Fere Ex Nihilo book reviewed by Gian Franco Zanoni, MD

Dear Elvio,

Your book was fantastic, very interesting. It contains a lot of relevant information and it is a mixture of ideas, experience and knowledge. Furthermore I liked your episodes in your life which make it more personal, enthusiastic and realistic. In particular I was fascinated by your experience in life and how you got to be where you are today.

In addition I think the your “fere ex nihilo” theory is  correct. Before your “fere ex nihilo” theory I had a personal one: like you, I did not believe that ovarian cancer arises from tube, because in my experience I have seen a few cases where there was an association between STIC and ovarian HGSC. But I noted that the mesothelium, when enters in contatc with the stroma, it becomes mullerian and develops positivity for PAX8 and ER e PR. So, in my opinion, I thought that endosalpingiosis was a metaplastic change, occuring from mesothelium. In every ovulation we have a scar and the membane which separates the surface epithelium and the stroma gets destroyed, It results in a contact between epithelial surface cells and stromal cells and, due to the presence of steroid hormones, the cells become mullerian.

Your theory, which suggests the mesenchymal-epihelial transitrion, is more fascinating because it explains why endosalpingiosis is sometimes in the inner part of the cortex.

Thank you again for giving me the opportunity to read your book and if you like to collaborate more about your last theory, I am ready and enthusiastic to do so.

Best regards,

Gian Franco

University Cattolica-Rome

Thanks Gian Franco.

Many years ago, I also thought that endosalpingiosis originated from invaginations of the ovarian surface because frequently we see invaginations of the surface in the ovarian cortex; however, a correct explanation would apply to ALL types of endosalpingiosis. Sometimes, foci of endosalpingiosis are seen in the ovarian medulla, far from the surface, and sometimes there are multiple foci of endosalpingiosis, as seen in Fig 5-5 in the book. In addition, in these cases, very often, there are no invaginations on the surface. Very difficult to explain these areas by invaginations.

But there is another very important point. The same explanation for the development of endosalpingiosis in the ovary, should apply to areas of endosalpingiosis developing in other areas where invaginations of the mesothelium are not seen, like in the submesothelial space or in the lymph nodes, where there is no overlying mesothelium. The dimensions of interconnectedness are without end. After reviewing numerous cases of endodalpingiosis in the submesothelial space and in lymph nodes, trying to find very early areas of endosalpingionsis, I got to the conclusion that they must be the result of mesenchymal-epithelial transition, similarly to the development of the Mullerian duct.

This concept is extremely important because endosalpingiosis is found in all cases of low-grade serous tumors, and therefore they must be very important in the development of these neoplasms. It is similar to the relationship of endometriosis and endometrioid tumors.