MULTICENTRICITY IN OVARIAN CANCER

Peritoneal Lesions in Tubo-Ovarian Serous Neoplasms. Metastases vs Independent Primaries.

Paper rejected by IJGC, 2023

Part 2. Unquestionable evidence of multicentricity.

Extraovarian sites of involvement of tubo-ovarian and peritoneal serous neoplasms and their relationship with endosalpingiosis/endometriosis. Prevalence in red

FT Uterine Recto Parietal

Cases Omentum Serosa Serosa Sigm Peritoneum LNs Diaphragm Bladder Cul de sac

HGSC 85 84 79 44 35 30 22 21 11

(n=105) 1 2 3 4 5 6 7 8 9

LGSC 104 67 64 44 52 31 13 15 22

(n=118) 1 2 3 5 4 6 9 8 7

SBT 35 30 27 16 23 15 4 14 25

(n=52) 1 2 3 6 5 7 9 8 4

Perit SC 11 2 5 6 6 3 2 2

(n=14) 1 5 3 2 2 4 3 3

Endosal/ 33 22 26 14 22 21 1 9 10

Endome.

(n=118) 1 3 2 5 3 4 8 7 6

FT: Fallopian tube; HGSC: high grade serous carcinoma; LGSC: low-grade serous carcinoma;

SBT: serous borderline tumor; Perit SC: peritoneal serous carcinoma with negative ovary and fallopian tube mucosa; Endosal/Endome: endosalpingiosis or endometriosis in cases of ovarian and peritoneal serous tumors.

Review of 289 untreated serous neoplasms show that the sites of “metastases” are the same for high-grade serous carcinoma, low-grade serous carcinoma, serous borderline tumors, or even for cases of serous carcinoma primary in the peritoneum without ovarian or fallopian tube mucosa involvement. Similarly to what we have reported in the ovary, serous tumors in the peritoneum are also associated with areas of endosalpingiosis and endometriosis, which are found with similar prevalence to the areas of involvement by the serous tumors. The association of serous tumors in the peritoneum with areas of endosalpingiosis or endometriosis is the best evidence that, at least in some cases, the serous tumors in the peritoneum are primary at these sites.

In the gastrointestinal tract the recto-sigmoid is the most frequently involved with”metastases”. In the following table we show the sites of involvement according to their frequency.

Cases with GI Recto- Colon Appendix Small

Involvement sigmoid bowel

HGSC 84/105(80%) 44(52%) 37(44%) 30(36%) 20(24%)

LGSC 83/118(70%) 44(53%) 38(46%) 24(29% 25(30%)

Considering the large amount of peritoneal surface associated with the small bowel, we would expect that, if the tumor cells are circulating with the ascitic fluid, the small bowel would represent the most common site of involvement in the gastrointestinal tract; however, the most common site is the recto-sigmoid, and the appendix is as frequently involved as the small bowel, in the LGSC, but in the HGSC the appendix is more frequently involved than the small bowel. It is also very interesting that the recto-sigmoid is also the most common site of endometriosis in the bowel.

It is obvious that the “metastases” of serous tumors in the peritoneum are not random, they follow a pattern, associated with endosalpingiosis and endometriosis.

Reviewers’ comments: It is amazing that no one of the three reviewers made a comment about this important pattern of “metastases” associated with endosalpingiosis and endometriosis. Both tables were included in the paper.