Difference between revisions of "Endometrial carcinoma"
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[[Image:Endometrial_adenocarcinoma_gross.jpg|thumb|300px|right|Gross image of endometrial adenocarcinoma.]] | |||
'''Endometrial carcinoma''', also '''endometrial adenocarcinoma''', is a common gynecologic malingnancy<ref name=pmid19072487>{{cite journal |author=Fowler W, Mutch D |title=Management of endometrial cancer |journal=Womens Health (Lond Engl) |volume=4 |issue=5 |pages=479–89 |year=2008 |month=September |pmid=19072487 |doi=10.2217/17455057.4.5.479 |url=}}</ref> that often arises from [[endometrial hyperplasia]]. The incidence of endometrial carcinoma is increasing, as the proportion of [[obese]] individuals is increasing. | '''Endometrial carcinoma''', also '''endometrial adenocarcinoma''', is a common gynecologic malingnancy<ref name=pmid19072487>{{cite journal |author=Fowler W, Mutch D |title=Management of endometrial cancer |journal=Womens Health (Lond Engl) |volume=4 |issue=5 |pages=479–89 |year=2008 |month=September |pmid=19072487 |doi=10.2217/17455057.4.5.479 |url=}}</ref> that often arises from [[endometrial hyperplasia]]. The incidence of endometrial carcinoma is increasing, as the proportion of [[obese]] individuals is increasing. | ||
| Line 11: | Line 12: | ||
*Diabetes. | *Diabetes. | ||
*Nulliparity. | *Nulliparity. | ||
*Unopposed estrogen (polycystic ovarian syndrome (PCOS), anovulation, hormone replacement therapy (HRT)). | *Unopposed estrogen ([[polycystic ovarian syndrome]] (PCOS), anovulation, hormone replacement therapy (HRT)). | ||
*Tamoxifen use. | *[[Tamoxifen]] use. | ||
**Used for breast cancer; the risk is quite small<ref name=pmid19505894>{{Cite journal | last1 = Brown | first1 = K. | title = Is tamoxifen a genotoxic carcinogen in women? | journal = Mutagenesis | volume = 24 | issue = 5 | pages = 391-404 | month = Sep | year = 2009 | doi = 10.1093/mutage/gep022 | PMID = 19505894 }}</ref> or possibly negligent.<ref name=pmid19827879>{{Cite journal | last1 = Ashraf | first1 = M. | last2 = Biswas | first2 = J. | last3 = Majumdar | first3 = S. | last4 = Nayak | first4 = S. | last5 = Alam | first5 = N. | last6 = Mukherjee | first6 = KK. | last7 = Gupta | first7 = S. | title = Tamoxifen use in Indian women--adverse effects revisited. | journal = Asian Pac J Cancer Prev | volume = 10 | issue = 4 | pages = 609-12 | month = | year = | doi = | PMID = 19827879 }}</ref> | **Used for breast cancer; the risk is quite small<ref name=pmid19505894>{{Cite journal | last1 = Brown | first1 = K. | title = Is tamoxifen a genotoxic carcinogen in women? | journal = Mutagenesis | volume = 24 | issue = 5 | pages = 391-404 | month = Sep | year = 2009 | doi = 10.1093/mutage/gep022 | PMID = 19505894 }}</ref> or possibly negligent.<ref name=pmid19827879>{{Cite journal | last1 = Ashraf | first1 = M. | last2 = Biswas | first2 = J. | last3 = Majumdar | first3 = S. | last4 = Nayak | first4 = S. | last5 = Alam | first5 = N. | last6 = Mukherjee | first6 = KK. | last7 = Gupta | first7 = S. | title = Tamoxifen use in Indian women--adverse effects revisited. | journal = Asian Pac J Cancer Prev | volume = 10 | issue = 4 | pages = 609-12 | month = | year = | doi = | PMID = 19827879 }}</ref> | ||
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|- | |- | ||
|Genetic <br>abnormalities | |Genetic <br>abnormalities | ||
| microsatellite instability, PTEN & KRAS | | microsatellite instability, PTEN & [[KRAS mutation]]s | ||
| p53 mutations | | p53 mutations | ||
|- | |- | ||
| Line 75: | Line 76: | ||
*Officially only sanctioned for ''[[endometrioid endometrial carcinoma]]''. | *Officially only sanctioned for ''[[endometrioid endometrial carcinoma]]''. | ||
**May be used for [[mucinous endometrial carcinoma]]. | **May be used for [[mucinous endometrial carcinoma]]. | ||
**Papillary serous carcinoma and clear cell carcinomas are ''not'' assigned a grade | **Papillary serous carcinoma and clear cell carcinomas are ''not'' assigned a grade; however, can be thought of as grade 3 by definition. | ||
==Staging== | ==Staging== | ||
| Line 136: | Line 137: | ||
*Clear cells - with moderate nuclear pleomorphism - '''key feature'''. | *Clear cells - with moderate nuclear pleomorphism - '''key feature'''. | ||
**Classically clear cells... but not always. | **Classically clear cells... but not always. | ||
*Hobnail pattern -- apical cytoplasm > cytoplasm on basement membrane. | *[[Hobnail pattern]] -- apical cytoplasm > cytoplasm on basement membrane. | ||
*Usually tubular/cystic, may be solid or papillary. | *Usually tubular/cystic, may be solid or papillary. | ||
**Papillae may be pseudopapillae -- with edema instead of vessels. | **Papillae may be pseudopapillae -- with edema instead of vessels. | ||
| Line 171: | Line 172: | ||
*CAM5.2 +ve. | *CAM5.2 +ve. | ||
*CK34betaE12 +ve. | *CK34betaE12 +ve. | ||
*WT1 -ve.<ref name=pmid15084838>{{Cite journal | last1 = Acs | first1 = G. | last2 = Pasha | first2 = T. | last3 = Zhang | first3 = PJ. | title = WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary, and endometrium. | journal = Int J Gynecol Pathol | volume = 23 | issue = 2 | pages = 110-8 | month = Apr | year = 2004 | doi = | PMID = 15084838 }}</ref> | |||
**Often +ve/-ve in serous carcinoma of the endometrium. | |||
*CK7 +ve.<ref name=pmid11444201>{{Cite journal | last1 = Vang | first1 = R. | last2 = Whitaker | first2 = BP. | last3 = Farhood | first3 = AI. | last4 = Silva | first4 = EG. | last5 = Ro | first5 = JY. | last6 = Deavers | first6 = MT. | title = Immunohistochemical analysis of clear cell carcinoma of the gynecologic tract. | journal = Int J Gynecol Pathol | volume = 20 | issue = 3 | pages = 252-9 | month = Jul | year = 2001 | doi = | PMID = 11444201 }}</ref> | |||
*CK20 -ve.<ref name=pmid11444201/> | |||
*Vimentin +ve.<ref name=pmid11444201/> | |||
*Napsin A +ve.<ref name=pmid25971546>{{Cite journal | last1 = Iwamoto | first1 = M. | last2 = Nakatani | first2 = Y. | last3 = Fugo | first3 = K. | last4 = Kishimoto | first4 = T. | last5 = Kiyokawa | first5 = T. | title = Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium. | journal = Hum Pathol | volume = 46 | issue = 7 | pages = 957-62 | month = Jul | year = 2015 | doi = 10.1016/j.humpath.2015.03.008 | PMID = 25971546 }}</ref> | |||
Note: | Note: | ||
| Line 183: | Line 190: | ||
=References= | =References= | ||
{{reflist|2}} | {{reflist|2}} | ||
=External links= | |||
*[http://www.cancer.org/cancer/endometrialcancer/detailedguide/endometrial-uterine-cancer-staging Endometrial cancer staging (cancer.org)]. | |||
[[Category:Gynecologic pathology]] | [[Category:Gynecologic pathology]] | ||
Latest revision as of 18:24, 30 August 2023
Endometrial carcinoma, also endometrial adenocarcinoma, is a common gynecologic malingnancy[1] that often arises from endometrial hyperplasia. The incidence of endometrial carcinoma is increasing, as the proportion of obese individuals is increasing.
An introduction to the endometrium is in the article endometrium.
Clinical
Risk factors
Risk factors for endometrial carcinoma - mnemonic COLD NUT:[2]
- Cancer Hx (ovarian, breast, colon).
- Obesity.
- Late menopause.
- Diabetes.
- Nulliparity.
- Unopposed estrogen (polycystic ovarian syndrome (PCOS), anovulation, hormone replacement therapy (HRT)).
- Tamoxifen use.
Family history
Several syndromes are seen in association with endometrial cancer:[5]
- Cowden syndrome (PTEN mutation) - most common.
- Associated with endometrioid endometrial carcinoma.
- Lynch syndrome (mutation of a mismatch repair gene - there are several[6]).
- Associated with non-endometrioid endometrial carcinoma.[5]
- Autosomal dominant.
Management
- Hysterectomy is the standard treatment for endometrial carcinoma.
Details:
- Low grade and low stage endometrioid carcinoma: total hysterectomy (includes cervix).
- Non-endometrioid or high stage endometrioid or high-grade endometrioid: radical hysterectomy (includes cervix, vaginal cuff, parametrial tissue).
Subtypes - overview
They are commonly grouped based on clinicopathologic features:[9][10]
| Feature | Type I | Type II |
|---|---|---|
| Histologic types | endometrioid endometrial carcinoma, mucinous endometrial carcinoma | serous carcinoma of the endometrium, clear cell carcinoma of the endometrium, undifferentiated carcinoma |
| Clinical characteristics |
premenopausal, estrogen excess, obesity | postmenopausal, no estrogen excess, atrophic endometrium |
| Prognosis | good | poor |
| Genetic abnormalities |
microsatellite instability, PTEN & KRAS mutations | p53 mutations |
| Precursor lesion(s) | endometrial hyperplasia | possibly endometrial intraepithelial carcinoma[11] † |
Notes:
- † Endometrial intraepithelial carcinoma should not be confused with endometrial intraepithelial neoplasia (EIN).
Grading (FIGO)
Based on gland formation & adjusted by nuclear pleomorphism:[12][13][14][15]
- Grade 1: <5% solid component.
- Grade 2: 5-50% solid component.
- Grade 3: >50% solid component.
Modifiers/adjustment:
- High grade nuclei upgrades cancer by one; high grade nuclei = increased size, irregular large nucleoli, irregular chromatin pattern (clumped, coarse).[16]
Notes:
- Officially only sanctioned for endometrioid endometrial carcinoma.
- May be used for mucinous endometrial carcinoma.
- Papillary serous carcinoma and clear cell carcinomas are not assigned a grade; however, can be thought of as grade 3 by definition.
Staging
- Stage I: confined to uterine body.
- Ia = less than half of myometrium.
- Ib = greater than half of myometrium.
- Stage II: uterus + cervix.
- II = cervical stroma involved.
- Cervical epithelium involvement does not change stage.
- II = cervical stroma involved.
- Stage III: outside uterus - but inside pelvis.
- IIIa - involves serosa and/or adnexa (direct extension or metastasis)
- IIIb - vaginal involvement (direct extension or metastasis) or parametrial involvement
- Stage IV: outside true pelvis or in mucosa of bladder or GI tract.
Specific types
Endometrioid endometrial carcinoma
- AKA endometrioid endometrial adenocarcinoma.
Main article: Endometrioid endometrial carcinoma
Mucinous carcinoma of the endometrium
- AKA endometrial mucinous carcinoma.
General
- Type I endometrial carcinoma.[citation needed]
- Good prognosis.
Microscopic
Features:[10]
- Cells with intracytoplasmic mucin (>50% of tumour).
- Usu. mild-to-moderate nuclear atypia.
DDx:
- Endometrioid endometrial carcinoma.
- Metastatic mucinous carcinoma.
IHC
Features:[21]
- ER-alpha +ve.
- PR-alpha +ve.
- PR-beta +ve.
Serous carcinoma of the endometrium
- AKA serous endometrial carcinoma.
- AKA serous carcinoma of the uterus.
- AKA uterine serous carcinoma.
- AKA uterine papillary serous carcinoma.
Main article: Serous carcinoma of the endometrium
Clear cell carcinoma of the endometrium
General
- Ten-year survival ~ 40%.[22]
- Uncommon <=5 % of endometrial carcinomas.[23]
- Type II endometrial cancer - estrogen-independent, usually post-menopausal women.
Microscopic
Features:[23]
- Clear cells - with moderate nuclear pleomorphism - key feature.
- Classically clear cells... but not always.
- Hobnail pattern -- apical cytoplasm > cytoplasm on basement membrane.
- Usually tubular/cystic, may be solid or papillary.
- Papillae may be pseudopapillae -- with edema instead of vessels.
Notes:
- May have psammoma bodies - esp. in papillary area; may lead to confusion with serous carcinoma.
DDx:
- Serous endometrial carcinoma - usually has more nuclear pleomorphism, esp. cell size variation.
- High grade endometrioid endometrial carcinoma - have non-clear areas.[23]
- Arias-Stella reaction - esp. in the context of pregnancy.
- Papillary cystadenoma - benign; bland nuclei.[23]
DDx weird stuff:[23]
- PEComa.
- Epithelioid leiomyosarcoma.
Images
www:
- Clear cell carcinoma of the endometrium - classical - high mag. (webpathology.com).
- Clear cell carcinoma of the endometrium - high mag. (webpathology.com).
- Clear cell carcinoma of the endometrium - low mag. (webpathology.com).
Stains
- PAS-D stain +ve ~ glycogen.[23]
IHC
Features:[24]
- p53 -ve usu. - unlike uterine serous carcinoma.
- ER -ve.
- PR -ve.
Others:[23]
- CAM5.2 +ve.
- CK34betaE12 +ve.
- WT1 -ve.[25]
- Often +ve/-ve in serous carcinoma of the endometrium.
- CK7 +ve.[26]
- CK20 -ve.[26]
- Vimentin +ve.[26]
- Napsin A +ve.[27]
Note:
- HNF1beta - not useful[28] - unlike for ovarian clear cell carcinoma.
See also
- Endometrium.
- Uterine tumours - other uterine tumours, e.g. carcinosarcoma, endometrial stromal sarcoma.
- Uterine cervix.
- Gynecologic pathology - overview.
References
- ↑ Fowler W, Mutch D (September 2008). "Management of endometrial cancer". Womens Health (Lond Engl) 4 (5): 479–89. doi:10.2217/17455057.4.5.479. PMID 19072487.
- ↑ Greenwald, J.; Heng, M. (2007). Toronto Notes for Medical Students 2007 (2007 ed.). The Toronto Notes Inc. for Medical Students Inc.. pp. GY40. ISBN 978-0968592878.
- ↑ Brown, K. (Sep 2009). "Is tamoxifen a genotoxic carcinogen in women?". Mutagenesis 24 (5): 391-404. doi:10.1093/mutage/gep022. PMID 19505894.
- ↑ Ashraf, M.; Biswas, J.; Majumdar, S.; Nayak, S.; Alam, N.; Mukherjee, KK.; Gupta, S.. "Tamoxifen use in Indian women--adverse effects revisited.". Asian Pac J Cancer Prev 10 (4): 609-12. PMID 19827879.
- ↑ 5.0 5.1 Okuda T, Sekizawa A, Purwosunu Y, et al. (2010). "Genetics of endometrial cancers". Obstet Gynecol Int 2010: 984013. doi:10.1155/2010/984013. PMC 2852605. PMID 20396392. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852605/.
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 120435
- ↑ Zivanovic O, Carter J, Kauff ND, Barakat RR (December 2009). "A review of the challenges faced in the conservative treatment of young women with endometrial carcinoma and risk of ovarian cancer". Gynecol. Oncol. 115 (3): 504–9. doi:10.1016/j.ygyno.2009.08.011. PMID 19758691.
- ↑ Ware, RA.; van Nagell, JR. (2010). "Radical hysterectomy with pelvic lymphadenectomy: indications, technique, and complications.". Obstet Gynecol Int 2010. doi:10.1155/2010/587610. PMID 20871657.
- ↑ Lim, D.; Oliva, E. (Nov 2010). "Nonendometrioid endometrial carcinomas.". Semin Diagn Pathol 27 (4): 241-60. PMID 21309259.
- ↑ 10.0 10.1 Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 241. ISBN 978-0443069208.
- ↑ Roelofsen, T.; van Kempen, LC.; van der Laak, JA.; van Ham, MA.; Bulten, J.; Massuger, LF. (Mar 2012). "Concurrent endometrial intraepithelial carcinoma (EIC) and serous ovarian cancer: can EIC be seen as the precursor lesion?". Int J Gynecol Cancer 22 (3): 457-64. doi:10.1097/IGC.0b013e3182434a81. PMID 22249577.
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1087-8. ISBN 0-7216-0187-1.
- ↑ URL: http://www.pathologyoutlines.com/uterus.html#endometrialcarc.
- ↑ URL: http://www.emedicine.com/med/topic2832.htm.
- ↑ Ayhan A, Taskiran C, Yuce K, Kucukali T (January 2003). "The prognostic value of nuclear grading and the revised FIGO grading of endometrial adenocarcinoma". Int. J. Gynecol. Pathol. 22 (1): 71–4. PMID 12496701.
- ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 240. ISBN 978-0470519035.
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1088. ISBN 0-7216-0187-1.
- ↑ http://www.emedicine.com/med/topic2832.htm
- ↑ Staging with groovy graphics (cancerfacts.com)
- ↑ URL: http://en.wikibooks.org/wiki/Radiation_Oncology/Endometrium/Staging. Accessed on: 2 May 2012.
- ↑ Shabani, N.; Mylonas, I.; Jeschke, U.; Thaqi, A.; Kuhn, C.; Puchner, T.; Friese, K.. "Expression of estrogen receptors alpha and beta, and progesterone receptors A and B in human mucinous carcinoma of the endometrium.". Anticancer Res 27 (4A): 2027-33. PMID 17649817.
- ↑ Abeler, VM.; Vergote, IB.; Kjørstad, KE.; Tropé, CG. (Oct 1996). "Clear cell carcinoma of the endometrium. Prognosis and metastatic pattern.". Cancer 78 (8): 1740-7. PMID 8859187.
- ↑ 23.0 23.1 23.2 23.3 23.4 23.5 23.6 Offman, SL.; Longacre, TA. (Sep 2012). "Clear cell carcinoma of the female genital tract (not everything is as clear as it seems).". Adv Anat Pathol 19 (5): 296-312. doi:10.1097/PAP.0b013e31826663b1. PMID 22885379.
- ↑ Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 250. ISBN 978-0443069208.
- ↑ Acs, G.; Pasha, T.; Zhang, PJ. (Apr 2004). "WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary, and endometrium.". Int J Gynecol Pathol 23 (2): 110-8. PMID 15084838.
- ↑ 26.0 26.1 26.2 Vang, R.; Whitaker, BP.; Farhood, AI.; Silva, EG.; Ro, JY.; Deavers, MT. (Jul 2001). "Immunohistochemical analysis of clear cell carcinoma of the gynecologic tract.". Int J Gynecol Pathol 20 (3): 252-9. PMID 11444201.
- ↑ Iwamoto, M.; Nakatani, Y.; Fugo, K.; Kishimoto, T.; Kiyokawa, T. (Jul 2015). "Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium.". Hum Pathol 46 (7): 957-62. doi:10.1016/j.humpath.2015.03.008. PMID 25971546.
- ↑ Fadare, O.; Liang, SX. (Apr 2012). "Diagnostic Utility of Hepatocyte Nuclear Factor 1-Beta Immunoreactivity in Endometrial Carcinomas: Lack of Specificity For Endometrial Clear Cell Carcinoma.". Appl Immunohistochem Mol Morphol. doi:10.1097/PAI.0b013e31824973d1. PMID 22495362.