Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy to Treat Pseudomyxoma Peritonei of Ovarian Origin: A Retrospective French RENAPE Group Study

Abstract

Background: Ovarian pseudomyxoma peritonei (OPMP) are rare, without well-defined therapeutic guidelines. We aimed to evaluate cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat OPMP.

Methods: Patients from the French National Network for Rare Peritoneal Tumors (RENAPE) database with proven OPMP treated by CRS/HIPEC and with histologically normal appendix and digestive endoscopy were retrospectively included. Clinical and follow-up data were collected. Histopathological and immunohistochemical features were reviewed.

Results: Fifteen patients with a median age of 56 years were included. The median Peritoneal Cancer Index was 16. Following CRS, the completeness of cytoreduction (CC) score was CC-0 for 9/15 (60%) patients, CC-1 for 5/15 (33.3%) patients, and CC-2 for 1/15 (6.7%) patients. The median tumor size was 22.5 cm. After pathological review and immunohistochemical studies, tumors were classified as Group 1 (mucinous ovarian epithelial neoplasms) in 3/15 (20%) patients; Group 2 (mucinous neoplasm in ovarian teratoma) in 4/15 (26.7%) patients; Group 3 (mucinous neoplasm probably arising in ovarian teratoma) in 5/15 (33.3%) patients; and Group 4 (non-specific group) in 3/15 (20%) patients. Peritoneal lesions were OPMP pM1a/acellular, pM1b/grade 1 (hypocellular) and pM1b/grade 3 (signet-ring cells) in 13/15 (86.7%), 1/15 (6.7%) and 1/15 (6.7%) patients, respectively. Disease-free survival analysis showed a difference (p = 0.0463) between OPMP with teratoma/likely-teratoma origin (groups 2 and 3; 100% at 1, 5, and 10 years), and other groups (groups 1 and 4; 100%, 66.6%, and 50% at 1, 5, and 10 years, respectively).

Conclusion: These results suggested that a primary therapeutic strategy using complete CRS/HIPEC for patients with OPMP led to favorable long-term outcomes.

Keywords: Cytoreduction; HIPEC; Mucinous tumor from teratoma; Ovarian carcinoma; Ovarian pseudomyxoma; Peritoneal pseudomyxoma.

Fig. 1

Case selection process. All patients included in the present study had been treated by CRS followed by HIPEC. In order to ensure with certainty the primary ovarian origin, all patients included had to have a normal digestive endoscopic and imaging assessment and a complete histopathological examination of the appendix (which had to be available for analysis at the time of the study). In addition, OPMP had to be histologically confirmed with the presence of mucus with or without tumor cells in the peritoneal samples. The primary ovarian tumor had to be mucinous (epithelial or developed on a teratoma). * Colonoscopy and gastroscopy. CRS cytoreductive surgery, HIPEC hyperthermic intraperitoneal chemotherapy, OPMP Pseudomyxoma peritonei from ovarian origin, RENAPE French National Reference Center for Rare Peritoneal Tumors

Fig. 2

Pathological and immunohistochemical features of OPMP developed on ovarian mucinous epithelial neoplasm (Group 1; case #2). (a) HES (×20). Mucinous tumor with complex architecture at low magnification and several components: (1) a first component of infiltrative mucinous adenocarcinoma with small glands composed of atypical cells infiltrating the stroma (b) HES (×200] corresponding to the red frame of (a): (2) a contingent of benign Brenner tumor consisting of transitional nest within a fibromatous stroma. (c) HES (×200) corresponds to the yellow frame of (a); and (3) a component of benign mucinous cystadenoma consisting of unistratified mucinous cells without atypia. (d) HES (×100) corresponds to the black frame of (a). (e) HES (×10). (f) HES (×100). On peritoneum, the pseudomyxoma peritonei consists of mucus dissociating the peritoneal tissue, accompanied by numerous siderophages (f corresponds to the black frame of e). (g) CK7 (×200). h CK20 (×200). (i) (SATB2; ×200). (j) PAX8 (×200). the mucinous neoplasm expressed CK7 intensely and diffusely, with a weak/focal expression of CK20, but no expression of PAX8 and SATB2 (ovarian-like profile). OPMP Pseudomyxoma peritonei from ovarian origin, HES hematoxylin-eosin-saffron

Fig. 3

Pathological and immunohistochemical features of OPMP developed on ovarian teratoma (Group 2; cases #4 and #5). (a) HES (×10; case #4). Ovarian teratoma with several features: (1) a first component of low-grade mucinous neoplasm; red frame of (a) corresponds to (b) HES (×80) and (c) HES (×400), consisting of papillae lined with mucinous epithelium, without atypia or mitoses; (2) a second component consisting of well-differentiated squamous epithelium; black frame of (a) corresponds to (d) HES (×200), giving peritoneal granulomatosis. (e) HES (×200), consisting of keratin deposits surrounded by a granulomatous inflammatory reaction, whose differential diagnosis with carcinosis can be tricky. On peritoneum, pseudomyxoma peritonei gives a viscous gross appearance with granulations (f; case #3), with tissue dissociation by mucus. (g) HES (×80; case #3). Other teratomatous contingents were observed: thryoid tissue [yellow stars on (h) HES (×20; case #3) and (i) HES (×200; case #3)] adjacent to the mucinous neoplasm [blue star on (h)], or respiratory epithelium [green star on (i)]. (j) CK7 (×200). (k) CK20 (×200). (l) PAX8 (×200). The mucinous neoplasm expressed CK20 intensely and diffusely, with no expression of CK7 or PAX8 (digestive-like profile). OPMP Pseudomyxoma peritonei from ovarian origin, HES hematoxylin-eosin-saffron

Fig. 4

Pathological and immunohistochemical features of OPMP developed on ovarian mucinous neoplasms, likely corresponding to ovarian teratoma not sampled during gross examination (Group 3; case #9). (a) Gross examination of ovarian tumor after formalin fixation: the multi-cystic tumor, poorly limited with external vegetations and mucus within the cysts. (b) HES (×10). The tumor consists of numerous cysts and glandular ruptures in the ovarian stroma. (c) HES (×80). The tumor consists of papillae lined with mucinous epithelium. (d) HES (×80). Glandular ruptures in the ovarian stroma giving falsely infiltrative features. (e) CK7 (×200). (f) CK20 (×200). (g) SATB2 (×200). (h) PAX8 (×200). The CK20 expression was intense and diffuse in the mucinous neoplasm, with no expression of CK7 or PAX8. SATB2 expression was very focal and mild and was considered negative (digestive-like profile). OPMP Pseudomyxoma peritonei from ovarian origin, HES hematoxylin-eosin-saffron

Fig. 5

Survival analysis: comparison of the DFS of ovarian pseudomyxoma peritonei from teratomatous origin and other origins. The comparison of DFS between OPMP of teratoma/suspected teratoma origin (Groups 2 and 3) and ovarian/non-specific origin (Groups 1 and 4) showed a statistically significant difference (p = 0.0463). HIPEC hyperthermic intraperitoneal chemotherapy, DFS disease-free survival, OPMP Pseudomyxoma peritonei from ovarian origin