Endometrial Carcinoma And Endometrial Hyperplasia

ENDOMETRIAL CARCINOMA AND ENDOMETRIAL HYPERPLASIA

 Endometrial

carcinoma is the most common gynaecologic malignancy (equal to or slightly more common than cancer cervix).  The incidence has shown a steady rise in the last 2 decades with prolonged postmenopausal period of life and with the liberal use of oestrogen replacement therapy in the menopause.

 The

disease affects predominantly postmenopausal women, with average age 55-65 years  less than 5% of cases are diagnosed in women under the age of 40 years.

AETIOLOGY  The

cause of endometrial carcinoma is unknown, however increased oestrogen levels, unopposed by progesterone, is the chief high risk factor. The majority of the circulating oestrogen in postmenopausal women is derived from peripheral aromatization of androgens in adipose tissue into oestrogen (oestrone E1).

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Risk Factors in Endometrial Carcinoma: 1. Obesity 2. Nulliparity 3. Chronic anovulation as PCOD 4. Delayed menopause 5. Unopposed oestrogen therapy 6. Functioning ovarian tumours (oestrogen producing) 7. Impaired carbohydrate tolerance

PRE-MALIGNANT LESIONS (Endometrial Hyperplasia)  Microscopically:

Under the effect of prolonged unopposed oestrogen, the endometrial lining of the uterus will grow and multiply resulting in an exaggerated proliferative activity known as "endometrial hyperplasia".

Three types of endometrial hyperplasia are defined; 

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Simple hyperplasia the glands and stroma are hyperplastic, glands show cystic dilatation with disparity in size, with no evidence of secretory activity; Such lesions have a very low malignant potential <1%. Complex hyperplasia; If simple hyperplasia goes on new glands in the endometrial lining will be formed resulting in crowding of the glands with minimal intervening stroma. Malignant potential is low <3% Complex hyperplasia with atypia; Finally, some cells may become atypical showing abnormal behaviour with nuclear or cytoplasmic atypia. Such lesions carry a high risk for progression to endometrial carcinoma in 15-20% of cases.

PATHOLOGY OF ENDOMETRIAL CARCINOMA

PATHOLOGY OF ENDOMETRIAL CARCINOMA  

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Adenocarcinoma is the commonest subtype of endometrial carcinoma, also called endometrioid carcinoma. Adenoacanthoma; is an adenocarcinoma in which benign squamous metaplasia may occur without change in the behaviour or prognosis. Adenosquamous; is the tem used to describe an adenocarcinoma in which the squamous element is also malignant. Primary squamous cell carcinoma, papillary serous carcinoma and clear cell carcinoma are particularly aggressive but fortunately very rare types of endometrial carcinoma.

SPREAD OF ENDOMETRIAL CARCINOMA 1. Direct spread:  EC usually spreads first on the surface of the endometrium, called surface rider tumour filling the whole uterine cavity. It may then invade the muscular layer of the uterus, the myometrium, by direct spread 2. Lymphatic spread:  EC also spreads through lymphatic channels draining the fundus, the cornu and the isthmus to the para-aortic, inguinal and paracervical lymph nodes respectively. 3. Vascular spread:  Such metastases may invade the ovaries, the adnexa or the vagina as near by organs with poor prognosis, or may be carried to distant organs as the liver, lungs, brain and bones where the disease reaches a terminal stage

GRADING AND STAGING  Grade:

Is the degree of differentiation of the cells forming the tumour. Well- differentiated cells look and behave almost like normal cells.

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Well differentiated tumours (grade I), consist of glandular formation with less than 5% solid parts, they are slowly invasive and carry the best prognosis. Poorly differentiated tumours (grade III), consist of more than 50% solid parts, they are highly aggressive with early deep myometrial invasion and generally poor prognosis. Moderately differentiated tumours (grade II) lie in between the previous two categories, and carry intermediate prognosis.

 Stage:

Determines how far has the tumour extended within or beyond the endometrial lining of the uterus, to the myometrium, cervix, vagina, ovaries, adnexa or further to near by or distant organs.

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a) Clinical staging: EC is first evaluated via a clinical staging procedure to detect whether the disease is confined to the uterus or has extended to the vagina, adnexa, or distant organs. b) Surgical staging is performed during laparotomy to evaluate the depth of myometrial invasion, the presence of malignant cells in peritoneal wash and the presence of positive lymph node affection.

FIGO SURGICAL STAGING OF ENDOMETRIAL CARCINOMA 

Stage I: Carcinoma confined to the corpus

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I a:Tumour restricted to the endometrium I bI:nvasion to less than the inner ½ of the myometrium I c:Invasion to more than the inner ½ of the myometrium

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Stage II:Carcinoma extending to the cervix, but not outside the uterus

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II a:Tumour invaded cervical glands (mucosa) II b:Tumour affected cervical stroma (tissue)

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Stage III:Carcinoma extending outside the uterus, but not outside true pelvis

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III a:Extension to uterine serosa, and or adnexa (tubes and ovaries) III b:Extension to the upper vagina III c:Affection of lymph nodes especially paraaortic or pelvic

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Stage IV:Carcinoma extending to other pelvic organs or metastasizing

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IV a:Invasion of bladder or rectum IV b:Distant extrapelvic metastases (Liver, lung, brain and bones)

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Staging of Endometrial Carcinoma

PROGNOSIS correlates with:  Both the stage and grade of the tumour.  Depth of myometrial invasion.  Lymph node involvement.

 Endometrial

carcinomas generally has a good prognosis with > 85% 5 year survival when diagnosed in stage I.  Grade III tumours have a poorer prognosis stage by stage compared to grade I and II.  The presence of tumour cells in the peritoneal cavity detected by cytology from peritoneal wash will upstage the tumour from stage I to stage III.

CLINICAL PRESENTATION 

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Post-menopausal bleeding is the chief clinical presentation in early cases of endometrial carcinoma to the extent that any bleeding in elderly women should be promptly investigated to exclude malignancy. Irregular uterine bleeding will be the main complaint in patients who still have their cycles. Bleeding is usually profuse, persistent and recurrent even after attempts using medical treatment. Other symptoms include vaginal discharge, lower abdominal pain & menstrual like cramps

DIAGNOSIS 

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Fractional Curettage (endocervical and endometrial curettage), under aneasthesia, is the gold standard in the diagnosis of endometrial carcinoma. Diagnosis on outpatient setting is established via TVS for determination of endomtrial thickness, and outpatient endometrial sampling using instruments as the pipette sampler, or Novak curette, in cases with abnormal endometrial thickness in the menopause (>6.0 mm)

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Outpatient hysteroscopy abdominal examination, PV & PR, bimanual pelvic vaginal examination Cytology is not very reliable, in contrast to cancer cervix, with < 50% accuracy in the diagnosis. Cystoscopy, CT scan and MRI may have a role in determining the spread of the disease within the myometrium and outside the uterine corpus

Curettage

Hysteroscopy

TREATMENT OF ENDOMETRIAL CARCINOMA  Treatment

depends on many factors, including the patient's general health, age, and stage of the disease.  In general, early stages of endometrial carcinoma are usually treated with surgery alone, or surgery and adjuvant radiotherapy.  Later stages are commonly managed with irradiation or hormonal therapy.

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Stage I: endometrial carcinoma: The treatment of choice is total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) Postoperative radiotherapy is necessary if cells are immature (Grade III), or if invasion of the myometrium has occurred to more than the inner half of the myometrium (stage Ic) or if lymph node sampling revealed positive node involvement.

 Stage

II: endometrial carcinoma: is treated similar to that of stage I cancer cervix. If the patient is surgically fit, a Wertheim’s radical hysterectomy is performed (TAH-BSO + pelvic lymphadenectomy and removal of upper cuff of the vagina). Additional paraaortic lymph node sampling should be also done. If the patient is surgically unfit then radiotherapy will be a better choice.

 Stage

III: cases; are generally treated with combined radical hysterectomy and adjuvant pre-operative or post-operative radiotherapy However the treatment in many cases is only palliative rather than curative, and this may limit the extent of surgical intervention.

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Stage IV: cases; are treated individually according to the condition of each case. Surgery is obviously not the first line of treatment. Radiotherapy is usually performed and in some cases residual disease is managed surgically. The aim of treatment is generally palliative not curative. Chemotherapy and especially hormonal therapy are superior to surgery in the treatment of stage IV disease and recurrent cases.

RADIOTHERAPY FOR ENDOMETRIAL CANCER 

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A. External beam irradiation: After an initial hysterectomy has been performed therapy may be beneficial for cases that are at higher risk for lymph node spread or pelvic recurrences. B. Intracavitary irradiation: Loading the uterine cavity and the vagina with radioactive cylinders. Its use in endometrial carcinoma is limited to cases that are unfit for surgery and /or having advanced disease. C. Postoperative Vaginal Vault Irradiation (brachytherapy): Postoperative vaginal vault irradiation is often used to minimize recurrences in the upper 1/3 of the vagina commonly due to possible retrograde lymphatic spread..

PROGESTAGENS  Synthetic

progestational compounds (progestagens) have long been used for prevention of endometrial carcinoma in highrisk cases by correcting the unopposed effect of oestrogen on endometrial cells.