History

Fact Explanation
Per vaginal bleeding Endometrial adenocarcinoma is an important cause of post-menopausal bleeding. The disease usually presents in the sixth and seventh decade of life. The mean age of presentation is 63 yrs.[1] Majority of patients present with abnormal vaginal bleeding. Patients who are menopaused present with post-menopausal bleeding. Pre-menopausal patients may present with inter-menstrual bleeding, post-coital bleeding and heavy menstrual bleeding.
Vaginal discharge The vaginal discharge may be blood stained and offensive.
Dyspareunia The patient may experience deep seated pain during sexual intercourse – Deep dyspareunia.
Pelvic pain Due to gradual spread into pelvic structures.
Presentation with features of metastasis Patients with advanced cancer may present with features of local spread – fistula formation, chronic pelvic pain. Distant metastases may cause respiratory symptoms, bone pain, right hypochondrial pain and jaundice.
Incidental finding in an asymptomatic patient May be detected during cervical carcinoma screening. Asymptomatic patients undergoing cervical smear testing may be found to have abnormal glandular cytology.
Fatigue/ malaise/ weakness/ exertional dyspnea Anemia may develop due to chronic vaginal bleeding.
Risk factors for development of endometrial carcinoma Endometrial carcinoma has being shown to be strongly associated with hyperestrogenic states. Common risk factors include obesity, nulliparity, early menarche, late menopause, tamoxifen therapy and HRT.[2] Genetic predisposition also plays an important role. Hereditary non-polyposis colorectal cancer syndrome (HNPCC), a genetic link with autosomal dominant inheritance is associated with colorectal, ovarian, endometrial and urothelial malignancy.[3] Use of the oral contraceptive pill has being shown to have a long lasting protective effect.
References
  1. COLOMBO N., PRETI E., LANDONI F., CARINELLI S., COLOMBO A., MARINI C., SESSA C.. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 22(Supplement 6):vi35-vi39 [viewed 26 July 2014] Available from: doi:10.1093/annonc/mdr374
  2. KAAKS R, LUKANOVA A, KURZER MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev [online] 2002 Dec, 11(12):1531-43 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12496040
  3. GARG K, SOSLOW R A. Lynch syndrome (hereditary non-polyposis colorectal cancer) and endometrial carcinoma. Journal of Clinical Pathology [online] December, 62(8):679-684 [viewed 26 July 2014] Available from: doi:10.1136/jcp.2009.064949

Examination

Fact Explanation
General examination : Pallor Chronic blood loss may lead to iron deficiency anemia.
Abdominal examination : lower abdominal pain Abdominal examination is usually normal. The patient may have mild tenderness in the suprapubic region. Examine for hepatomegaly and ascites in advanced disease.[1]
Speculum examination : Vaginal bleeding Speculum examination is normal except for bleeding from the cervical os.
Vaginal examination : Enlarged uterus On bimanual examination the uterus will be enlarged. Rest of the examination is usually normal.
Examine the patient for evidence of disseminated disease Examine the respiratory system for signs of pleural effusion. Examine the bones for tenderness.[1]
References
  1. PLATANIOTIS G., CASTIGLIONE M.. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 21(Supplement 5):v41-v45 [viewed 26 July 2014] Available from: doi:10.1093/annonc/mdq245

Differential Diagnoses

Fact Explanation
Endometrial polyp Endometrial polyps are growths of the endometrium which can be sessile or pedunculated. Pedunculated polyps may extend into the cervix and vagina. Polyps can be asymptomatic or if symptomatic present with inter-menstrual bleeding, menorrhagia, spotting and postmenopausal bleeding. Polyps that protrude through the cervix may cause local discomfort and dyspareunia. Diagnosis of polyps is by sonohysterography where the uterine cavity is viewed after injection of saline into it. Hysteroscopy may also aid in diagnosis. Endometrial polyps are associated with an increased risk of malignancy.[1] The currently endometrial polyps are treated by transcervical resection. Further studies are required to determine the most appropriate treatment strategy for endometrial polyps.[2]
Cervical carcinoma Malignancy of the uterine cervix is an important differential diagnosis for endometrial carcinoma. The presentation is usually in the 20-30yr or 60-70 yr old age group. Risk factors for cervical carcinoma are Human papilloma virus infection and smoking. The patient presents with post-coital bleeding, intermenstrual bleeding, blood stained vaginal discharge and pelvic pain. Cervical carcinoma spreads directly to the bladder, rectum or metastasizes along the lymphatics. On vaginal examination the cervix may appear eroded, discolored and ulcerated. A tumor mass may be seen in advanced disease. Diagnosis of cervical carcinoma is usually by biopsy.[3] Squamous cell carcinoma is the commonest histological variety.
Atrophic vaginitis Atrophy of the female genitalia in the postmenopausal period is due to decreased estrogen level within the body. This results in atrophy of the fibrous support structures of the cervix, vagina and vulva. It may be present in about 50% of postmenopausal women. Vulvovaginal atrophy presents with dryness and soreness of the vagina which is more prone to trauma and infection. Urinary symptoms such as dysuria, frequency and incontinence may be seen. Atrophy of the vulva and vaginal walls is evident at physical examination. The mucosa of the vagina appears dry, pale and may have petechiae. Vaginal rugae are absent and the cervix may appear reddened. Diagnosis of atrophic vaginitis is clinical. The vagina pH is more than 4.6. Treatment consists of topical estrogen therapy.[4]
References
  1. LEE SC, KAUNITZ AM, SANCHEZ-RAMOS L, RHATIGAN RM. The oncogenic potential of endometrial polyps: a systematic review and meta-analysis. Obstet Gynecol [online] 2010 Nov, 116(5):1197-205 [viewed 26 July 2014] Available from: doi:10.1097/AOG.0b013e3181f74864
  2. LIENG M, ISTRE O, QVIGSTAD E. Treatment of endometrial polyps: a systematic review. Acta Obstet Gynecol Scand [online] 2010 Aug, 89(8):992-1002 [viewed 26 July 2014] Available from: doi:10.3109/00016349.2010.493196
  3. PETIGNAT P., ROY M.. Diagnosis and management of cervical cancer. BMJ [online] 2007 October, 335(7623):765-768 [viewed 26 July 2014] Available from: doi:10.1136/bmj.39337.615197.80
  4. MAC BRIDE MB, RHODES DJ, SHUSTER LT. Vulvovaginal Atrophy Mayo Clin Proc [online] 2010 Jan, 85(1):87-94 [viewed 26 July 2014] Available from: doi:10.4065/mcp.2009.0413

Investigations - for Diagnosis

Fact Explanation
Transvaginal ultrasound scan (TVS) Patients who are suspected with endometrial cancer should undergo a TVS. Endometrial thickness of more than 4mm carries a high risk of endometrial cancer and requires hysteroscopy and biopsy. Patients who have an endometrial thickness less than 4mm have a low cancer risk. This measurement alone is inaccurate as it carries a high false positivity rate.[1] Concomitant cancer of the ovaries may also be detected. TVS can assess depth of myometrial invasion.
Endometrial biopsy A biopsy is required for diagnosis of endometrial carcinoma. Technoques for obtaining a smaple : hysteroscopy, curettage and via an endometrial sampler – Pipelle. For accurate diagnosis an adequate sample should be taken.[2] The biopsy sample should be evaluated for histology and cytology. Grading of the tumor and type of tumor can be determined by histological assessment. The commonest cancer arising from the endometrium is endometrial adenocarcinoma. Endometrial adenocarcinoma is classified into two subtypes : Type 1-Endometrioid carcinoma and Type 2-Serous papillary carcinoma. Clear cell carcinoma is a rare type of endometrial carcinoma.
Pipelle endometrial sampler This is a hand held syringe like structure which is introduced into the endometrial cavity vaginally. An endometrial sample is collected by aspiration. This procedure can be conducted in a clinic setting. Anesthesia is not required.
Hysteroscopy Hysteroscopy is considered the gold standard in diagnosis of endometrial cancer.[3] It can be carried out both as a out-patient procedure and under general anesthesia in a theater. Hysteroscopy allows visualization of the whole endometrium. The tumor mass can be directly visualized and a targeted biopsy can be taken.
Curettage This involves dilation of the cervix and curettage of the endometrial lining. The procedure is usually carried out under general anesthesia. The tissue products produced during curettage are collected for analysis. This procedure is considered to be sensitive and specific for the diagnosis of endometrial carcinoma.[4]
References
  1. TABOR A, WATT HC, WALD NJ. Endometrial thickness as a test for endometrial cancer in women with postmenopausal vaginal bleeding. Obstet Gynecol [online] 2002 Apr, 99(4):663-70 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12039131
  2. CLARK TJ, MANN CH, SHAH N, KHAN KS, SONG F, GUPTA JK. Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative review. BJOG [online] 2002 Mar, 109(3):313-21 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11950187
  3. CLARK T. JUSTIN, VOIT DORIS, GUPTA JANESH K., HYDE CHRISTOPHER, SONG FUJIAN, KHAN KHALID S.. Accuracy of Hysteroscopy in the Diagnosis of Endometrial Cancer and Hyperplasia. JAMA [online] 2002 October [viewed 26 July 2014] Available from: doi:10.1001/jama.288.13.1610
  4. SAADIA A, MUBARIK A, ZUBAIR A, JAMAL S, ZAFAR A. Diagnostic accuracy of endometrial curettage in endometrial pathology. J Ayub Med Coll Abbottabad [online] 2011 Jan-Mar, 23(1):129-31 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22830167

Investigations - Fitness for Management

Fact Explanation
Full blood count To check for anemia in preparation for surgery.
Renal function tests/ Serum electrolytes Assess fitness for surgery.
Liver function tests Assess liver functions to assess fitness for surgery.
Blood grouping and save Reserve blood if the patient is planning to undergo curative surgery.
Investigate for cardio-pulmonary function In preparation for surgery patient fitness should be assessed. In elderly patients electrocardiography and echocardiography may be required to determine cardiac function. Patients with chronic lung conditions need lung function assessment.
References

Investigations - Followup

Fact Explanation
Transvaginal ultrasound scan Follow up the patient for recurrence of malignancy. Recurrence of disease is commonly seen in the vagina and the vault. Close follow-up is required in the first 2 years after therapy.[1]
References
  1. NG TY, PERRIN LC, NICKLIN JL, CHEUK R, CRANDON AJ. Local recurrence in high-risk node-negative stage I endometrial carcinoma treated with postoperative vaginal vault brachytherapy. Gynecol Oncol [online] 2000 Dec, 79(3):490-4 [viewed 26 July 2014] Available from: doi:10.1006/gyno.2000.6005

Investigations - Screening/Staging

Fact Explanation
Staging of endometrial carcinoma Endometrial carcinoma is staged according to a surgico-pathological staging system introduced by the International federation of Obstetricians and Gynaecologists (FIGO). Stage 1 – Tumor confined to uterine body, Stage 2 – Tumor invading the cervical stroma, Stage 3 – Local and/or regional spread of tumor, Stage 4- Tumor invading bladder and/or bowel or presence of distant metastases. Imaging investigations may be used to aid staging of disease. The currently used system was last revised in 2009.[1]
Magnetic resonance imaging (MRI) Used to determine the extent of the disease. MRI can assess depth of myometrial invasion and detect pelvic lymphadenopathy. MRI helps in staging the disease and in deciding the optimum surgical treatment option. MRI is considered the the most accurate investigation for diagnosis and staging even though it is not included in the FIGO staging system.
Chest X-ray To exclude lung metastasis.
References
  1. LEWIN SN. Revised FIGO staging system for endometrial cancer. Clin Obstet Gynecol [online] 2011 Jun, 54(2):215-8 [viewed 26 July 2014] Available from: doi:10.1097/GRF.0b013e3182185baa
  2. SALA E, WAKELY S, SENIOR E, LOMAS D. MRI of Malignant Neoplasms of the Uterine Corpus and Cervix. American Journal of Roentgenology, 2007, 188, 1577-1587.

Management - General Measures

Fact Explanation
Patient education and counseling Provide information regarding the natural course of the disease, aetiology, investigation and treatment options available. Counsel the patient regarding the prognosis of the condition. Adequate information should be provided on the stage of the disease and proposed management plan. Patient ideas and wishes should be considered when finalizing the management plan.
Psychological support Diagnosis of malignancy may cause distress in the patient and family. Provide counseling and psychological support.[1]
Optimize patient fitness if surgery is considered Correct anemia if present. A diagnosed patient with diabetes, hypertension and hyperlipidaemia require optimization of treatment. Monitor and control blood glucose and blood pressure prior to surgery.
References
  1. LALOS A. The impact of diagnosis on cervical and endometrial cancer patients and their spouses. Eur J Gynaecol Oncol [online] 1997, 18(6):513-9 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9443025

Management - Specific Treatments

Fact Explanation
Treatment options The appropriate treatment option should be selected according to the stage of disease, patient comorbities and patient wishes. Available treatment options include curative surgery, radiotherapy and chemotherapy. The multi-disciplinary team comprised of gynaecologist, oncologist, pathologist, surgeon, nurses and rehabilitation professionals should be involved in the management of the patient.
Surgery Surgery is the treatment of choice since a majority of patients present with early disease. The extent of surgery depends on MRI stage of disease and grade of malignancy. The standard procedure includes total abdominal hysterectomy with bilateral salpingo-oophorectomy.[1] Peritoneal washings are carried out and the resected tumor is sent for histological assessment. This clearance is adequate for stage 1 disease. Patients with stage 2 and 3 disease require a more wider clearance and a radical hysterectomy with pelvic node dissection is performed. The extent of nodal dissection required is a controversial subject which requires further research. Some centers opt for pelvic and para-aortic lymph node dissection in higher stages of disease and if the tumor is found to be grade 3. Surgery may be difficult and inappropriate in patients with stage 4 malignancy.
Radiotherapy Radiotherapy is usually used as adjuvant therapy for stage 2 and above. This is in combination with surgery in operable patients. Radiotherapy alone may be used in inoperable advanced disease. Radiotherapy may be administered as external beam therapy or as brachytherapy to the vault. The advantage of brachytherapy is the ability to use higher doses with minimal damage to surrounding organs. Postoperative radiotherapy reduces risk of local recurrence rate.[2] While most centers use radiotherapy as an adjuvant immediately after surgery, some centers may observe the patient and use radiotherapy only if recurrences occur.
Chemotherapy The use of chemotherapy in treating endometrial cancer is limited. Chemotherapy is usually used as a palliative option in advanced disease for distant metastatic disease. Use of chemotherapy in metastatic endometrial carcinoma has shown to improve overall survival. Further research is required to determine the optimum treatment regimen required in these patients.[3]
Hormonal therapy Hormonal therapy is not recommended as adjuvant treatment due to inadequate evidence.[4] Studies have being carried out with oral medroxyprogesterone acetate alone or in combination with Tamoxifen. The response rate is poor, patients with positive progesterone receptor status showed a better response.
Follow-up Review the patient postoperatively with the histopathology report. Further treatment is planned according to the stage and grade of disease. Arrange for regular follow-up to determine treatment success and identify recurrence. At follow-up visits, clinical history and examination should look for evidence of cancer recurrence. Pelvic imaging may be required in some patients.
References
  1. EN-SHACHAR I, PAVELKA J, COHN DE, COPELAND LJ, RAMIREZ N, MANOLITSAS T, FOWLER JM. Surgical staging for patients presenting with grade 1 endometrial carcinoma. Obstet Gynecol [online] 2005 Mar, 105(3):487-93 [viewed 26 July 2014] Available from: doi:10.1097/01.AOG.0000149151.74863.c4
  2. MAGGI R, LISSONI A, SPINA F, MELPIGNANO M, ZOLA P, FAVALLI G, COLOMBO A, FOSSATI R. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial. Br J Cancer [online] 2006 Aug 7, 95(3):266-71 [viewed 26 July 2014] Available from: doi:10.1038/sj.bjc.6603279
  3. VALE CL, TIERNEY J, BULL SJ, SYMONDS PR. Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma. Cochrane Database Syst Rev [online] 2012 Aug 15:CD003915 [viewed 26 July 2014] Available from: doi:10.1002/14651858.CD003915.pub4
  4. MUECK AO, SEEGER H. Hormone therapy after endometrial cancer. Endocr Relat Cancer [online] 2004 Jun, 11(2):305-14 [viewed 26 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15163305