Neoplastic Conditions

A range of benign and malignant neoplasms can involve both the endometrium and myometrium.

Endometrial hyperplasias: these are a spectrum of preneoplastic conditions which confer an increased risk of subsequent development of endometrial adenocarcinoma. The WHO classification of endometrial hyperplasias is used with hyperplasias categorised as simple or complex in type based on architectural features. These are further subdivided into typical and atypical forms, depending on the presence or absence of cytological atypia.

Endometrial carcinomas: a variety of different carcinomas may arise from the endometrium. There are two main types (type I and type II) although not all neoplasms fall neatly into either category. The prototype of type I endometrial carcinoma is endometrioid adenocarcinoma and type II uterine serous carcinoma. type I and type II neoplasms have different clinicopathologic characteristics, although it is emphasised that there may be overlap. In general, type II carcinomas behave in a much more aggressive manner. Endometrial carcinomas (especially type I) may be associated with obesity, hypertension and diabetes and with unopposed oestrogen hormone therapy. There may also be an association with oestrogen-secreting ovarian tumours, mainly those within the sex cord-stromal group. Endometrial carcinomas are more common in women of low-parity, high socio-economic status and in the postmenopausal age group. There is some evidence that continuous combined hormone replacement therapy may be protective against endometrial carcinoma. Occasionally, there is a familial predisposition to developing endometrial cancer. Endometrial carcinoma is the second most common neoplasm to arise in patients with hereditary nonpolyposis colorectal cancer.

Type I endometrial carcinomas usually arise in a background of endometrial hyperplasia. This association is not apparent with type II endometrial cancers, which arise within an atrophic endometrium from a precursor known as endometrial intraepithelial carcinoma (EIC).

Endometrial carcinomas may be polypoid in appearance and project into the endometrial cavity. Conversely, some tumours diffusely infiltrate the underlying myometrium.

Uterine smooth muscle tumours: uterine leiomyomas (fibroids) are one of the most common benign neoplasms to occur in women, especially within the reproductive and early postmenopausal age group. They are often multiple but may be solitary. Uterine leiomyomas can be submucosal, intramural or subserosal. Occasionally they may separate from the uterus and lie within the pelvic cavity, so-called parasitic leiomyomas. They are usually well circumscribed, white in colour with a typical firm whorled appearance and bulge above the surrounding myometrium. Degeneration may result in a variety of different gross appearances.

Adenomyosis: adenomyosis is a common condition characterised by extension of endometrial glands and stroma into the underlying myometrium. Usually this results in diffuse uterine enlargement although occasionally well-circumscribed nodular masses are formed, so-called adenomyomas. Typically, adenomyosis results in a trabeculated appearance to the myometrium because of the associated smooth-muscle hypertrophy around the pale or haemorrhagic adeno-myotic foci. Adenomyosis is most common in the reproductive age group and is thought to develop under oestrogenic influence. It is a common cause of irregular uterine bleeding.

Malignant uterine mesenchymal lesions: malignant uterine mesenchymal lesions comprise endometrial stromal sarcomas, leiomyosarcomas and undifferentiated uterine sarcomas. Endometrial stromal sarcomas usually cause diffuse uterine enlargement due to infiltration of the myometrium by irregular tongues of neoplastic endometrial stromal cells. There is often marked vascular permeation and the tumour may extend beyond the uterus. Leiomyosarcomas and undif-ferentiated uterine sarcomas are generally high-grade malignant neoplasms, usually comprising a dominant mass with or without satellite nodules. Grossly, areas of haemorrhage and necrosis are common.

Other uterine neoplasms: endometrial stromal nodules are benign, well-circumscribed proliferations of endometrial stroma. Histologically, they are identical to endometrial stromal sarcomas and are differentiated from the latter due to their circumscription and lack of infiltrative myome-trial permeation or vascular invasion. They may involve both the endometrium and myometrium or may be predominantly located within the myometrium.

Uterine carcinosarcomas (Malignant Mixed Mullerian Tumours) are highly aggressive neoplasms composed of carcinomatous and sarcomatous elements. Although traditionally regarded as a subtype of uterine sarcoma there is now ample evidence that these are, in fact, metaplastic carcinomas. They are usually bulky neoplasms in elderly patients, often with a polypoid appearance and exhibiting deep myometrial infiltration and vascular invasion.

Treatment: treatment of malignant uterine lesions (carcinomas, sarcomas, carcinosarcomas) usually comprises total abdominal hysterectomy and bilateral salpingo-oophorectomy. Peritoneal washings are performed as part of the staging procedure. Lymph nodes may be sampled, especially when preoperative endometrial biopsy shows a high-grade endometrioid or serous carcinoma or when radiological investigations suggest deep myometrial invasion or extrauterine spread. Preoperative staging comprises MRI scanning to assess the extent of tumour spread. Postoperative radiotherapy or chemotherapy is often needed. This is especially so with high-grade or Type II endometrial carcinomas or where there is cervical involvement or deep myometrial penetration. The FIGO staging system for endometrial carcinoma is used. Occasionally with advanced tumours, surgical resection is not feasible and primary treatment is radiotherapy or chemotherapy. Adjuvant treatment of all malignancies should be discussed at a multidisciplinary gynaecological oncology meeting.

Uterine leiomyomas may be treated by total abdominal hysterectomy or, in those who wish to preserve their fertility, medical treatment or myomectomy (simple removal of the fibroids). Adenomyosis is often not expected clinically and is only diagnosed on a hysterectomy specimen performed for menorrhagia.

Troublesome menorrhagia can in most cases be managed by endometrial ablation (balloon dilatation, laser ablation or hysteroscopic resection) with resort to simple hysterectomy in a minority of cases with post-ablation recurrence of symptoms.

Prognosis: the prognosis of low-grade, early-stage (Stage Ia or Ib) endometrial adenocarcinoma of endometrioid type is excellent but overall survival decreases with increasing tumour stage. Prognosis is also poor with Type II endometrial adenocarcinomas, especially uterine serous carcinoma. Leiomyosarcoma, undifferentiated uterine sarcoma and carcinosarcoma usually have a poor prognosis, especially if large and of advanced stage. Endometrial stromal sarcomas are usually low-grade neoplasms. The overall prognosis is usually favourable although there is a significant risk of late recurrence after many years and subsequent metastasis with these tumours. Adjuvant progesterone therapy may be indicated, since these tumours may be hormone responsive.

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