PRECANCER DISEASES OF THE FEMALE SEXUAL ORGANS
PRECANCERous CERVICAL DISEASES
n Cervical intraepithelial neoplasia (CIN) - Dysplasia
n Erythroplakia with atypia
n Leukoplakia with atypia
n Adenomatosis
Dysplasia – abnormal growing and mitosis of epithelial cells
n CIN I: Mild dysplasia; abnormal cells can be found in 1/3 of the lining of the cervix
n CIN II: Moderate dysplasia; abnormal cells can be found in 2/3 of the lining of the cervix
n CIN III: Severe dysplasia; abnormal cells can be found in more than 2/3 of the lining of the cervix and up to the full thickness of the lining
DIAGNOSIS OF ALL CERVICAL LESIONS
n Speculum examination
n PAP – smear
n Processing of 3 % acetic acid of a cervix and revealing a white spot
n Colposcopy
n Cervical biopsy
n Endocervical curettage
n HPV - testing
TREATMENT:
· CIN1 – 70 % spontaneous regression.
·
CIN 2/3 lesions are usually surgically
removed by:
destruction (ablation) by carbon
dioxide laser (photoablation) and cryocautery and removal
(resection) by
electrosurgical excision procedure (LEEP), cold knife conization.
Leukoplakia with atypia - it does not differ from the simple leukoplakia. The processes of keratinization of the cells in this disease are mistologicaly marked to be reinforced as compared with leukoplakia. Cytological research of the stratified squamous epithelium reveals cells without nucleus at simple leukoplakia. Basal and parabasal cells without nucleoses are also present in the patients with leukoplakia and atypia.
Erythroplakia
Erythroplakia - is a prettily heterogeneous form of dyskeratoses. The changes of cervical mucous membrane are in thinning and keratinizing of epithelium. It looks like scarlet area in the result of translucence of the basal membrane cells through thinned epithelial layer. It easily bleeds at contact. The seats are single or plural with transition on fornices and vaginal walls. Thinning of epithelial layer to 1-2 layers with nuclear atypia and cellular polymorphism is revealed during the histological research.
Glandular hyperplasia with atypia - local hyperplasy of the glands that looks like a clew, similar to endometrial glands at histological research are found. The glands which have different form and size are covered by epithelium, that is unlike the cervical one. It frequently occurs in the first trimester of pregnancy, and disappears after delivery. The adenomatosis frequently transforms into cancer in situ outside the pregnancy.
CERVICAL CARCINOMA
Risk factors
n Human Papillomavirus (HPV) Infection - (16, 18, 31, 33, 35 and 6 more)
n Family History of Cervical Cancer
n Age – 35-55
n Sexual and Reproductive History
n Socioeconomic Status
n Smoking
n HIV Infection
n In Utero DES Exposure
n Oral contraceptives
Forms of tumor growth are: endophytic, exophytic, mixed.
Clinic. It depends on the process stage. The duration of preinvasive and microinvasive cancer is without any symptoms (preclinical stage). Serous or serous-bloody discharge, contact bleeding after sexual intercourse, vaginal examination, speculum examination may be used in the first stage. Pain in the hypogastrium and back, serous-purulent discharge, resembling meat slops with unpleasant smell (caused by lymph and blood effluence during tumor disintegration) on the second and third stage appears. Patients’ general state is suffered. fast tiredness and irritability can appear. The tumor can erode urinary bladder and rectum due to growing inside of them. Constipation and urinary disorders can occur in the result of this.
CLASSIFICATION
Diagnosis
n Complaints
n Speculum examination.
n The cytological examination
n HPV screening involves a Polymerase Chain Reaction (PCR)
n Bimanual vaginal examination
n Rectovaginal examination
n Application of acetic acid and Colposcopy
n Biopsy.
Treatment
· The intraepithelial and microinvasive cancer in young women undergo surgical treatment by cervical conization or its amputation.
· In the middle-aged or elderly women with uterine myoma, or ovarian cyst presence it is expedient to perform total hysterectomy with adnexa.
· The I-b – II stage of cancer are treated by combined (radiation + surgery) or combined-radical method (if contraindications for surgical intervention are present). Surgical intervention foresees the total hysterectomy or Wertheim’s operation (removal of the uterus with its adnexa, the upper third of vagina and cellular tissue with regional lymphatic nodes).
· Treatment of cervical carcinoma at the III stage is performed by combined-radical method: distant irradiation of the initial focus and parametria followed by intracavitary curie-therapy
· Patients with stage IV are treated individually, the therapy is usually symptomatic.
Precancerous
uterine diseases
(uterine carcinoma precursors)
· Glandular endometrial hyperplasia with cellular proliferation
· Adenomatous hyperplasia
· Adenomatous polyps
Ethiology. The main causes of endometrial hyperplastic processes are different hormonal disorders at hypothalamic-pituitary-ovarian levels. The correlation between estrogen production and endometrial growth is direct. Endometrial proliferation represents a normal part of the menstrual cycle and occurs during the follicular or estrogen — dominant phase of the cycle with the continued estrogen stimulation through either endogenous mechanisms (hyperglycemia, obesity, conversion of androstenedione) or by exogenous administration (medications). Simple endometrial proliferation will become endometrial hyperplasia.
Factors affecting the risk of endometrial hyperplasia are diabetes mellitus, late menopause, women who have never childbeared.
Clinic. The precancerous processes manifest with acyclic uterine bleeding which can be either appreciable or insignificant, but they are continuous. More often these bleedings arise after some weeks or months delay of menses. Cyclic bleedings which appear during menses and last for a long period of time may be also present. Reproductive age women complain of infertility as a result of anovulation.
Diagnosis.
· Ultrasound examination of uterine cavity determines the endometrial depth. At glandular-cystic hyperplasia echogenic inclusions are up to 1cm in size, in adenomatosis — up to 2-3 cm.
· Hysteroscopy
· Hysterography
· Cytological research of the smears from uterine cavity.
The diagnosis of endometrial hyperplasia can be made by taking a sample of the endometrium for histological evaluation during uterine and cervical curettage. Cystic glandular endometrial hyperplasia is characterised by the increased number of glands, some of which look like cysts.
Therapy should start from endometrial curretage
n Intramuscular progesterone therapy. MPA (500mg)therapy for 3 months;
n Micronized progesterone -cyclic natural micronized progesterone for 3 to 6 months;
n Levonorgestrel intrauterine device
n GnRH analogue for 6 months with sampling every 3 months is a reasonable option in patients without atypia.
All the patients with endometrial hyperplasia should be monitored during 5 years. In-therm treatment of precancerous endometrial lesions is the main factor in cancer’s prevention.
Endometrial carcinoma
Classification
n endometrioid adenocarcinoma
n serous carcinoma
n clear cell carcinoma
n mucinous carcinoma
n serous carcinoma
n mixed types of carcinoma
n undifferentiated carcinoma
Clinic.
n Irregular vaginal bleeding, intermenstrual or post menopausal
n Watery vaginal discharge may be present in postmenopausal women
n Mass in late stages
There are three types of cancer clinical course.
Slow, rather favourable clinical course. This form is observed in patients with significant hyperestrogenemia and lipids and carbohydrates dysmetabolism impairment. Continuous uterine bleeding as a result of endometrial hyperplasia is the most common symptom. Lymphatic way of metastasing is absent. Histologycally, it is well-differentiated cancer with superficial invasion of the myometrium.
Unfavourable clinical course. Metabolism disorder is absent. The course of the disease is rather short. Endometrial carcinoma involves all layers of myometrium, extends to cervix, parametrium and vagina. It is a poorly differentiated tumor.
Acute, extremely unfavourable clinical course. It is characterised by unfavourable factors combination, such as deep extension of tumor, lymph nodes and peritoneal metastases. “Ovarian” type of metastases would be present. It is characterised by ascitis and omentum metastases.
Diagnosis of uterine carcinoma:
· History
· clinics,
· physical and pelvic examination.
· Transvaginal ultrasound
· Hysteroscopy and biopsy
· M.R.I. Or C.T. scan
Treatment. Surgical, combined treatment, combining of radiation and hormones should be used.
n Operative: total abdominal hysterectomy and Bilateral Salpengo-oophorectomy +/_ lymph node dissection is the operation of choice.
n Adjuvant Radiotherapy for >1b
n Chemotherapy ineffective
n Hormonal therapy, progestogens, in early or recurrent cases
Uterine sarcoma
All not epithelial malignant tumors belong to sarcomas.
Presence of uterine myoma in pre- and postmenopausal women, especially during its fast growing belong to the risk factors of uterine sarcomas.
There are four histological types of uterine sarcomas:
l leiomyosarcoma
l endometrial stromal sarcoma
l carcinosarcoma (malignant mixed homologous mesodermal tumor)
l mixed heterologous mesodermal tumor
l other types of sarcomas
Clinical findings. Uterine bleeding and pelvic pain are the most common presenting symptoms.
General weakness, weight loss, subfebril temperature for a long period of time are the symptoms of uterine sarcoma presence for a long period of time.
Metastasis. The preferential way of spread is via the bloodstream. other less frequent ways of spread are via the lymph nodes and by contiguity.
Diagnosis. In many cases, the diagnosis is an unexpected finding at the time of hysterectomy done for other indications (fig. 163). Sampling research of the endometrial cavity either by biopsy and curettage can assist in diagnosis less than 50% of cases owing to the fact that many of these tumors are intramural and thus without endometrial extension. Hysterography or hysterocervicography should be performed. Investigation of the adjacent organs should be recommended in all types of uterine sarcomas.
Plain film of breast, liver and X-ray examination of skeleton should be prescribed for diagnostics of distant metastases.
Treatment. The preferred treatment is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Careful intraperitoneal and retroperitoneal revision is performed. Radiation therapy and chemotherapy are indicated for palliation of patients with distant metastases or recurrences. Adriamycin and Karminozine are used.
Malignant ovarian neoplasms
classification
n Primary (neoplasms derived from the ovarian surface epithelium, i.e. epithelial tumors),
n Secondary (neoplasms derived from papillary or pseudomucinous cystadenomas)
n Metastatic (intestinal and breasts’ metastasis
Clinic. Early diagnosis of ovarian cancer is difficult, because symptoms are often absent or vague until the neoplasm has attained a large size and metastasized. Even large tumors usually produce nonspecific symptoms. Early symptoms include vague sensations of pelvic or abdominal discomfort, urinary frequency, and alterations in gastrointestinal function. When the neoplasm attains a diameter of about 15 cm, it rises into abdominal cavity, which leads to feelings of abdominal fullness or distension and early safety. Abdominal enlargement can also be secondary to ascites. General weakness, weight loss, continuos dull pain in the lower part of abdomen are common. In 15% of patients they experience abnormal vaginal bleeding.
Hemorrhage into the tumor or torsion of the ovary containing neoplasm can produce sudden pain and other symptoms of acute abdomen.
The physical findings in patients with ovarian neoplasms in early stages are similar to benign ovarian cystadenomas.
DIAGNOSIS OF OVARIAN CANCER
n Physical examination
n Pelvic examination
n Rectovaginal examination
n Ultrasound
n Magnetic resonance imaging
n CA-125 high false-positive rate
n HE4 marker more sensitive than CA125
n Laparoscopy, microscopy
The combination of HE4 and CA 125 was more sensitive than either marker alone - Risk of Ovarian Malignancy Algorithm (ROMA) is calculated
TREATMENT OF OVARIAN CANCER
Stage I
Generally women with Stage I ovarian cancer have a total abdominal hysterectomy, removal of both ovaries and fallopian tubes, omentectomy, biopsy of lymph nodes and other tissues in the pelvis and abdomen. Young women whose disease is confined to one ovary are often treated by a unilateral salpingo-oophorectomy (removal of the affected ovary and fallopian tube) without a hysterectomy and removal of the opposite ovary being performed. Omentectomy and the other parts of the staging procedure are performed. Depending on the pathologist's interpretation of the tissue removed, there may be no further treatment if the cancer is low grade, or if the tumor is high grade the patient may receive combination chemotherapy.
Stage II
Treatment is almost always hysterectomy and bilateral salpingo-oophorectomy as well as debulking of as much of the tumor as possible and sampling of lymph nodes and other tissues in the pelvis and abdomen that are suspected of harboring cancer. After the surgical procedure, treatment may be one of the following: 1) combination chemotherapy with or without radiation therapy or 2) combination chemotherapy.
Stage III
Treatment is the same as for Stage II ovarian cancer. Following the surgical procedure, the patient may either receive combination chemotherapy possibly followed by additional surgery to find and remove any remaining cancer.
Stage IV
Treatment will probably be surgery to remove as much of the tumor as possible followed by combination chemotherapy.
Dysgerminoma is the most common malignant germ cell tumor which is arising from undifferenting gonades that are present in the ovarian sinus.
Clinic. The tumor is common in the infantile patients of 30 years of age. Patients generally can observe pelvic or abdominal mass, abdominal enlargement or pain. The duration of symptoms ranges from 1 month to 2 years with a median of 4 months. The metastases are present in lungs.
Diagnosis is difficult and it is based on the results of clinical findings, laparoscopy and histologic investigation results.
Treatment is surgical with the following radiation therapy and chemotherapy.
Ovarian teratoblastoma is a rare malignant tumor which is found in childhood in juvenile period.
Clinic. Pain in the lower part of the abdomen and general weakness are common. In the advanced cases ascites is present. Metastatses arise very quickly.
Diagnosis is based on the histologic results.
Treatment is surgical with the following radiation therapy.
PROGNOSIS
n The five-year survival rate for all stages of ovarian cancer is 45.5%.