Subtypes of adenomyosis
While various disease classifications have been suggested for adenomyosis, to date there is no international consensus. Adenomyosis is typically described in 3 forms: diffuse, focal, or adenomyoma.8 As implied, the term focal adenomyosis refers to discrete lesions surrounded by normal myometrium, whereas abnormal glandular changes are pervasive throughout the myometrium in diffuse disease. Adenomyomas are a subgroup of focal adenomyosis that are thought to be surrounded by leiomyomatous smooth muscle and may be well demarcated on imaging.9
Recent research uses novel histologic imaging techniques to explore adenomyotic growth patterns in 3-dimensional (3D) reconstructions. Combining tissue-clearing methods with light-sheet fluorescence microscopy enables highly detailed 3D representations of the protein and nucleic acid structure of organs.10 For example, Yamaguchi and colleagues used this technology to explore the 3D morphological features of adenomyotic tissue and observed direct invasion of the endometrial glands into the myometrium and an “ant colony ̶ like network” of ectopic endometrial glands in the myometrium (FIGURE 2).11 These abnormal glandular networks have been visualized beyond the IM, which may not be captured on ultrasonography or MRI. While this work is still in its infancy, it has the potential to provide important insight into disease pathogenesis and to inform future therapy.
Pathogenesis
Proposed mechanisms for the development of adenomyosis include endometrial invasion, tissue injury and repair (TIAR) mechanisms, and the stem cell theory.12 According to the endometrial invasion theory, glandular epithelial cells from the basalis layer invaginate through an altered IM, slipping through weak muscle fibers and attracted by certain growth factors. In the TIAR mechanism theory, micro- or macro-trauma to the IM (whether from pregnancy, surgery, or infection) results in chronic proliferation and inflammation leading to the development of adenomyosis. Finally, the stem cell theory proposes that adenomyosis might develop from de novo ectopic endometrial tissue.
While the exact pathogenesis of adenomyosis is largely unknown, it has been associated with predictable molecular changes in the endometrium and surrounding myometrium.12 Myometrial hypercontractility is seen in patients with adenomyosis and dysmenorrhea, whereas neovascularization, high microvessel density, and abnormal uterine contractility are seen in those with abnormal uterine bleeding.13 In patients with infertility, increased inflammation, abnormal endometrial receptivity, and alterations in the myometrial architecture have been suggested to impair contractility and sperm transport.12,14
Differential growth factor expression and abnormal estrogen and progesterone signaling pathways have been observed in the IM in patients with adenomyosis, along with dysregulation of immune factors and increased inflammatory oxidative stress.12 This in turn results in myometrial hypertrophy and fibrosis, impairing normal uterine contractility patterns. This abnormal contractility may alter sperm transport and embryo implantation, and animal models that target pathways leading to fibrosis may improve endometrial receptivity.14,15 Further research is needed to elucidate specific molecular pathways and their complex interplay in this disease.
Continue to: Diagnosis...