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Sequential occurrence within three years in a premenopausal woman of cervical, ovarian, and endometrial cancers

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Q1: What is the management of a 1B squamous cervical carcinoma in a patient who wishes to preserve fertility?

Standard practice for the management of patients with cervical 1B carcinoma is either radical hysterectomy and bilateral pelvic lymphadenopathy for small volume disease (<4 cm diameter) or radiotherapy for large volume disease. The initial step at laparotomy is to assess the pelvic lymph nodes and to send for frozen section any that are thought to be “suspicious”. If the pelvic lymph nodes are shown to be involved with disease, surgery is abandoned and radiotherapy instituted. In patients who wish to preserve their fertility and have small volume stage 1B disease then there is increasing evidence that conservative surgery may be a therapeutic option.1 It must be stressed that the literature advocating conservative interventions are small and no randomised controlled trials have been performed. Accepting these caveats and after appropriate counselling a patient may undergo cone biopsy and pelvic lymphadenectomy (either performed via the laparoscope or at open surgery) or radical trachelectomy and pelvic lymphadenectomy.2

Q2: What are the guidelines in the investigation of menorrhagia in a women under 40 years?

A history should be taken, abdominal and pelvic examination performed, and a full blood count obtained in all women presenting with a history suggestive of menorrhagia. Tests for thyroid function and bleeding disorders should be performed only if clinically indicated.3 If the menorrhagia persists despite evidence based medical therapy then endometrial assessment is indicated.4 This should be by transvaginal scan and endometrial biopsy. Hysteroscopy may also be considered.

Q3: What further course of management should be recommended for this patient?

This patient should be referred to the clinical geneticists for advice regarding her potential risk of developing breast and colonic cancers.5 Furthermore she should be offered entry into any trial where genes for human non-polyposis colorectal cancer are being studied. Breast and gastrointestinal tract surveillance should be offered.


The occurrence of metachronous cancers in an individual is well recognised.6 However the occurrence of three different gynaecological primaries in a premenopausal women within three years is a unique clinical occurrence.

This case serves as a salutary reminder that in patients who develop cervical malignancies of the genital tract, the possibility of a new primary carcinoma must be considered in addition to possible recurrence of the original tumour. These patients are at greater risk than the normal population for the development of a new primary carcinoma.7

The incidence of invasive carcinoma of the cervix in women aged 25–34 has increased8 and with this the challenge of tailoring surgery to preserving fertility. Burghardt et al, in a series of 16 patients with small volume, stage 1B disease reported no recurrence of disease after five years after treatment with cone biopsy or simple hysterectomy.1 More recently, Shepherd et al, described radical trachelectomy with pelvic lymphadenectomy as a surgical option for preserving fertility potential in early stage cervical carcinoma.2

Our patient had early, small volume disease and although technically had stage 1B disease was managed as having stage 1A1 disease. Nevertheless, the subsequent histological reports of her uterus, cervix, para-aortic and pelvic lymph nodes after her surgery for her ovarian and endometrial cancers found this management to have been successful in treating her cervical disease. The question arises therefore—is it absolutely necessary to add pelvic lymphadenectomy after cone biopsy for stage 1B small volume disease?

In view of the increased predisposition to developing a new malignancy, the initial laparotomy for the ovarian cyst should have been a staging laparotomy despite a normal CA 125 and reassuring scan. Furthermore because of this increased predisposition to a further malignancy, the preferred option would have been referral to a gynaecological oncological centre, following the recommendations of the NHS Executive.9

This patient's personal and family history is strongly suggestive of hereditary non-polyposis colorectal cancer (HNPCC). People from families fulfilling criteria for HNPCC have a 50% risk of being a gene carrier and a 30% sex average life time risk of developing colorectal cancer. In addition they have an excess risk of developing other cancers, namely endometrial (40%), ovarian (10%), and gastric (20%) and other tumours where the risk is lower.5

There is class B evidence for implementing biannual colonoscopy as a screening tool to improve survival in these HNPCC families. In addition it would be prudent to perform endoscopy at the same time. Unfortunately, there are morbidity and mortality risks associated with colonoscopy and therefore in an ideal world, gene testing should be employed to identify those carriers of the gene in whom targeting of colonoscopy could be implemented.

Although the gene has been mapped, this test is only available in some centres on the NHS. Families of HNPCC patients must therefore be counselled accordingly regarding the probabilities of being a carrier of the HNPCC gene and the risks and benefits of gastrointestinal tract surveillance.

In this patient's case ulcerative colitis also predisposes to colorectal cancer. If there had been no personal or family history of bowel pathology the patient would have been at risk of a gastrointestinal tract primary on the basis of her endometrial and ovarian cancer and would have been offered gastrointestinal tract surveillance, although she would have been at less risk than if she had the HNPCC mutation.

In addition to gastrointestinal tract surveillance the patient should also be offered entry into the breast screening programme. Again the exact risk is not known.

Finally, this case highlights the fact that guidelines are precisely that—guidelines. The Royal College of Obstetricians and Gynaecologists in their evidence based clinical guidelines suggest that an endometrial biopsy is not necessary in the initial management of menorrhagia.3 4 The Gynaecology Audit Project in Scotland II are more stringent in their recommendations by suggesting an age cut off of 40 years before endometrial sampling should be routinely employed.10 Although both bodies acknowledge that endometrial evaluation is warranted in a subgroup of women for whom the risk of endometrial cancer is greater than that of the general population, neither body recognises a previous history of genital tract neoplasm as a risk factor. We argue therefore that this is an oversight and that in a woman with a history of a previous gynaecological malignancy, an endometrial biopsy should be performed as part of the initial investigation of menorrhagia regardless of age.

Learning points

  • Incidence of invasive carcinoma of the cervix in women of childbearing potential is increasing.

  • After conservative surgery for cancer, new symptoms must be regarded with a high index of suspicion as occurring from another possible primary.

  • Guidelines are only guidelines and a low threshold for implementing them must be employed in patients with a previous history of carcinoma.

  • In patients with a previous history of gynaecological malignancy and presenting with a new symptom referable to the genital tract early referral to the regional gynaecological centre should be employed.

  • Referral to clinical geneticists is prudent so that risk regarding other systems can be calculated and appropriate management employed.