent data also emphasize the importance of histologic grade of the peritoneal tumors in defining prognosis of these patients.
Appendiceal mucinous tumors include a spectrum of tumors, but within that spectrum is a fascinating low-grade tumor that has been the subject of considerable debate. These tumors challenge our very definition of malignancy and force us to consider whether biology, morphology, or both should form the basis of tumor classification. Despite their rather innocuous gross and microscopic appearance, these low-grade tumors can penetrate into or through the appendix wall, rupture the appendix, and ultimately disseminate to the peritoneal cavity as pseudomyxoma peritonei (PMP; Figures 1 and 2). Biologically, then, these tumors behave as low-grade malignancies and as such are managed aggressively when they have disseminated widely in the peritoneum. Predicting which appendiceal tumors will disseminate to the peritoneum is often a challenge for pathologists faced with a low-grade mucinous tumor in the appendix that has perforated. Because these low-grade appendiceal tumors have bland cytologic features, non-neoplastic conditions that result in reactive epithelial atypia and mucin extrusion are commonly misinterpreted as a low-grade appendiceal mucinous neoplasm (LAMN). In this article, I describe the classification, biology, and management of mucinous appendiceal tumors with an emphasis on low-grade tumors. Their differential diagnosis, natural history, and management are reviewed. In addition, entities commonly mistaken for appendiceal neoplasia will be addressed. Finally, the pathology of PMP will be reviewed, with an emphasis on tumor grade and its prognostic implications.