Was your endometriosis biopsy histologically tested for PGP9.5 & Ki67 ?

A CALL TO ACTION: STANDARDIZE ENDOMETRIOSIS HISTOLOGY PROTOCOLS

How Insufficient Immunohistochemical Testing May Be Missing Early-Stage Neoplasms and Producing Misleading Endometriosis Diagnoses

In this age of spectacular AI, omics, and single-cell molecular medicine breakthroughs, there is no better time than now to call for similarly transformative breakthroughs in endometriosis histology — an often overlooked yet critical field of diagnostics. We propose that endometriosis thought leaders around the world work together to establish endometriosis-specific histology protocols, so that immunohistochemical testing of surgical biopsies can finally be modernized, standardized, and democratized.

An international consensus statement with updated guidelines would be game-changing for millions of endometriosis sufferers. It could help reduce histologic misdiagnoses that contribute to the lengthy diagnostic delays endometriosis patients already face, and aid in the early detection of occult neoplasms, potentially lowering mortality linked to endometriosis-associated cancers. With endometriosis still reigning as one of the world's leading causes of severe disability and hospitalization — and with mounting evidence linking endometriosis to a significantly heightened risk for ovarian cancer, one of the deadliest gynecological cancers worldwide — the time has come to galvanize change in the often-forgotten field of histology.

A BRIDGE TO NOWHERE

Endometriosis is a whole-body (systemic) inflammatory chronic condition that is much more than the lesions alone. However, if we fail to establish rigorous standards for investigating these excruciatingly destructive, pathological cells at their single-cell molecular, genomic, epigenetic, and immunohistochemical levels, we will never escape our current heartbreaking circumstances — where unconscionably substandard "shoot in the dark" practices continue to cause ruinous outcomes for millions of people worldwide who deserve better.

A LOOK BACK AT HISTOLOGY MILESTONES THROUGH THE AGES

It has been nearly 150 years since hematoxylin and eosin (H&E) staining first emerged as the cornerstone of the then-nascent field of histology. The pioneers of that era could scarcely have imagined just how profoundly those two tiny letters would impact millions of endometriosis sufferers around the world, whose H&E pathology reports would one day confirm that their struggle to survive one of the most potentially devastating chronic conditions known to medicine was, in fact, real.

H&E: "PIRATES' MOST DESIRED TREASURE"

The two H&E dyes are both derived from the Palo de Campeche logwood tree (ek in the Mayan language) — "mesoamerica's gift to histopathology," as one historian described what even pirates of the actual Caribbean once found irresistible. With roots stretching back to the pre-classical Mayans of circa 400 BCE, these "pirates' most desired treasure" dyes feature into the story of endometriosis as well. H&E stains black and green, respectively, in the presence of normal eutopic endometrial glands and stroma — but also in the pathological, ectopic forms found in endometriosis.

(Note: the word "gift" is used euphemistically here to describe what was more like a plundering of resources — but that is a topic for a different post.)

Perhaps most importantly, H&E staining provided the field with some of the earliest clues that endometriosis is not the endometrium, due to observable, substantial histopathological differences when compared to normal eutopic endometrium. In endometriosis, ectopic glands often present as inactive, with some resemblance to the basalis or proliferative endometrium. H&E also revealed higher levels of apoptosis in endometriotic glandular cells than is generally observed in normal endometrium. Variations in ectopic gland cell sizes — categorized by pathologists as small, medium, and large — can also be identified, along with important cell shape differences such as canalicular or collapsed forms that provide diagnostic clues.

Immune and inflammatory markers — including neutrophils, lymphocytes, macrophages, and plasmocytes — also react to H&E staining, making H&E useful for providing additional insight into disease severity. Compared to normal endometrium, elevated levels of these immune markers are often seen in endometriosis and may be associated with more severe disease.

H&E AND HEMOSIDERIN-LADEN MACROPHAGES

Remarkably, H&E can also stain for the presence of hemosiderin-laden macrophages (HLMs) — white blood cells filled with hemosiderin, a by-product of hemoglobin released after the rupture of red blood cells (hemolysis). HLMs are commonly found in many disease processes, including in liver and lung disease. Composed of lysosomes and partially digested ferritin molecules (essentially storage containers for iron), the presence of hemosiderin is considered a putative sign of hemorrhage that may have occurred at some point in a lesion's history.

This is not to suggest that endometriosis lesions bleed like menstruation: the source of hemorrhage, and hemorrhagic endometriotic lesions in general, remain topics of intense debate, which we will explore further in upcoming posts.

So far, this means H&E appears to hit the right notes for capturing a histologically-confirmed endometriosis diagnosis — composed of what pathologists refer to as the "diagnostic triad": positive staining for endometrial-like glands, endometrial-like stroma, and hemosiderin-laden macrophages. With H&E alone, the coloring of HLMs can vary from golden yellow to brown — but will appear as blue granule-like pigments when Prussian blue dye is included.

The ability to detect HLMs is a particularly useful advantage of H&E. Not all biopsied lesions classified as suggestive of endometriosis actually stain positive for both ectopic glands and stroma; unusual subtypes fall outside this classical diagnostic criteria. In fact, some studies suggest only 50–70% of endometriosis lesions test fully positive for both glands and stroma when evaluated histologically. More comprehensive panels would improve our understanding of these anomalous findings — but without established guidelines, it is unlikely that profit-driven hospital systems will pursue such investments without prompting from advocacy groups.

STROMAL ENDOMETRIOSIS

Stromal endometriosis is an example of a predominantly stromal-only unusual subtype. As the name implies, it is composed primarily of stroma, with either completely negative or only faint glandular staining discernible. In such cases, pathologists instead look for other signs considered highly suggestive of endometriosis — including the presence of macrophages engorged with hemosiderin, as well as fibrosis and signs of chronic inflammation.

PERLS PRUSSIAN BLUE: STILL GOING STRONG SINCE 1867

As useful as H&E has turned out to be, one cannot help but wonder whether it is the most reliable immunohistochemical marker available. The Perls Prussian Blue staining technique is actually preferred by many pathologists for the detection of hemosiderin, as it generally (but not always) demonstrates greater sensitivity and specificity. In one study, for example, nearly 20% of tissue samples with hemosiderin were missed with H&E but were detected when the Perls method was applied. Yet even the Perls Prussian Blue test is not new — it was introduced in 1867 by its eponymous German founder, Max Perls.

STROMAL ENDOMETRIOSIS: BUT ARE WE SURE?

Circling back to cases in which lesions appear to be without glands — like stromal endometriosis — in an ideal world, these would be retested with more modern antibodies that provide better predictive value for detecting glandular elements that may not be showing up using standard protocols. These distinctions are critical: stromal and/or glandular irregularities may indicate early signs of potential malignant transformation. For example, in one case of misclassified stromal endometriosis involving the bowel, a customized immunohistochemical panel including CK7, CK20, CDX2, and ER was performed. The panel not only helped identify glands in the previously misdiagnosed stromal endometriosis — it also revealed a previously misclassified malignancy in the process.

DECIDUALIZED AND PSEUDODECIDUALIZED ENDOMETRIOSIS

Another subtype with a putatively stromal-predominant or inconclusive histologic staining pattern is decidualized endometriosis — a clinically challenging presentation involving the decidualization of ectopic stromal cells during pregnancy. (Decidualization occurs monthly with menstruation, with or without pregnancy, but is shed if no pregnancy occurs. Cases of pseudodecidualization, covered below, can occur outside of pregnancy.) In an obstetric setting, decidualized endometriomas can mimic ovarian malignancy on imaging, thereby triggering a series of potentially devastating clinical decisions based on an incorrect initial diagnosis. Although one literature review from 2016 found only 60 cases of decidualized endometriomas during pregnancy in the literature, this is nevertheless an important potential presentation of endometriosis that more obstetricians should be trained to recognize. In the setting of histology, misdiagnoses can also occur because decidualized endometriosis can stain negatively for glands — due to mutations that cause the glandular components to become flattened and therefore potentially undetectable using the standard H&E plus CD10 panel. Pseudodecidualized endometriosis can occur outside of pregnancy and is thought to be triggered by exogenous progesterone-based medications so commonly prescribed to people with endometriosis. In this case especially, it is important to make histopathological distinctions, as this is a prime example of when the treatment itself may be upstaging endometriosis — thereby causing more pain and suffering. Ectopic decidua (also referred to as deciduosis) is a benign condition — some even refer to it as a natural, physiological phenomenon — that occurs in pregnancy or in the setting of progesterone medications. With the availability of AI-enhanced histopathology, this is another potentially related condition that deserves a closer look, since some of these cases may actually be endometriosis being triggered and/or upstaged during pregnancy. (Contrary to popular myth, some patients experience a worsening of their endometriosis symptoms during pregnancy and/or immediately after giving birth.) Like decidualized endometriosis/endometriomas, ectopic decidua can even be mistaken for metastatic disease, mesothelioma, diffuse peritoneal carcinomatosis, or granulomas during pregnancy.

Differentiating these vastly different conditions is critical for both fetus and mother. AI-enhanced histology, plus next-generation pan-cytokeratin-based antibodies, could potentially help differentiate between countless cases of potential neoplasms and other clinically questionable lesions. These are just a few examples, but there are numerous case studies of H&E-based tests likely contributing to false negatives and false positives, with potentially adverse impact on millions of patients. If we extrapolate data from multiple studies, it appears that as many as 20–30% (perhaps more) of today's immunohistochemical results may be significantly misleading or substantially inaccurate. Current histology conventions are often getting it wrong where it matters most: identifying ectopic endometrial-like glands and stroma — the two main cell types foundational to a histologically-confirmed endometriosis diagnosis.

1919: CULLEN AND ZENKER'S FIXATIVE

In 1919, the acclaimed endometriosis pioneer Dr. Thomas Cullen was keen to adopt the latest in histology technologies. Cullen noted his particular fondness for Zenker's Fixative — a relatively new breakthrough in histology in the early 20th century — which had fast-acting properties that aided in the collection and storage of surgical biopsies in an era before modern refrigeration became widely available. Despite being derived from one of the most toxic of all mercury salts — mercuric chloride — Cullen and his contemporaries somehow survived the compound's choking, malodorous fumes and remained captivated by its remarkable ability to not only stabilize tissue structures and cellular components quickly, but also effectively stain for chromatin and nucleoli within cell nuclei. Though Cullen was one of the world's leading endometriosis surgeons at the time, he credited this lowly, toxic mordant — nearly lost to history by now — as the single most important factor in allowing for his routine histologic analysis of endometriotic surgical biopsies. 2002–

2004: THE INTRODUCTION OF CD10

Many significant advancements have been made in histology since the days of Zenker's Fixative, but few have been as impactful for the diagnosis of endometriosis as the groundbreaking 2002 work of Sumathi and McCluggage, who were among the earliest to introduce the CD10 immunohistochemical test as an important new method for detecting ectopic endometrial-like stroma in endometriosis. Other early investigators in this space include Groisman and Meir in 2003, and Potlog-Nahari and colleagues, who added to the literature in 2004 with crucial new insights. The CD10 protein is highly expressed in normal endometrial stromal cells but is also present in varying degrees in ectopic and neoplastic endometrial stroma. In the early 2000s, investigators hypothesized that the ectopic endometrial-like stroma found in endometriosis would also respond positively to the CD10 antibody — which turned out to be correct in most cases. What captured the attention of endometriosis specialists the most was the ability of CD10 tests to detect endometriosis where H&E tests alone had failed. Although CD10 staining is not infallible, it was an absolute breakthrough in endometriosis diagnostics and has played a significant role in recognizing the now higher prevalence estimates of 1 in 5–7 (compared to the older statistics of 5–6%). Since the early 2000s, CD10 plus H&E testing has been the standard protocol most pathologists have adopted for endometriosis. (Note: the introduction of video laparoscopy in the late 1970s and early 1980s is the technological breakthrough that has contributed the most to deepening our understanding of the true magnitude of prevalence, with the CD10 test later further enhancing diagnostic efforts.) CD10 testing is not bulletproof. Ovarian endometriomas may not always consistently test positive with CD10 staining. In other cases, endometriotic lesions may only be sparsely populated with stroma, which can lead to false negatives. CD10 is also not a specific immunohistochemical marker just for endometriosis, meaning false positives are also possible.

The CD10 protein is abundant in many different types of cells throughout the human body, in both males and females, and is commonly applied to detect a substantial array of tissue, including prostate cancer and normal breast tissue. Due to this non-specific nature, experienced pathologists recommend that other antibodies be included as part of a more comprehensive panel. PGP9.5 Several promising new immunohistochemical tests have been identified in recent years that deserve consideration as part of a recommended endometriosis-specific histology panel. One such candidate is the PGP9.5 antibody (protein gene product 9.5), which can detect aberrant nerve cells and nerve bundles in both endometriosis and the eutopic myometrium. Its utility is especially notable because it can differentiate several important characteristics, including nerve fiber density and nerve fiber type. Since its introduction, the unexpected presence of various types of nerve cells in endometriosis has shaken up the world of endometriosis research, introducing a previously unknown puzzle piece that has likely been contributing to the extreme pain symptoms that often occur — even in the presence of so-called minimal, stage I disease. Patients have been vindicated yet again — though this small victory is bittersweet, considering how tragically "too little, too late" this breakthrough has been for so many millions around the world. KI-67 Our next candidate for inclusion in a potential histological arsenal for enhancing the detection of endometriosis subtypes associated more strongly with cancer is the Ki-67 antibody, which is showing promise for identifying early-stage cellular atypia associated with malignant transformation. Ki-67 testing is used to measure the mitotic index in proliferating cells. In the context of atypical endometriosis, the Ki-67 test will indicate a higher level of Ki-67-positive staining than in typical endometriosis. In cancer cells, a high mitotic index indicates a poor prognosis — especially in tumors exhibiting aggressive characteristics. In view of recent findings, which suggest ovarian cancer may be significantly more likely in endometriosis patients than previously reported, we hope more endometriosis specialists will consider including Ki-67 in their pathology panels.

OTHER IMMUNOHISTOCHEMICAL MARKERS USED IN ENDOMETRIOSIS HISTOLOGY

Other staining antibodies that leading pathologists have included in their endometriosis-specific immunohistochemical panels are: ERα (estrogen receptor alpha), ERβ (estrogen receptor beta), PRα (progesterone receptor alpha), PRβ (progesterone receptor beta), CK7, CD44, CD133, P53, CA125, PAX8, HOXA11, CA199, WT1, HNF-1β, P450A, BAF250a, COX-2, MIB1, BCl2, and P16. ESTROGEN AND PROGESTERONE RECEPTOR ABNORMALITIES In the case of estrogen and progesterone receptors, testing in endometriosis should be done as part of a standard protocol. It would help clinicians identify many potentially useful clinical features, including progesterone resistance and estrogen resistance (hormone-resistant disease). Similar protocols have been in place for years in oncology, to help detect the most effective treatments depending on the specific tumor histotype involved. Without the crucial insights that ER and PR testing would yield in endometriosis diagnostics, patients will continue to suffer needlessly — effectively treated like guinea pigs as their often well-meaning healthcare providers chase one futile lead after another in search of an elusive elixir that never existed in the first place. As one of the earliest reports by Bulun et al. in 2012 highlighted, endometriotic lesions frequently exhibit significant abnormalities in steroid receptors. For instance, endometriosis often contains much higher levels of the ERβ estrogen receptor isoform compared to the ERα receptor found in normal eutopic endometrium — with Bulun et al. detecting up to 100 times greater levels of ERβ than in normal endometrium. Researchers suspect this profoundly mutated steroid receptor functionality is likely a key culprit involved in the secondary progesterone resistance that endometriosis often exhibits. Analogous insights from oncology are helpful here. Inactivated or dysregulated ERα is widely recognized as a key driver in the development of certain cancers, as disruption of this critical regulatory receptor can trigger uncontrolled cell growth and tumor progression. In the case of endometriosis, similar pathomechanisms are believed to play a major role in onset and progression — although with significantly lower rates of mitosis and progression compared to cancers. Loss of progesterone receptors is associated with more aggressive tumors and worse prognoses for endometrial cancer, while ER-negative tumors are predictive of poor prognoses in breast cancer. Might similar histologic patterns found in endometriosis also hold crucial predictive power? Could there be an equivalent of a "triple negative" endometriosis subtype sitting right under our collective noses, waiting to be included as an important new update to the current subtype classifications? (Nezhat et al. original research, publication-in-progress.) We will never be able to answer these critical questions if we do not even routinely test for the presence of two of the most consequential steroid receptors in endometriosis. THE WHOLE-BODY IMPACT OF ENDOMETRIOSIS As a quick side note — though one of critical importance — mutant estrogen receptors can profoundly affect the expression of thousands of genes and cofactors throughout the body. This can significantly impact crucial physiological functions in all 12 organ systems of the human body, even beyond those typically assumed to be regulated by estrogen. If there is one statement that effectively sums up the concept of endometriosis as a whole-body (systemic) chronic disease — with potential to cause body-wide symptoms beyond the visible lesions and beyond the reproductive tract — this most certainly is it. As for the other antibodies listed above, the role they may play in optimizing histological testing is still under investigation in some cases, so this list is not intended as an endorsement at this time. Rather, we hope this brief overview of some of the customized panels that have been used recently to successfully differentiate between clinically challenging presentations of endometriotic lesions may be useful in your own health advocacy efforts.

OTHER ENDOMETRIOSIS DIAGNOSTIC PITFALLS

Our analysis for this particular blog centers predominantly on antibodies used in immunohistochemical tests, but there are a host of other deeply problematic deficiencies vexing endometriosis diagnostics. Inexperienced surgeons can miss large areas of endometriosis during surgery, which means pathologists do not even receive the right type or number of surgical biopsies to begin with. In an earlier blog, we covered the topic of improper risk stratification by endometriosis subtypes, which has led to the decades-long systematic underreporting of cancer risk in endometriosis patients. Even contaminated reagents have figured into incorrect immunohistochemical test results.

DIAGNOSTIC FAILURES CONTRIBUTE TO STAGGERING DIAGNOSTIC DELAYS GLOBALLY

We have not even begun to discuss the notorious imaging deficiencies that are among the most damaging initial diagnostic blunders — contributing to the appalling 7-to-11-year diagnostic delays endometriosis sufferers face, despite Herculean efforts to increase awareness in recent years. (Ranges vary by country: a 2024 preliminary finding reported an average 11-year delay in the USA, while researchers from the University of York have suggested a staggering 27-year delay.)

2026: "'TIS BUT A SCRATCH"

Concerns about potentially harmful practices in medicine are often brushed off for decades, until a crisis erupts that mobilizes a community into action. At this point, we are not only far beyond the crucible of crisis — we have practically entered an interminable doom loop of one spectacular failure after another, a cruel summer year after bloody year. It is truly unbearable to think of the millions of people around the world trapped in this never-ending hellscape: losing lives because a preventable deadly cancer was missed due to outdated, inaccurate tests; suffering irreparable harm to fertility because all tests came back normal; losing 6, 7, 8 organs unnecessarily, resulting in permanent disability; barely surviving multiple egregious medical errors — like actual wrong-organ surgeries — resulting in even more crippling pain than before; clinging to life by one final, intolerable thread, yet all casually dismissed as imaginary illusions because all the tests and experts and authorities said everything was A-okay. Much of this soul-crushing suffering would have been largely avoidable, had we only believed patients in the first place.

PATIENTS DESERVE GOLD STANDARD CARE, INCLUDING IN HISTOLOGY

Unless we act now to insist that endometriosis-specific histology standards be updated, the painful reality is that we will remain years away from seeing meaningful widespread adoption of the available new advances in histology — advances which hold so much potential for reducing diagnostic errors and catching occult malignancies at much earlier stages than we do today. While the veneer of modern-day immunohistochemical tests may seem fancy and unfathomably advanced, it is important to remember that many are still rooted in century-old technologies.

BETTER THAN AI: TOGETHER, WE ARE THE BEST NEURAL NETWORK IN THE WORLD

With so many deeply entrenched deficiencies plaguing the landscape of endometriosis histology, the challenges seem nearly insurmountable. Where do we even begin to untangle these knowledge gaps that have persisted for decades?

UPDATED HISTOLOGY PROTOCOLS COULD HELP REDUCE ENDOMETRIOSIS-ASSOCIATED CANCER MORTALITY

In situations like this, going back to the basics could be transformative. Take the enigma mentioned earlier: that only 50–70% of endometriotic lesions test positive for ectopic glands and stroma. With such a significant portion of lesions potentially falling outside the actual current definition of endometriosis, it is clear this area is in dire need of a systematic, first-principles reassessment. This is especially true considering that mutations in stroma and glands are often associated with early-stage neoplasms that are not being caught with conventional histological staining practices. Left untreated, this particular festering scientific sinkhole will remain an inscrutable black box of mystery — and misery — that will continue to inflict untold preventable suffering upon tens of thousands of endometriosis patients each year, whose early-stage malignancies may be at risk of being missed due to outdated protocols. We are at a pivotal moment in history. The advanced technologies available now present one of the greatest opportunities we have had in years to finally make strides toward achieving meaningful progress. AI, in particular, is uniquely positioned to unravel the seemingly impenetrable complexities of endometriosis by analyzing billions of data points with unprecedented precision. (You can check out AI for Endo now, with Endo Bot — the Human-AI joint venture our Nezhat et al. team has launched on the nezhat.org website — which is helping to answer many complex questions about endometriosis, based on our vetted library of peer-reviewed literature.) However, the true power lies in the global endometriosis community: our own OG and unmatched neural network of beautiful minds that, collectively, can surpass any AI alone. By working together, this resilient community holds the key to solving these seemingly insoluble quandaries that have stood in the way of progress for decades.

TEAM END ENDO FOREVER: LET'S SHOOT THE SHOT

Bold action will be required to move forward, and we will have to brace for some uncomfortable turbulence. Even so, there is nothing more unstoppable than a united force for change — something we have already proven, from Team USA to Team Algeria, Argentina, Barbados, Botswana, Brazil, Cameroon, Colombia, Cyprus, Czech Republic, Democratic Republic of Congo, Ecuador, France, Germany, Greece, Guadeloupe Island, Hungary, India, Ireland, Israel, Italy, Jamaica, Kenya, Malaysia, Mexico, Nigeria, Northern Ireland, Panama, Peru, Poland, Portugal, Singapore, Spain, Switzerland, Sweden, Trinidad and Tobago, Uruguay, Venezuela, Zimbabwe, and 70+ more — along with Chelsea in Ohio, Nioma in California, Chandelis and Judy of Virginia Hope in Virginia, Karla in Wales, and countless other Endo Fighters of the World. There is no doubt we are destined to shake up the world and make that Mars Shot in Medicine — the shot of the century — to finally free endometriosis survivors from this centuries-long saga of unconscionable indifference to the suffering of millions. From there, we could finally have a fighting chance to fundamentally shift endometriosis healthcare in our own lifetimes, with AI-enhanced precision diagnostics guiding the way toward optimized clinical decisions and helping set the field on course toward early-stage disease detection, cancer prevention, more effective treatments, and potentially even preventive therapies. What an incredible moment this would be — to finally move beyond ineffective mouse models and outdated theoretical frameworks that have been failing patients for decades. In other words: the kind of progress patients have been calling for all along. Improved patient outcomes and hope for a better future. Now that is a future worth fighting for.

— Barbara Page

JOIN US TO HELP BUILD THIS FUTURE

To start the ball rolling in addressing these challenges, you can join in on these conversations through the upcoming 13th Annual Worldwide EndoMarch Conference (ENDOMARCH-AGCES), where the world's leading endometriosis experts and patient advocates will be weighing in on the subject of standardized and updated endometriosis histology protocols. For patients especially, having a platform to join in on discussions about standards can better equip you to take an active role in normally inaccessible medical decisions — decisions which exert outsized impact on your health, yet currently offer no meaningful way of participating in the sometimes irreversibly fateful outcomes. We know this is quite the Hail Mary — to presuppose that your healthcare provider would actually order additional tests for you that were requested by you (that is a subject for a different blog). All the same, we will take the shot and remain hopeful that, one day soon, true patient-practitioner shared decision-making could be possible — even in spaces that have traditionally been kept under lock and key from the discerning gaze of world-wise endometriosis patients who now know to check under the hood when it comes to all that glitters in the ever-illusory landscape of modern medicine.

DO YOU HAVE A HISTOLOGY EXPERIENCE YOU'D LIKE TO SHARE?

If you would like to add to these discussions, but cannot make the live or Virtual EndoMarch conference, you can share your views or stay in the loop on these and other topics by joining our mailing list and receiving a forthcoming full summary on best practices for endometriosis-specific immunohistochemical testing. In the interim, we have also compiled below a preliminary list of articles that provide additional background on emerging advances in the field of histology and endometriosis.

FREE, ONLINE ENDOMETRIOSIS SCREENING TEST

If you suspect you or a loved one may have endometriosis but have not been able to access a formal diagnosis, there is a free screening test you can take to at least assess your risk (with more than 90% accuracy) until you can see a specialist. While this diagnostic screening tool is not meant to replace a formal diagnosis through the gold standard of video laparoscopic evaluation with biopsy, thousands of people with suspected cases of endometriosis (and/or adenomyosis) from around the world have found the test helpful for determining next steps in their diagnostic journey.

RECOMMENDED READING: RECENT ADVANCES IN ENDOMETRIOSIS HISTOLOGY AND IMMUNOHISTOCHEMISTRY

1. Endometriosis Nerve Involvement: A standardized protocol to measure PGP9.5 nerve bundle density in endometriosis.

2. Endometriosis Mitotic Rate: Ki-67 immunohistochemical staining to detect the rate of mitosis in endometriosis.

3. Atypical Endometriosis: Prognostic importance of architectural atypia versus cytologic atypia.

4. HOXA11 and CD10: This combined antibody panel enhances histological detection of endometriosis, with potential for early detection of malignant transformation in progress.