Adenomyosis


Adenomyosis is a medical condition characterized by the growth of cells that proliferate on the inside of the uterus atypically located among the cells of the uterine wall, as a result, thickening of the uterus occurs. As well as being misplaced in patients with this condition, endometrial tissue is completely functional. The tissue thickens, sheds and bleeds during every menstrual cycle.
The condition is typically found in women between the ages of 35 and 50, but also affects younger women. Patients with adenomyosis often present with painful menses, profuse menses, or both. Other possible symptoms are pain during sexual intercourse, chronic pelvic pain and irritation of the urinary bladder.
In adenomyosis, basal endometrium penetrates into hyperplastic myometrial fibers. Unlike the functional layer, the basal layer does not undergo typical cyclic changes with the menstrual cycle. Adenomyosis may involve the uterus focally, creating an adenomyoma. With diffuse involvement, the uterus becomes bulky and heavier.
Adenomyosis can be found together with endometriosis; it differs in that patients with endometriosis present endometrial-like tissue located entirely outside the uterus. In endometriosis, the tissue is similar to, but not the same as, the endometrium. The two conditions are found together in many cases yet often occur separately. Before being recognized as a distinct condition, adenomyosis was called endometriosis interna. The less-commonly-used term adenomyometritis is a more specific name for the condition, specifying involvement of the uterus.

Signs and symptoms

Adenomyosis can vary widely in the type and severity of symptoms that it causes, ranging from being entirely asymptomatic 33% of the time to being a severe and debilitating condition in some cases. Women with adenomyosis typically first report symptoms when they are between 40 and 50, but symptoms can occur in younger women.
Symptoms and the estimated percent affected may include:
Clinical signs of adenomyosis may include:
Women with adenomyosis are also more likely to have other uterine conditions, including:
The cause of adenomyosis can be associated with Caesarean births, although it has been associated with any sort of uterine trauma that may break the barrier between the endometrium and myometrium, known as the junctional zone, such as a caesarean section, surgical pregnancy termination, and any pregnancy. It can be linked with endometriosis, but studies looking into similarities and differences between these two conditions have conflicting results.
The pathogenesis of adenomyosis still remains unclear, but the functioning of the inner myometrium, also called the junction zone, is believed to play a major role in the development of adenomyosis. It is also a matter of discussion whether the link between reproductive disorders and major obstetrical disorders also lies here. Parity, age, and previous uterine abrasion increase the risk of adenomyosis. Hormonal factors such as local hyperestrogenism and elevated levels of s-prolactin as well as autoimmune factors have also been identified as possible risk factors. As both the myometrium and stroma in an adenomyosis affected uterus show significant differences from those of a non-affected uterus, a complex origin that includes multifactorial changes on both genetic and biochemical levels is likely.
The tissue injury and repair theory is now widely accepted and suggests that uterine hyperperistalsis, during early periods of reproductive life will induce micro-injury at the endometrial-myometrial interface region. That again leads to elevation of local estrogen in order to heal the damage. At the same time, estrogen treatment will increase uterine peristalsis again, leading to a vicious circle and a chain of biological alterations essential for the development of adenomyosis. Iatrogenic injury of the junctional zone or physical damage due to placental implantation most likely results in the same pathological cascade.

Mechanism

Pathophysiology

Misplaced endometrial tissue proliferation in the myometrium causes symptoms through different mechanisms.
Uterine menstrual contractions are caused by prostaglandin, which is produced by normal endometrial tissue. Dysmenorrhea is the main characteristic for this disease which are the result for high prostaglandin levels. Endometrial proliferation is also led by estrogen; some treatments try to reduce its levels in order to decrease symptoms.
Adenomyosis patients present with heavy menstrual bleeding due to the increase of endometrial tissue, greater degree of vascularization, atypical uterine contractions and increased levels of prostaglandins, estrogen and eicosanoids.

Histopathology

The diagnosis of adenomyosis is through a pathologist microscopically examining small tissue samples of the uterus. These tissue samples can come from a uterine biopsy or directly following a hysterectomy. Uterine biopsies can be obtained by either a laparoscopic procedure through the abdomen or hysteroscopy through the vagina and cervix.
The diagnosis is established when the pathologist finds invading clusters of endometrial tissue within the myometrium. Several diagnostic criterion can be used, but typically they require either the endometrial tissue to have invaded greater than 2% of the myometrium, or a minimum invasion depth between 2.5 and 8mm.File:Uterine adenomyosis.JPG|thumb|Histopathological image of uterine adenomyosis observed in hysterectomy specimen. Hematoxylin & eosin stain.
Gross findings:
  1. Enlarged uterus
  2. Thickened uterine wall with trabeculated appearance
  3. Hemorrhagic pinpoint or cystic spaces throughout wall
Microscopic findings:
  1. Endometrial glands and stroma haphazardly distributed throughout myometrium
  2. Concentric myometrial hyperplasia frequent around adenomyotic foci
  3. Variants: Gland-poor, stroma-poor, intravascular
Differential diagnosis:
  1. Adenomyoma
  2. Myo-invasive endometrial endometrioid carcinoma
  3. Low-grade endometrial stromal sarcoma

    Diagnosis

Imaging

Adenomyosis can vary widely in the extent and location of its invasion within the uterus. As a result, there are no established pathognomonic features to allow for a definitive diagnosis of adenomyosis through non-invasive imaging. Nevertheless, non-invasive imaging techniques such as transvaginal ultrasonography and magnetic resonance imaging can both be used to strongly suggest the diagnosis of adenomyosis, guide treatment options, and monitor response to treatment. Indeed, TVUS and MRI are the only two practical means available to establish a pre-surgical diagnosis.

Transvaginal ultrasonography

Transvaginal ultrasonography is a cheap and readily available imaging test that is typically used early during the evaluation of gynecologic symptoms. Ultrasound imaging, like MRI, does not use radiation and is safe for examination of the pelvis and female reproductive organs. Overall, it is estimated that transvaginal ultrasonography has a sensitivity of 79% and specificity of 85% for the detection of adenomyosis.
Common transvaginal ultrasound findings are defined by the European MUSA group in 2015 and are defined in 2022 by the MUSA group. The ultrasound characteristics can be divided in direct and indirect features.
Direct features:
  • myometrial cysts - pockets of fluid within the smooth muscle of the uterus
  • Hyperechogenic islands - usually white endometrium islands within the myometrium
  • Echogenenic subendometrial lines and buds - usually white lines and knobs attached to the endometrium, protruding into the myometrium.
Indirect features:
  • Globular, enlarged, and/or asymmetric uterus
  • Fan shaped shadowing - differentiating from fibroids with linear shadowing
  • Anterior/posterior wall asymmetry
  • Translational vascularity - diffuse spread of small vessels within the myometrium
  • Irregular or interrupted junctional zone - the borderline between the endometrium and myometrium
The power Doppler or Doppler ultrasonography function can be used during transvaginal ultrasonography to help differentiate adenomyomas from uterine fibroids. This is because uterine fibroids typically have blood vessels circling the fibroid's capsule. In contrast, adenomyomas are characterized by widespread blood vessels within the lesion. Doppler ultrasonography also serves to differentiate the static fluid within myometrial cysts from flowing blood within vessels.
The junction zone, or a small distinct hormone-dependent region at the endometrial-myometrial interface, may be assessed by three-dimensional transvaginal ultrasound and MRI. Features of adenomyosis are disruption, thickening, enlargement or invasion of the junctional zone. There is no consensus about the actual histology of the junctional zone and a recent review showed that the ultrasound, MRI and histology all define and describe the junctional zone differently.
File:Adenomyosis MRI.jpg|thumb|Sagittal MRI of a woman's pelvis showing a uterus with adenomyosis in the posterior wall. Gross enlargement of the posterior wall is noted, with many foci of hyperintensity.