Pseudomyxoma peritonei in women: A clinicopathologic analysis of 30 cases with emphasis on site of origin, prognosis, and relationship to ovarian mucinous tumors of low malignant potential

Abstract

Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by the accumulation of abundant mucinous material within the peritoneal cavity and associated with a mucinous tumor of the gastrointestinal tract or ovaries. Recently there has been considerable debate over the primary site of origin of the tumor associated with PMP in women. Some investigators have proposed a primary site in the ovaries, whereas others favor the gastrointestinal tract or the peritoneum. Another confusing issue has been the nature of the ovarian mucinous tumors associated with PMP. Although these neoplasms may be frankly malignant, more often they show minimal cytologic atypia and epithelial proliferation and have been classified as borderline or low malignant potential tumors. In order to address the issues of site of origin and nature of the associated ovarian mucinous tumors, we studied 68 cases of PMP in women, 30 of whom had mucinous tumors involving the ovaries. All 30 of these cases had an associated mucinous appendiceal or intestinal tumor. The PMP cases with ovarian tumors were compared with 30 ovarian mucinous tumors of low malignant potential (LMP). Based on the analysis of the primary ovarian mucinous LMP tumors, a set of criteria was formulated and used to determine the probable site of origin of PMP in the 30 women with mucinous tumors involving the ovaries. The following gross and microscopic features of the ovarian tumor were considered to be inconsistent with a primary ovarian origin: (1) surface involvement with or without superficial stromal involvement only; (2) adenocarcinoma with signet ring cell differentiation, with a previously diagnosed or concurrent appendiceal tumor of similar morphology; (3) bilateral adenocarcinoma consistent with colonic or appendiceal morphology; and (4) unilateral adenocarcinoma consistent with colonic or appendiceal morphology with a history of a co-. Ionic or appendiceal adenocarcinoma. When any one of these features was present the ovarian tumor was diagnosed as secondary. The following additional features also were considered to be more typical of secondary ovarian involvement: (1) normal or only slightly enlarged ovaries; (2) bilateral ovarian involvement; (3) simple or only focally proliferative mucinous epithelium with abundant extracellular mucin in cases with predominantly surface involvement of the ovaries, with or without a history of/or concurrent appendiceal adenoma; (4) multifocal or extensive pseudomyxoma ovarii in cases with stromal involvement, with or without a history of/or concurrent appendiceal adenoma; (5) ruptured appendiceal adenoma and unruptured ovarian tumor of similar histology; and (6) presence of an associated mucinous intestinal tumor. If at least three of the above features were present, the ovarian tumor also was diagnosed as secondary. When classified according to all of these criteria 28 of the 30 cases of PMP (93.3%) were attributed to primary mucinous appendiceal or colonic tumors, and the remaining two were compatible with either intestinal or ovarian origin. No cases were of unequivocal ovarian origin. Analysis of multiple histologic features of the ovarian, intestinal, and peritoneal mucinous tumors showed that the PMP cases could be separated into two pathologically and prognostically distinct groups based on the associated intestinal tumor diagnosis. Appendiceal adenomaassociated cases showed a significantly better prognosis than appendiceal or intestinal carcinoma-associated cases ( P < .0001). Nearly all appendiceal adenoma-associated cases were characterized by appendiceal, ovarian, and peritoneal tumors with no significant atypia or epithelial proliferation and absence of lymph node involvement and parenchymal organ invasion. In contrast, the carcinoma-associated cases displayed significant atypia and epithelial proliferation in the intestinal, ovarian, and peritoneal tumors. In addition, these tumors were frequently associated with lymph node and parenchymal organ metastases. Accordingly, we recommend that the term PMP be restricted to those cases that have the features of appendiceal adenoma-associated cases. The carcinoma-associated cases should be classified as mucinous carcinomas and not included in the category of PMP. Finally, the conclusion that PMP is virtually always of appendiceal origin provides the basis for reassessing the entire concept of ovarian mucinous LMP tumors because malignant behavior associated with the latter tumors has virtually always been confined to women with PMP.