Endometriosis Cancer Mimic: Three-Feature Rule, Adenomyosis Staging Pitfall, Mimics, Virtual Slides and MCQs

Endometriosis, the cancer mimic: an endometriotic gland with a cuff of endometrial stroma and haemosiderin-laden macrophages

Subtitle: How to recognise endometriosis when it mimics cancer: the three-feature rule, high-risk sites, the adenomyosis staging pitfall, decidualized and atypical endometriosis, key mimics, virtual slides and 10 MCQs.

Author: PathologyMCQ Editorial Board

Category: Gynaecological Pathology / Benign Mimics

Last Updated: October 2026

Read Time: 10 minutes

At-a-Glance

Why it mimics cancer: endometriosis can infiltrate, spread to distant sites, cause fibrosis and raise CA-125.
Diagnosis: endometrial-type glands plus endometrial-type stroma, usually with haemorrhage or haemosiderin. Stroma alone (stromal endometriosis) is enough.
Staging pitfall: carcinoma confined to adenomyosis is not myometrial invasion.
Watch for: decidualization in pregnancy and atypical endometriosis, the precursor of clear cell and endometrioid ovarian carcinoma.

Why Endometriosis Mimics Cancer

Endometriosis is endometrial-type tissue outside the uterus. It behaves in ways we usually teach as signs of malignancy, which is why it is so often overcalled on small biopsies and frozen sections.

Benign, but it looks malignantFour ways endometriosis mimics cancer

InfiltrationDeep lesions invade muscularis propria and nerves

Distant spreadLung, pleura, umbilicus, scars, lymph nodes

Fibrosis and massSmooth muscle hyperplasia, strictures, solid-cystic masses

Raised CA-125Can be markedly raised, especially with endometriomas

Key point: the diagnosis rests on the endometrial-type stroma around the glands, not on how aggressive the lesion looks.

Step 1: detecting unexpected glands in an extrauterine biopsy — Unexpected glands in an extrauterine biopsy should trigger this workup.

Ectopic glands often show crowding, stratification, tubal metaplasia or squamous metaplasia from chronic inflammation. On their own these reactive changes do not mean malignancy.

The Three-Feature Rule

1Endometrial-type glandsColumnar epithelium, may be atrophic, metaplastic or reactive

2Endometrial-type stromaSmall blue cells with fine vessels; CD10, ER and PR positive

3HaemorrhageFresh blood or haemosiderin-laden macrophages from cyclical bleeding

How strict is it? Glands with stroma are diagnostic. Stroma without glands is still endometriosis (stromal endometriosis). Haemosiderin is supportive but not required, and it is not specific on its own.

The three-feature rule: endometrial glands, CD10-positive stroma and haemosiderin — Glands, CD10-positive stroma and haemosiderin.

Pitfall, the burnt-out lesion: in old fibrotic lesions the glands may be destroyed, leaving fibrous tissue and haemosiderin-laden macrophages. CD10 with ER/PR can reveal the residual stromal cells. Remember that CD10 is not specific: endometrial stromal sarcoma, some smooth muscle tumours and some carcinomas also express it, so always interpret it with the morphology.

Virtual Slides

Annotated slide: endometriosis of the appendix

Use the region list to jump to the ectopic glands, the stromal cuff and the haemosiderin.

Endometriosis of the appendix

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Compare: appendix, ovarian endometriotic cyst and a key mimic

Virtual slides · real casesEndometriosis and a CD10-positive mimic

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What to look for

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High-Risk Sites and Their Mimics

High-risk ectopic sites of endometriosis: bowel wall, ovaries, vaginal cuff, abdominal scars and lungs — Sites where endometriosis most often mimics cancer.

Where endometriosis mimics cancer

Site	What happens	Mimics	Tip
Bowel wall (rectosigmoid)	Infiltrates muscularis propria; smooth muscle hyperplasia and fibrosis; stricture	Colorectal carcinoma	Mucosa is usually intact, so endoscopic biopsies are often non-diagnostic
Ovary	Endometrioma; polypoid or solid-cystic growth; marked CA-125 rise	Epithelial ovarian cancer; peritoneal carcinomatosis	Sample solid areas well to exclude atypia or carcinoma
Vaginal cuff	Nodule after hysterectomy	Recurrent carcinoma	Look for stroma and haemorrhage around glands
Abdominal scar	Implantation after caesarean section; mass in rectus sheath	Desmoid tumour, sarcoma	Cyclical pain and swelling
Lung and pleura	Pleural and diaphragmatic implants; diaphragmatic defects	Lung carcinoma, mesothelioma	Catamenial timing; ER/PR and CD10 help on small biopsies

The Adenomyosis Staging Pitfall

Adenocarcinoma with glands only compared with endometriosis with glands and stroma — Invasive carcinoma (glands only) compared with a benign gland and its stromal cuff.

Not myometrial invasionCarcinoma within adenomyosisMalignant glands colonise adenomyosis but remain surrounded by benign endometrial stroma (CD10 positive), with smooth, rounded contours and no stromal reaction.

Myometrial invasionCarcinoma infiltrating the myometriumIrregular glands sit directly against smooth muscle with no stromal cuff, often with desmoplasia, inflammation or a MELF pattern.

Why it matters: only true invasion counts. Depth is measured from the endomyometrial junction, and less than half versus half or more of the myometrium separates FIGO stage IA from IB. Counting adenomyosis as invasion overstages the tumour.

Related mimic, atypical polypoid adenomyoma: a benign polypoid lesion of complex, often atypical glands with squamous morules in a fibromyomatous stroma. It lacks the desmoplasia and destructive invasion of endometrioid carcinoma, but careful sampling is needed because carcinoma can coexist.

Thoracic Endometriosis and the Catamenial Clue

The catamenial clue: chest symptoms that recur with menstruation — Chest symptoms that recur with menstruation.

Presentation: recurrent pneumothorax, haemothorax, haemoptysis or chest pain around menstruation.
Right side: most cases are right-sided, linked to diaphragmatic defects and the clockwise flow of peritoneal fluid towards the right hemidiaphragm.
Small biopsies: glands are often absent. CD10 with ER/PR highlights scattered endometrial-type stromal cells and improves diagnostic yield.

Decidualization and Atypical Endometriosis

Decidualized endometriosis (pregnancy, progestins)

Stromal cells enlarge into epithelioid cells with abundant glassy eosinophilic cytoplasm.
Forms mural nodules in endometriomas that can mimic ovarian cancer on imaging.
Histological mimic: deciduoid mesothelioma.
Decidual cells are PR positive and keratin negative; mesothelioma is keratin and calretinin positive.

Atypical endometriosis (precursor)

Cytological atypia (enlarged hyperchromatic or hobnail nuclei) or architectural crowding in the glands.
Linked to clear cell and endometrioid ovarian carcinoma.
Shares ARID1A loss (BAF250a) and PIK3CA or PTEN alterations with the adjacent carcinoma.
Report it and sample the lesion extensively.

Differential Diagnosis

Glands outside the uterus: how to sort them

Entity	Glands	Stroma	Key clue
Endometriosis	Endometrial type, may be reactive	Endometrial-type, CD10 positive	Stromal cuff, haemorrhage
Invasive adenocarcinoma	Irregular, infiltrative, atypical	No stromal cuff; desmoplasia	Glands only, destructive growth
Endosalpingiosis	Ciliated tubal type	None	No endometrial stroma or haemorrhage
Low-grade endometrial stromal sarcoma	Usually none, occasionally entrapped	Uniform stromal cells, CD10 positive	Tongue-like permeation and vascular plugs
Deciduoid mesothelioma	None	Epithelioid cells	Keratin and calretinin positive; BAP1 loss
Atypical polypoid adenomyoma	Atypical glands with morules	Fibromyomatous	Polypoid, no desmoplasia

Test Yourself: 10 MCQs

Endometriosis and its mimics: 10 MCQs

Diagnosis, staging pitfall, thoracic disease, decidualization, atypia and mimics.

Score: 0 / 10

More practice: the gynaecological pathology MCQ bank →

Exam Pearls

Endometriosis = endometrial-type glands with endometrial-type stroma; stroma alone is enough.
Aggressive behaviour, atypia and a raised CA-125 do not prove malignancy.
Carcinoma confined to adenomyosis is not myometrial invasion.
Catamenial pneumothorax is usually right-sided.
Decidualized endometriosis is keratin negative; deciduoid mesothelioma is keratin positive.
Atypical endometriosis with ARID1A loss is the precursor of clear cell and endometrioid carcinoma.
CD10 supports endometrial stroma but is not specific.

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References

WHO Classification of Tumours Editorial Board. Female Genital Tumours. 5th edition. IARC; 2020.
Clement PB. 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. 2007;14:241–260.
Wiegand KC, et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med. 2010;363:1532–1543.
Berek JS, et al. FIGO staging of endometrial cancer: 2023. Int J Gynaecol Obstet. 2023;162:383–394.