Endometrial cancer

Endometrial cancer
Classification and external resources

Micrograph of endometrioid endometrial adenocarcinoma, the most common form of endometrial cancer. H&E stain.
ICD-10 C54.1
ICD-9 182
OMIM 608089
DiseasesDB 4252
MedlinePlus 000910
eMedicine med/674 radio/253
MeSH D016889

Endometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the obesity epidemic. The most common subtype, endometrioid adenocarcinoma, typically occurs within a few decades of menopause, is associated with obesity, excessive estrogen exposure, often develops in the setting of endometrial hyperplasia, and presents most often with vaginal bleeding. Endometrial carcinoma is the third most common cause of gynecologic cancer death (behind ovarian and cervical cancer). A total abdominal hysterectomy (surgical removal of the uterus) with bilateral salpingo-oophorectomy is the most common therapeutic approach.

Endometrial cancer may sometimes be referred to as uterine cancer. However, different cancers may develop not only from the endometrium itself but also from other tissues of the uterus, including cervical cancer, sarcoma of the myometrium, and trophoblastic disease.

Contents

Classification

Carcinoma

Most endometrial cancers are carcinomas (usually adenocarcinomas), meaning that they originate from the single layer of epithelial cells that line the endometrium and form the endometrial glands. There are many microscopic subtypes of endometrial carcinoma, including the common endometrioid type, in which the cancer cells grow in patterns reminiscent of normal endometrium, and the far more aggressive papillary serous carcinoma and clear cell endometrial carcinomas. Some authorities have proposed that endometrial carcinomas be classified into two pathogenetic groups:[1]

Sarcoma

In contrast to endometrial carcinomas, the uncommon endometrial stromal sarcomas are cancers that originate in the non-glandular connective tissue of the endometrium. Uterine carcinosarcoma, formerly called Malignant mixed müllerian tumor, is a rare uterine cancer that contains cancerous cells of both glandular and sarcomatous appearance - in this case, the cell of origin is unknown.[2]

Histological types: I- Endometrial Adenocarcinoma Commonest . 3 grades:- G1: Highly differentiated (composed of glands and 5% of lesion is of solid growth pattern). G2: Moderately differentiated ( 6%-50% of lesion composed of solid sheets of cells). G3: Undifferentiated ( > 50% of lesion composed of solid sheets of cells). Subtypes of endometrial adenocarcinoma: Endometrioma --> most common. Clear cell.--> most malignant. Secretory. Mucinous. Papillary serous.--> common with hereditary types.

II- Adenoacanthoma (adenocarcinoma with squamous metaplasia). Less than 10%. Malignant glandular element + benign squamous element low grade tumour good prognosis.

III- Adenosquamous carcinoma Malignant glandular element + malignant squamous element high grade malignancy poor prognosis.

IV- Carcinosarcoma Highly malignant. Epithelial and stromal malignant elements.

Signs and symptoms

Risk factors

Diagnosis

Clinical evaluation

Routine screening of asymptomatic women is not indicated, since the disease is highly curable in its early stages. Results from a pelvic examination are frequently normal, especially in the early stages of disease. Changes in the size, shape or consistency of the uterus and/or its surrounding, supporting structures may exist when the disease is more advanced.

Diagnostic test study of S-p53 Ab and agreement study for high-risk endometrial cancer Kappa: 0.70 Sensitivity (%): 64 Specificity(%): 96 PPV: 78 NPV: 92

Pathology

The histopathology of endometrial cancers is highly diverse. The most common finding is a well-differentiated endometrioid adenocarcinoma, which is composed of numerous, small, crowded glands with varying degrees of nuclear atypia, mitotic activity, and stratification. This often appears on a background of endometrial hyperplasia. Frank adenocarcinoma may be distinguished from atypical hyperplasia by the finding of clear stromal invasion, or "back-to-back" glands which represent nondestructive replacement of the endometrial stroma by the cancer. With progression of the disease, the myometrium is infiltrated.[2] However, other subtypes of endometrial cancer exist and carry a less favorable diagnosis such as the uterine papillary serous carcinoma and the clear cell carcinoma.

Further evaluation

Patients with newly-diagnosed endometrial cancer do not routinely undergo imaging studies, such as CT scans, to evaluate for extent of disease, since this is of low yield. Preoperative evaluation should include a complete medical history and physical examination, pelvic examination and rectal examination with stool guaiac test, chest X-ray, complete blood count, and blood chemistry tests, including liver function tests. Colonoscopy is recommended if the stool is guaiac positive or the woman has symptoms, due to the etiologic factors common to both endometrial cancer and colon cancer. The tumor marker CA-125 is sometimes checked, since this can predict advanced stage disease.[8] In addition to this, both D&C and Pipelle biopsy curettage give 65-70% positive predictive value. But most important of these is hysteroscopy which gives 90-95% positive predictive value.

Staging

Endometrial carcinoma is surgically staged using the FIGO cancer staging system. Although the FIGO staging has recently been updated, the older staging described below is still commonly used.

The 2010 Figo staging system is as follows: Carcinoma of the Endometrium

Treatment

The primary treatment is surgical. Surgical treatment should consist of, at least, cytologic sampling of the peritoneal fluid, abdominal exploration, palpation and biopsy of suspicious lymph nodes, abdominal hysterectomy, and removal of both ovaries (bilateral salpingo-oophorectomy). Lymphadenectomy, or removal of pelvic and para-aortic lymph nodes, is sometimes performed for tumors that have high risk features, such as pathologic grade 3 serous or clear-cell tumors, invasion of more than 1/2 the myometrium, or extension to the cervix or adnexa. Sometimes, removal of the omentum is also performed.

Abdominal hysterectomy is recommended over vaginal hysterectomy because it affords the opportunity to examine and obtain washings of the abdominal cavity to detect any further evidence of cancer.

Women with stage 1 disease who are at increased risk for recurrence and those with stage 2 disease are often offered surgery in combination with radiation therapy.[9] Chemotherapy may be considered in some cases, especially for those with stage 3 and 4 disease. hormonal therapy with progestins and antiestrogens has been used for the treatment of endometrial stromal sarcomas.[10]

The antibody Herceptin, which is used to treat breast cancers that overexpress the HER2/neu protein, has been tried with some success in a phase II trial in women with uterine papillary serous carcinomas that overexpress HER2/neu.[11]

Complications of treatment

Prognosis

While endometrial cancers are 40% more common in Caucasian women, an African American woman who is diagnosed with uterine cancer is twice as likely to die (possibly due to the higher frequency of aggressive subtypes in that population, but more probably due to delay in the diagnosis).

Survival rates

The 5-year survival rates for endometrial adenocarcinoma following appropriate treatment are[12]:

Stage 5 year survival rate
I-A 90%
I-B 88%
I-C 75%
II 69%
III-A 58%
III-B 50%
III-C 47%
IV-A 17%
IV-B 15%

Epidemiology

It's the most frequent cancer occurring in the female genital tract in the United States and many other Western countries. It appears most frequently between ages of 55 and 65, and uncommon below 40. There are two pictures of this disease, perimenopausal women with estrogen excess and in older women with endometrial atrophy.[14]

See also

Additional images

References

  1. ^ Bokhman JV (1983). "Two pathogenetic types of endometrial carcinoma". Gynecol. Oncol. 15 (1): 10–7. doi:10.1016/0090-8258(83)90111-7. PMID 6822361. 
  2. ^ a b Richard Cote, Saul Suster, Lawrence Weiss, Noel Weidner (Editor) (2002). Modern Surgical Pathology (2 Volume Set). London: W B Saunders. ISBN 0-7216-7253-1. 
  3. ^ J.C.E. Underwood and S.S. Cross (2009). General and Systemic pathology. London: Elsevier (Churchill Livingstone). ISBN 9780443068898. 
  4. ^ Goodman, ET; et al (1997). "Diet, body size, physical activity, and the risk of endometrial cancer.". Cancer Res 57: 5077. 
  5. ^ Friedenreich, CM; Neilson, HK, Lynch, BM (2010 Sep). "State of the epidemiological evidence on physical activity and cancer prevention.". European journal of cancer (Oxford, England : 1990) 46 (14): 2593-604. PMID 20843488. 
  6. ^ "Thirteen studies to date have reported on the relationship between endometrial cancer and alcohol consumption. Only two of these studies have reported that endometrial cancer incidence is associated with consumption of alcohol; all the others have reported either no definite association, or an inverse association." (Six studies showed an inverse association; that is, drinking was associated with a lower risk of endometrial cancer) "…if such an inverse association exists, it appears to be more pronounced in younger, or premenopausal, women."[3] "Our results suggest that only alcohol consumption equivalent to 2 or more drinks per day increases risk of endometrial cancer in postmenopausal women."
  7. ^ Yamazawa, K; Shimada, H; Hirai, M; Hirashiki, K; Ochiai, T; Ishikura, H; Shozu, M; Isaka, K (2007). "Serum p53 antibody as a diagnostic marker of high-risk endometrial cancer.". American journal of obstetrics and gynecology 197 (5): 505.e1–7. doi:10.1016/j.ajog.2007.04.033. PMID 17980190. 
  8. ^ Dotters, DJ (2000). "Preoperative CA 125 in endometrial cancer: is it useful?". American journal of obstetrics and gynecology 182 (6): 1328–34. doi:10.1067/mob.2000.106251. PMID 10871446. 
  9. ^ Chong, I; Hoskin, PJ (2008). "Vaginal vault brachytherapy as sole postoperative treatment for low-risk endometrial cancer.". Brachytherapy 7 (2): 195–9. doi:10.1016/j.brachy.2008.01.001. PMID 18358790. 
  10. ^ [1] American Cancer Society - Uterine Sarcomas - Hormonal Therapy (accessed 5-25-07)
  11. ^ Santin AD, Bellone S, Roman JJ, McKenney JK, Pecorelli S. (2008). "Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu". Int J Gynaecol Obstet 102 (2): 128–31. doi:10.1016/j.ijgo.2008.04.008. PMID 18555254. 
  12. ^ American Cancer Society (2009-10-22). "How Is Endometrial Cancer Staged?". http://www.cancer.org/Cancer/EndometrialCancer/DetailedGuide/endometrial-uterine-cancer-staging. Retrieved 2010-03-09 [Note Stage I definitions in ref differed from those used on Wiki page, so adjusted table labels from 0, IA, IB, to IA, IB, IC matching definitions used here]. 
  13. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved Nov. 11, 2009. 
  14. ^ DiCristofano A, Ellenson LH: Endometrial carcinoma. Annual Review of Pathology: Mechanisms of Disease, Vol. 2:57 , 2007. [A comprehensive discussion of pathogenesis.]

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