Ovary nontumor
Nonneoplastic cysts / other
Endometriosis

Author: Aurelia Busca, M.D., Ph.D. (see Authors page)
Editor: Carlos Parra-Herran, M.D.

Revised: 13 September 2017, last major update August 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Endometriosis ovary [title]
Cite this page: Busca, A. Endometriosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/ovarynontumorendometriosis.html. Accessed October 18th, 2017.
Definition / general
  • Presence of ectopic endometrial glands or stroma in the ovary
Essential features
  • Benign but associated with an increased risk of ovarian carcinoma of clear cell and endometrioid subtypes
    • Has some overlapping molecular changes with clear cell and endometrioid carcinomas (PI3KCA, ARID1A, p53 mutations)
  • In addition, endometriosis in patients without cancer has been demonstrated to harbor oncogenic mutations in ARID1A, PIK3CA, KRAS and PPP2R1A, suggesting a neoplastic nature for some cases (N Engl J Med 2017;376:1835)
  • CD10 immunohistochemistry used to confirm the presence of endometrial stroma in cases not evident by morphology
Terminology
  • Endometrioma, chocolate cyst, endometrioid cyst, endometrial cyst
Epidemiology
Sites
  • Ovaries are the most common site, followed by posterior cul de sac, broad ligament, uterosacral ligament, rectosigmoid colon and bladder
Pathophysiology
  • Three proposed theories (N Engl J Med 1993;328:1759)
    • Metaplastic: due to metaplasia of pelvic peritoneal cells
    • Metastatic: retrograde menstruation and implantation of endometrial cells
    • Induction: a combination of the first two: shed endometrial cells mediate the differentiation of mesenchymal cells to endometriotic tissue
Clinical features
  • Typically dysmenorrhea, dyspareunia, pain, irregular bleeding and infertility
  • Endometriosis is reported in up to 50% of women with infertility (Ann N Y Acad Sci 2002;955:11)
  • Rarely, infection or rupture of an endometriotic cyst with ascites or hemoperitoneum
Diagnosis
  • Laparoscopy with visualization of endometriotic foci is required for diagnosis
Laboratory
Radiology description
  • Ultrasound mostly used for ovarian endometriotic cysts
  • Typically multilocular cysts with septations and hyperechoic mural nodules (Radiology 1999;210:739)
Prognostic factors
  • Endometriosis increases the risk of ovarian cancer, with clear cell and endometrioid carcinomas as the most common endometriosis associated ovarian cancers, with a prevalence of ovarian cancer in 2 - 17% of women with endometriosis (Acta Obstet Gynecol Scand 2014;93:20)
  • Risk of developing cancer is associated with a long standing history of endometriosis (over 10 years) and early diagnosis (before 30 years or age)
  • In a study of 144 ovarian cancers, endometriosis was associated with 53% of clear cell carcinomas, 33% of endometrioid carcinomas and 45% of mixed tumors (Am J Surg Pathol 2012;36:688)
  • However, the presence of endometriosis as an independent prognostic factor in cancers arising from endometriosis, including clear cell carcinoma, remains elusive, with conflicting reports in the literature
    • In a study of 196 ovarian cancers, endometriosis was an independent predictor for progression free survival and overall survival in patients with ovarian cancer, after controlling for FIGO stage
    • In a study of 73 patients with clear cell and mixed endometrioid clear cell ovarian carcinoma, those with associated endometriosis were younger
    • Endometriosis in patients with stage I ovarian clear cell carcinoma was associated with better overall and progression free survival in univariate analysis but not in multivariate analysis (Gynecol Oncol 2016;143:526)
Case reports
Treatment
  • Laparoscopic or hormonal treatment
  • Hormonal treatment is aimed at suppression of menstrual cycles using danazol, oral contraceptives or gonadotropin releasing hormone (GnRH) analogues
Clinical images

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Endometriosis on surface of ovaries

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Chocolate cysts

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Kissing ovaries

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Opened endometrioma

Gross description
  • Ovarian endometriosis is usually cystic (endometriotic cysts or endometriomas), with fibrotic walls, a smooth lining and dark brown cyst contents fluid (chocolate cyst)
  • Fibrous adhesions may be present on the surface and attach the cysts to adjacent organs
  • Polypoid endometriosis: endometriosis lesions have a polypoid configuration that raises the differential diagnosis with a neoplasm on gross and intraoperative examination
Gross images

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External surfaces of the ovarian wedges show red, blue and brown areas, some associated with fibrotic puckering (AFIP)

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Cyst contains chocolate colored fluid
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Cyst has dark brown discoloration

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Chocolate cyst

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Ovarian endometriotic cyst

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Irregular hemorrhagic areas

Microscopic (histologic) description
  • At least two of the following three microscopic features:
    • Endometrial type glands
    • Endometrial type stroma
    • Evidence of chronic hemorrhage (hemosiderin laden macrophages)
  • Glandular epithelium commonly has metaplastic changes (tubal, mucinous, squamous, hobnail)
  • Atypical endometriosis: epithelial lining of the glands may show enlargement with abundant eosinophilic cytoplasm, cellular stratification and hyperchromatic nuclei; can be reactive but also has malignant potential and is considered the precursor lesion for endometriosis associated carcinomas (clear cell or endometrioid) (Histopathology 1997;30:249, Case Rep Oncol 2013;6:480)
  • Burnt out endometriosis: this term has been proposed for changes suggestive of endometriosis, namely central necrosis with surrounding fibrosis and pseudoxanthoma cells but lacking confirmatory features as listed above
  • Liesegang rings: acellular ring-like structures seen in areas of chronic inflammation
Microscopic (histologic) images

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Surrounded by denser ovarian stroma

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Cyst contains pseudoxanthoma cells

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Endometriotic cyst is fibrotic

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Scattered Liesgang rings

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Polyp composed mainly of cystic glands


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Pseudoxanthomatous necrotic nodules

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Marked decidual change of stroma

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Smudgy nuclei resembling Arias-Stella reaction



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H&E and CD10

Cytology description
  • Presence of hemosiderin laden macrophages, endometrial glandular cells and endometrial stromal cells for diagnosis of endometriotic cyst and distinction from hemorrhagic corpus luteum
Cytology images

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Endometriosis cyst

Positive stains
  • CD10 highlights endometrial stroma
Negative stains
Molecular / cytogenetics description
  • ARID1A mutations are associated with progression to carcinoma (Mod Pathol 2012;25:885)
  • p53 mutations were present in 30% of cases of ovarian endometriosis associated with clear cell carcinoma and absent in uncomplicated endometriosis (Int J Gynecol Pathol 2007;26:345)
  • In a study of 30 benign ovarian endometriotic cysts, 24 endometriotic cysts containing endometrioid carcinomas and 19 endometriotic cysts harboring clear cell carcinomas, p53 staining was negative in the benign endometriotic cysts and positive in 25% of the benign endometriotic lesions next to the endometrioid carcinoma and in 9% of the benign endometriotic lesions next to clear cell carcinoma, suggesting a role in the malignant transformation of endometriosis (Cancer 2002;94:2935)
  • In a study of 13 ovarian endometrioid adenocarcinomas arising from endometriosis and 15 ovarian endometrioid adenocarcinomas without associated endometriosis, there was a significantly higher expression of p53 in those cases arising from endometriosis compared to their counterparts not associated with endometriosis, suggesting that different molecular pathways may be involved in their pathogenesis (Int J Gynecol Pathol 2003;22:83)
  • PTEN tumor suppressor gene inactivation is an early event in the development of both ovarian endometrioid carcinoma and clear cell carcinoma associated with endometriosis (Cancer Res 2000;60:7052)
  • PIK3CA and ARID1A were the most frequently mutated genes in endometriosis (J Mol Med (Berl) 2016;94:835, N Engl J Med 2017;376:1835, Int J Gynaecol Obstet 2015;130:27)
Differential diagnosis
  • Clear cell adenofibroma / borderline tumor: extensively fibrotic background with scattered glandular elements displays clear cell cytologic features
  • Cystic corpus luteum: lining is composed of luteinized cells with cord-like arrangement, abundant eosinophilic cytoplasm and round nuclei
    • Lack of glandular elements
  • Endocervicosis: endocervical type mucinous epithelium, absence of endometrial type stroma
  • Endometrioid adenofibroma: mass forming lesion with a prominent solid, fibromatous component
  • Endosalpingiosis: diffuse / circumferential tubal differentiation with ciliated and peg cells
    • Absence of cellular, endometrial type stroma
    • Absence of hemorrhage
  • Peritoneal inclusion cysts: simple flat epithelial lining (instead of columnar), hypocellular and collagenized subepithelial stroma