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Ovary-nontumor

Non-neoplastic cysts / other

Endometriosis


Reviewer: Mohiedean Ghofrani, M.D. (see Reviewers page)
Revised: 6 June 2012, last major update August 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

Definition
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● Endometrial glands or stroma outside the uterus

Terminology
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● Limited knowledge has hampered useful classification of different manifestations of endometriosis

Epidemiology
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● 10% of women in Western countries
● More common in younger women, high socioeconomic status, no oral contraception and with family history
● Accounts for 25% of laparotomies and laparoscopies by gynecologists, second in frequency only to leiomyomas

Sites
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● Ovary is most common site of involvement by endometriosis; however, ovarian endometriosis is often also associated with extraovarian pelvic endometriosis

Etiology
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● Two main hypotheses based on the “reflux theory” (or “retrograde menstruation”): implantation of endometrial cells on peritoneum (favored “metastatic theory”) or peritoneal stimulation by substances released by shed endometrium (alternative “metaplastic theory”)
● Growth stimulated by estrogen
● Diminished peritoneal immune response
● It has been proposed that regurgitated endometrial tissue causing endometriosis is inherently abnormal; eutopic (normally placed) endometrium in women with endometriosis shows increased cell proliferation, higher aromatase expression, increased angiogenesis and reduced apoptosis
● Risk factors include nulliparity, short menstrual cycles and abundant menses

Clinical features
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● Classic triad: dysmenorrhea, dyspareunia and infertility
● Abdominal or pelvic pain frequently extends to the back
● Rarely ascites or perforation with hemoperitoneum
● Mechanism of infertility is unclear (Fertil Steril 2008;90:247)

Laboratory
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● Elevated CA-125

Prognostic factors
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● Although not life-threatening, may be associated with significant morbidity
● Although endometriosis is the best documented precursor of 20% of ovarian carcinomas, the risk of malignant transformation in any given patient is negligible (0.3-0.8%)
● Carcinomas associated with endometriosis are most often endometrioid (70%) and clear cell (14%) (Gynecol Oncol 2006;101:331), particularly if endometriosis is associated with atypical hyperplasia (Hum Pathol 1988;19:1080)

Case reports
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● With ovarian ossification (Clin Exp Obstet Gynecol 2007;34:113)

Treatment
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● Radical surgery with removal of uterus and ovaries to reduce estrogenic stimulation requires hormone replacement at a level that has minimal recurrence risk
● Conservative surgery and hormone therapy is an alternative for patients who wish to maintain fertility

Gross description
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● Small, raised, red to brown-white to blue spots on ovarian surface with fibrinous adhesions
● Chocolate cysts are due to repeated hemorrhage
● Rarely have granulomatous nodules attached to peritoneum or free within peritoneal cavity (Am J Surg Pathol 1988;12:390)

Gross images
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Chocolate cyst

   
Intraoperative images with adhesions

   

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


Cyst has outer surface with many foci of red-brown discoloration and adhesions, contains chocolate-colored fluid (AFIP)


Cyst has predominantly pale and smooth lining plus several foci of dark brown discoloration consistent with endometriosis (AFIP)

Micro description
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● Needs 2 of 3 features of endometrial glands, endometrial stroma or hemorrhage
● Stromal cells have naked nuclei and are surrounded by reticulin and spiral arterioles
● Smooth muscle stroma is common
● Repeated hemorrhage may destroy stromal tissue
● Specimen may be composed of necrotic, pseudoxanthomatous nodules
● May see endometrial glandular atypia (atypical endometriosis), hyperplasia and carcinoma (endometrioid most common)
● Rarely, liesegang rings (acellular, ring-like structures that may form near inflamed or necrotic tissue (Int J Gynecol Pathol 1998;17:358), stromal elastosis
● Rarely presents as polypoid endometriosis, which is usually also associated with non-polypoid endometriosis with no atypia and no hypercellularity (Am J Surg Pathol 2004;28:285)

Micro images
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H&E and CD10


Smooth muscle actin+ wall of endometriotic cyst


Endometrioid glands with variable size are within cellular endometrial-type stroma surrounded by denser ovarian stroma (AFIP)


The wall of an endometriotic cyst contains pseudoxanthoma cells filled with hemofuscin pigment (AFIP)


Deeper portion of the wall of an endometriotic cyst is fibrotic; the subepithelial layer is composed of hemorrhagic cellular stroma (AFIP)


Liesegang rings are scattered in debris (AFIP)


Polyp composed mainly of cystic glands projects into the lumen of an endometriotic cyst (AFIP)


Two pseudoxanthomatous, necrotic nodules are seen at the top and bottom, and an endometriotic gland is seen in the upper nodule (AFIP)


A pseudoxanthomatous nodule is centrally necrotic with a surrounding granulomatous reaction (AFIP)


Patient taking norethynodrel with mestranol has marked decidual change of stroma (AFIP)


During pregnancy, a gland is lined by cells with hyperchromatic, smudgy nuclei resembling Arias-Stella reaction; the adjacent stroma shows decidual change (AFIP)

Cytology images
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Cyst of endometriosis #1;  #2

Positive stains
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● CD10 (highlights endometrial stromal cells, Arch Pathol Lab Med 2003;127:1003)

Virtual slides
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Endometriotic cyst

Videos
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Video

Molecular description
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● Trisomy 1 and 7 and monosomy 9 and 17 are more common in ovarian versus non-ovarian endometriosis (Mod Pathol 2006;19:1615)
● DNA aneuploidy has been reported in severely atypical cells lining endometriotic cysts (Am J Clin Pathol 1994;102:415)
● Loss of heterozygosity on multiple chromosomes in 28% (Cancer Res 1996;56:3534)
● Monoclonal X-inactivation pattern in 3 of 5 endometriotic cysts (Int J Gynecol Cancer 1995;5:61)
● Monoclonal methylation of androgen receptor locus in all of 11 cases (Am J Pathol 1997;150:1173)

End of Ovary-nontumor > Non-neoplastic cysts / other > Endometriosis


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