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Endometrial Adenocarcinoma

Endometrial adenocarcinoma or cancer of the uterine corpus accounts for more than 80% of endometrial cancers and is one of the most common female genital tract malignancies. Obesity, nulliparity, tamoxifen therapy, long-term unopposed estrogen action, genetic predisposition, and hyperinsulinemia are supposed to be risk factors associated with it.


Presentation

Cancerous tumors in the uterine corpus are called endometrial cancers as 92% occur in the endometrium [1] and more than 80% of these are endometrial adenocarcinomas.

Although most endometrial cancers are diagnosed in the elderly with a median age of 65 years [2], it is also seen in younger women [3]. It presents commonly with abnormal uterine bleeding or spotting, dysuria (pain during urination), and dyspareunia. In 90% of endometrial cancer patients, uterine bleeding is the only symptom [4] and this cardinal presentation leads to an early diagnosis of the condition. Rarely, abnormal cervical cytology is the first clue to the presence of a uterine corpus malignancy in asymptomatic women. In perimenopausal women, the menstrual periods appear further apart and become scantier and so, any intermenstrual bleeding or heavy frequent menses should raise a cause for concern. In postmenopausal women, unprovoked vaginal bleeding may be the first symptom of endometrial adenocarcinoma.

Several risk factors have been reported to be associated with the development of endometrial adenocarcinoma and these are endometrial hyperplasia, obesity, hormonal treatment [5] [6], tamoxifen medication [7] [8], early menarche, late menopause or polycystic ovarian syndrome (PCOS) -conditions associated with prolonged unopposed estrogen effect, genetic predisposition [9] [10], hyperinsulinemia [11].

Anemia
  • Grade 3 TRAEs occurred in 16.7% and included asthenia and back pain; anemia, hyperglycemia, and hyponatremia; chills and pyrexia; diarrhea. There were no grade 4 or 5 events, and no immune-related adverse events were reported.[cancertherapyadvisor.com]
  • In advanced stages, symptoms include intense pain, weight loss and anemia (low red blood cell count) Causes and Risk Factors The following factors may put a woman at higher risk of developing endometrial cancer: Being older than 40 years old (Less than[cedars-sinai.edu]
  • Common side effects include: Dry, reddened skin in the treated area Fatigue Diarrhea Discomfort when urinating Narrowing of the vagina Anemia Most of these side effects are temporary.[foundationforwomenscancer.org]
  • Complications may include any of the following: Anemia due to blood loss (before diagnosis) Perforation (hole) of the uterus, which may occur during a D and C or endometrial biopsy Problems from surgery, radiation, and chemotherapy Call for an appointment[medlineplus.gov]
Arthritis
  • A paraneoplastic syndrome with palmar fasciitis and arthritis was then suspected and an evolutive peritoneal carcinomatosis was confirmed by abdominal CT scan.[ncbi.nlm.nih.gov]
Vaginal Bleeding
  • CASE: 74-year-old woman status after supracervical hysterectomy presented with profuse vaginal bleeding. Biopsy confirmed high-grade adenocarcinoma, suggesting endometrial origin.[ncbi.nlm.nih.gov]
  • The bone metastasis was treated successfully by radiotherapy, but three years later the patient noted vaginal bleeding, which led to the diagnosis and treatment of the primary endometrial cancer.[ncbi.nlm.nih.gov]
  • CASE: Two patients had a Mirena IUS inserted to treat abnormal vaginal bleeding. After 12 and 36 months with the device in place they presented with a recurrence of their heavy, irregular menstrual bleeding.[ncbi.nlm.nih.gov]
  • CONCLUSION: A hematotrachelos, although rare, can prevent vaginal bleeding, which is often the earliest symptom of a uterine malignancy.[ncbi.nlm.nih.gov]
  • CASE: A 44-year-old woman, gravida 3, para 2, was admitted due to abnormal vaginal bleeding. After complete history, physical examination, and laboratory evaluation, she was diagnosed with spontaneous abortion and underwent a suction curettage.[ncbi.nlm.nih.gov]
Pelvic Pain
  • CASE REPORT: We present the case of a 65-year-old patient who presented with association of pelvic pain, enlarged uterine cavity with an underlying hematometra and an irregular, thickened endometrium who was submitted to surgery for total histerectomy[ncbi.nlm.nih.gov]
  • Other symptoms include unusual pelvic pain or pressure, difficult or painful urination, and pain during intercourse.[breastcancer.org]
  • Usually the bleeding is painless, but sometimes it can be associated with other symptoms, including: Pelvic pain or cramping (That's the area where the uterus is located.)[study.com]
  • pain; pelvic mass; weight loss.[myriadmyrisk.com]
  • Prevention Premium: 3 Ways To Keep Your Thyroid Healthy Pelvic pain that won't go away Not everyone with endometrial cancer will have pain, but it can show up for some, especially if your cancer has been around for a while.[prevention.com]
Dyspareunia
  • It presents commonly with abnormal uterine bleeding or spotting, dysuria (pain during urination), and dyspareunia.[symptoma.com]
Metrorrhagia
  • CASE: This is a report on the coexistence of a uterine adenomatoid tumor and an endometrial adenocarcinoma, both chance findings in a 41-year-old woman undergoing hysterectomy because of a preoperative diagnosis of metrorrhagia due to leiomyomas.[ncbi.nlm.nih.gov]
Enlarged Uterus
  • After a thorough evaluation by an Ob/Gyn, the patient was found to have an enlarged uterus, a large fibroid, fluid in the endometrial cavity, and a growth in the lining of the uterus that was about an inch thick.[thedoctorwillseeyounow.com]

Workup

As endometrial adenocarcinomas can occur in peri as well as postmenopausal women, heavy menstrual bleeding or intermenstrual bleeding, irrespective of amount or duration, should be thoroughly investigated. It is important to elicit a detailed menstrual history, intake of contraceptive pills, hormonal therapy (for PCOS etc), hyperinsulinemia, and a family history of endometrial malignancy. Physical examination includes an examination of the pelvis, uterus, cervix and vagina as well as the inguinal region for lymphadenopathy. In most cases the uterine size is normal and no gross abnormalities are noticed.

Transvaginal ultrasonography is performed to detect abnormal endometrial thickening as it has good sensitivity [12] and this can be further confirmed with hydro ultrasonography i.e ultrasonography after injection of saline in the uterine cavity. If the abnormal endometrial thickness is detected, then routine laboratory studies, electrocardiogram and chest radiography should be obtained as part of the preoperative assessment. The patient is examined under anesthesia and an endometrial or hysteroscopic biopsy can be obtained for histopathological examination and final confirmation of endometrial adenocarcinoma. Further staging of the tumor may require a laparotomy to detect extrauterine spread and lymph node involvement.

Prognostic biomarkers like estrogen receptor (ER) and progesterone receptor (PR) are also tested as endometrial tumors associated with these markers are reported to have a good prognosis [13]. Immunohistochemistry to identify the absence of phosphatase and tensin homolog (PTEN) marker, a tumor suppressor, has also been reported as a sensitive method to predict cell proliferation and survival [14].

Estrogen Increased
  • Because any condition that increases exposure to unopposed estrogen increases the risk of endometrial cancer, tamoxifen therapy, estrogen replacement therapy without progestin and the presence of estrogen-secreting tumors are all risk factors.[aafp.org]
  • Hormone replacement therapy and estrogen: Either oral or body-produced estrogen increases the risk of this cancer. Environmental chemicals: Pesticides and air pollution have a direct effect on the risk of endometrial cancer.[vitamindcouncil.org]

Treatment

  • Clinicopathologic, treatment, and recurrence data were recorded. Pre/post-treatment pathologic evaluation was performed. SAS 9.2 was used for statistical analyses. RESULTS: Forty-six patients were included.[ncbi.nlm.nih.gov]
  • BACKGROUND: There have been several reports about successful fertility-preserving treatment of endometrial carcinoma with subsequent pregnancy. However, conservative hormonal treatment for early-stage endometrial cancer still entails some risk.[ncbi.nlm.nih.gov]
  • This is an unusual case regarding simultaneous diagnosis and treatment of bilateral breast carcinoma and endometrial adenocarcinoma. The clinical aspects and treatment of this unique case are presented.[ncbi.nlm.nih.gov]
  • We conclude that ART combined with progesterone treatment might be a powerful option for the treatment of infertile patients with early stage, well-differentiated endometrial adenocarcinoma. Copyright 2001 S. Karger AG, Basel[ncbi.nlm.nih.gov]
  • Consequently, conservative treatment may be indicated in patients with well-differentiated endometrial adenocarcinoma at an early stage who desire to preserve their fertility. Copyright 2004 S. Karger AG, Basel[ncbi.nlm.nih.gov]

Prognosis

  • Further investigations on larger sample size may provide additional data about prognosis of adenomyosis malignant transformation.[ncbi.nlm.nih.gov]
  • OBJECTIVE: To study the association between metabolic syndrome (MS) and the prognosis of patients with endometrial adenocarcinoma.[ncbi.nlm.nih.gov]
  • DISCUSSION: Patients with endometrial adenocarcinoma presenting an isolated skeletal metastasis may exhibit an unusual group with a better prognosis.[ncbi.nlm.nih.gov]
  • CONCLUSION: The disease is diagnosed usually in its early stage and has a good prognosis. Appropriately selected patients with fertility desire have the opportunity to conceive with conservative management.[ncbi.nlm.nih.gov]
  • CONCLUSION: Potential consequences in treatment recommendations and prognosis urge attention to the detected increase of G3 endometrioid cancers.[ncbi.nlm.nih.gov]

Etiology

  • PURPOSE: Endometrial cancer can be divided into two types: endometrioid Type 1 (G1, G2) has a hormonal driven etiology, while Type 2 is more aggressive (G3 endometrioid, clear cell and serous cancer type) and estrogen independent.[ncbi.nlm.nih.gov]
  • Brinton LA, Felix AS, McMeekin DS, Creasman WT, Sherman ME, Mutch D et al (2013) Etiologic heterogeneity in endometrial cancer: evidence from a Gynecologic Oncology Group trial.[link.springer.com]
  • […] of the cases among other histologic types, type I includes mucinous and secretory carcinomas, whereas type II includes clear-cell carcinomas and adenosquamous carcinomas Embryonic origin tumour developped from the epithelium of the endometrial mucosa Etiology[atlasgeneticsoncology.org]
  • GYNECOLOGIC NEOPLASMS ENDOMETRIAL CANCER Etiology and Pathology Symptoms, Signs, and Diagnosis Staging, Prognosis, and Treatment OVARIAN CANCER Etiology and Pathology Symptoms, Signs, and Diagnosis Treatment CERVICAL CANCER Pathology Symptoms and Signs[health.am]
  • Am J Surg Pathol 7: 839– 847, 1983 5 Gambrell RD, Bagnell CA, Greenblatt RB: Role of estrogens and progesterone in the etiology and prevention of endometrial cancer [Review].[glowm.com]

Epidemiology

  • METHODS: We analyzed all women diagnosed with FIGO stage IIIC endometrial adenocarcinoma in the Surveillance, Epidemiology, and End Results database from 2004 to 2012 (n 2177).[ncbi.nlm.nih.gov]
  • METHODS AND MATERIALS: Data between 1998 and 2011 from the National Cancer Institute's Surveillance, Epidemiology and End Results database were analyzed.[ncbi.nlm.nih.gov]
  • The chapters are comprehensive and logically organized, covering the epidemiology and pathogenesis of endometrial adenocarcinoma, endometrial sampling techniques and the spectrum of cytomorphologic appearance from benign through hyperplasia to adenocarcinoma[karger.com]
  • We discuss the epidemiology, diagnosis, and treatment of endometrial cancer on the basis of a review of observational research, randomised trials, reviews, and meta-analyses.[bmj.com]
  • BMJ. 2011;343:d3954 Links: aetiology epidemiology pathology clinical features staging of endometrial cancer investigation diagnosis treatment prognosis recurrent endometrial cancer female genital tract cancers follow-up if history of endometrial cancer[gpnotebook.co.uk]
Sex distribution
Age distribution

Pathophysiology

  • CONCLUSION: Recent association between first-trimester spontaneous abortions and subsequent endometrial cancer makes these rare cases of concurrent endometrial cancer and first trimester of pregnancy attractive in that they may disclose insights into the pathophysiology[ncbi.nlm.nih.gov]
  • The book emphasizes the correlation between clinical and pathologic features of female genital tract disease by examining the pathophysiology of individual organ systems.[books.google.ro]
  • Overview Historical Perspective Classification Pathophysiology Causes Differentiating Endometrial Cancer from other Diseases Epidemiology and Demographics Risk factors Screening Natural History, Complications and Prognosis Diagnosis Staging History and[wikidoc.org]
  • […] post-menopausal woman with an intact uterus) tamoxifen treatment Hereditary Nonpolyposis Colon Cancer (HNPCC or Lynch Syndrome) on family history factors that decrease risk include: ovulation OCP progestin menopause normal weight multiparity smoking return to top Pathophysiology[sharinginhealth.ca]
  • […] the PEPI trial involved a randomly selected cohort. 14 These findings suggest that patients at high risk for endometrial disease should receive higher dosages of progestins than patients at low risk, a suggestion that is supported, in theory, by the pathophysiology[aafp.org]

Prevention

  • Abstract Diethylstilbestrol (DES) was used widely in the late 1940s in an attempt to prevent adverse pregnancy outcomes.[ncbi.nlm.nih.gov]
  • CONCLUSION: A hematotrachelos, although rare, can prevent vaginal bleeding, which is often the earliest symptom of a uterine malignancy.[ncbi.nlm.nih.gov]
  • To prevent upper airway compromise, we performed transoral endoscopic debulking surgery with postoperative regional low-dose radiotherapy, instead of traditional tracheostomy. The patient underwent palliative chemotherapy after the surgery.[ncbi.nlm.nih.gov]
  • Investigation of the occurrence of CTCs in cancer patients would aid in the prevention of metastasis and thereby refine treatment.[ncbi.nlm.nih.gov]
  • Their treatment of choice is open, classical splenectomy that must be followed by chemotherapy in order to prevent the development of other possible micrometastases.[ncbi.nlm.nih.gov]

References

Article

  1. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. http://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2016/cancer-facts-and-figures-2016.pdf. Accessed January 23, 2016
  2. Huang CY, Chen CA, Chen YL, et al. Nationwide surveillance in uterine cancer: survival analysis and the importance of birth cohort: 30-year population-based registry in Taiwan. PloS One. 2012; 7: 51372.
  3. Park JY, Seong SJ, Kim TJ, et al. Pregnancy outcomes after fertility-sparing management in young women with early endometrial cancer. Obstet Gynecol. 2013;121:136-42.
  4. Colombo N, Preti E, Landoni F, et al. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2011; 22: 35-9.
  5. Ziel HK, Finkle WD. Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 1975; 293 (23): 1167-70.
  6. Jick SS, Walker AM, Jick H. Estrogens, progesterone, and endometrial cancer. Epidemiology 1993; 4 (1): 20-4
  7. van Leeuwen FE, Benraadt J, Coebergh JW, et al. Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet. 1994;343 (8895): 448-52
  8. Fisher B, Costantino JP, Redmond CK, et al. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst. 1994;86 (7): 527-37
  9. Lynch HT, Lynch J, Conway T, et al. Familial aggregation of carcinoma of the endometrium. Am J Obstet Gynecol 1994; 171 (1): 24-7
  10. Lu KH, Schorge JO, Rodabaugh KJ, et al. Prospective determination of prevalence of lynch syndrome in young women with endometrial cancer. J Clin Oncol. 2007; 25 (33): 5158-64
  11. Nead KT, Sharp SJ, Thompson DJ, et al. Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis. J Natl Cancer Inst. 2015;107 (9)
  12. Smith-Bindman R, Kerlikowske K, Feldstein VA, et al. Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities, JAMA. 1998;280(17):1510–1517.
  13. Ferrandina G, Ranelletti FO, Gallotta V, et al. Expression of cyclooxygenase-2 (COX-2), receptors for estrogen (ER), and progesterone (PR), p53, ki67, and neu protein in endometrial cancer, Gynecol Oncol, 2005, 98(3):383–389.
  14. Djordjevic B, Hennessy BT, Li J, et al. Clinical assessment of PTEN loss in endometrial carcinoma: immunohistochemistry outperforms gene sequencing. Mod Pathol. 2012; 25(5):699–708.

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Last updated: 2018-06-21 20:57