Pseudomyxoma Peritonei: More Questions Than Answers

Chances are, if you ask most physicians and surgeons about pseudomyxoma peritonei (PMP), they will respond with more questions than answers. The confusion that surrounds PMP is not surprising because the origin, pathology, treatment, prognosis, and very definition of PMP are still under debate. PMP is a clinical syndrome that is characterized by mucinous ascites that result from rupture of a mucin-producing neoplasm, typically of appendiceal origin. Whereas surgical resection alone of an intact, mucin-producing neoplasm of the appendix (mucocele) is curative, rupture of an appendiceal mucocele may lead to diffuse peritoneal spread of mucin that may contain epithelium of a low-grade or high-grade nature (ie, PMP), which causes fatal bowel obstruction without treatment. The appendix is the primary cause of PMP; the ovaries are typically only secondarily involved. The two types of mucin-producing appendiceal neoplasms that give rise to PMP exhibit a different biology and prognosis. The outcome is consistently more favorable for patients with PMP that results from the rupture of a mucin-producing adenoma of the appendix (low-grade process) than from the rupture of a mucin-producing appendiceal adenocarcinoma (high-grade process). A detailed pathologic classification of PMP is therefore critical to define patient prognosis, to determine the appropriate treatment, and to permit comparison of results among studies. Unfortunately, the pathologic classification of PMP is controversial and confusing. In 1995, Ronnett et al described three distinct categories of PMP on the basis of pathologic specimens (n 109): diffuse peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinoma (PMCA), and an intermediate/discordant subtype (PMCA-I/D). DPAM originates from an appendiceal mucinous adenoma and produces abundant mucin but minimal mucinous epithelium that lacks significant cytologic atypia and mitoses. The prognosis for DPAM is good. An appendiceal adenocarcinoma causes PMCA, which features more mucinous epithelium and pathology that is typical of adenocarcinoma. The prognosis for PMCA is poor. The third category, PMCA-I/D, has characteristics of both DPAM and PMCA, and the prognosis is intermediate between the two. When the same surgeon treated patients with PMP tumors uniformly, the 5-year overall survival was 75% for DPAM, 50% for PMCA-I/D, and 14% for PMCA. This range suggests inherent differences in biology among DPAM, PMCA, and PMCA-I/D tumors that greatly affect patient prognosis. Two different two-group classifications have been proposed. One, by Bradley et al, is based on an analysis of patients with PMP of appendiceal origin (n 101). It consists of low-grade mucinous carcinoma peritonei, which includes DPAM and PMCA-I/D tumors, and high-grade mucinous carcinoma peritonei, which includes PMCA. When patients were treated uniformly, the 5-year overall survival did not differ significantly (68% for DPAM and 62% for PMCA-I/D). The second two-group classification of PMP was proposed by Misdraji et al and was also based on an analysis of patients with PMP of appendiceal origin (n 52). It also consists of low-grade and high-grade tumors. All of these classifications, based as they are on a limited number of patients, leave it unclear whether a two-or threegroup classification system best categorizes patients with PMP into unique prognostic groups. In the report that accompanies this editorial, Chua et al examine the outcome of nearly 2,300 patients from 16 institutions worldwide who were treated uniformly over an 18-year period for PMP that arose from the appendix. A major strength of this registry study is the detailed pathologic classification of PMP as either DPAM, PMCA, or PMCA-I/D (hybrid) tumors. The study confirmed the paramount importance of PMP histopathologic subtype with respect to outcome. Five-year overall survival was 81% for DPAM, 78% for hybrid tumors, and 59% for PMCA. Multivariable analysis showed that the PMCA histopathologic subtype was an independent predictor of poorer overall survival. Interestingly, the outcome seemed similar for DPAM and for hybrid tumors, supporting a two-group, low-grade versus highgrade classification system, as previously proposed by Bradley et al. Future classification of patients with PMP of appendiceal origin into low-grade (DPAM, hybrid tumors) and high-grade (PMCA) groups should permit the meaningful comparison of results among studies. Aside from underlying tumor biology, another important, previously described prognostic factor for patients with PMP is the ability to remove all gross disease; this concept was supported by the study by Chua et al. Intuitively, this makes sense because the cause of death for most patients with PMP is multifocal bowel obstruction. Five-year overall survival was 85% when no macroscopic residual cancer remained (completeness of cytoreduction [CCR] score of 0) and 80% when no nodule greater than 2.5 mm in diameter remained (CCR1). In contrast, 5-year overall survival was only 24% when gross residual tumor remained (CCR2/3), which was significantly worse. Importantly, most patients with PMP in this study had a CCR0 (51%) or a CCR1 (32%) score, and only a few (17%) underwent debulking surgery (CCR2/3). Does the high proportion of patients with CCR0 and JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 20 JULY 1