{"paper_id":"0c63eef1-7286-4c1a-a882-7e2935233f94","body_text":"Integrative Gynecology and Obstetrics Journal\nVolume 2 Issue 4Research Open\nIntegr Gyn Obstet J, Volume 2(4): 1–3, 2019 \nCommentary\nMicroscopic Adenomyosis\nPietro G Signorile1, Rosa Viceconte1 and Alfonso Baldi2*\n1Fondazione Italiana Endometriosi, Rome, Italia \n2*Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Campania University “L. Vanvitelli”, Caserta, Italy\n*Corresponding author: Alfonso Baldi, Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Campania University “L. Vanvitelli” , \nCaserta, Italy; Email: alfonsobaldi@tiscali.it\nReceived: September 03, 2019; Accepted: September 17, 2019; Published: October 06, 2019; \n \nCommentary\nEndometriosis is a frequent, chronic inflammatory estrogen-\ndependent gynecological disease characterized by the presence \nof extrauterine endometrial tissue,  that affects up to 10% of all \nreproductive-aged women. The incidence increases to 30–50% in \nwomen with chronic pelvic pain and infertility [1, 2]. Most common \nsites of the ectopic endometrial-like tissue are the pelvic peritoneum \nand ovaries, but they can be found also under the peritoneal surface, \nwhere endometriosis is strongly associated with pelvic pain symptoms \n[3]. This disease has a noteworthy morbidity, with harmful effect upon \nwomen’s social working, personal life, and relations with physicians \n[4]. Notwithstanding, the pathogenesis, as well as the diagnosis and \ntherapy for endometriosis are still not perfectly delineated [5]. Recently, \nour group and others have generated convincing experimental data \nsuggesting that perturbation of the fine-tuning of the female genital \nsystem development during a critical window of time in fetal life as \nthe pathogenetic event prompting to the progression of endometriosis \nlater in life [6–12]. \nThe lack of knowledge about this disease justifies the fact that, \nto date, endometriosis is an incredibly under-diagnosed and under-\ntreated disease, with an excessively long-time interval between the \ncommencement of the symptoms and conclusive diagnosis of 8–12 \nyears [1]. This is due to the fact that most of the symptoms are non-\nspecific and there are no non-invasive diagnostic investigations \nable to reach a definitive diagnosis [13]. The definite diagnosis of \nendometriosis can be obtained only by histological examination of the \nectopic tissue implants collected by invasive surgical or exploratory \nprocedures [1].\nThe histologic diagnosis of endometriosis is, usually, quite simple \nand is based essentially on the recognition of both endometriosic \nglands and stroma, or at least by one of these two elements [1]. \nThe histological appearance of these elements is straightforward; \nnevertheless, immunohistochemical staining for cytokeratin markers \nand for CD10 can aid in identification of glands and stroma in doubtful \ncases [14]. The different histopathological aspects of endometriosis \nare well known and have been described in detail in an elegant work of \nClement some years ago [14]. Even though the histological diagnosis \nof endometriosis is relatively easy, also for pathologists who are not \nexperts in this pathology, it has been reported that approximately only \n50% of biopsy specimens from areas suggestive of endometriosis at \nlaparoscopic examination have been proven microscopically to be \nendometriosis. Since the definitive diagnosis of this disease is based on \nhistological examination, it is important for the correct management \nof the patients, to avoid false negative results at histology. \nThis phenomenon is particularly true in the case of adenomyosis, \na condition of endometriosis in which the endometrial glands \nare embedded into the myometrium of the uterus [15] . Based on \nthe Sampson’s theory, endometriosis and adenomyosis have been \nconsidered for a long time two different clinical entities and it took \napproximately 80 years to put forward a new theory reunifying \ntheir pathogenesis [16]. Indeed, adenomyosis is still considered \ntoday an ‘elusive’ or ‘enigmatic’ disease because of the struggle in \ndiagnosis, and of the indefinite and vague pattern of symptoms \nwhich may accompany it. Nevertheless, the frequent association \nof adenomyosis with other pelvic pathologies is a further aspect \nwhich complicates the understanding of related symptoms [17]. \nFinally, since the moderate to severe degrees of adenomyosis can be \naccurately diagnosed preoperatively by good-quality ultrasound or \nmagnetic resonance imaging, it would be desirable in the near future \nto correlate symptomatology with specific findings on imaging and \nwith pathological data. \nIn our experience it has happened more than once to review cases, \nreported as negative for adenomyosis, which showed the presence \nof microscopic adenomyosis foci that had escaped the observation \nof the pathologist. As an example, in Figure 1  we show a case of \nmultiple microscopic adenomyosis in the posterior wall of the uterus \nof patients with endometriosis. Indeed, ultrasound analysis had \nshown alterations suggestive of adenomyosis of the posterior uterine \nwall, but the histological analysis of the tissue taken was negative.  A \ncareful analysis of the histological preparation, however, showed the \npresence of microscopic endometriotic glands. Immunohistochemical \nanalysis with cytokeratin antibodies confirmed the epithelial nature \nof these structures. In Figure 2 we show another case of microscopic \nadenomyosis, in which two small glandular structures were found in the \nwall of the uterus, as clearly demonstrated by immunohistochemical \nanalysis for cytokeratin. Interestingly, analysis by CD10 clearly showed \nthat in microscopic adenomyosis the stromal component is absent.\n\nAlfonso Baldi (2019) Microscopic Adenomyosis\nIntegr Gyn Obstet J, Volume 2(4): 2–3, 2019 \nFigure 1. A case of microscopic adenomyosis in the posterior wall of the uterus is depicted. In this case a multifocal microscopic adenomyosis with several very small glands was evidenced\nA) Histological appearance of the multifocal adenomyosis (Hematoxylin and Eosin; original magnification X20)\nB) Immunohistochemical staining for pan-cytokeratin (ABC; original magnification X10)\nC) Higher magnification of figure 1B (ABC; original magnification X20)\nFigure 2. A different case of microscopic adenomyosis in the posterior wall of the uterus is shown. In this case a single small glandular structure was found\nA) A small glandular structure evidenced by the immunohistochemical staining for pan-cytokeratin (ABC; original magnification X10)\nB) Higher magnification of figure 1° (ABC; original magnification X20)\nC) The microscopic adenomyosis does not include stroma, as demonstrated by the negative stainining for CD10 (ABC; original magnification X20)\nCurrently, by mean s of ultrasound and magnetic resonance \nimaging analyses, is possible to define for adenomyosis a spectrum \nof lesions, ranging from increased thickness of the junctional zone \nto evident adenomyosis and adenomyomas, which in turn can \nbe sub classified [18]. Moreover, it is commonly accepted by the \nscientific community that adenomyosis is a progressive disease that \nchanges in appearance during the reproductive years. Therefore, it \nhas been recognized the need of a consensus classification of uterine \nadenomyosis [18].\nBased on our experience, microscopic  adenomyosis could be \nconsidered the earliest form of adenomyosis and should enter the \nconsensus classification of adenomyosis. Furthermore, in the light of \nthis observation, we claim that such an initial state of adenomyosis \nis a source of symptomatology, thus explaining the presence, as \noften happens, of patients with negative diagnostic tests but with \nsymptomatology in place, for which even doubts are often raised \nabout the presence of this pat hology. Microscopic adenomyosis also \nprovides a rational basis for the occurrence that surgical interventions \noften do not resolve the symptoms of chronic pelvic pain. \nNevertheless, the histological features of microscopic adenomyosis \ngive us clues to the developmental dynamics of endometriosis and \nadenomyosis. The prevalent glandular-epithelial composition in \nmicroscopic adenomyosis may lead to the hypothesis that the role of \nthe stromal component becomes fundamental in a successive phase, \nproviding an essential support to the glandular structures by virtue \nof its sensitivity to the higher estrogenic growth input with respect to \nthe epithelial component [19]. Finally, we also noted that the greater is \ntthe multifocal representation of the glands present, the greater is the \nsymptomatic component of pelvic pain.\nIn conclusion, we propose to consider microscopic adenomyosis \nas a specific clinical entity and to include it in the classification of \nuterine adenomyosis Careful histological analysis and, in doubtful \ncases, the use of immunohistochemistry should always be performed, \nto eventually confirm the presence of microscopic glands in patients \n\nAlfonso Baldi (2019) Microscopic Adenomyosis\nIntegr Gyn Obstet J, Volume 2(4): 3–3, 2019 \nwith clinical and instrumental signs suggestive for adenomyosis. This \nwould be very important to reduce the delay in the diagnosis of this \nclinical entity, which is still high today and causes significant problems \nfor both patients and physicians.\nReferences\n1. Bulun SE (2009) Endometriosis. N Engl J Med 360: 268–279.\n2. Signorile PG, Campioni M, Vincenzi B, D’Avino A, Baldi A (2009) Rectovaginal \nseptum endometriosis: an immunohistochemical analysis of 62 cases. In Vivo 23: \n459–464.\n3. Baldi A, Campioni M, Signorile PG(2008) Endometriosis: pathogenesis, diagnosis, \ntherapy and association with cancer. Oncol Rep 19: 843–846.\n4. Fuldeore M, Chwalisz K, Marx S, Wu N, Boulanger L, et al. (2001) Surgical \nprocedures and their cost estimates among women with newly diagnosed \nendometriosis: a US database study. J Med Econ 14: 115–123.\n5. Benagiano G, Brosens I (2006) History of adenomyosis. Best Pract Res Clin Obstet \nGynaecol 20: 449–463.\n6. Signorile PG, Baldi F, Bussani R, D’Armiento M, De Falco M, Baldi A (2009) \nEctopic endometrium in human fetuses is a common event and sustains the theory \nof mullerianosis in the pathogenesis of endometriosis, a disease that predisposes to \ncancer. J Exp Clin Cancer Res 9: 28–49.\n7. Signorile PG, Baldi A (2010) Endometriosis: new concepts in the pathogenesis. Int \nJ Biochem Cell Biol 42: 778–780.\n8. Signorile PG, Spugnini EP, Mita L, Mellone P, D’Avino A, et al. (2010) Pre-natal \nexposure of mice to bisphenol A elicits an endometriosis-like phenotype in female \noffspring. Gen Comp Endocrinol 168: 318–325.\n9. Signorile PG, Baldi F, Bussani R, D’Armiento M, De Falco M, et al. (2010) New \nevidence of the presence of endometriosis in the human fetus . Reprod Biomed \nOnline 21: 142–147.\n10. Signorile PG, Baldi F, Bussani R, Viceconte R, Bulzomi P, et al. (2012) Embryologic \norigin of endometriosis: analysis of 101 human female fetuses. J Cell Physiol 227: \n1653–1656.\n11. Bouquet de Jolinière J, Ayoubi JM, Lesec G, Validire P, Goguin A, et al. (2012) \nIdentification of displaced endometrial glands and embryonic duct remnants in \nfemale fetal reproductive tract: possible pathogenetic role in endometriotic and \npelvic neoplastic processes. Front Physiol 3: 444.\n12. Crispi S, Piccolo MT, D’Avino A, Donizetti A, Viceconte R, et al. (2013) \nTranscriptional profiling of endometriosis tissues identifies genes related to \norganogenesis defects. J Cell Physiol 228: 1927–1934.\n13. Ballard KD, Lowton K, Wright JT (2006) What’s the delay? A qualitative study \nof women’s experience of reaching a diagnosis of endometriosis. Fertil Steril 85: \n1296–1301.\n14. Clement PB (2007) The pathology of endometriosis: a survey of the many faces of a \ncommon disease emphasizing diagnostic pitfalls and unusual and newly appreciated \naspects. Adv Anat Pathol 14: 241–260.\n15. Thylan S Adenomyosis (1995) an ignored uterine disease. Nurse Pract 20: 8–9.\n16. Benagiano G, Brosens I, Carrara S. Adenomyosis (2009) new knowledge is \ngenerating new treatment strategies. Womens Health (Lond) 5: 297–311.\n17. Peric H, Fraser IS (2006) The symptomatology of adenomyosis. Best Pract Res Clin \nObstet Gynaecol 20: 547–555.\n18. Gordts S, Brosens JJ, Fusi L, Benagiano G, Brosens I (2008) Uterine adenomyosis: \na need for uniform terminology and consensus classification. Reprod Biomed \nOnline 17: 244–248.\n19. Dyson MT, Kakinuma T, Pavone ME, Monsivais D, Navarro A, et al. (2015) \nAberrant expression and localization of deoxyribonucleic acid methyltransferase \n3B in endometriotic stromal cells. Fertil Steril 104: 953–963.\nCitation: \nPietro G Signorile, Rosa Viceconte and Alfonso Baldi (2019) Microscopic Adenomyosis. Integr Gyn Obstet J V olume 2(4): 1–3.","source_license":"CC0","license_restricted":false}