short presentation on endocervical adenocarcinoma, and we were lucky in a sense that a new WHO was published just three months ago, so it's a fifth edition of the Female and Genital Tumors Pathology Classification, and I'll base that talk purely on that new WHO. So just a little background. Sorry, I'll just fix those couple of things. Okay. So it's a cervical carcinoma. It's the fourth most common malignancy in women worldwide. Majority are squamous cell carcinomas, and most of the cervical carcinomas are HPV-related. Almost all squamous cell carcinomas of the cervix are HPV-related, but rare HPV-independent squamous cell carcinomas were reported. About 15 to 25 percent of endocervical adenocarcinomas are unrelated to HPV infection, and HPV-independent tumors have a more aggressive behavior compared to HPV-related carcinomas. One important point that you're obviously all aware, and there is a significant change in stage 1 and stage 3 cervical carcinoma classification. We staged it totally different now based on the stromal depth. And in terms of the cervical cancer, we divided to squamous cell carcinoma. As we said, almost everything is HPV-infected. And then endocervical adenocarcinoma, majority are driven by HPV infection. And then others, something like neuroendocrine carcinoma or any other subtypes of carcinoma. There is a significant shift in the classification from descriptive subtypes to pattern-based. And we have two new classifications in the new WHO. One is silver classification, and I was really interested to know how everybody uses that. That's linked to prognosis. And then there is a second classification, international endocervical adenocarcinoma criterion classification, based on the fact that the tumor is HPV-related versus HPV-independent. And of course, it's also linked to prognosis. So when we look at the 2020 WHO classification, you can see here almost all endocarcinomas, we don't have any description anymore, whether it's mucinous, not mucinous. It's either HPV-related versus HPV-not related. And among non-HPV-related, there is also some change. There is only gastric type, clear cell carcinoma, mesonephric type. As you can see, there is no serous carcinoma anymore. All serous carcinoma of the cervix considered to be metastasis, either from uterus or from other sites. So there is really no primary serous carcinoma of the cervix. And then a separate, totally separate, is a neuroendocrine carcinoma of the cervix. In terms of the gastric type, I just want to say maybe a couple of words. When it was first described by the Japanese group in early 2000, it looked to them as a pyloric gland metaplasia, so they called it gastric type. But apparently to all genomic studies, it's very close to pancreatic endocarcinoma. Even though it's called gastric type, it has nothing to do with stomach. You don't need to go and check the stomach. You don't need to do upper endoscopy. And again, on genomic studies, it's very close to pancreatic type endocarcinoma. So how do we decide if the tumor is HPV-related versus non-HPV-related? When you look on the endocarcinoma on the low power, you have to see really two features, presence of apical mitosis and apoptosis. And if they are present, it's HPV-related endocarcinoma. And if they are absent, it's a non-HPV-related endocarcinoma. It's pretty straightforward. You can see here it's a complex glandular structures. There are mitosis and apoptotic bodies. This is apoptotic bodies, and this is mitosis, and this is a sign of HPV-related endocarcinoma. So let's go to a pattern-based classification from Elvira Silva that used to work at MD Anderson. So why really was a need for the new classification? As a pathologist, we don't use, obviously, Sadler's and Petter's criteria. This is a clinical help. And for us, we were looking for something that can help to determine prognosis of the patient. The pattern-based classification system potentially can be used to complement treatment decision based on the difference in recurrence and lymph node metastasis. It's something new, even in candidates reported by some institutions, but others do not use this classification. So there are three patterns. Pattern A is non-destructive. It's well-demarcated glands, no single cells with dysmoplastic stromal reaction. There is no solid growth and no lymphovascular invasion. And for many years, pathologists were struggling between differential diagnosis of AIS versus early invasion. And with that classification, it's really helpful because there is really no difference between AIS and that very early pattern A type of invasion. We'll talk about prognosis in just two minutes. So here you can see a well-demarcated tumor. The lobular architecture is preserved. It's a little bit more complex than one would like to have for AIS, a little bit more tumor. So it will be consistent with pattern A and the early cervical adenocarcinoma. And for those cases, we always have a problem. How would you measure it? Where to start? Where the AIS starts? Where invasion? And again, that's pattern A is really a resolution for that situation. In pattern B, there is early destructive stromal invasion from well-demarcated glands. There is no solid growth and it can be either positive or negative for lymphovascular invasion. And again here, so you can see a well-differentiated adenocarcinoma and little buds of the tumor with reaction of the stroma. So it's quite different from the previous case. It's not extensive. It's very focal areas. It will be consistent with pattern B. And pattern C is totally different. It's either solid growth, diffusely infiltrated for ungulated glands invasion. And that's a very good example of such a tumor where you can see ungulated glands, solid growth, a lot of invasion, a lot of the stromal reactions around the invasive nests. So why is really that important? So it has been shown in Silva's paper that he originally published in 2013, and then there were multiple studies to confirm that, that for pattern A, almost no patients have a lymph node metastasis. There are no recurrences and there are no deaths of disease. Pattern B and C are quite different. And for pattern C, you can see up to 25% of the patient will have a positive lymph nodes. They will have recurrences and they could die from disease. Important thing to remember, if there is a lymphovascular invasion, it could not be pattern A, regardless how the tumor looks like. And I think it's a really good tool for us and for clinicians. When you have sort of a borderline situation, you can, you might consider and look at those things as well. So what is it, why is it important? So basically when you see pattern A, it's a low risk patient. There is no need in aggressive surgery and cone may be enough and you don't need to do lymph node dissection. While if you see pattern B and C, it's a high risk tumor and probably the surgeon will go for more aggressive surgery, either radical hysterectomy, trachelectomy and lymph node dissection. And I think the last case discussion is probably illustration of that. In terms of another classification is International Antiservical Adenocarcinoma Criterion Classification. It was published in 2018 by a large group of pathologists, including one of the Israeli pathologists as well. And basically what they said that all non-HPV related carcinomas, again, gastric, clear cell, mesonephric, they have worse prognosis than the usual type. They generally present at older age. They have a large horizontal extent. They usually deeply invasive and LVSI is more often present. They predominantly associated with invasive pattern C. So for non-HPV related carcinoma, we do not use silver classification and they generally have a worse outcome, more recurrences and more cancer related deaths. One thing that I want to also remind everybody that the MDA, minimally a deviation carcinoma is taken out of the classification as well because it's considered a well differentiated gastric type adenocarcinoma. And that's it. If you have any questions, I'm open to answer.

Female and Genital Tumors Pathology Classification

WHO

endocervical adenocarcinoma

squamous cell carcinomas

HPV infection