Endometrial Cancer

endometrial cancer hysteroscopy

Epidemiology

  • The 6th most common malignancy in women worldwide.
  • The 4th most common malignancy in women in developed countries.
  • The median age is 63 years, while >90% of the cases involve women >50 years of age.
  • An autosomal-dominant inherited cancer susceptibility syndrome called Lynch syndrome type II or hereditary nonpolyposis colorectal cancer (HNPCC) syndrome may be responsible for up to 5% of total cases.
  • The uterine carcinosarcoma is a high grade endometrial cancer variant (“like grade 4 out of 3”) that represents about 5% of all uterine corpus cancers and accounts for 15% of the mortality.
Endometrial cancer 3d ultrasound
The three-diamensonal image of endometrial cancer.

Factors that Increase the Risk

  • Obesity
  • Polycystic ovarian syndrome
  • Tamoxifen
  • Anovulation
  • Nulliparity
  • Hypertension
  • Diabetes mellitus
  • Lynch syndrome type II
  • Pelvic radiation

Factors that Decrease the Risk

  • Combined oral contraceptives
  • Parity
  • Late age at last birth
  • Physical activity
  • Metformin use

Staging

FIGO 2009

  • IA : Zero or <50% myometrial invasion
  • IB: Invasion 50% of the myometrium
  • II: Tumor invades cervical stroma, but does not extend beyond the uterus
  • IIIA: Tumor invades the serosa of the corpus uteri and/or adnexae
  • IIIB: Vaginal and/or parametrial involvement
  • IIIC1: Positive pelvic lymph node
  • IIIC2: Positive paraaortic lymph node
  • IVA: Invasion of bladder and/or bowel mucosa
  • IVB: Distant metastasis

Diagnosis

Clinical Image

90% of cases present with abnormal uterine bleeding. Sometimes incidental finding of enlarged uterus (hematometra). Rarely presentation with hydronephrosis, hematuria or melena in a late stage.

Ultrasound

The following ultrasound features may be associated with endometrial cancer:

  1. Thick endometrium (>3mm in the postmenopause)
  2. Large tumor volume
  3. Irregular endometrial-myometrial junction
  4. Non-uniform echogenicity
  5. Multiple vessels

Always bear in mind that endometrial cancer can also be found within adenomyosis.

endometrial cancer
This image shows a transverse section of the uterine body in a patient with endometrial cancer FIGO IB, G3. The endometrium is characterized by increased thickness, it has homogenous background with irregular cystic areas, the midline is not clearly defined and the endometrial-myometrial junction is interrupted.
endometrial cancer doppler ultrasound
A suspicious finding inside the uterine cavity bearing multiple vessels which proved to be an endometrioid adenocarcinoma FIGO IA G1.
Hysteroscopy with biopsy

Remains the gold standard in providing the histopathological diagnosis.

Endometrial cancer hysteroscopic image
Hysteroscopic image of endometrial cancer.

Screening

There is currently no evidence to support the screening of asymptomatic women. However one should not underestimate the value of ultrasound (i.e. patients with cervical stenosis and hematometra).

Patients with Lynch syndrome Type II besides having regular colonoscopies should at least keep a menstrual calendar and report abnormal bleeding. Furthermore annual screening with an endometrial biopsy starting at age 35 is justifiable. A reasonable case for the prophylactic hysterectomy with salpingectomy can be made as early as at 40 years of age, as the lifetime endometrial cancer risk in women with Lynch syndrome type II is about of 30-60%.

Patients taking tamoxifen should have an endometrial biopsy if they present with abnormal bleeding.

The sonographic appearance of a giant hematometra in a case of severe cervical stenosis that showed no symptoms (incidental finding). Do not underestimate the value of sonography.

Types

  • Type 1: Estrogen-dependent endometrioid adenocarcinomas 80% of cases.
  • Type 2: Estrogen-independent non-endometrioid carcinomas (serous, clear-cell, undifferentiated).

Treatment

  • IA G1-G2, Type 1: Hysterectomy with bilateral salpingo-oophorectomy
  • IA G3, IB: Hysterectomy with bilateral salpingo-oophorectomy with bilateral pelvic and paraaortic lymphadenectomy, radiation, brachytherapy, chemotherapy
  • II: Radical hysterectomy with bilateral salpingo-oophorectomy and paraaortic lymphadenectomy, radiation, brachytherapy, chemotherapy
  • ΙΙΙ: Maximal surgical cytoreduction with a good performance status, radiation, brachytherapy, chemotherapy
  • IVA: Anterior and/or posterior pelvic exenteration, radiation, brachytherapy, chemotherapy.
  • IVB: Chemotherapy, sequential radiation of positive lymph nodes, palliative pelvic radiation, palliative Surgery

The above images show a case of a giant hematometra in a case of cervical stenosis and mucinous endometrial cancer. See how the uterus shrinks after its contents have been safely evacuated. There was no difficulty removing it afterwards.

Prognostic Factors

  • Stage (higher stage, worse prognosis)
  • Grade (higher grade, worse prognosis)
  • LVSI Lymph-vascular space invasion (worse prognosis)
  • Histological subtype (Type II endometrial cancer has worse prognosis)

Follow-Up

Gynecological examination and ultrasound

  • Years 1-3: every 3 months
  • Years 4-5: every 6 months
Bibliography
  1. Colombo, N., Preti, E., Landoni, F., Carinelli, S., Colombo, A., Marini, C., Sessa, C., & ESMO Guidelines Working Group (2013). Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology : official journal of the European Society for Medical Oncology24 Suppl 6, vi33–vi38. https://doi.org/10.1093/annonc/mdt353
  2. Raglan, O., Kalliala, I., Markozannes, G., Cividini, S., Gunter, M.J., Nautiyal, J., Gabra, H., Paraskevaidis, E., Martin‐Hirsch, P., Tsilidis, K.K. and Kyrgiou, M. (2019), Risk factors for endometrial cancer: An umbrella review of the literature. Int. J. Cancer, 145: 1719-1730. https://doi.org/10.1002/ijc.31961
  3. Cantrell, L. A., Blank, S. V., & Duska, L. R. (2015). Uterine carcinosarcoma: A review of the literature. Gynecologic oncology137(3), 581–588. https://doi.org/10.1016/j.ygyno.2015.03.041
  4. Biller, L. H., Syngal, S., & Yurgelun, M. B. (2019). Recent advances in Lynch syndrome. Familial cancer18(2), 211–219. https://doi.org/10.1007/s10689-018-00117-1
  5. Epstein, E. , Fischerova, D. , Valentin, L. , Testa, A. C., Franchi, D. , Sladkevicius, P. , Frühauf, F. , Lindqvist, P. G., Mascilini, F. , Fruscio, R. , Haak, L. A., Opolskiene, G. , Pascual, M. A., Alcazar, J. L., Chiappa, V. , Guerriero, S. , Carlson, J. W., Van Holsbeke, C. , Giuseppe Leone, F. P., De Moor, B. , Bourne, T. , van Calster, B. , Installe, A. , Timmerman, D. , Verbakel, J. Y. and Van den Bosch, T. (2018), Ultrasound characteristics of endometrial cancer as defined by International Endometrial Tumor Analysis (IETA) consensus nomenclature: prospective multicenter study. Ultrasound Obstet Gynecol, 51: 818-828. doi:10.1002/uog.18909
  6. Breijer, M. C., Peeters, J. A., Opmeer, B. C., Clark, T. J., Verheijen, R. H., Mol, B. W. and Timmermans, A. (2012), Capacity of endometrial thickness measurement to diagnose endometrial carcinoma in asymptomatic postmenopausal women: a systematic review and meta‐analysis. Ultrasound Obstet Gynecol, 40: 621-629. doi:10.1002/uog.12306
  7. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom, Langversion 1.0, 2018, AWMF Registernummer: 032/034-OL, http://www.leitlinienprogramm-onkologie.de/leitlinien/endometriumkarzinom/
    (abgerufen am: 02.07.2018).
  8. Naftalin, J. , Nunes, N. , Hoo, W. , Arora, R. and Jurkovic, D. (2012), Endometrial cancer and ultrasound: why measuring endometrial thickness is sometimes not enough. Ultrasound Obstet Gynecol, 39: 106-109. doi:10.1002/uog.9062.

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