Uterine Leiomyoma

Description

Uterine leiomyomas, also known as fibroids, are benign tumours composed of smooth muscle and fibrous connective tissue. They are the most common benign tumours in females and often occur within the uterus. Uterine leiomyomas exhibit a broad range of presentations and complications depending on their size, number, and location.

Pathogenesis

The exact pathogenesis of leiomyomas is unknown, but it is believed to be multi-factorial, involving genetic, hormonal, and environmental factors. They are monoclonal tumours, arising from the abnormal proliferation of a single myometrial smooth muscle cell. Oestrogen and progesterone are thought to play a pivotal role in the development and growth of these tumours, which explains their frequent occurrence in the reproductive years and tendency to regress after menopause.

Subtypes

Leiomyomas can be classified into several subtypes depending on their location and morphological features:

• Intramural leiomyomas are the most common type, developing within the myometrium.
• Subserosal leiomyomas develop on the outer surface of the uterus and may become pedunculated, forming a stalk.
• Submucosal leiomyomas protrude into the uterine cavity and are more likely to cause menorrhagia or infertility.
• Parasitic leiomyomas are rare variants that have lost their original attachment to the uterus and receive their blood supply from another organ.
• Benign metastasising leiomyomas are a very rare variant characterised by the benign proliferation of smooth muscle cells in distant locations, often the lungs or lymph nodes.
• Diffuse leiomyomatosis presents as a diffusely enlarged uterus without the formation of discrete masses.
• Intravenous leiomyomatosis is characterised by the growth of leiomyoma cells within the venous channels of the uterus.
• Disseminated peritoneal leiomyomatosis involves numerous small leiomyomas scattered throughout the peritoneal cavity.
• Lipoleiomyomas are a rare subtype composed of adipose tissue and smooth muscle cells.

Epidemiology, Risk Factors & Associations

• Leiomyomas are extremely common, with a lifetime risk of more than 70% in the female population (60-70%).
• Increased incidence is observed in women of African descent (up to three times more likely).
• Peak incidence occurs in the fourth to fifth decades of life.
• Obesity (BMI > 30) increases the risk by 2-3 times.
• Early menarche (<10 years) is associated with an increased risk.
• Use of oral contraceptive pills from a young age has been shown to reduce the risk.
• Pregnancy appears to have a protective effect.
• Growth of lesion with tamoxifen use – has a weak oestrogen agonist effect in the uterus (despite being an antagonist in the breast).

Clinical Features

Leiomyomas may be asymptomatic, particularly when small, but can cause symptoms including:

• Heavy menstrual bleeding (menorrhagia)
• Pelvic pain or pressure
• Urinary frequency or constipation due to pressure on adjacent organs
• Infertility or recurrent miscarriages

Complications

• Severe menorrhagia may lead to anaemia.
• Large or multiple fibroids can distort the uterus, leading to infertility.
• As fibroids enlarge, they may outgrow their blood supply, resulting in various types of degeneration: hyaline or myxoid degeneration, calcification, cystic degeneration, and red degeneration. Red (haemorrhagic) degeneration often occurs in pregnancy.
• Torsion of a pedunculated fibroid
• In rare cases, malignant transformation to leiomyosarcoma can occur.

Pathological Features

Histopathology

• Macroscopic: Leiomyomas are typically round, well-circumscribed with a pseudocapsule, and firm masses that can range from a few millimetres to several centimetres in diameter. On cut section, they have a whorled appearance similar to that of a uterine myometrium.
• Microscopic: Histologically, leiomyomas consist of bundles of smooth muscle cells with abundant eosinophilic cytoplasm and cigar-shaped nuclei. There is minimal cellular atypia, and mitoses are infrequent.

Radiological Features

General Features

• Leiomyomas typically appear as well-defined, round, or lobulated mass(es)
• May cause deformation of uterine contour

Plain Radiograph

• Popcorn calcification within the pelvis may suggest the diagnosis.

US

• Uterine leiomyomas are typically hypoechoic, but can be isoechoic, or even hyperechoic compared to normal myometrium.
  • Echogenic mass may represent lipoleiomyoma
• Calcification is seen as echogenic foci with shadowing (25%)
• Cystic areas of necrosis or degeneration rarely seen.
• Venetian blind artefact may be seen, but edge shadowing +/- dense posterior shadowing from calcification is also typically seen.
• US may appear normal in 20%.
• Exophytic subserosal leiomyomas may demonstrate a bridging vessel sign, which represents tortuous vascular structures passing between the uterus and the lesion and confirms the lesion originates from the uterus, not the ovary. It is best seen on post-gadolinium MRI, which demonstrates vascular flow voids, but can also be seen on US.

CT

• Leiomyomas often appear as soft tissue density lesions and may exhibit coarse peripheral or central calcification.
• They may distort the usually smooth uterine contour.
• Usually same density as unenhanced myometrium.
• The enhancement pattern is variable.

MRI

• T1WI:
  • Typical fibroids and calcification appear as low to intermediate signal intensity compared to the normal myometrium.
  • Characteristic high T1 signal or an irregular, T1 hyperintense rim around a centrally located leiomyoma suggest red degeneration, caused by venous thrombosis.
• T2WI:
  • Typical fibroids and coarse calcification appear as low signal intensity.
  • Flow voids are often observed around them due to their hypervascular nature.
  • Atypical fibroids that have undergone cystic, mucoid or myxoid degeneration/necrosis usually demonstrate high T2 signal.
  • Completely hyalinised fibroids have low T2
  • After successful embolisation, fibroids may undergo progressive liquefaction with increasing T2 signal
• T1 C+ (Gd):
  • Variable enhancement is seen with contrast administration.
  • Marked high signal intensity with gradual enhancement suggests myxoid degeneration.
  • Most uterine fibroids receive blood supply from both uterine arteries
  • Persistent enhancement post-embolisation is sign of incomplete fibroid infarction.
  • Bridging vessel sign may be seen with pedunculated/exophytic subserosal leiomyoma.

Grading and Staging

There is no standardised grading or staging system for leiomyomas due to their benign nature. However, they can be categorised based on their location (intramural, subserosal, submucosal) and number (solitary or multiple).

Diagnosis

Diagnosis is typically made on clinical and imaging grounds, with histological confirmation from a biopsy rarely necessary unless malignancy is suspected.

Differential Diagnosis

• Focal Adenomyosis: Also known as adenomyoma. Typically seen in women in their 40s-50s and presents with dysmenorrhea and menorrhagia. Focal adenomyosis exhibits ill-defined low signal intensity on both T1WI and T2WI with multifocal punctate high signal intensity foci on T2WI, located at the junctional zone.
• Leiomyosarcoma: A rare malignant tumour with similar imaging features to leiomyomas but typically shows rapid growth and may demonstrate areas of necrosis and haemorrhage. Usually a larger mass. Assess for intermediate T2 signal that enhance or focal areas of arterial enhancement.

Management

• Observation in asymptomatic women to medical management (hormonal therapy)
• Interventional radiology procedures (uterine artery embolisation), or surgical intervention (myomectomy or hysterectomy) for those with symptomatic or large fibroids.
  • Pedunculated subserosal fibroids with a narrow stalk (<2–3 cm) are a relative contraindication to UFE because of the potential risk of detachment.
  • Cervical fibroids tend to respond less favourably
  • In most cases, bilateral UAE is needed, due to dual blood supply of most fibroids
  • The maximum size threshold for embolisation is 13–15 cm. Above this, the post-embolisation volume may still result in bulk symptoms, and the necrosis from a large fibroid may result in a protracted post-embolisation syndrome.
• Decisions regarding treatment should be made in consultation with a gynaecologist.