What Is an Endometriosis Lesion?

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Full transcript of the original video, lightly edited for readability.

When people hear the phrase endometriosis lesion they usually imagine one vague blob of tissue stuck somewhere outside the uterus. So let's define this correctly an endometriosis lesion has a core structure and then it has a living support environment around and through it the core structure of the lesion is the actual ectopic endometriotic tissue itself in classic histology. That means the lesion proper aka the physical lesion is made of two defining structural components the glandular or epithelial compartment and the stromal compartment.

That is the lesion in its most direct structural sense endometriosis is classically identified as endometrial like tissue outside the uterus and the historical and pathological descriptions repeatedly describe it in terms of glands and stroma. Think of it this way the glans are the part that act like the lining of the uterus the endometrium and the stroma is the connective structural tissue that surrounds the glans dysfunctional unit is what we call the lesion proper in pathology you can officially call a sample endometriosis unless a doctor sees both under a microscope.

So first let's talk about the lesion itself. The first structural part is the epithelial or glandular component. This is the gland forming side of the lesion these are the endometrial like epithelial cells that create the glandular architecture they are part of what gives the lesion its identity as endometrial like tissue historically one of the clearest pathological descriptions of ectopic endometrial tissue described areas that were an exact prototype of the uterine glands arranged like normal uterine mucosa that glandular architecture is one of the hallmarks.

That tells you. This is not just random scar tissue or random inflammation this is organized ectopic endometrial like tissue. Now what role does this glandular side play it gives the lesion its endometrial like functional identity. This is the side that behaves most like misplaced endometrium it participates in cyclical activity. This is the part that bleeds just like your menstrual cycle every month it is part of why the lesion can behave like hormonally responsive tissue in the wrong place it helps make the lesion biologically recognizable as endometrial like rather than just a scar or inflammatory nodule.

In simple terms the glandular side gives the lesion its face it is the part that most clearly says I am endometrial like tissue. The second structural part is the stroma component. This is the endometrial like connective tissue side of the lesion if the glands are the face the stroma is the engine room. This is not passive filler this is an active biological compartment historically pathology descriptions of endometriosis emphasized not just ectopic glands but also interglandular connective tissue meaning the stromal side was recognized as part of the lesion itself from the beginning.

Now what role does the stromal side play the stromal side is a major reason the lesion is able to survive signal adapt and expand the stromal cells are highly interactive they respond to inflammatory signals they participate in hormone driven behavior they influence the surrounding environment and critically endometriotic stromal cells along with platelets are involved in secreting thrombin and TX eight two and induce platelet activation and aggregation meaning the stroma compartment is not just sitting there it is actively helping create the conditions that support lesion growth and progression.

In other words the stroma side does not merely support the glands structurally it helps support the lesion biologically. So if I had to define the lesion proper very plainly I would say this the lesion proper is the ectopic gland and stroma unit the glandular compartment gives it identity the stromal compartment gives it biological drive one tells you what it is the other helps it keep going. That is the structural lesion. Now here is where most people are wrong because they stop at an incomplete truth because the lesion is not just its structure it is also its ecosystem and.

This is where the micro environment comes in the micro environment may not be part of the lesions defining core architecture in the strict histologic sense but it is absolutely part of the lesion as a living pathological entity and that distinction matters because if you only talk about gland and stroma you explain what the lesion is made of but if you talk about the micro environment you explain how the lesions stays alive. So yes the micro environment is part of the lesions in the broader biological sense even if it is not the same thing as the lesions two defining structural compartments it is not separate from the lesions behavior it is not separate from the lesions maintenance it is not separate from the lesions progression it is part of the lesions total living system.

Now let's walk through that carefully. The first major part of the lesions micro environment is the vascular environment a lesion cannot grow remain active or maintain itself without access to oxygen nutrients and molecular traffic. That means the lesion needs a blood supply active lesions especially red lesions have greater macrophage accumulation and greater micro vessel density tissue proliferation and angiogenesis is intimately linked to over expression of HGF and C met in more active endometriotic tissue. That tells you something crucial the lesion is not just sitting in the pelvis waiting to die it is building and maintaining a supply network so the vascular micro environment is part of the lesion because it keeps the lesion fed oxygenated and capable of persistence without blood vessels the lesion starves with blood vessels the lesion stabilizes and expands.

The next major part of the micro environment is the inflammatory and immune environment endometriosis is increasingly recognized as a pelvic inflammatory condition characterized by over expression of inflammatory genes release of pro inflammatory cytokines NF Capa B activation and infiltration of macrophages and lymphocytes. That means the lesion is not just surrounded by inflammation incidentally the inflammatory field is part of the lesions biology it is part of how the lesion behaves and among immune cells one of the most important players is the macrophage macrophages are not part of the lesions defining gland and stroma structure but they are part of the lesions living micro environment and are deeply involved in its maintenance our benchmark analysis explains that growth of endometriosis is affected not only by the lesions own mitogenic and angiogenic factors but also by infiltrated macrophages markedly accumulated in the lesion and adjacent peritoneum the peritoneum next to active lesions also harbors substantial macrophage accumulation.

That means the lesion does not live alone it actively recruits and sits inside an immune field that helps sustain it. So what do macrophages do for the lesion they help create a pro growth pro inflammatory and pro angiogenic environment they help amplify tissue activity they help amplify pelvic inflammatory signaling they help support angiogenesis and lesion vitality so while macrophages are not the structural lesion itself they are absolutely part of the lesions total pathological system then there are platelets and platelets are one of the clearest examples of why the micro environment is part of the lesion additionally our benchmark research has seen that endometriotic lesions are practically and fundamentally wounds undergoing repeated tissue injury and repair.

That means cyclic bleeding is not just a symptom it is a biological event that recruits platelet activity again and again activated platelets then initiate hemostasis and the tissue repair process of inflammation proliferation and tissue remodeling. But here's what makes this even more important the stromal compartment of the lesion itself helps activate platelets specifically we found that endometriotic stromal cells secrete thrombin and TXA2 and induce platelet activation and aggregation going further endometriotic lesions and platelets engage in active cross talk to maintain lesion growth and facilitate lesion progression and fibrogenesis so platelets are not just bystanders they are not just clotting debris they are not just clean up they are part of the lesions living support machinery they help drive inflammation they help drive repair signalling they help drive progression they help drive fibrogenesis.

That means the lesion structure and the lesion micro environment are constantly talking to each other the stromal side activates platelets the platelets reinforce the lesion and together they make the lesion harder to clear. The next major part of the micro environment is the fibrotic and matrix environment overtime repeated injury repeated platelet activation repeated inflammation and repeated tissue repair do not leave the surrounding area unchanged they remodel it lesion platelet cross talk facilitates lesion progression and fibrogenesis platelets may work with other immune cells in a lesional micro environment conducive to progression and fibrogenesis so the lesion does not simply sit in normal tissue it reshapes the tissue around it the environment becomes more adhesive more fibrotic more structurally altered more supportive of persistence that remodeled matrix is part of the lesions total existence it may not be the gland and stroma core but it becomes part of the lesion as a living disease unit as the lesion remains active inflammatory mediators macrophages platelet signaling vascular changes and fibrosis all contribute to a more pain generating environment even if nerves are not one of the two classic structural compartments becomes part of what the lesion is in real life because the lesion is not just a histology slide it is a living painful pathological system.

So when you zoom all the way out the clearest way to explain it is the lesion has a core structure and a functional environment the core structure is made of the glandular or epithelial compartment and the stromal compartment. That is the lesion proper in the narrow structural sense but the lesion as a living disease unit is bigger than that because the lesion also includes its micro environment its blood supply its macrophages its inflammatory signals its platelet cross talk its extra cellular remodeling its fibrosis its pain generating neuroimmune field that micro environment may not be the same thing as the lesions defining structure but it is still part of the lesions total pathological identity because it is part of what allows the lesions to grow persist adapt and maintain itself.

So if I were to say it in one clean line I would say this the glands and stroma are the lesions structural core the micro environment is the lesions living support system one defines what the lesion is the other explains how the lesion survives and if you leave either one out you are no longer explaining the lesion completely.