Have you had your endometriosis confirmed via surgery?

[TennisAM]

Hello

I am looking to ask if any of you have had endometriosis confirmed via histology (biopsies) during surgery? If so, do you have a copy of your histology report? If you do could you please let me know what they found to decide that it is endometriosis? E.g. "endometrial stroma" "glands" "epithelium".

Any questions please let me know.

Thank you

[Lindle]

In order for histology to be positive there must be glands and stroma but their absence doesn’t mean it’s not endo. Histology often shows fibrosis or ‘haemosiderin laden macrophages’ which are white blood cells containing old blood staining. But the latter two don’t confirm endo without glands and stroma.

Deep endo is mostly fibrosis and often comes back negative due to the sample not containing endo glands when it is still endo. The existing histology requirements are flawed and go back decades. when there was less understanding of endo. There has been a call for it to be reviewed to take account of fibrosis in the absence of endometrial glands.

Laparoscopy with it without histology is no longer the gold standard for diagnosis and when deep endo shows on scans it is now a diagnosis.

[TennisAM in reply to Lindle]

Pathologists do not need to find both endometrial-type stroma and epithelium (glands) to diagnose endometriosis.

The Royal College of Pathologists issue guidelines for Gynaecological Pathology. It's called "Tissue pathways for gynaecological pathology".

From January 2015 (version 2), to the current version, February 2023 the guidelines has had the following definition for determining endometriosis. It is the only definition in the guidelines and this is the one Pathologists should be using when assessing whether endometriosis is present.

"fibrous capsular adhesions may be present as a result of endometriosis or past pelvic inflammatory disease. Note the presence of inflammation and evidence of old/recent bleeding. Two of three features (organising blood, endometrial-type stroma and endometrioid epithelium) are usually required for a diagnosis of endometriosis. Occasionally stromal endometriosis, i.e. endometriosis that consists only of endometrial-type stroma and no endometrial glands, is seen"

Therefore all of these scenarios can lead to a histological confirmation of endometriosis:

1. Organising blood and endometrioid epithelium

2. Organising blood and endometrial-type stroma

3. Endometrial-type stroma only

They also recognise fibrosis in the process of endometriosis.

This is (sort of) in line with the definition that's been in place for Gynaecologists for approximately 10 years. ESHRE Endometriosis Guidelines 2013 (page 17) and ESHRE Endometriosis Guidelines 2022 (page 8) both state that either endometrial type stroma and / or epithelium is enough to diagnose a patient with endometriosis. The latter has removed the need for a laparoscopy.

Therefore, although not completely similar, the definitions have overlap. Both need improvement as most endometriosis lesions have a consistent presence of smooth muscle cells and fibrosis.

The other interesting info is from ESHRE Endometriosis guildelines 2022 regarding recurrence of the disease (page 114):

"Recurrence in endometriosis has been defined as recurrence of pain (dysmenorrhea, dyspareunia, or pelvic pain), as clinical (pelvic fibrotic areas or tender nodules) or radiological detection of recurrent endometriosis lesions, surgically confirmed lesions or as repeat rise of the marker CA-125 after surgery (Ceccaroni, et al., 2019).

Recently, recurrence was defined as lesion recurrence on reoperation or imaging after previous complete excision of the disease, with 4 subtypes:

(1) Symptom based suspected recurrence: Symptom recurrence based on patient history, but not proven/confirmed by imaging and/or surgery

(2) Imaging based suspected recurrence: Endometriosis recurrence based on imaging (in patients with or without symptoms).

(3) Laparoscopically proven recurrence: Recurrence of visual endometriosis without histological proof: during laparoscopy endometriosis is visually observed but either not biopsied or biopsied without histologically proven endometriosis.

(4) Histologically proven recurrence: Recurrence of histologically proven endometriosis: during laparoscopy endometriosis is visually observed and confirmed histologically (International working group of AAGL ESGE ESHRE and WES, et al., 2021)."

Therefore based on the 2019 definition fibrosis (fibrotic areas) alone is enough to confirm a recurrence of the disease for example.

I agree that Pathologists need to improve their definition and so do gynaecologists but neither need to find both stroma and epithelium to diagnose women with endometriosis.

[Lindle in reply to TennisAM]

Thank you so much for this.

I was familiar with the definition of recurrence in the ESHRE guideline - I think this is less problematic when there is already a previous diagnosis.

I'll look up the pathology guidelines as they'll be very useful. For initial diagnosis I had missed those sections of both ESHRE guidelines. There are so many publications such as articles from various scientists, whether endo specialists or researchers, that refer to the definition of endo as 'endometrial-like tissue' or 'endometrial glands and stroma' that I hadn't looked beyond that. One such article is 'Time to redefine endometriosis including its pro-fibrotic nature' published in Human Reproduction (Oxford University Press) in 2017, so after the 2015 reference you have given for 'Tissue pathways for gynaecological pathology', that says:

'Endometriosis is currently defined as presence of endometrial epithelial and stromal cells at ectopic sites. This simple and straightforward definition has served us well since its original introduction. However, with advances in disease knowledge, endometrial stromal and glands have been shown to represent only a minor component of endometriotic lesions and they are often absent in some disease forms.'

academic.oup.com/humrep/art...

It seems the authors didn't do their homework either!

I also see so many histology reports which only give a diagnosis based on what is now clearly an outdated definition, not confirming endo when there is just fibrosis and even when there are hemosiderin-laden macrophages noted - is that what they mean by 'organising blood'? I haven't heard that before and nothing comes up when googling. There will be phrases such as 'no active glands' and no diagnosis given. So I have clearly placed too much weight on pathologists' reports as well when it seems that many can't be up to date on this either.

This is so important as we get women with endo having it confirmed by their surgeons when their pelvis might be rock solid with fibrosis, being told it's not endo when it comes back negative when clearly it is. I've long thought that what an experienced surgeon actually sees should be a confirmation in itself on the basis that in the presence of symptoms it can't be anything else and they know what they are looking at. . If a pathologist does use all this up to date criteria how do you think they should be phrasing their conclusions regarding a confirmed diagnosis? Is it up to the pathologist to give a confirmed diagnosis - this would seem the safest. Sometimes they do but when they find any of the three criteria above, so merely just stroma, should the pathologist be confirming the diagnosis or should the surgeon based on reported findings, which then introduces a variable subjective element? We have had endo surgeons actually dismissing pathologists' diagnoses saying they are wrong.

When you say in reference to the ESHRE definition 'the latter has removed the need for a laparoscopy' they have to do a lap to get the sample?

Thanks again for what will be invaluable info.

[TennisAM]

Hey Lindle ,

I've replied in two parts and tagged you in the second one below too.

You're welcome. I noticed that on the Vigano et al publication too. I do like that article though as it sets out nicely how sometimes stroma and/or epithelium isn't found in many samples. I liked the examples it gave.

So in ESHRE 2013 it says

The combination of laparoscopy and the histological verification of endometrial glands and/or stroma is considered to be the gold standard for the diagnosis of the disease

In 2022 ESHRE it simply says when endometrial type stroma and / or epithelium is found.

Much smarter as we could get samples via the vagina, colonoscopy, cystoscopy, or on the skin with women who get endometriosis in the skin due to c section. The first definition is problematic that it has to be via laparoscopy.

The problem I find regarding fibrosis on a repeat laparoscopy is quite a few experts have not got the knowledge that fibrosis can cause as many problems as active endometriosis. Also some don't even consider it a form of the disease. I know someone that had a previous diagnosis and she was told she didn't have a recurrence of endometriosis on the second lap. I had to show her all the evidence. It's so worrying as some patients would celebrate that they haven't had a recurrence and maybe might be less inclined to seek care in the future.

In my case stroma was seen and Pathologist said its not diagnostic because glands weren't seen. This is wrong based on the guidelines. Got to cut my reply short but will continue later

[TennisAM]

Part 2: Sorry Lindle was at the dentist earlier! So organising blood isn't defined in the pathology guidelines unfortunately. I am planning to write to the authors of the Pathology guidelines so happy to ask and to update you. I plan to ask several questions about their choices and why their definition isn't in line with the gynaecologist one. I also want them to think about using some endo experts as stakeholders as at the moment the stakeholders are only other pathologists. The definition is also hidden in a random section of the guidelines. When you look at the 2023 version of the pathology guidelines I recommend looking at section 7.2. It discusses the immunoreactivity testing they can do to determine if it is endometrial stroma. If you need any help with interpretation of it, get in touch happy to if I can help. But essentially testing such as SMA (smooth muscle actin) or desmin can help deferentiate between endometrial stroma (endometriosis) and smooth muscle lesions. But there seems to be some overlap, it's not conclusive. But then again what is 100% accurate!

I spoke to a reliable endo expert about organising blood and they said they felt its the chocolate material that's expressed from within the lesions. But they were not 100% sure.

In answer to your question, if endometrial stroma alone is found, the Pathologist should state a confirmed diagnosis of endometriosis. Luckily my surgeon knew the eshre definition and confimed my diagnosis based on visual and pathology. My samples also had CD34 positive blood vessels which are associated with endometriosis, and they had smooth muscle cells and fibrofatty connective tissue. So I had a lot of indcators of endometriosis apart from the endometrial stroma.

I think I've covered everything but pls let me know if I missed something.