Endometrial carcinoma

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Gross image of endometrial adenocarcinoma.

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.
    • Used for breast cancer; the risk is quite small[3] or possibly negligent.[4]

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.
    • In low-grade carcinomas (i.e. low grade endometrioid type), if the woman isn't done with their childbearing, the treatment may be hormones and surveillance biopsies.[7]
    • Endometrial carcinomas with involvement of the endocervical canal are treated with a radical hysterectomy.[8]

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:

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:

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.
  • 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.

References: [17][18][19][20].

Specific types

Endometrioid endometrial carcinoma

  • AKA endometrioid endometrial adenocarcinoma.

Mucinous carcinoma of the endometrium

  • AKA endometrial mucinous carcinoma.

General

Microscopic

Features:[10]

  • Cells with intracytoplasmic mucin (>50% of tumour).
  • Usu. mild-to-moderate nuclear atypia.

DDx:

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.

Clear cell carcinoma of the endometrium

  • AKA clear cell endometrial carcinoma.
  • AKA endometrial clear cell carcinoma.

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:

DDx weird stuff:[23]

Images

www:

Stains

IHC

Features:[24]

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:

See also

References

  1. 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.
  2. 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.
  3. Brown, K. (Sep 2009). "Is tamoxifen a genotoxic carcinogen in women?". Mutagenesis 24 (5): 391-404. doi:10.1093/mutage/gep022. PMID 19505894.
  4. 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. 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2852605/.
  6. Online 'Mendelian Inheritance in Man' (OMIM) 120435
  7. 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.
  8. 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.
  9. Lim, D.; Oliva, E. (Nov 2010). "Nonendometrioid endometrial carcinomas.". Semin Diagn Pathol 27 (4): 241-60. PMID 21309259.
  10. 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.
  11. 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.
  12. 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.
  13. URL: http://www.pathologyoutlines.com/uterus.html#endometrialcarc.
  14. URL: http://www.emedicine.com/med/topic2832.htm.
  15. 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.
  16. Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 240. ISBN 978-0470519035.
  17. 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.
  18. http://www.emedicine.com/med/topic2832.htm
  19. Staging with groovy graphics (cancerfacts.com)
  20. URL: http://en.wikibooks.org/wiki/Radiation_Oncology/Endometrium/Staging. Accessed on: 2 May 2012.
  21. 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.
  22. 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. 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.
  24. 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.
  25. 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. 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.
  27. 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.
  28. 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.

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