Topic Completed: 16 March 2020

Minor changes: 7 October 2020

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PubMed search: Uterus[TI] endometriosis[TI]

Lisa Han, M.D.
Rochelle Garcia, M.D.
Page views in 2019: 10,774
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Cite this page: Han L, Garcia R. Endometriosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusendometriosis.html. Accessed October 26th, 2020.
Definition / general
  • Presence of endometrial tissue outside of endometrium and myometrium, consisting of both endometrial glands and stroma
Essential features
  • Ectopically located endometrial tissue consisting of both endometrial type glands and stroma
  • Endometriosis is associated with ovarian clear cell carcinoma and endometrioid carcinoma and shares similar molecular alterations
  • Endometrioma: endometriosis involving ovary, often cystic
  • Endometriosis with neoplasm (“complex atypical hyperplasia”, carcinoma)
  • Atypical endometriosis: endometriosis with cytologic atypia (Adv Anat Pathol 2007;14:241)
ICD coding
  • ICD-10: N80 - Endometriosis of uterus
    • N80.0 - Endometriosis of uterus
    • N80.1 - Endometriosis of ovary
    • N80.2 - Endometriosis of fallopian tube
    • N80.3 - Endometriosis of pelvic peritoneum
    • N80.4 - Endometriosis of rectovaginal septum and vagina
    • N80.5 - Endometriosis of intestine
    • N80.6 - Endometriosis in cutaneous scar
    • N80.8 - Other endometriosis
    • N80.9 - Endometriosis, unspecified
  • Affects 5 - 15% women of reproductive age
  • Peak incidence: 30 - 45 years of age
  • Estrogen dependent; rarely affects men taking large doses of estrogen (Fertil Steril 2012;98:511)
  • Ovary (67%) > anterior and posterior cul-de-sac > posterior broad ligaments, uterosacral ligaments > uterus >fallopian tubes > sigmoid colon and appendix > round ligaments (Eur J Obstet Gynecol Reprod Biol 2018;230:36)
  • Rarely in remote sites such as lung
  • Retrograde menstruation theory: endometrial lining cells travel backwards through fallopian tubes during menses to reach peritoneal cavity, proliferate and cause chronic inflammation with formation of adhesions (Nat Rev Endocrinol 2014;10:261)
  • Coelomic metaplasia theory: metaplastic transformation of coelomic cells lining the pelvic peritoneum (J Lab Physicians 2010;2:1)
  • Development of malignant neoplasm occurs in < 1% of cases; 75% of malignant neoplasms arise in ovarian endometriosis (J Lab Physicians 2010;2:1)
  • Organochlorine pollutant exposure
Clinical features
  • Laparoscopy required for definitive diagnosis, although ~50% laparoscopic biopsy specimens contain microscopic endometriosis (Am J Obstet Gynecol 2001;184:1407)
  • Endometriosis in pelvis categorized as superficial peritoneal, ovarian and deeply infiltrating
Prognostic factors
  • Risk of development of malignant neoplasm estimated at 1% for premenopausal women and up to 2.5% for postmenopausal women
  • ~75% neoplasms complicating endometriosis arise within ovary; most common extraovarian site is rectovaginal septum
    • Increased risk of endometrioid carcinoma followed by clear cell carcinoma (Clin Chim Acta 2019;493:63)
    • Other associated neoplasms include seromucinous neoplasms (mainly borderline), endometrioid adenofibromas and borderline neoplasms, adenosarcomas and endometrial stromal sarcomas (Histopathology 2020;76:76)
  • Women with carcinoma arising in endometriosis tend to be premenopausal, obese and with history of unopposed estrogens (Gynecol Oncol 2000;79:18)
  • Endometriosis associated carcinoma (other than clear cell) tend to be lower grade and stage than similar ovarian carcinoma without associated endometriosis (Gynecol Oncol 2001;83:100)
Case reports
Gross description
Gross images

Contributed by University of Washington Medical Center

Uterus with shaggy hemorrhagic adhesions

Images hosted on other servers:

Small foci resembling "powder burns"

"Chocolate" cyst

Frozen section description
  • Presence of endometrial glands or endometrial stroma (Taiwan J Obstet Gynecol 2019;58:328)
    • Sometimes only macrophages and hemosiderin present (diagnose as “consistent with clinical impression of endometriosis” as other causes are possible)
  • Can be associated with fibrous adhesions
  • Negative for neoplastic features such as glandular complexity
Frozen section images

Contributed by University of Washington Medical Center

Endometriosis involving omental nodule

Endometriosis in peritoneal nodule

Microscopic (histologic) description
  • Ectopic endometrial type glands and stroma
    • Epithelial component:
      • Müllerian type epithelium (can be atrophic to cycling endometrium)
      • Can show degenerative atypia (enlarged smudgy nuclei) or metaplasia
    • Stromal component:
      • Often contains fine capillary network
      • May undergo smooth muscle metaplasia, fibrosis (longstanding), decidual change
      • May be myxoid (particularly in pregnancy)
      • Stroma may be only identifiable component (stromal endometriosis)
  • Often with hemorrhage, hemosiderin, pigmented or foamy histiocytes
  • Other rare findings:
    • Necrotic pseudoxanthomatous nodules: central necrosis surrounded by histiocytes and outer fibrous zone
    • Liesegang rings: eosinophilic acellular rings within necrotic tissue (Histopathology 2020;76:76)
Microscopic (histologic) images

Contributed by University of Washington Medical Center

Uterine serosa with endometriosis

Endometriosis with partially denuded endometrial epithelium

Endometrial stroma with abundant hemosiderin and capillary network

Endometriosis involving appendix



Virtual slides

Images hosted on other servers:

Ovarian endometriotic cyst

Cytology description
  • Reported in peritoneal fluid and fine needle aspiration of scar tissue following gynecologic procedure (e.g., Cesarean section) (J Cytol 2017;34:61)
  • Variably sized three dimensional spherules with periphery of polygonal endometrial cells with larger, hyperchromatic nuclei and moderate amount of cytoplasm, often with center of stroma cells with hyperchromatic nuclei, scant cytoplasm and indistinct cytoplasmic borders ​(Cancer Cytopathol 2013;121:582)
  • May have admixed hemosiderin laden macrophages
Cytology images

Contributed by Dr. Carmen Luz

FNA from abdominal wall

Positive stains
Molecular / cytogenetics description
  • Endometriosis and synchronous carcinoma share similar genetic alterations including ARID1A, PTEN and PIK3CA
  • Mutations in ARID1A, a tumor suppressor gene, identified in up to 57% of ovarian endometrioid carcinoma and up to 30% of clear cell carcinoma
    • Multiple studies suggest ARID1A mutation occurs at early stage of canceration of endometriosis (Oncol Rep 2016;35:607)
    • Endometriosis occurring distant from ARID1A deficient carcinomas are more likely to retain ARID1A expression
  • Other associated genetic alterations include loss of BAF250a, ER and PR and upregulation of hepatocyte nuclear factor - beta and Skp2
  • In one study, loss of DNA mismatch repair protein expression was found in 10% of patient with endometriosis associated ovarian carcinoma (Int J Gynecol Pathol 2012;31:524)

Causes, symptoms, diagnosis, treatment, pathology

Histopathology - ovary

Sample pathology report
  • Uterus, hysterectomy:
    • Proliferative endometrium negative for neoplasm
    • Cervix with parakeratosis and Nabothian cysts negative for neoplasm
    • Myometrium with leiomyomata
    • Uterine serosa with multifocal endometriosis
  • Right ureterosacral peritoneum, excision:
    • Fibrous tissue with focal endometrial type stroma and hemorrhage, suggestive of endometriosis
    • Negative for neoplasm
Differential diagnosis
  • Endocervicosis:
    • Glandular component is endocervical mucinous type, no endometrial stroma, no hemorrhage
  • Endosalpingiosis:
    • Glandular component is tubal (ciliated with peg / intercalated) cells, no endometrial stroma, no hemorrhage
  • Adenomyosis:
    • Endometrial glands and stroma in myometrium
  • Endometrioid adenocarcinoma:
    • Complex glandular growth and cytologic atypia
  • Metastatic carcinoma:
    • Morphology varies by site of origin; however, no endometrial stroma, other features of neoplasm present including crowded irregular glands, nuclear atypia or elevated mitotic activity
Board review style question #1
A 39 year old woman presents with pelvic pain and menorrhagia. Hysterectomy was performed and the following histologic findings were present on the serosal surface and right ovary. What malignant neoplasm is most associated with the lesion?

  1. Immature teratoma
  2. Ovarian endometrioid carcinoma
  3. High grade serous carcinoma
  4. Clear cell sarcoma
  5. Endometrial stromal sarcoma
Board review answer #1
B. Endometriosis, particularly atypical endometriosis is associated with endometrioid and clear cell carcinoma, with the greatest association identified in the former neoplasm. Endometrial stromal sarcomas and adenosarcomas have been reported to arise in association with endometriosis; however the incidence is rare. There is no reported link between germ cell tumors and clear cell sarcomas with endometriosis.

Reference: Endometriosis

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Board review style question #2
What gene of the ones listed is most commonly altered identified in endometriosis associated carcinomas?

  1. PTEN
  2. p16
  3. BRAF
  4. ARID1A
  5. p53
Board review answer #2
D. Of the five genes listed, mutations in tumor suppressor gene, ARID1A, is most commonly identified in endometriosis and endometriosis-associated carcinoma. Many studies suggest loss of ARID1A expression is an early driver mutation. Other common molecular alterations include mutations in PTEN, PIK3CA, KRAS and to a lesser extent microsatellite instability with MMR protein loss. Although p53 and p16 mutations may occur in some high grade carcinomas, they are less associated with those occurring in association with endometriosis. BRAF mutations are not associated with endometriosis.

Reference: Endometriosis

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