Precancer diseases of the female sexual organs. Female cancer. N. Bahnij

Precancer cervical lesions Cervical intraepithelial neoplasia (CIN) Erythroplakia with atypia Leukoplakia with atypia Adenomatosis

Risk factors for cervical dysplasia Human papillomavirus is a common virus that most women will be infected with at some time in their life. smoking multiple sexual partners pregnancy before the age of 20 suffering from conditions that affect the immune system, like HIV

Layers of squamosus epithelium of cervix

CIN Classification CIN I: Mild dysplasia; abnormal cells can be found in 1/3 of the lining of the cervix CIN II: Moderate dysplasia; abnormal cells can be found in 2/3 of the lining of the cervix 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 cervical dysplasia Speculum examination PAP – smear Processing of 3 % acetic acid of a cervix and revealing a white spot Colposcopy Cervical biopsy Endocervical curettage HPV - testing

Dysplasia is initially detected through a Pap smear

What is the thinnest and the more effected place of the cervix???

The smear should be taken from squamocolumnar junction – transition zone !

Types of PAP smears I – normal II a- inflammatory process II b – mild dysplasia III a - moderate dysplasia III b – severe dysplasia IV – carcinoma in situ V – cancer VI – smear is not informative

Frequency of Pap Smears Begin no later than age 21. If patient is sexually active - <21. Once initiated, screening should be performed annually After 30, for women who have had 3 consecutive, normal Pap smears, screening frequency may be reduced to every 3 years. Screening may stop after total hysterectomy, >70 if the the patient is at low risk, and has had three consecutive normal Pap smears within the last 10 years.

Treatment for cervical dysplasia CIN1 – 70 % spontaneous regression Treatment for cervical dysplasia 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.

Cancer of the cervix is the most common female genital cancer in developing countries every year about 500,000 women , acquire the disease and 75% are from frame developing countries. About 300,000 women also die from the disease annually and of these 75% are from developing countries

CERVICAL CARCINOMA 10 years from CIN III to cancer Risk factors Human Papillomavirus (HPV) Infection - (16, 18, 31, 33, 35 and 6 more) Family History of Cervical Cancer Age – 35-55 Sexual and Reproductive History Socioeconomic Status Smoking HIV Infection In Utero DES Exposure Oral contraceptives From initial infection to CIN III – 6 years

Types Squamous cell Carcinomas Cancer of flat epithelial cell 80% to 90% Adenocarcinomas Cancer from glandular epithelium 10% - 20% Mixed carcinoma Features both types

Stages of Cervical Carcinoma

What are the symptoms of cervical cancer? Abnormal bleeding Between periods With intercourse After menopause Unusual vaginal discharge Other symptoms Leg pain Pelvic pain Bleeding from the rectum or bladder Some women have no symptoms Usually women with cervical cancer have no symptoms, particularly if the cancer is small. The common symptoms of cervical cancer are: Bleeding between periods Bleeding or spotting after sexual intercourse Bleeding or spotting in women who have already gone through menopause Unusual, continuous, foul-smelling vaginal discharge In women with more advanced cervical cancer additional symptoms may occur, such as: Progressive and ultimately constant pelvic pain One-sided leg pain caused by nerve involvement A pelvic mass Bleeding from the bladder or rectum. It is not unusual for a woman with cervical cancer to have no symptoms. 19

Diagnosis Complaints Speculum examination. The cytological examination HPV screening involves a Polymerase Chain Reaction (PCR) Bimanual vaginal examination Rectovaginal examination Application of acetic acid and Colposcopy Biopsy.

What should I do if I have just been diagnosed with cervical cancer? Discuss treatment options Conization Hysterectomy Radical trachelectomy Surgical removal of the cervix and upper vagina with the surrounding tissues. uterine body remains Radical hysterectomy Radiation with chemotherapy Ask about clinical trials (Gynecologic Oncology Group) Other considerations Preserve your fertility Preserve your ovaries There are many treatment options for cervical cancer. It all depends on how big it is, your medical history and your concerns for future fertility. You should discuss your treatment options with a gynecologic oncologist. 21

Cervical cancer: What is the chance of survival after treatment? FIGO Stage 5-Year Survival Stage I 81-96% Stage II 65-87% Stage III 35-50% Stage IVA 15-20% The survival rate five years after diagnosis varies depending upon the stage of cervical cancer. The risk increases with higher stages of disease. However, there are treatment options for everyone. 22

Vaccines

Who should get the vaccine? The FDA has recommended the following groups of women get vaccinated: Girls 11–12: Recommended Age Group (can be started as young as age 9). Women 13–26: the benefit of the vaccine may be lower depending on prior HPV exposure. The vaccine does not work to eliminate current HPV infections The vaccine only prevents certain types of HPV infection 24

Endometrial cancer precursors Endometrial hyperplasia - an overgrowth of the lining of the uterus, is a precursor to the development of cancer. Abnormal uterine bleeding is usually the first symptom

Risk Indicators for Endometrial Cancer and Precursors   Age   60 years Obesity (with upper body fat pattern)a   Estrogen-only replacement therapy Previous breast cancer   Tamoxifen therapy for breast cancer Chronic liver disease Infertility   Low parity   Chronic anovulation (Polycystic ovarian disease, estrogen-secreting ovarian stroma or tumors)

WHO Classification and Diagnostic Criteria of Endometrial Hyperplasia   Simple Hyperplasia Without Cytologic Atypia   Increased number of glands relative to stroma   Dilated glands with irregular outlines   Crowded, clustered glands   Tall, columnar epithelium with nuclear pseudostratification   Complex Hyperplasia Without Cytologic Atypia   Increased number of glands relative to stroma   Back-to-back glands (crowded glands with little or no intervening stroma)   Hyperplasia With Cytologic Atypia   Variation of size and shape of nuclei   Nuclear enlargement   Loss of polarity   Coarse chromatin clumping   Prominent nucleoli   Hyperchromatism

Endometrial hyperplasia Cystic hyperplasia Simple hyperplasia

Endometrial hyperplasia Atypical hyperplasia Simple hyperplasia

Endometrial biopsy

Diagnosis and treatment Intramuscular progesterone therapy. MPA (500mg)therapy for 3 months; Micronized progesterone -cyclic natural micronized progesterone for 3 to 6 months; Levonorgestrel intrauterine device GnRH analogue for 6 months with sampling every 3 months is a reasonable option in patients without atypia.

Staging According to the U.S. Gynecologic Oncology Group histologic grading system,1 grade 1, well-differentiated carcinoma, consists of a neoplasm with less than 5% of solid cancer grade 2, moderately differentiated carcinoma, contains between 6% and 50% solid cancer grade 3, poorly differentiated carcinoma, is made up of more than 50% of solid tumor.

Modified WHO classification endometrioid adenocarcinoma serous carcinoma clear cell carcinoma mucinous carcinoma mixed types of carcinoma undifferentiated carcinoma

Staging

Clinical signs Irregular vaginal bleeding, intermenstrual or post menopausal Watery vaginal discharge may be present in postmenopausal women Mass in late stages

Endometrial cancer: investigations T.V.S. and biopsy Hysteroscopy and biopsy ? M.R.I. Or C.T. scan

Endometrial cancer: investigations

Endometrial cancer: treatment Operative: total abdominal hysterectomy and Bilateral Salpengo-oophorectomy +/_ lymph node dissection is the operation of choice. Adjuvant Radiotherapy for >1b Chemotherapy ineffective Hormonal therapy, progestogens, in early or recurrent cases

5 – year survival rate for endometrial cancer

Ovarian Cancer The 2nd most common gynecologic malignancy 27% of gynecologic cancers The most frequent cause of death from gynecologic cancers Due to advanced stage at the time of diagnosis 53% of all deaths from gynecologic cancers Incidence increases with age, most marked beyond 50 years, with increase continuing to age 70 years, and decrease after age 80 years

Risk factors Family history of cancer Personal history of cancer: Women who have had cancer of the breast, uterus, colon, or rectum have a higher risk of ovarian cancer Age over 55 Never pregnant: Menopausal hormone therapy: estrogen taking

OVARIAN CANCER primary (neoplasms derived from the ovarian surface epithelium, i.e. epithelial tumors), secondary (neoplasms derived from papillary or pseudomucinous cystadenomas) metastatic (intestinal and breasts’ metastasis).

Classification 1.Surface epithelial – 65-70%: 2. Stromal – 15-20%: Serous (tubal) Mucinous (endocx & intestinal) Endometrioid Transitional cell - Brenners. Clear cell 2. Stromal – 15-20%: Granulosa-cell tumor Thecoma Fibroma Sertoli-Leydig cell tumors 3.Germ cell tumors – 5-10%: Teratoma – Benign cystic (dermoid cysts) Solid immature Monodermal – struma ovarii, carcinoid Dysgerminoma Yolk sac tumor Choricarcinoma Mixed germ cell tumor 4.Metastatic tumors – 5%

Serous Cystadenoma

Papillary serous cystadenoma (solid/cystic)-borderline

Papillary cystadenoma (bor)

Thecoma Solid tumor with variegated yellow - orange appearance. Produces estrogens

Krukenberg Tumor

FIGO classification

Ovarian cancer - “silent killer” Bloating Pelvic or abdominal pain Pain in the back or legs Diarrhea, gas, nausea, constipation, indigestion Difficulty eating or feeling full quickly Urinary symptoms (urgency or frequency) Pain during sex Abnormal vaginal bleeding Trouble breathing

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Diagnosis Physical examination Pelvic examination Rectovaginal examination Ultrasound Magnetic resonance imaging CA-125 high false-positive rate HE4 marker more sensitive than CA125 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

Prognosis The five-year survival rate for all stages of ovarian cancer is 45.5%. For cases where a diagnosis is made early in the disease, when the cancer is still confined to the primary site, the five-year survival rate is 92.7%.

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