Problems of the female genital tract

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7 Problems of the female genital tract

Chapter Contents

Benign conditions of the vulva

Vulvar intraepithelial neoplasia

Carcinoma of the vulva

Benign conditions of the cervix

Cervical ectropion

Cervical polyps

Cervical neoplasia

Carcinoma of the cervix

Adenocarcinoma of the cervix

Benign tumours of the uterus

Polyps

Uterine fibroids

Adenomyosis

Congenital abnormalities of the uterus

Endometrial carcinoma

FIGO staging of endometrial cancer (updated 2009)

Microscopic appearance

Ovarian cysts in postmenopausal women

Microscopic appearance

Presentation

Management

Gynaecological cancer in pregnancy

Carcinoma of the cervix

Carcinoma of the ovary

Carcinoma of the vulva and endometrium

Summary

Benign conditions of the vulva

Bartholin’s cyst

Bartholin’s glands are located on the posterolateral aspects of the introitus. Cysts can often be asymptomatic, but can become infected and result in pain, dyspareunia and often discomfort on sitting. If unresolved after a course of antibiotics, the infected cyst may need to be opened, drained and marsupialized under anaesthetic. Marsupialization involves a series of sutures between the cyst edge and vagina so that the cyst is left open to heal by secondary intention. Rarely, a recurrent cyst may need to be excised completely, although this is best done when the infection has resolved.

Vulvodynia

Definition

Vulvodynia is the term used to describe a specific type of vulval pain characterized by burning, stinging, irritation or rawness. However, the majority of women presenting with vulval symptoms will complain of pruritus.

Assessment

Management is aimed at identifying the cause and treating appropriately. A full history must include information about previous treatments, other skin or systemic disorders, hygiene measures, drugs taken and allergies known. Examination should include inspection of skin surfaces, the mouth, hands and nails, and palpation of the inguinal nodes. The vulva, including the mons pubis and the perianal skin, the vagina, urethral meatus and cervix should be inspected. Colposcopy of the vulva can define lesions that are not otherwise visible and a biopsy should be performed if epithelial abnormalities are suspected.

Causes of vulvodynia include vulvar dermatoses and vulvar vestibulitis.

Dermatoses

The dermatoses are classified as non-neoplastic epithelial disorders of the skin and mucosa, and they are outlined below.

Vulvar vestibulitis

This is a very difficult condition to treat and is a diagnosis of exclusion. There are three cardinal criteria for this diagnosis: pain on entry or touch, vestibular erythema and tenderness to pressure.

Management of acute vulvar vestibulitis is medical, with the removal of any allergen or irritant, treatment of infection and local corticosteroid application. Treatment with a topical steroid preparation containing antifungal and antibacterial components (Trimovate) may relieve symptoms.

Vulvar intraepithelial neoplasia

Vulvar intraepithelial neoplasia (VIN) is a condition in which atypical or neoplastic cells are present within the boundaries of the surface epithelium of the vulva. Like its cervical counterpart (cervical intraepithelial neoplasia (CIN)), VIN has been divided into three categories depending on the extent of epithelial involvement and is also associated with CIN in around one-quarter of cases. VIN is uncommon, although it is believed that its incidence is increasing, particularly in young women. As well as the association with CIN there is also an association with human papillomavirus and lichen sclerosus. There are also strong associations between sexually transmitted diseases and VIN, in particular condyloma, herpes simplex, gonorrhoea, syphilis, trichomoniasis and Gardnerella vaginalis.

Diagnosis

Diagnosis of VIN is made on microscopy and, therefore, a biopsy, which can be performed under local anaesthesia, is always required. Thorough assessment of the whole lower genital tract, including cervical cytology and colposcopy, is mandatory in patients with VIN.

Circumstances where excisional biopsies should be considered, rather than limited sampling, are:

• Elevated lesions, irregular surfaces

• Areas with distinct vascular patterns, e.g. mosaic, abnormal vessels

• Excessive hyperkeratosis in hair-bearing areas

• Pigmented lesions

• Elderly women with unifocal lesions.

Management

Management of VIN should be individualized, taking into consideration the presence or absence of symptoms and whether risk factors are present, i.e. postmenopausal presentation, immunosuppressed/immunodeficient patients, women with histologically progressive lesions on serial biopsy or excessively hyperkeratotic lesions.

If the risk of invasion is thought to be low and malignancy is excluded, then major vulval surgery can be avoided. Options include topical 5 fluorouracil, dinitrochlorobenzene, cryosurgery, carbon dioxide laser ablation, vulvectomy and wide local excision.

Small lesions can be dealt with in the outpatient clinic using local anaesthesia. Large areas of VIN require general anaesthesia for laser treatment.

Carcinoma of the vulva

This accounts for approximately 5% of genital tract cancers, with just over 1000 cases diagnosed in the UK each year. It is most common (over 80% of cases) after the menopause in the 60–70-year age group, although it can occur in younger women with a history of premalignant VIN.

The majority are squamous cell in origin, with the remainder including the rarer lesions of melanoma, basal cell carcinoma, sarcoma and adenocarcinomas of the Bartholin’s gland.

Clinical features

Patients will usually experience symptoms of pruritus, bleeding or discharge or may present with a vulval mass. Examination will reveal an ulcer or mass, usually on the labia majora or clitoris, and often palpable inguinal lymph nodes.

FIGO staging

Staging is performed following surgical removal and histological assessment. Approximately one-half present with stage 1 disease and spread is via the lymphatic drainage of the vulva to the superficial and then deep inguinal nodes, and finally to the external iliac nodes. Pelvic lymph node spread is slow and will, therefore, indicate advanced disease with poor prognosis.

• Stage 0 – carcinoma in situ (preinvasive)

• Stage 1 – tumour confined to vulva or vulva and perineum < 2 cm in diameter with no nodal involvement

• stage 1a – stromal invasion < 1 mm

• stage 1b – stromal invasion > 1 mm with negative nodes

• Stage 2 – tumour > 2 cm in diameter with no nodal involvement

• Stage 3 – spread of tumour to urethra, vagina or anus or unilateral involvement of nodes. This stage has been subdivided into A, B or C according to number and nature of lymph node metastases. These changes reflect the fact that the number of nodes involved is a more significant prognostic factor than fully resected local disease

• Stage 4 – tumour within rectum, bladder, bone or distant metastases and bilateral nodal involvement.

Investigations

A biopsy is taken for histological diagnosis. Following diagnosis, the patient is prepared for surgery with routine bloods (including full blood count, urea and electrolytes, group and crossmatch) and chest X-ray and electrocardiograph. For tumours > 2 cm, computed tomography (CT) of chest, abdomen and pelvis can detect disease above the inguinal ligament.

Management

In stage 1a carcinoma, a wide local excision is appropriate with regular follow-up. In all other stages, a wide local excision and lymphadenectomy should be carried out. Sentinel lymph node mapping (the sentinel node receives the primary lymphatic drainage from the tumour) can be performed peroperatively as part of the staging procedure in order to reduce morbidity of radical lymphadenectomy. If the lesion is greater than 2 cm from the midline, then a unilateral inguinal lymphadenectomy is appropriate, but if < 2 cm from the midline, a bilateral inguinal lymphadenectomy should be performed. This type of surgery can cause postoperative problems with wound breakdown, infection and lymphoedema.

Radiotherapy can be considered in cases of local recurrence or nodal disease but chemotherapy is rarely used, except in younger patients with positive nodes.

Prognosis

For stage 1 carcinoma the 5-year survival rate is 80%; it is 50% for stage 2, 30% for stage 3 and 10–15% for stage 4.

Benign conditions of the cervix

The outer surface of the cervix within the vagina is covered with stratified squamous epithelium, which becomes columnar within the cervical canal at the squamocolumnar junction. With the onset of puberty, the ovarian hormones cause eversion of the lower cervical canal so that this junction approaches the external cervical os. Squamous metaplasia occurs when the columnar epithelium at this junction is replaced by squamous epithelium.

Cervical ectropion

This is the florid appearance of the lower cervical canal that is often mistakenly described as an ‘erosion’ and is caused by the hormonal changes during puberty, pregnancy and by the oral contraceptive pill. It is usually asymptomatic, but may cause a persistent vaginal discharge or postcoital bleeding. In the presence of a normal smear test, this can be treated by diathermy or cryocautery in the office.

Cervical polyps

These are usually found protruding through the external cervical os and can either be asymptomatic or cause chronic discharge, postcoital or intermenstrual bleeding. In this situation they can simply be avulsed and the base cauterized with diathermy.

Cervical neoplasia

Role of human papillomavirus

Over 60 genotypes of human papillomavirus (HPV) have been identified; in particular, HPV 16, 18 and 33 have been shown to be associated with cervical neoplasia and with increasing grades of CIN.

Up to 10% of women will have HPV on cervical cytology at some stage and of these, 35–40% will have CIN. However, there is no increased risk of cancer in those patients with HPV without CIN. Most women will contract HPV at some point in their lives but will build up immunity and expel the virus before dysplasia can develop.

Cervical cytology

Definitions:

• Inflammatory – this means that there are increased polymorphs and this may occur during the premenstrual or menstrual phases of the cycle.

• Mild squamous changes – mainly due to inflammation or an artefact of poor fixation, which will require a repeat smear in 6 months.

• Hyperkeratosis – may be due to HPV or uterovaginal prolapse, but CIN may be present in less than 5%.

• Dyskaryosis – this is the term used for cells that come from a dysplastic or neoplastic lesion.

• Transformation zone – this is the area between the original and existing squamocolumnar junction and is where the columnar epithelium undergoes metaplasia. This zone may extend up the cervical canal, especially in the postmenopausal patient.

Cervical screening

Screening for premalignant disease of the cervix is by cytology of cervical smears where cells are taken from the squamocolumnar junction using an Ayres spatula or cervical brush. This sample is spread on a glass slide and fixed with an alcohol spray. More recently liquid-based cytology has been introduced, with similar sampling of the cells with a brush instead of spatula.The slides are then screened for dyskaryosis. Cervical smears are best taken in midcycle and should be taken every 3–5 years from 20–25 to 60 years of age (depending on national protocols). If the woman has had a hysterectomy for benign disease, no further smears are necessary.

Cervical smears and cytology are 99.7% specific (false-positive rate of 0.3%), 80% sensitive (false-negative rate of 20%). Referral for colposcopy is advised if the cytology report shows moderate dyskaryosis or worse or if the woman has had two mildly dyskaryotic smears with 6 months.

Cervical intraepithelial neoplasia

CIN or cervical premalignant disease is classified from CIN 1 to CIN 3. Normally, cells differentiate and move to the surface, but abnormalities can occur, resulting in mitotic figures, nuclear pleomorphism and changes in nuclear to cytoplasmic ratio (dysplasia) or change to a different cell type (metaplasia).

CIN 1 is when two-thirds or more of the upper epithelium shows good differentiation, but the basal third of the epithelium demonstrates nuclear atypia. The majority of CIN 1 will resolve spontaneously. CIN 2 shows differentiation in the upper third of the epithelium, but with mitotic figures in the basal two-thirds. CIN 3 means that less than a third of the upper epithelium shows differentiation.

CIN 1 can progress to higher CIN lesions in approximately 20% of cases within 2–4 years. CIN 3 can progress to carcinoma in 20–30% of cases within 20 years.

Management

Colposcopy involves the microscopic examination of the transformation zone of the cervix to identify abnormal areas. This is not a diagnostic test, but simply a means of identifying an abnormal lesion on the cervix. To aid with identification, the cervix can be painted with various solutions. Acetoacetic acid will turn abnormal epithelium acetowhite since this epithelium contains more proteinaceous nuclei and less glycogenated cytoplasm. Aqueous iodine may also be used since it is taken up by normal epithelium, but not by columnar or abnormal squamous epithelium (Schiller’s test). The identified area can then be biopsied or excised and the histology then will give the diagnosis.

Other CIN lesions include punctation (vessels running perpendicular to the surface), mosaic pattern (capillaries running parallel to the surface) and any other irregular vasculature.

Treatment

• Local ablative techniques:

• laser vaporization

• cold coagulation

• diathermy

• cryocautery (only for CIN 1).

• Excision techniques:

• loop excision of the transformation zone, which can be performed in the clinic with local anaesthesia

• ‘cold knife’ or laser cone biopsy, which is performed under general anaesthesia.

The excisional techniques are recommended to treat CIN 2 and 3 rather than ablative techniques. If smears are normal 12 months following treatment, then annual follow-up is recommended. Hysterectomy may be considered if there are any other gynaecological reasons and then the patient must be followed up annually with vaginal vault smears as there is an increased risk of vaginal intraepithelial neoplasia. If cervical abnormality occurs in pregnancy then a colposcopy can be performed, but the treatment of CIN is best left until postpartum. However, if invasion is suspected then resection must be performed.

Cervical intraepithelial glandular neoplasia

Adenocarcinoma coexists with CIN in 70% of cases.

Carcinoma of the cervix

The development of cervical carcinoma occurs mainly in the squamous epithelium (within the transformation zone) or endocervix. Approximately 90% are squamous cell and the remainder are adenocarcinomas.

Cervical cancer is the second commonest malignancy in women worldwide after breast carcinoma, with approximately 470 000 cases occurring annually. The vast majority of women diagnosed with invasive carcinoma of the cervix have not had regular screening.

The mean age at diagnosis is 52 years, with two peaks at 35–39 and 60–64 years. It is associated with early onset of sexual activity, multiple partners and smoking.

The carcinoma can metastasize directly to the pelvic side wall, involving the ureters, bladder or rectum or via lymphatics to the pelvic nodes.

Presentation

Approximately 80% of affected patients are symptomatic. The most common presentation is with abnormal vaginal bleeding, e.g. postcoital, intermenstrual or postmenopausal or, alternatively, some may present with a chronic vaginal discharge that can be purulent, watery or mucoid and not necessarily malodorous. Pain is usually an indicator of advanced disease.

Examination should include general assessment for lymphadenopathy, speculum to assess the appearance of the cervix (bleeding, irregular or ulcerated), vaginal examination to assess for parametrial extension and a rectal examination.

Investigations

These should include full blood count, urea and electrolytes (renal function), liver markers, chest X-ray, CT and occasionally renal ultrasound scan.

Formal surgical staging will include examination under anaesthesia, including pelvic and rectal examination, cervical biopsy and endocervical/uterine curettage, cystoscopy and occasionally proctoscopy.

International Federation of Gynecology and Obstetrics (FIGO) clinical staging for cervical carcinoma is as follows:

• Stage 1: carcinoma confined to the cervix

• stage 1a: invasive carcinoma identified only microscopically

• stage 1a1: invasion of stroma ≤ 3 mm and ≤ 7 mm diameter

• stage 1a2: invasion of stroma > 3 mm but < 5 mm and < 7 mm diameter

• stage 1b: clinically obvious lesions confined to the cervix or preclinical lesions greater than stage 1a

• stage inical lesions ≤ 4 cm

• stage 1b2: clinical lesions > 4 cm.

• Stage 2: carcinoma extending beyond the cervix but not to pelvic side walls. The carcinoma involves the vagina but not the lower third of vagina

• stage 2a: no parametrial involvement

• stage 2b: parametrial involvement

• Stage 3: carcinoma spread to pelvic side wall or lower third of vagina. Would include all cases of hydronephrosis or renal failure secondary to ureteric obstruction

• Stage 4: carcinoma extending beyond the true pelvis or involving the mucosa of bladder or rectum.

Management

Surgery

Preoperative assessment:

This involves the following:

• Imaging – CT/magnetic resonance imaging (MRI)

• Routine bloods, including full blood count, urea and electrolytes, liver function test

• Group and crossmatch for 2 units of blood

• Bowel preparation

• Correction of medical problems

• Intraoperative antibiotic prophylaxis

• Anticoagulation prophylaxis.

Technique:

Radical hysterectomy involves the following:

• Vertical midline or Cherney/Maylard incision. Minimal-access surgery is now an option, either laparoscopically or robot-assisted

• Assess for ascites, assess liver, spleen, undersurface of diaphragm, kidneys, ureters, omentum, appendix

• Removal of uterus, cervix, plus or minus ovaries and tubes, parametria, upper third of vagina and pelvic nodes.

Locally radical fertility-sparing surgery (radical trachelectomy) should be considered in young women with early-stage cervical cancer.

Complications:

• Haemorrhage, infection and thromboembolus

• Urinary tract infection – 10%

• Other infective morbidities, including pulmonary (secondary to atelectasis) infections, wound infection or pelvic haematoma – 10–20%

• Small-bowel obstruction – 1%

• Pelvic lymphocyst formation – 1–2%

• Fistula (ureteric or vesicovaginal).

Radiotherapy

Radiation treatment is used for stage 2b or greater, if the woman is unfit for surgery or as adjuvant therapy if the nodes are positive. The typical radiation dose is 60 Gray, or 30 Gray as a palliative dose, usually delivered in fractions over a 6-week period.

Complications of radiotherapy include proctitis, ileitis with diarrhoea and skin reactions. Other later complications may include bladder irritability and occasionally fistulae.

Chemoradiation is the incorporation of cisplatin-based chemotherapy with radiation therapy and has recently been recommended for patients with high-risk or advanced (stage 1b2 or greater) cervical carcinoma.

Follow-up

Review patient for routine postoperative check at 6 weeks. Review 3-monthly for 2 years, 6-monthly until year 5, then annually until year 10. Assessment includes general examination, including breast (and nodes), abdominal examination, vault smear, vaginal and rectal examination. Other investigations, if appropriate, include chest X-ray or colposcopy/biopsy.

Prognosis

This depends on the stage of the disease and is usually expressed in terms of 5-year survival rates:

• Stage 1 – up to 90%

• Stage 2 – 55%

• Stage 3 – 30–55%

• Stage 4 – < 10%.

Adenocarcinoma of the cervix

This occurs in approximately 30% of cervical cancers. It involves a greater tumour mass and, therefore, carries a worse prognosis than squamous cell carcinoma.

Benign tumours of the uterus

Polyps

Endometrial polyps are very common and are usually multiple in premenopausal, but usually single in postmenopausal women. They are usually benign adenomatous lesions that are found in the body of the uterus and often occur as part of a hyperplastic endometrium, presenting with menstrual irregularity. Occasionally, they can protrude through the cervix to cause dysmenorrhoea or postcoital bleeding. Ideally, they should be removed with a hysteroscopic resectoscope and the excised tissue analysed histologically.

Uterine fibroids

Fibroids or leiomyomata are the commonest tumours of the female genital tract occurring in 20–30% of women over 30 years of age. They are particularly common in Afro-Caribbean and nulliparous women. Fibroids may be found in various sites; intramural are within the uterine wall; subserous are beneath the serosal surface of the uterus; and submucous are found beneath the mucosal surface of the uterus, often distorting it or increasing the surface area of the endometrium. Fibroids are usually multiple in number and can vary widely in size. They often undergo degenerative change as a result of poor vascularity, described as:

• Hyaline degeneration

• Cystic degeneration

• Calcification (in postmenopausal women)

• Necrosis and infection

• Red degeneration (during pregnancy).

Malignant change is rare (leiomyosarcoma), occurring in < 0.5% of cases, but should be suspected in rapidly growing fibroids.

Presentation

The majority of fibroids are asymptomatic, but can cause symptoms depending on their size and position in the uterus.

Menorrhagia is the commonest symptom but symptoms can vary between menorrhagia, intermenstrual bleeding and abdominal swelling. If situated under the bladder, they can cause irritative bladder symptoms or incontinence. In pregnancy, fibroids may increase in size as they are hormone-dependent or degenerate (red degeneration), resulting in pain. They can also cause obstruction in labour, depending on their site.

Management

Fibroids are oestrogen-dependent and will, therefore, reduce in size after the menopause and so can be treated conservatively.

However, if symptomatic, fibroids can be treated either medically or surgically.

Medical

• Progesterone tablets

• Gonadotrophin-releasing hormone (GnRH) analogues – will cause rapid reduction in fibroid size, but will regrow when treatment is ceased. Side effects are unavoidable and include menopausal symptoms pelvic pain from fibroid necrosis and reduced bone density.

Surgery

Myomectomy can be performed through an abdominal incision, laparoscopically or hysteroscopically, depending on the site of the fibroid and skill of the operator. Pretreatment with GnRH analogues will shrink the fibroids and reduce blood loss during surgery. Myomectomy can be technically difficult and may result in excessive blood loss. It is, therefore, a procedure that is reserved for women who wish to preserve their fertility, but these patients should be carefully counselled regarding the risk of proceeding to hysterectomy in the case of excessive blood loss.

Adenomyosis

This is a benign condition of the uterus caused by invasion of endometrium and its underlying stroma into the myometrial layer of the uterus. It is often undiagnosed, but is found in at least 40% of hysterectomy specimens on histological examination. It is thought to be a variant of endometriosis and so it often presents in a similar way, with menstrual pain and also with menorrhagia.

Presentation

Adenomyosis may be asymptomatic, but characteristically will present as dysmenorrhoea and menorrhagia. On vaginal bimanual examination the uterus is often found to be enlarged and tender. Diagnosis, however, can usually only be made on histological examination of the removed uterus following hysterectomy.

Management

Management is aimed at control of dysmenorrhoea and menorrhagia. Non-steroidal anti-inflammatory medication or progestogens (either as an oral preparation or the intrauterine system) can be effective, but often hysterectomy may be necessary if the patient does not wish to preserve her fertility.

Congenital abnormalities of the uterus

The uterus is derived embryologically from fusion of the müllerian (paramesonephric) ducts. If these ducts fail to fuse during development varying degrees of uterine abnormality will result. Complete failure to fuse results in two separate uterine cavities and crevices often associated with a longitudinal vaginal septum (uterine didelphys). Partial failure to fuse will result in varying degrees of abnormality, including rudimentary horn (where one duct develops to a lesser extent than the other) or where a uterine septum is present to a varying degree (from an arcuate uterus to a bicornuate uterus to a subseptate uterus). These abnormalities are often discovered during investigation of pregnancy-related problems such as recurrent first- and second-trimester miscarriage, cervical incompetence or preterm labour.

Endometrial carcinoma

Endometrial carcinoma is the most common gynaecological cancer in the developed world, particularly amongst postmenopausal women. The majority of tumours of the body of the uterus are adenocarcinomas of the endometrium, whereas malignant tumours of the myometrium, sarcomas, account for only 4%. Endometrial carcinoma usually presents with abnormal bleeding or discharge after 45 years of age or alternatively with postmenopausal bleeding. Most occur after the menopause, with only 5% of cases occurring in women under 40 years of age. These clinical situations should be investigated promptly with ultrasound, hysteroscopy and endometrial sampling.

There are two broad categories of endometrial cancer – type 1 (80% of cases) is slow-growing and oestrogen-dependent and is therefore associated with long-term unopposed oestrogen administration, oestrogen-secreting tumours of the ovary or adiposity (since adiposity increases oestrogen levels) and type 2 (20% of cases) is a more aggressive malignancy with a poorer prognosis than type 1. Other associations include nulliparity and late menopause.

Microscopic appearance

Most endometrial carcinomas are adenocarcinomas and are graded according to their differentiation. Grade 1 is well differentiated, grade 2 moderately differentiated and grade 3 is poorly differentiated. The pathology report should state the tumour type and the degree of differentiation.

Management

Approximately 90% of tumours will present at stage 1 or 2. When the diagnosis has been made, a total abdominal hysterectomy with bilateral salpingo-oophorectomy must be performed. Although it seems apparent that lymphadenectomy should be performed in order to stage the disease, the role of concurrent lymphadenectomy in the treatment of endometrial cancer remains controversial.

Radiotherapy has been shown to reduce the risk of vault recurrence in high-risk patients and should, therefore, be offered to patients with stage 2 or greater disease.

The role of chemotherapy is still debatable when balancing the morbidity associated with it with the short-term palliative benefits.

Prognosis

5-year survival

Follow-up

It is essential that patients are routinely followed up with history and clinical examination but the routine use of vault smears is controversial. The role of hormone replacement treatment is also controversial, but combined oestrogen–progestogen therapy has been shown to have no effect on tumour recurrence and so should be considered, especially in young women.

Ovarian cysts

Functional cysts of the ovaries are common and usually asymptomatic. Follicular cysts are usually found in women with anovulatory cycles or in women undergoing infertility treatment. They are usually < 5 cm in diameter and can be diagnosed by ultrasound. They usually resolve and only rarely require surgery if the increased bulk of the ovary causes it to tort. Corpus luteal cysts are usually found in women with irregular cycles or with amenorrhoea followed by heavy vaginal bleeding. Functional cysts of the ovary usually resolve spontaneously. Occasionally, they can rupture, resulting in severe acute pelvic pain that again tends to resolve, but may require hospital admission for investigation. Persistent cysts can be removed laparoscopically and the combined oral contraceptive pill may be used to prevent recurrence by inhibiting ovulation.

Ovarian cysts in postmenopausal women

Ovarian cysts are less common after the menopause, but are increasingly picked up incidentally on routine screening or pelvic ultrasound for other reasons. Since diagnostic tests have become more accurate the need to resort to surgery has decreased. These tests include transvaginal ultrasound (or abdominal if the cyst is large) and cancer antigen 125 (CA 125), both of which can be useful in assessment, whereas the role of CT and MRI scanning is limited. The management of ovarian cysts in this age group can be influenced by these tests, which can classify the cyst according to its risk of malignancy.

Low risk

Ultrasound features include simple, unilateral, unilocular and a size < 5 cm with a normal serum CA 125. These cysts can be managed conservatively, if the patient is asymptomatic, with 3–4-monthly follow-up, as more than 50% resolve. Otherwise these cysts can be removed laparoscopically, with the most appropriate surgery in this age group including a bilateral salpingo-oophorectomy.

High risk

Ultrasound features include complex (solid parts or papillary formation), bilateral, multilocular and size > 5 cm with an elevated CA 125. These cysts need to be managed surgically in a specialist centre. The appropriate surgery is the same as for any ovarian malignancy – a total abdominal hysterectomy, bilateral salpingo-oophorectomy and full staging procedure (peritoneal washings, omentectomy and possibly para-aortic lymphadenectomy).

Tumours of the ovary

Ovarian tumours can be primary or secondary. When considering primary neoplasms of the ovary, it is sensible to classify benign and malignant neoplasms together, as a benign cyst may undergo malignant change. There are three main groups of primary ovarian neoplasm: (1) epithelial tumours; (2) germ cell tumours; and (3) sex cord tumours.

Epithelial tumours

These are the most common ovarian tumours in postmenopausal women (85% of ovarian tumours) and may undergo malignant change. There are four types:

1. Serous cystadenoma or adenocarcinoma – this is the commonest form of ovarian carcinoma, accounting for 50% of ovarian malignancy, but both benign and malignant varieties exist.

2. Mucinous cystadenoma or adenocarcinoma – these are less commonly malignant, accounting for 10% of ovarian carcinomas. They are usually large ovarian cysts.

3. Endometrioid carcinoma – this malignant variety of ovarian carcinoma accounts for 25% of ovarian carcinomas and is associated with endometrial malignancy in 20% of cases.

4. Clear-cell carcinoma – this is a malignant tumour that accounts for 10% of ovarian carcinoma and carries a particularly poor prognosis.

Brenner’s tumour is a rare form of ovarian neoplasm that is usually small and benign.

Germ cell tumours

Germ cell tumours arise from the undifferentiated germ cells of the ovary. There are two main varieties:

1. Teratoma (dermoid cyst) – this is a common benign cyst in young women that may contain tissue from all the cell lines derived from the primordial germ cells of the ovary, including hair and teeth. They are usually small, bilateral and asymptomatic, but can cause pain if the ovary torts or the cyst ruptures. They can, rarely, undergo malignant change to solid teratomas.

2. Dysgerminoma – this is a rare tumour of the ovary overall, but is the commonest type of ovarian malignancy in the younger age group.

Sex cord tumours

This type of ovarian tumour is derived from the ovarian stroma and there are three varieties:

1. Granulosa cell tumours – these are slow-growing malignant tumours of the ovary, which are usually malignant. They are rare and secrete oestrogen, and so may cause postmenopausal bleeding or endometrial hyperplasia or carcinoma in this group of women.

2. Thecomas – these are similar to the granulosa cell tumours, secreting oestrogen and, therefore, causing similar effects, but are rare and usually benign, e.g. Sertoli–Leydig tumours.

3. Fibromas – these are benign tumours that are uncommon and are often associated with ascites and pleural effusions as part of Meigs’ syndrome.

Secondary ovarian malignancies are common, accounting for 10% of ovarian masses, since the ovary is a common area for metastatic spread from the breast, lung and gastrointestinal tract. The prognosis for secondary ovarian malignancy is poor.

Ovarian carcinoma

This is the commonest gynaecological malignancy in the UK, where there are approximately 5000 cases per year. It characteristically presents late and is, therefore, the main cause of mortality from gynaecological cancer.

Aetiology

Benign ovarian cysts will frequently undergo malignant change and so all ovarian cysts need to be carefully managed. Risk factors include a history of early menarche, late menopause, nulliparity or infertility (i.e. increased number of ovulatory cycles), family history and other cancers that are linked include breast, endometrial or colonic cancer. Factors that reduce the number of ovulatory cycles are, therefore, protective, including the oral contraceptive pill, multiparity and breastfeeding. There is a familial predisposition in approximately 5% of cases, with mutations of the BRCA1 and 2 genes being strongly implicated.

Microscopic appearance

The majority of ovarian carcinomas (85%) are epithelial, and germ cell tumours are more common in young women. Ovarian carcinoma will spread directly to the peritoneum and thereby to the peritoneal surfaces of the diaphragm, liver, bowel and omentum. In the later stages, metastatic spread occurs via the blood and lymphatic circulation. Ovarian carcinoma will vary from well to poorly differentiated with obvious prognostic implications.

Presentation

Ovarian carcinoma presents late (stage 3–4 disease) in over 70% of cases, as it is commonly asymptomatic in its early stages.

Typical non-specific symptoms or signs include weight loss, generalized abdominal pain or distension, back pain, urinary symptoms, constipation or deep venous thrombosis.

Examination may reveal an abdominal or pelvic mass, ascites or lymphadenopathy. It is therefore important to examine the abdomen, pelvis and rectum, as well as breasts and lymph nodes for evidence of metastases.

The clinical features consistent with malignancy include:

• Older age of patient: postmenopause

• Rapid growth of adnexal mass

• Bilateral adnexal masses

• Ascites.

Management

Ultrasound and tumour markers are useful in guiding the management of ovarian tumours. However, definitive staging is at the time of surgery.

Ultrasound

The features consistent with malignancy include:

• Solid appearance

• Thickened cyst wall

• Presence of septa within cyst

• Bleeding within cyst

• Bilateral cysts.

Tumour markers

CA 125 levels are raised in over 80% of epithelial ovarian malignancies and are useful in aiding diagnosis, monitoring treatment response during follow-up and in recurrence. Other tumour markers include alpha-fetoprotein and human chorionic gonadotrophin, which are characteristically raised in germ cell tumours amongst younger women.

Surgery

If malignancy is suspected, then laparotomy should be performed through a midline incision in order to stage the carcinoma accurately. This includes peritoneal washings, total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy. If extensive malignancy is present, then a debulking procedure is performed in which as much tumour as possible is removed. Surgery, is usually followed by chemotherapy in all patients except those with early stage 1a or borderline tumours. In young women with well-differentiated tumours who wish to preserve their fertility, a more conservative approach would involve a unilateral oophorectomy and partial omental biopsy.

Chemotherapy

This treatment is best performed under the supervision of a medical oncologist and usually involves a course of platinum-based compounds, e.g. carboplatin or cisplatin or alkylating agents such as cyclophosphamide in conjunction with taxol.

Regular follow-up is essential, with tracking of disease progression with CA 125 levels for epithelial tumours.

Gynaecological cancer in pregnancy

Approximately 1 in 1000 pregnancies are complicated by gynaecological malignancy, of which cervical and ovarian carcinomas are the most common, and this figure is increasing as women delay childbirth into their later reproductive years.

Carcinoma of the cervix

Seventy per cent of cervical carcinoma in pregnancy is diagnosed at an early stage (2a or less). The antenatal clinic offers a good opportunity to follow up on cervical screening of pregnant women.

Management

1. Low-grade abnormality on smear – followed up with a further smear test in 12 months.

2. High-grade abnormality on smear – mandatory colposcopy, avoid biopsy if possible (but this will be unavoidable if invasive carcinoma is suspected), but repeat colposcopy at 24–28 weeks’ gestation to exclude progression of disease. Follow up postpartum for biopsy if necessary.

3. Suspected microinvasion – may indicate need for cold-knife cone biopsy during pregnancy. This procedure carries a significant risk of morbidity for both mother and fetus.

4. Invasive carcinoma – adequate staging is essential. Management will depend on extent of stage, gestation at diagnosis and patient’s wishes for continuing pregnancy. Generally, definitive treatment can be deferred if the carcinoma is diagnosed in the third trimester. If the carcinoma is at a stage that responds to surgery, most gynaecologists would advise elective caesarean section followed by a radical hysterectomy.

Carcinoma of the ovary

This is less common than cervical carcinoma in pregnancy. It also tends to be picked up at an earlier stage than in the non-pregnant setting, because of the routine use of ultrasound in pregnancy. Tumour markers are of limited value in pregnancy as their values tend to fluctuate and are generally elevated. Suspicious features on ultrasound include size > 5 cm, persistence of cyst throughout pregnancy and bilateral or solid components within the cyst. Surgical intervention is usually delayed until 16–20 weeks’ gestation and frozen-section analysis is useful to guide further management. Since the majority of ovarian carcinomas in pregnancy are germ cell in origin, often a unilateral salpingo-oophorectomy with staging is appropriate. This is also true for the early-stage, low malignant epithelial and sex cord tumours, allowing for continuation of the pregnancy. The higher-risk malignancies will require chemotherapy, with the obvious dilemmas of teratogenicity.

Carcinoma of the vulva and endometrium

These are very uncommon in pregnancy.

Summary

• Cervical smears are an effective screening technique for cervical carcinoma.

• Cervical carcinoma is the second commonest female cancer after breast carcinoma, followed by ovarian and then endometrial.

• Uterine fibroids are the commonest benign tumours of the female genital tract.

• Ovarian cysts are common and management has been improved with the development of ultrasound and tumour markers.

• Ovarian carcinoma usually presents late and is therefore the main cause of mortality from gynaecological cancer.

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