Definition

Adenomyosis is defined as the presence of endometrial tissue, including endometrial glands and stroma, in the myometrium and is associated with smooth muscle proliferation in the inner myometrium [2]. It may be either diffuse or focal. Adenomyosis typically results in uterine enlargement and an irregular endo‐myometrial border or junctional zone. The histological definition of adenomyosis usually includes a depth of penetration between 2.5 and 5 mm [3].

Incidence

The reported incidence of adenomyosis in hysterectomy specimens varies considerably, ranging from 9 to 62% [4]. This wide range is likely to reflect the varying diagnostic methodologies used by different pathologists.

Aetiology

The ectopic endometrium is responsive to steroid hormones. In addition, gene polymorphisms have been identified in the oestrogen receptor, with mutations of oestrogen receptor alpha [5]. This ectopic tissue may respond to the cyclical hormone changes of the menstrual cycle, contributing to the symptoms of heavy menstrual bleeding (HMB) and dysmenorrhoea. Abnormal prostaglandin production also occurs and this could exacerbate both pelvic pain and heavy bleeding.

Clinical presentation

The commonest presentation is HMB and dysmenorrhoea, the latter being worse in deep infiltrating disease [6]. However, adenomyosis is often diagnosed in women without bleeding or pain symptoms, leading Weiss et al. [4] to challenge the causative relationship between adenomyosis and symptoms. The condition is reportedly characteristic of the fifth decade of life, with 45 years being the commonest age of presentation. It is uncommon in nulliparous women and occurs less frequently in smokers [7].

Diagnosis

The diagnosis is made on histological examination of the uterus after hysterectomy but the preoperative diagnosis may be suggested on ultrasound examination. Typical ultrasound features of adenomyosis include an asymmetrical thickening of the myometrium or a globular uterus, myometrial cysts, myometrial echogenic islands, fan‐shaped shadowing, subendometrial echogenic lines and buds, translesional vascularity and an irregular or interrupted junctional zone [8,9] (Fig. 59.1).

On MRI, adenomyosis has historically been linked with a thickened junctional zone [10]. According to Brosens et al. [11], the thickening seen on MRI relies on the disruption of the inner myometrial architecture secondary to smooth muscle hyperplasia but, unlike the ultrasound features, does not evidence mucosal invasion of the myometrium.

Treatment

The treatment is mainly symptomatic, and aims to relieve HMB and dysmenorrhoea. Various medical and minor surgical techniques have been shown to be of some benefit in the short term. Antifibrinolytics, non‐steroidal anti‐inflammatory drugs, the oral contraceptive pill and progestins may be considered as first‐line methods of treatment. The levonorgestrel‐releasing intrauterine system (LNG‐IUS) has been shown to be effective for reducing uterine volume and relief of adenomyosis‐related symptoms at 1 year, but the efficacy of this device declines with time [12]. Endometrial ablation is not used as a first‐line treatment of adenomyosis as it fails to remove deeply infiltrating endometrial glands. It has been shown to improve menorrhagia and dysmenorrhoea in some women, and those with superficial disease have good results from this treatment option. Those with deeply infiltrating disease, however, tend to have persistent symptoms and, if conservative therapy fails, should be offered hysterectomy if fertility is not an issue [13].

The minimally invasive radiological technique of uterine artery embolization (UAE) is used in some centres for the treatment of symptomatic adenomyosis. It has been shown to be effective in the short term, but there is a high rate of symptom recurrence within 2 years of treatment [14].

Definition

Endometrial polyps are discrete outgrowths of the endometrium containing a variable amount of glandular tissue, stroma and blood vessels. Polyps may be pedunculated or sessile, single or multiple. They are relatively insensitive to cyclical hormonal changes and thus are not shed at the time of menstruation. Hyperplastic or malignant foci within a polyp are infrequent. The incidence of cancer in asymptomatic women and in women with postmenopausal bleeding diagnosed with a polyp is 0.1–1.5% and 1.0–4.5%, respectively [15,16].

Epidemiology

In symptomatic women the prevalence of polyps is reported as ranging between 6 and 32% [17]. In the general population aged 20–74 years, Dreisler et al. [17] reported the presence of endometrial polyps in 7.8%, the occurrence being very low below age 30. In their study they did not find an association between the presence of polyps and abnormal bleeding.

Presentation

Postmenopausal uterine bleeding, HMB, intermenstrual bleeding, dysmenorrhoea and subfertility have been related to endometrial polyps.

Diagnosis

Both fluid instillation sonography and hysteroscopy have a comparable diagnostic accuracy in detecting focal intracavitary lesions [18].

On transvaginal ultrasound examination a polyp typically is a relatively hyperechogenic lesion with or without small and regular internal cysts. The interface between the endometrium and the lesion often appears as a bright echogenic edge. On colour imaging a dominant vessel is often visible [19]. In a premenopausal woman with a spontaneous menstrual cycle, an echogenic polyp is more readily detected in the proliferative phase of the cycle, when the endometrium is more hypoechogenic (three‐layer pattern). In women on hormonal therapy or who are postmenopausal, where timed examination is not feasible, instillation of fluid into the uterine cavity will create a negative contrast against which focal intracavitary lesions are easily visualized (fluid instillation sonography) (Fig. 59.2). Both saline infusion sonography and gel instillation sonography may be used [20].

Hysteroscopy enables direct visualization of the uterine cavity and is often considered the reference test. On hysteroscopy, polyps can be distinguished from pedunculated fibroids as they have fewer vessels over their surface. Malignant polyps are more likely to be irregular, vascular and/or friable. Hysteroscopic‐guided biopsy (preferably total excision of the lesion) and pathological analysis confirm the diagnosis, as visual appearance alone is insufficient.

Endometrial polyps are frequently missed with blind endometrial sampling, including dilation and curettage. There is no place for blind sampling without imaging in modern gynaecology [21,22].

Treatment

There is consensus that symptomatic women with endometrial polyps should undergo hysteroscopically guided removal under direct vision. In the vast majority this will result in cessation of the abnormal uterine bleeding [23]. The resection may be performed either under general anaesthesia or in an outpatient setting with or without local anaesthesia or sedation [24].

Definition

Uterine leiomyomata or fibroids are the most common benign tumours of the female genital tract, arising from neoplastic transformation of single smooth muscle cells of the myometrium. They usually appear as well‐circumscribed firm tumours with a characteristic white‐whorled appearance on cross‐section. Fibroids are paler than the surrounding myometrium and there is usually a very sharp line of demarcation between the tumour and the normal uterine muscle (Fig. 59.3).

Histologically, they are typically composed of varying proportions of spindled smooth muscle cells and fibroblasts. The size of fibroids varies greatly. The vast majority of fibroids are found in the corpus (body) of the uterus, but they may also occur in the cervix, uterine ligaments and ovary. Fibroids may be single but are commonly multiple and should be reported using the FIGO classification [25] (Fig. 59.4):

1. 0 pedunculated intracavitary;
   
2. 1 submucosal, <50% intramural;
   
3. 2 submucosal, ≥50% intramural;
   
4. 3 100% intramural, but in contact with the endometrium;
   
5. 4 intramural;
   
6. 5 subserosal, ≥50% intramural;
   
7. 6 subserosal, <50% intramural;
   
8. 7 subserosal pedunculated;
   
9. 8 other (e.g. cervical, parasitic).

Incidence

The incidence of fibroids increases with age: it has been reported to occur in 20–40% of women during reproductive life and in as many as 70% of uteri removed at the time of hysterectomy [7]. Especially in postmenopausal women, conservative treatment including myomectomy, myoma morcellation, UAE or endometrial ablation [26] should be considered only after malignancy has been excluded [27,28].

The incidence of malignancy (leiomyosarcoma) is 0.64 per 100 000 women per year and is extremely uncommon in women below the age of 40. Unlike a fibroid, which consists of spindled cells arranged in fascicles with abundant eosinophilic cytoplasm and uniform nuclei, a leiomyosarcoma is hypercellular and consists of atypical smooth muscle cells with hyperchromatic enlarged nuclei and shows increased mitotic activity and tumour cell necrosis [29]. However, the pathogenesis of leiomyosarcomas remains unclear and no evidence exists to suggest that fibroids undergo neoplastic change.

There are significant racial differences in the incidence of fibroids, with Afro‐Caribbean women having a twofold to ninefold greater risk. In addition, they tend to present at a younger age compared with Caucasian women and have multiple fibroids and higher uterine weights and are more prone to both anaemia and severe pelvic pain [30,31]. Reproductive factors also influence the risk of fibroids, with a reduction in incidence with increasing parity (beyond 24 weeks’ gestation) and the prolonged use of the oral contraceptive pill [31,32]. Environmental factors also influence the risk of fibroid development. Independent of body mass index, smoking appears to decrease the risk of fibroid development [33,34].

Aetiology

The pathophysiology of fibroids remains poorly understood. Clonality studies using the homozygosity of glucose 6‐phosphate dehydrogenase forms show that multiple tumours in the same uterus are derived from individual myometrial cells rather than occurring through a metastatic process. This, together with their high prevalence, suggests that initial development arises from a frequently occurring event, the nature of which is currently unknown. Growth of fibroids is partly dependent on the ovarian steroids that act through receptors present on both fibroid and myometrial cells. It is likely that the control of growth is due, in part, to alterations in apoptosis. Bcl‐2, an inhibitor of apoptosis, is significantly increased in cultured leiomyoma cells. It is also influenced by the steroid hormone milieu.

Cytogenetic abnormalities occur in 40% of uterine fibroids. Most commonly, these involve translocation within or deletion of chromosome 7, translocations of chromosomes 12 and 14, and occasionally structural aberrations of chromosome 6 [35]. These cytogenetic abnormalities are not observed in normal myometrial tissue and may not be present in all the fibroids in a single uterus [36]. Abnormalities in uterine blood vessels and angiogenic growth factors are also involved in the pathophysiology of uterine fibroids. The myomatous uterus has increased numbers of arterioles and venules and is also associated with venule ectasia or dilatation. It has been noted that there are no mature vessels running through uterine fibroids despite the fact that they have a well‐developed blood supply.

Control of growth

More information is available on the control of uterine fibroid growth than on the aetiology of these benign tumours. Growth factors are of importance in controlling the growth of fibroids and their composition. Higher concentrations of the angiogenic fibroblast growth factor have been found in fibroids than in the surrounding myometrium. In addition, the functions of transforming growth factor‐β, granulocyte–macrophage colony‐stimulating factor and epidermal growth factor (EGF), amongst others, have been shown to differ between fibroid and normal myometrial tissue [36].

As fibroids have not been identified in prepubertal girls and usually shrink at the time of the menopause, it has long been assumed that these lesions are dependent on the presence of the sex steroids, oestrogen and progesterone. The sex steroids act via receptors. The steroid combines with the receptor, which is then translocated to the nucleus of the cell. Studies have identified that steroid receptors are present in higher concentrations in fibroids than in the surrounding myometrium and that the concentration of receptors is significantly affected by the administration of agents which alter circulating estradiol concentration. Further work has centred on the relationship between steroid hormones and growth factors, such as EGF and insulin‐like growth factor (IGF), which would appear to be important, possibly as mediators for oestrogen action. The number of progesterone receptors is greater in fibroids than in the surrounding myometrium. Like oestrogen, it has an impact on EGF receptor content and also suppresses apoptosis. Progesterone stimulates and inhibits fibroid growth, the former by upregulating EGF and Bcl‐2 and downregulating tumour necrosis factor‐α expression, the latter by downregulating IGF‐1 [37].

Symptoms associated with uterine fibroids

It is estimated that only 20–50% of women with one or more fibroids will experience symptoms that are directly attributable to them. However, it is not always clear why some produce symptoms and others do not [7]. In the case of small fibroids, it is often the assumed that only those impinging on the uterine cavity cause symptoms. This may be a result of the presence of surface vessels on the fibroid and/or the resultant increased surface area of the uterine cavity.

Symptoms associated with fibroids may be variable, ranging from mild to severe, causing distress and impinging significantly on health‐related quality of life. Women commonly present with menstrual problems, particularly HMB [38]. Dysmenorrhoea may be an additional problem leading to a further negative impact on a woman’s health. Not all women will present with a menstrual problem, some experiencing symptoms related purely to the size of the fibroid. This may be a dragging sensation or feeling of pressure in the pelvis, abdominal swelling or urinary symptoms. Table 59.1 highlights the commonly encountered symptoms associated with fibroids. The relationship between fibroids and fertility is discussed in Chapters 51 and 52.

Diagnosis

The uterus is often found to be enlarged and presents as a pelvic mass (often central and mobile) on both abdominal and vaginal examination. However, it may be difficult to distinguish between an enlarged uterus and an ovarian mass and so further imaging is mandatory. Ultrasonography, especially transvaginal, is very useful as a first‐line diagnostic test (Fig. 59.5). Fibroids are typically well‐defined round or lobulated myometrial lesions. The echogenicity is highly variable: it may be uniform hypoechogenic, isoechogenic or hyperechogenic as compared with the surrounding myometrium, or non‐uniform due to mixed echogenicity, internal hyperechogenic spots or calcifications. These calcifications may cause intense shadowing. On colour Doppler a fibroid typically has circumferential vascularization, and sometimes some internal vascularization.

Abdominal ultrasound and MRI may be of additional value in the case of larger fibroids. MRI is useful for examining large fibroids or in obese women where adequate imaging on transvaginal or transabdominal ultrasonography is precluded, or in cases of suspected malignancy. There are no pathognomonic features for a leiomyosarcoma on any imaging technique. A large (≥8 cm), solitary, oval‐shaped, heterogeneous myometrial tumour, with strong and irregular vascularization, central necrosis/degenerative cystic changes and absence of calcifications should raise the suspicion of a leiomyosarcoma. Rapid increase in size has been reported in leiomyosarcoma. MRI with gadolinium enhancement gives an indication of the vascularity and may prove helpful in differentiating between a leiomyosarcoma and a fibroid. Total lactate dehydrogenase (LDH) and LDH isozyme 3 are reportedly elevated in leiomyosarcoma. Elevated CA125 levels are seen in advanced‐stage leiomyosarcoma only [27,28].

Treatment of uterine fibroids

The management of fibroids depends on the symptoms, the type and size of the fibroid, the patient’s age and the desire to preserve fertility. Surgical treatment includes hysterectomy and myomectomy. Medical treatments do not eradicate fibroids but are designed to provide symptomatic relief.