Endometriosis and Endometriosis-Associated Tumors

Endometriosis is a chronic, estrogen-dependent, inflammatory disorder that affects ~10% of reproductive-aged women. The condition, characterized by the presence of endometrial glands and stroma outside of the uterine cavity, is multifactorial and highly recurrent, and causes chronic pelvic pain and other morbidities (e.g., depression, asthma, and migraines) that significantly diminish quality of life. The disease is linked to immune dysfunctions, infertility, and increased risk for ovarian and other (e.g., breast and endometrial) cancers. Its pathophysiology is poorly understood but is considered to have a significant genetic component and may involve abnormal endometrial epithelial progenitors. The histological diagnosis of endometriosis may be compromised by the cellular complexity and heterogeneity of the endometriotic foci which can manifest a spectrum of lesions with distinct and atypical features of stromal and glandular components. Moreover, signs and symptoms of endometriosis remain nonspecific, and a current lack of predictive noninvasive biomarkers precludes early diagnosis. This chapter aims to provide current understanding of the etiology, pathogenesis, and clinicopathologic features of endometriosis, and how emerging information from state-of-the-art technologies may be exploited for the diagnosis, management of symptoms, and therapy in women with this condition. Angela S. Kelley was an author in the previous edition, but has not contributed to the current edition. Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

(1997) Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 67:817–821 Aghajanova L, Giudice LC (2011) Molecular evidence for differences in endometrium in severe versus mild endometriosis. Reprod Sci 18:229–251 Ahmad SF, Akoum A, Horne AW (2015) Selective modulation of the prostaglandin F2alpha pathway markedly impacts on endometriosis progression in a xenograft mouse model. Mol Hum Reprod 21:905–916 Ahn SH, Khalaj K, Young SL et al (2016) Immune-inflammation gene signatures in endometriosis patients. Fertil Steril 106:1420–1431.e7 Akbarzadeh-Jahromi M, Shekarkhar G, Sari Aslani F et al (2015) Prevalence of endometriosis in malignant epithelial ovarian tumor. Arch Iran Med 18:844–848 Albee RB Jr, Sinervo K, Fisher DT (2008) Laparoscopic excision of lesions suggestive of endometriosis or otherwise atypical in appearance: relationship between visual findings and final histologic diagnosis. J Minim Invasive Gynecol 15:32–37 Alhallak I, Quick CM, Graham GL, Simmen RCM (2023) A pilot study on the co-existence of diabetes and endometriosis in reproductive-age women: potential for endometriosis progression. Reprod Sci 30:2429. https://doi.org/10.1007/s43032-023-01190-3 Al-Sabbagh M, Lam EW, Brosens JJ (2012) Mechanisms of endometrial progesterone resistance. Mol Cell Endocrinol 358:208–215 Andersen CL, Boisen MM et al (2018) The evolution of estrogen receptor signaling in the progression of endometriosis to endometriosis-associated ovarian cancer. Horm Cancer 9(6):399–407 Anglesio MS, Papadopoulos N, Ayhan A et al (2017) Cancer-associated mutations in endometriosis without cancer. N Engl J Med 376:1835–1848 Atiya HI, Frisbie L, Goldfeld E et al (2022) Endometriosis-associated mesenchymal stem cells support ovarian clear cell carcinoma through iron regulation. Cancer Res 82(24):4680–4693 Ayhan A, Mao T-L, Seckin T et al (2012) Loss of ARID1A expression is an early molecular event in tumor progression from ovarian endometriotic cyst to clear cell and endometrioid carcinoma. Int J Gyn Cancer 22:1310 Bedaiwy MA, Alfaraj S, Yong P, Casper R (2017) New developments in the medical treatment of endometriosis. Fertil Steril 107:555–565 Benacerraf BR, Groszmann Y, Hornstein MD, Bromley B (2015) Deep infiltrating endometriosis of the bowel wall: the comet sign. J Ultrasound Med 34:537–542 Bendifallah S, Dabi Y, Suisse S et al (2022) Endometriosis associated-miRNome analysis of blood samples: a prospective study. Diagnostics (Basel) 12(5):1150 Blanco LZ Jr, Kuhn E, Morrison JC et al (2017) Steroid hormone synthesis by the ovarian stroma surrounding epithelial ovarian tumors: a potential mechanism in ovarian tumorigenesis. Mod Path 30:563 Boyle DP, McCluggage WG (2009) Peritoneal stromal endometriosis: a detailed morphological analysis of a large series of cases of a common and under-recognised form of endometriosis. J Clin Pathol 62:530–533 Brown DM, Lee HC, Liu S et al (2018) Notch-1 signaling activation and progesterone receptor expression in ectopic lesions of women with endometriosis. J Endocr Soc 2(7):765–778 Browne H, Taylor H (2006) HOXA10 expression in ectopic endometrial tissue. Fertil Steril 85:1386–1390 Brunty S, Clower L, Mitchell B et al (2021) Peritoneal modulators of endometriosis-associated ovarian cancer. Front Oncol 11:793297 Buis CC, van Leeuwen FE, Mooij TM, Burger CW, OMEGA Project Group (2013) Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis. Hum Reprod 28:3358–3369 Bulun SE, Zeitoun KM, Takayama K, Sasano H (2000) Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance. J Mol Endocrinol 25:35–42 Bulun SE, Monsavais D, Pavone ME et al (2012) Role of estrogen receptor-beta in endometriosis. Semin Reprod Med 30:39–45 Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of endometriosis. Fertil Steril 98:511–519 Burns KA, Thomas SY, Hamilton KJ et al (2018) Early endometriosis in females is directed by immune-mediated estrogen receptor alpha and IL-6 cross-talk. Endocrinology 159:103–118 Chen M, Zhang Y, Xu M et al (2022) Primary high-grade serous cancer arising from uterosacral ligament endometriosis: two case reports. J Int Med Res 50(7):030006052211093 Chene G, Ouellet V, Rahimi K et al (2015) The ARID1A pathway in ovarian clear cell and endometrioid carcinoma, contiguous endometriosis, and benign endometriosis. Int J Gynaecol Obstet 130:27–30 Cho MK, Kim CH, Oh ST (2009) Endometriosis in a patient with Rokitansky-Kuster-Hauser syndrome. J Obstet Gynaecol Res 35:994–996 Clement PB (2007) The pathology of endometriosis: a survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects. Adv Anat Pathol 14:241–260 Cochrane DR, Tessier-Cloutier B, Lawrence KM et al (2017) Clear cell and endometrioid carcinomas: are their differences attributable to distinct cells of origin? J Pathol 243(1):26–36 Colarossi C, Picardo MC, Colarossi L et al (2021) Clear cell carcinoma arising in an abdominal wall cesarean section scar: a case report with description of pathological and molecular features. Front Surg 8:735381 Cordeiro MR, Carvalhos CA, Figueiredo-Dias M (2022) The emerging role of menstrual-blood-derived stem cells in endometriosis. Biomedicines 11(1):39 Corzo C, Iniesta MD, Patrono MG et al (2017) Role of fallopian tubes in the development of ovarian cancer. J Minim Invasive Gynecol 24:230–234 Cousins FL, McKinnon BD, Mortlock S et al (2023) New concepts on the etiology of endometriosis. J Obstet Gynaecol Res 49:1090. https://doi.org/10.1111/jog.15549 Cozzolino M, Nasioudis D, Sisti G, Coccia ME (2017) Malignant transformation of vaginal endometriosis-a review of literature. Gynecol Obstet Investig 82:105–112 Crespi BJ, Evans SF (2023) Prenatal origins of endometriosis pathology and pain: reviewing the evidence of a role for low testosterone. J Pain Res 16:307–316 Czernobilsky B, Morris WJ (1979) A histologic study of ovarian endometriosis with emphasis on hyperplastic and atypical changes. Obstet Gynecol 53:318–323 D’Hooghe TM, Bambra CS, Suleman MA et al (1994) Development of a model of retrograde menstruation in baboons (Papio anubis). Fertil Steril 62:635–638 Dehoux JP, Defrere S, Squifflet J et al (2011) Is the baboon model appropriate for endometriosis studies? Fertil Steril 96:728–733.e3 DiVasta AD, Vitonis AF, Laufer MR, Missmer SA (2018) Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs adulthood. Am J Obstet Gynecol 218:324.e1–324.e11 Donnez J, Taylor RN, Taylor HS (2017) Partial suppression of estradiol: a new strategy in endometriosis management? Fertil Steril 107:568–570 Drosdzol-Cop A, Skrzypulec-Plinta V (2012) Selected cytokines and glycodelin a levels in serum and peritoneal fluid in girls with endometriosis. J Obstet Gynaecol Res 38:1245–1253 Er TK, Su YF, Wu CC et al (2016) Targeted next-generation sequencing for molecular diagnosis of endometriosis-associated ovarian cancer. J Mol Med (Berl) 94:835–847 Erickson BK, Conner MG, Landen CN Jr (2013) The role of the fallopian tube in the origin of ovarian cancer. Am J Obstet Gynecol 209:409–414 Fang Z, Yang S, Gurates B et al (2002) Genetic or enzymatic disruption of aromatase inhibits the growth of ectopic uterine tissue. J Clin Endocrinol Metab 87:3460–3466 Fassbender A, Verbeeck N, Bornigen D et al (2012) Combined mRNA microarray and proteomic analysis of eutopic endometrium of women with and without endometriosis. Hum Reprod 27:2020–2029 Fassbender A, Burney RO, Dorien FO et al (2015) Update on biomarkers for the detection of endometriosis. Biomed Res Int 2015:130854 Ferrandina G, Palluzzi E, Fanfani F et al (2016) Endometriosis-associated clear cell carcinoma arising in caesarean section scar: a case report and review of the literature. World J Surg Oncol 14:300 Fritz MA, Speroff L (2011) Clinical gynecologic endocrinology and infertility. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia Fukunaga M, Nomura K, Ishikawa E, Ushigome S (1997) Ovarian atypical endometriosis: its close association with malignant epithelial tumours. Histopathol 30:249–255 Fuldeore M, Yang H, Du EX et al (2015) Healthcare utilization and costs in women diagnosed with endometriosis before and after diagnosis: a longitudinal analysis of claims databases. Fertil Steril 103:163–171 Furuya M, Masuda H, Hara K et al (2017) ZEB1 expression is a potential indicator of invasive endometriosis. Acta Obstet Gynecol Scand 96:1128–1135 Gemmell LC, Webster KE, Kirtley S et al (2017) The management of menopause in women with a history of endometriosis: a systematic review. Hum Reprod Update 23:481–500 Govatati S, Kodati VL, Deenadayal M et al (2014) Mutations in the PTEN tumor gene and risk of endometriosis: a case-control study. Hum Reprod 29:324–336 Grandi G, Mueller M, Bersinger N et al (2016a) Progestin suppressed inflammation and cell viability of tumor necrosis factor-alpha-stimulated endometriotic stromal cells. Am J Reprod Immunol 76:292–298 Grandi G, Mueller MD, Papadia A et al (2016b) Inflammation influences steroid hormone receptors targeted by progestins in endometrial stromal cells from women with endometriosis. J Reprod Immunol 117:30–38 Greaves E, Temp J, Esnal-Zufiurre A et al (2015) Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis. Am J Pathol 185:2286–2297 Gui B, Valentini AL, Ninivaggi V et al (2017) Shining light in a dark landscape: MRI evaluation of unusual localization of endometriosis. Diagn Interv Radiol 23:272–281 Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM (1984) Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol 64:151–154 Han SJ, Hawkins SM, Begum K et al (2012) A new isoform of steroid receptor coactivator-1 is crucial for pathogenic progression of endometriosis. Nat Med 18:1102–1111 Han SJ, Jung SY, Wu SP et al (2015) Estrogen receptor beta modulates apoptosis complexes and the inflammasome to drive the pathogenesis of endometriosis. Cell 163:960–974 Harris HR, Costenbader KH, Mu F et al (2016) Endometriosis and the risks of systemic lupus erythematosus and rheumatoid arthritis in the Nurses’ Health Study II. Ann Rheum Dis 75:1279–1284 Hashiguchi M, Kai K, Nishiyama S et al (2018) Clear cell carcinoma of the uterine cervix presented as a submucosal tumor arising in a background of cervical endometriosis. Int J Gynecol Pathol 37:88–92 Hauptmann S, Friedrich K, Redline R, Avril S (2017) Ovarian borderline tumors in the 2014 WHO classification: evolving concepts and diagnostic criteria. Virchows Arch 470:125–142 Heard ME, Simmons CD, Simmen FA, Simmen RC (2014) Kruppel-like factor 9 deficiency in uterine endometrial cells promotes ectopic lesion establishment associated with activated notch and hedgehog signaling in a mouse model of endometriosis. Endocrinology 155:1532–1546 Heard ME, Melnyk SB, Simmen FA et al (2016) High-fat diet promotion of endometriosis in an immunocompetent mouse model is associated with altered peripheral and ectopic lesion redox and inflammatory status. Endocrinology 157(7):2870–2882 Heinze K, Nazeran TM, Lee S et al (2022) Validated biomarker assays confirm that ARID1A loss is confounded with MMR deficiency, CD8+ TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas. J Pathol 256(4):388–401 Hensen JH, Van Breda Vriesman AC, Puylaert JB (2006) Abdominal wall endometriosis: clinical presentation and imaging features with emphasis on sonography. AJR Am J Roentgenol 186:616–620 Hirsch M, Duffy JMN, Deguara CS, Davis CJ, Khan KS (2017) Diagnostic accuracy of cancer antigen 125 (CA125) for endometriosis in symptomatic women: a multi-center study. Eur J Obstet Gynecol Reprod Biol 210:102–107 Hogg C, Horne AW, Greaves E (2020) Endometriosis-associated macrophages: origin, phenotype, and function. Front Endocrinol (Lausanne) 11:7 Houshdaran S, Nezhat CR, Vo KC et al (2016) Aberrant endometrial DNA methylome and associated gene expression in women with endometriosis. Biol Reprod 95:93 Houshdaran S, Oke AB, Fung JC et al (2020) Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis. PLoS Genet 16(6):e1008601 Hudson QJ, Proestling K, Perricos A et al (2021) The role of long non-coding RNAs in endometriosis. Int J Mol Sci 22(21):11425 Hufnagel D, Li F, Cosar E et al (2015) The role of stem cells in the etiology and pathophysiology of endometriosis. Semin Reprod Med 33:333–340 Ishizaka A, Taguchi A, Tsuruga T et al (2022) Endometrial cancer with concomitant endometriosis is highly associated with ovarian endometrioid carcinoma: a retrospective cohort study. BMC Womens Health 22(1):332 Jaiman S, Gundabattula SR, Pochiraju M, Sangireddy JR (2014) Polypoid endometriosis of the cervix: a case report and review of the literature. Arch Gynecol Obstet 289:915–920 Jansen RP, Russell P (1986) Nonpigmented endometriosis: clinical, laparoscopic, and pathologic definition. Am J Obstet Gynecol 155:1154–1159 Jiang QY, Wu RJ (2012) Growth mechanisms of endometriotic cells in implanted places: a review. Gynecol Endocrinol 28:562–567 Johnson NP, Hummelshoj L, Adamson GD et al (2017) World endometriosis society consensus on the classification of endometriosis. Hum Reprod 32:315–324 Karpathiou G, Chauleur C, Corsini T et al (2017) Seromucinous ovarian tumor a comparison with the rest of ovarian epithelial tumors. Ann Diagn Pathol 27:28–33 Kilzieh R, Rakislova N, Torné A et al (2017) Endometrial stromal sarcoma arising in colorectal endometriosis. Int J Gynecol Pathol 36:433–437 Kim SI, Lee JW, Lee M et al (2018) Genomic landscape of ovarian clear cell carcinoma via whole exome sequencing. Gynecol Oncol 148:375–382 Kim H, Kim HJ, Ahn HS (2023) Does endometriosis increase the risks of endometrial hyperplasia and endometrial cancer? Gynecol Oncol 169:147–153 Klingbeil KD, Azab B, Moller MG (2017) Low-grade appendiceal mucinous neoplasm and endometriosis of the appendix. World J Surg Oncol 15:226 Koninckx PR, Ussia A, Adamyan L et al (2012) Deep endometriosis: definition, diagnosis, and treatment. Fertil Steril 98:564–571 Krawczyk N, Banys-Paluchowski M, Schmidt D et al (2016) Endometriosis-associated malignancy. Geburtshilfe Frauenheilkd 76:176–181 Krishnamoorthy K, Decherney AH (2017) Genetics of endometriosis. Clin Obstet Gynecol 60:531–538 Lakshminarasimhan R, Andreu-Vieyra C, Lawrenson K et al (2017) Down-regulation of ARID1A is sufficient to initiate neoplastic transformation along with epigenetic reprogramming in non-tumorigenic endometriotic cells. Cancer Lett 401:11–19 Li J, Abushahin N, Pang S et al (2011) Tubal origin of ‘ovarian’ low-grade serous carcinoma. Mod Pathol 24:1488 Li J, Fadare O, Xiang L et al (2012) Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis. J Hematol Oncol 5:8 Lin SC, Li YH, Wu MH et al (2014) Suppression of COUP-TFII by proinflammatory cytokines contributes to the pathogenesis of endometriosis. J Clin Endocrinol Metab 99:E427–E437 Liu H, Leng J, Lang J, Cui Q (2014) Clear cell carcinoma arising from abdominal wall endometriosis: a unique case with bladder and lymph node metastasis. World J Surg Oncol 12:51 Long Roche KC, Abu-Rustum NR, Nourmoussavi M, Zivanovic O (2017) Risk-reducing salpingectomy: let us be opportunistic. Cancer 123:1714–1720 Lu J, Zhu Q, Jia X et al (2016) In vitro and in vivo effects of tumor suppressor gene PTEN on endometriosis: an experimental study. Med Sci Monit 22:3727–3736 Marchino GL, Gennarelli G, Enria R et al (2005) Diagnosis of pelvic endometriosis with use of macroscopic versus histologic findings. Fertil Steril 84:12–15 Matalliotakis I, Cakmak H, Matalliotakis M et al (2012) High rate of allergies among women with endometriosis. J Obstet Gynaecol 32:291–293 Matsumoto T, Yamazaki M, Takahashi H et al (2015) Distinct β-catenin and PIK3CA mutation profiles in endometriosis-associated ovarian endometrioid and clear cell carcinomas. Am J Clin Pathol 144:452–463 Mederos MA, Villafañe N, Dhingra S et al (2017) Pancreatic endometrial cyst mimics mucinous cystic neoplasm of the pancreas. World J Gastrol 23:1113 Mendes da Silva D, Gross LA, Neto EPG et al (2017) The use of resveratrol as an adjuvant treatment of pain in endometriosis: a randomized clinical trial. J Endocr Soc 1:359–369 Milingos S, Protopapas A, Drakakis P et al (2003) Laparoscopic management of patients with endometriosis and chronic pelvic pain. Ann N Y Acad Sci 997:269–273 Millischer AE, Santulli P, Da Costa S et al (2023) Adolescent endometriosis: prevalence increases with age on magnetic resonance imaging scan. Fertil Steril 119(4):626–633 Mok-Lin EY, Wolfberg A, Hollinquist H, Laufer MR (2010) Endometriosis in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome and complete uterine agenesis: evidence to support the theory of coelomic metaplasia. J Pediatr Adolesc Gynecol 23:e35–e37 Moll UM, Chumas JC, Chalas E, Mann WJ (1990) Ovarian carcinoma arising in atypical endometriosis. Obstet Gynecol 75:537–539 Monsanto SP, Edwards AK, Zhou J et al (2016) Surgical removal of endometriotic lesions alters local and systemic proinflammatory cytokines in endometriosis patients. Fertil Steril 105:968–977.e5 Mounsey AL, Wilgus A, Slawson DC (2006) Diagnosis and management of endometriosis. Am Fam Physician 74:594–600 Naqvi H, Ilagan Y, Krikun G, Taylor HS (2014) Altered genome-wide methylation in endometriosis. Reprod Sci 21:1237–1243 Nezhat C, Kazerooni T, Berker B et al (2005) Laparoscopic management of hepatic endometriosis: report of two cases and review of the literature. J Minim Invasive Gynecol 12:196–200 Nezhat C, Main J, Paka C et al (2014) Multidisciplinary treatment for thoracic and abdominopelvic endometriosis. JSLS 18:e2014.00312 Nezhat C, Li A, Falik R et al (2018) Bowel endometriosis: diagnosis and management. Am J Obstet Gynecol 218(6):549–562 Nisenblat V, Bossuyt PM, Shaikh R et al (2016) Blood biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev 2016(5):CD012179 Ogi Y, Yamaguchi T, Kinugasa Y et al (2016) A case of small intestinal endometrioid adenocarcinoma. Surg Case Rep 2:97 Pabona JM, Simmen FA, Nikiforov MA et al (2012) Kruppel-like factor 9 and progesterone receptor coregulation of decidualizing endometrial stromal cells: implications for the pathogenesis of endometriosis. J Clin Endocrinol Metab 97:E376–E392 Parasar P, Ozcan P, Terry KL (2017) Endometriosis: epidemiology, diagnosis and clinical management. Curr Obstet Gynecol Rep 6:34–41 Park Y, Han SJ (2022) Interferon signaling in the endometrium and in endometriosis. Biomol Ther 12(11):1554 Park J-Y, Kim D-Y, Suh D-S et al (2018) Significance of ovarian endometriosis on the prognosis of ovarian clear cell carcinoma. Int J Gynecol Cancer 28:11–18 Parker RL, Dadmanesh F, Young RH, Clement PB (2004) Polypoid endometriosis: a clinicopathologic analysis of 24 cases and a review of the literature. Am J Surg Pathol 28:285–297 Pearce CL, Templeman C, Rossing MA et al (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies. Lancet Oncol 13:385–394 Perez-Lopez FR, Ceausu I, Depypere H et al (2017) Interventions to reduce the risk of ovarian and fallopian tube cancer: a European Menopause and Andropause Society Postition Statement. Maturitas 100:86–91 Pluchino N, Taylor HS (2016) Endometriosis and stem cell trafficking. Reprod Sci 23:1616–1619 Practice Committee of American Society for Reproductive M (2012) Multiple gestation associated with infertility therapy: an American Society for Reproductive Medicine Practice Committee opinion. Fertil Steril 97:825–834 Rahmioglu N, Mortlock S, Ghiasi M et al (2023) The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet 55(3):423–436 Redwine DB (2002) Diaphragmatic endometriosis: diagnosis, surgical management, and long-term results of treatment. Fertil Steril 77:288–296 Rudzitis-Auth J, Menger MD, Laschke MW (2013) Resveratrol is a potent inhibitor of vascularization and cell proliferation in experimental endometriosis. Hum Reprod 28:1339–1347 Saavalainen L, Lassus H, But A et al (2019) A cohort study of 49 933 women with surgically verified endometriosis: increased incidence of breast cancer below the age of 40. Acta Obstet Gynecol Scand 98(9):1113–1119 Samartzis EP, Labidi-Galy SI, Moschetta M et al (2020) Endometriosis-associated ovarian carcinomas: insights into pathogenesis, diagnostics, and therapeutic targets-a narrative review. Ann Transl Med 8(24):1712 Sasson IE, Taylor HS (2008) Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci 1127:106–115 Schenken RS (2016) Endometriosis: pathogenesis, clinical features, and diagnosis. Walters Kluwer Health, Waltham Schnack TH, Høgdall E, Thomsen LN, Høgdall C (2017) Demographic, clinical, and prognostic factors of ovarian clear cell adenocarcinomas according to endometriosis status. Int J Gynecol Cancer 27:1804–1812 Scott RB (1953) Malignant changes in endometriosis. Obstet Gynecol 2:283–289 Seeber B, Sammel MD, Fan X et al (2008) Panel of markers can accurately predict endometriosis in a subset of patients. Fertil Steril 89:1073–1081 Seifer BJ, Su D, Taylor HS (2017) Circulating miRNAs in murine experimental endometriosis. Reprod Sci 24:376–381 Seval MM, Cavkaytar S, Atak Z, Guresci S (2013) Postcoital bleeding due to cervical endometriosis. BMJ Case Rep 2013:bcr2012008209 Simmen RC, Kelley AS (2016) Reversal of fortune: estrogen receptor-beta in endometriosis. J Mol Endocrinol 57:F23–F27 Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P (2002) High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod 17:2715–2724 Smorgick N, Marsh CA, As-Sanie S, Smith YR, Quint EH (2013) Prevalence of pain syndromes, mood conditions, and asthma in adolescents and young women with endometriosis. J Pediatr Adolesc Gynecol 26:171–175 Soliman AM, Yang H, Du EX, Kelley C, Winkel C (2016) The direct and indirect costs associated with endometriosis: a systematic literature review. Hum Reprod 31:712–722 Somigliana E, Parazzini F, Stoppelli S et al (2006) Association between endometriosis and cancer: a comprehensive review and a critical analysis of clinical and epidemiological evidence. Gynecol Oncol 101:331–341 Somigliana E, Vigano P, Benaglia L et al (2017) Management of endometriosis in the infertile patient. Semin Reprod Med 35:31–37 Song X, Zhu L, Ding J et al (2016) Clinical characteristics of congenital cervical atresia and associated endometriosis among 96 patients. Int J Gynaecol Obstet 134:252–255 Sourial S, Tempest N, Hapangama DK (2014) Theories on the pathogenesis of endometriosis. Int J Reprod Med 2014:1 Stamp JP, Gilks CB, Wesseling M et al (2016) BAF250a expression in atypical endometriosis and endometriosis-associated ovarian cancer. Int J Gynecol Cancer 26:825–832 Stewart CJ, Bharat C (2016) Clinicopathological and immunohistological features of polypoid endometriosis. Histopathology 68:398–404 Suda K, Nakaoka H, Yoshihara K et al (2018) Clonal expansion and diversification of cancer-associated mutations in endometriosis and normal endometrium. Cell Rep 24(7):1777–1789 Syrcle S, Pelch K, Schroder A et al (2011) Altered gene expression profile in vaginal polypoid endometriosis resembles peritoneal endometriosis and is consistent with increased local estrogen production. Gynecol Obstet Investig 71:77–86 Taguchi A, Wada-Hiraike O, Kawana K et al (2014) Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: a possible role of the sirtuin 1 pathway. J Obstet Gynaecol Res 40:770–778 Tamaresis JS, Irwin JC, Goldfien GA et al (2014) Molecular classification of endometriosis and disease stage using high-dimensional genomic data. Endocrinology 155:4986–4999 Tan Y, Flynn WF, Sivajothi S et al (2022) Single-cell analysis of endometriosis reveals a coordinated transcriptional programme driving immunotolerance and angiogenesis across eutopic and ectopic tissues. Nat Cell Biol 24(8):1306–1318 Tanase Y, Furukawa N, Kobayashi H, Matsumoto T (2013) Malignant transformation from endometriosis to atypical endometriosis and finally to endometrioid adenocarcinoma within 10 years. Case Rep Oncol 6:480–484 Tarumi Y, Mori T, Kusuki I, Ito F, Kitawaki J (2015) Endometrioid adenocarcinoma arising from deep infiltrating endometriosis involving the bladder: a case report and review of the literature. Gynecol Oncol Rep 13:68 Taylor J, McCluggage WG (2015) Ovarian seromucinous carcinoma: report of a series of a newly categorized and uncommon neoplasm. Am J Surg Pathol 39:983–992 Taylor HS, Giudice LC, Lessey BA et al (2017) Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med 377:28–40 Teasley HE, Beesley A, Kim TH et al (2020) Differential expression of KRAS and SIRT1 in ovarian cancers with and without endometriosis. Reprod Sci 27(1):145–151 Terada T (2012) Endometrioid adenocarcinoma of the ovary arising in atypical endometriosis. Int J Clin Exp Pathol 5:924–927 Tomohiro M, Matsumoto T, Miura R et al (2019) Alterations in β-catenin, microsatellite instability, and HNF-1β levels are independently associated with ovarian endometriosis-associated tumorigenesis. Hum Pathol 89:10–23 Tosti C, Pinzauti S, Santulli P, Chapron C, Petraglia F (2015) Pathogenetic mechanisms of deep infiltrating endometriosis. Reprod Sci 22:1053–1059 Tosti C, Biscione A, Morgante G et al (2017) Hormonal therapy for endometriosis: from molecular research to bedside. Eur J Obstet Gynecol Reprod Biol 209:61–66 Troncon JK, Zani AC, Vieira AD et al (2014) Endometriosis in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome. Case Rep Obstet Gynecol 2014:376231 Vallvé-Juanico J, George AF, Sen S et al (2022) Deep immunophenotyping reveals endometriosis is marked by dysregulation of the mononuclear phagocytic system in endometrium and peripheral blood. BMC Med 20(1):158 Vercellini P, Vigano P, Somigliana E, Fedele L (2014) Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 10:261–275 Vinatier D, Orazi G, Cosson M, Dufour P (2001) Theories of endometriosis. Eur J Obstet Gynecol Reprod Biol 96:21–34 Walker JL, Powell CB, Chen LM et al (2015) Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer. Cancer 121:2108–2120 Walter AJ, Hentz JG, Magtibay PM et al (2001) Endometriosis: correlation between histologic and visual findings at laparoscopy. Am J Obstet Gynecol 184:1407–1411; discussion 11–13 Wang W-T, Zhao Y-N, Han B-W et al (2013) Circulating microRNAs identified in a genome-wide serum microRNA expression analysis as noninvasive biomarkers for endometriosis. J Clin Endocrinol Metab 98:281–289 Wang Y, Mang M, Wang Y et al (2015) Tubal origin of ovarian endometriosis and clear cell and endometrioid carcinoma. Am J Cancer Res 5:869–879 Wang Y, Hong S, Mu J et al (2019) Tubal origin of “ovarian” low-grade serous carcinoma: a gene expression profile study. J Oncol 8659754:1 Wang D, Guo C, Li Y et al (2022) Oestrogen up-regulates DNMT1 and leads to the hypermethylation of RUNX3 in the malignant transformation of ovarian endometriosis. Reprod Biomed Online 44(1):27–37 Wang Y, Li Q, Zhao R et al (2023) Fallopian tubal histogenesis of ovarian endometriosis-a study of folate receptor-alpha expression. Front Med (Lausanne) 10:1138690 Wei JJ, William J, Bulun S (2011) Endometriosis and ovarian cancer: a review of clinical, pathologic, and molecular aspects. Int J Gynecol Pathol 30:553–568 Wiegand KC, Shah SP, Al-Agha OM et al (2010) ARID1A mutations in endometriosis-associated ovarian carcinomas. New Engl J Med 363:1532–1543 Wilbur MA, Shih IM, Segars JH, Fader AN (2017) Cancer implications for patients with endometriosis. Semin Reprod Med 35:110–116 Wu CH, Mao TL, Vang R et al (2012) Endocervical-type mucinous borderline tumors are related to endometrioid tumors based on mutation and loss of expression of ARID1A. Int J Gynecol Pathol 31:297–303 Xu T, Zhang L, Jiang Y et al (2023) Clinical characteristics and serum CA19-9 combined with HE4 are valuable in diagnosing endometriosis-associated ovarian cancer. Int J Gynaecol Obstet 162:472. https://doi.org/10.1002/ijgo.14695 Yachida N, Yoshihara K, Suda K et al (2020) ARID1A protein expression is retained in ovarian endometriosis with ARID1A loss-of-function mutations: implication for the two-hit hypothesis. Sci Rep 10(1):14260 Yamamoto S, Tsuda H, Takano M et al (2012) Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell carcinoma development and frequently coexists with PIK3CA mutations. Mod Pathol 25:615 Yamamoto A, Harris HR, Vitonis AF et al (2018) A prospective cohort study of meat and fish consumption and endometriosis risk. Am J Obstet Gynecol 219(2):178.e1–178.e10 Yantiss RK, Clement PB, Young RH (2001) Endometriosis of the intestinal tract: a study of 44 cases of a disease that may cause diverse challenges in clinical and pathologic evaluation. Am J Surg Pathol 25:445–454 Yoo JY, Kim TH, Fazleabas AT et al (2017) KRAS activation and over-expression of SIRT1/BCL6 contributes to the pathogenesis of endometriosis and progesterone resistance. Sci Rep 7:6765 Yu J, Boicea A, Barrett KL et al (2014) Reduced connexin 43 in eutopic endometrium and cultured endometrial stromal cells from subjects with endometriosis. Mol Hum Reprod 20:260–270 Yuan Z, Wang L, Wang Y et al (2014) Tubal origin of ovarian endometriosis. Mod Pathol 27:1154–1162 Zhao Y, Gong P, Chen Y et al (2015) Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis. Sci Transl Med 7:271ra9 Zhao Y, Chen Y, Kuang Y et al (2016) Multiple beneficial roles of repressor of estrogen receptor activity (REA) in suppressing the progression of endometriosis. Endocrinology 157:900–912 Zheng W, Li N, Wang J et al (2005) Initial endometriosis showing direct morphologic evidence of metaplasia in the pathogenesis of ovarian endometriosis. Int J Gynecol Pathol 24:164–172 Zondervan KT, Rahmioglu N, Morris AP et al (2016) Beyond endometriosis genome-wide association study: from genomics to phenomics to the patient. Semin Reprod Med 34:242–254 Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2025 Springer Nature Singapore Pte Ltd. About this entry Cite this entry Simmen, R.C.M., Quick, C.M., Zheng, W. (2025). Endometriosis and Endometriosis-Associated Tumors. In: Zheng, W., Fadare, O., Quick, C.M. (eds) Gynecologic and Obstetric Pathology. Springer, Singapore. https://doi.org/10.1007/978-981-97-4822-8_12 Download citation DOI: https://doi.org/10.1007/978-981-97-4822-8_12 Published: Publisher Name: Springer, Singapore Print ISBN: 978-981-97-4821-1 Online ISBN: 978-981-97-4822-8 eBook Packages: MedicineReference Module Medicine