Endometriosis

Uterus
Nontumor
Endometriosis

Authors: Lisa Han, M.D., Rochelle Garcia, M.D.

Editor-in-Chief: Debra Zynger, M.D.

Topic Completed: 16 March 2020

Minor changes: 16 March 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed search: Uterus[TI] endometriosis[TI]

Page views in 2019: 10,774

Page views in 2020 to date: 5,539

Table of Contents

Cite this page: Han L, Garcia R. Endometriosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusendometriosis.html. Accessed July 8th, 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

Terminology

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

Epidemiology

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)

Sites

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

Pathophysiology

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)

Etiology

Organochlorine pollutant exposure

Clinical features

Pelvic pain (Arch Gynecol Obstet 2015;292:1295)
Dyspareunia
Dysmenorrhea
Infertility

Diagnosis

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

35 year old woman presenting with hematuria and abdominal pain (BMJ Case Rep 2018;11)
37 year old woman with history of pelvic surgery presenting with pelvic pain (Medicine (Baltimore) 2018;97:e0376)
40 year old woman with elevated CA125 and pelvic mass (Medicine (Baltimore) 2019;98:e15741)
49 year old Japanese woman with abnormal vaginal bleeding and adenocarcinoma diagnosed by cervical cytology (J Obstet Gynaecol Res 2019)
55 year old woman with peritoneal endometriosis and smooth muscle metaplasia (Int J Clin Exp Pathol 2015;8:3370)
62 year old woman presented with hematuria (Pathology 2017;49:441)

Treatment

Pain treated with NSAIDs, hormonal contraceptives, GnRH analogues and aromatase inhibitors (Arch Gynecol Obstet 2015;292:1295)
Surgical resection

Gross description

Red, brown, white plaques (Arch Gynecol Obstet 2015;292:1295, Taiwan J Obstet Gynecol 2019;58:328)
Sometimes gelatinous or with adhesions

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

CD10

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

CD10 is positive in endometrial stroma
ER, PR and PAX2 are often positive in endometrial glands and stroma (Am J Surg Pathol 2013;37:1342)

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)

Videos

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

Additional references

Annu Rev Pathol 2019 [Epub ahead of print], Pathology 2018;50:190, Mutat Res 2018;809:1

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?

Immature teratoma
Ovarian endometrioid carcinoma
High grade serous carcinoma
Clear cell sarcoma
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?

PTEN
p16
BRAF
ARID1A
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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