3.1.4: Adenomyosis
- Page ID
- 94913
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)3.1.4.1 Definition and Morphological Features
Adenomyosis is the presence of ectopic endometrial tissue (endometrial glands and stroma) in the myometrium
Figure 3.1.10 Macroscopic and microscopic appearance of adenomyosis. Thickened and trabeculated appearing myometrial wall with ill-defined hypertrophic swirls of smooth muscle of sectioned uterus with adenomyosis (a, inset). Histopathological image of uterine adenomyosis observed in hysterectomy specimen, with endometrial glandular and stroma invading the muscular myometrium (within circle) (a). Higher-power view showing ectopic endometrial glands and stroma surrounded by hyperplastic myometrium (asterisk) (b). Ectopic glandular epithelium is proliferative type and stroma is inactive, non-mitotic and composed of monotonous cells (b). A specimen showing an endometroid carcinoma infiltrating myometrial wall on the right (black line) and adenomyosis foci on the left (within line) (c). Hematoxylin and eosin stain.
Image Source: Camboni, Alessandra, and Etienne Marbaix. "Ectopic Endometrium: The Pathologist’s Perspective" International Journal of Molecular Sciences 22, no. 20 (2021): 0974. This work is openly licensed via CC BY 4.0 license. doi.org/10.3390/ijms222010974
3.1.4.2 Differential Diagnosis
It is important to differentiate adenomyosis from leiomyoma because the latter could be treated via uterine-conserving therapy, whereas hysterectomy is the definitive treatment for severe adenomyosis. Cystic adenomyosis needs to be differentiated from a leiomyoma with central hemorrhagic degeneration. MRI could accurately differentiate between these conditions.9 Adenomyosis and endometriosis can coexist.
3.1.4.3 Pathogenesis
Several theories exist regarding the pathogenesis of adenomyosis
- The invagination of the endometrial basalis into the myometrium due to a process of tissue injury and repair (TIAR).
- De novo development from metaplasia of displaced embryonic pluripotent Müllerian or epithelial remnants and differentiation of adult endometrial stem cells within the myometrium.
Several mechanisms are involved in adenomyosis pathogenesis. The endocrine mechanisms include steroid imbalances, pituitary influences, and genetic and epigenetic contributions. Several environmental factors are potential endocrine disrupters (Figure 3.1.11). Other mechanisms include dysregulation of cell proliferation, resistance to apoptosis, inflammatory responses, neurogenesis, angiogenesis, and fibrosis.
Figure 3.1.11
Image Source: d’Otreppe, Juliette, Daniel Patino-García, Patryk Piekos, Matthieu de Codt, Diego D. Manavella, Guillaume E. Courtoy, and Renan Orellana. “Exploring the Endocrine Mechanisms in Adenomyosis: From Pathogenesis to Therapies.” Endocrines 5, no. 1 (2024). This work is distributed under CC
For more details on pathogenesis, please refer to Juliette d'Otreppe et al., "Exploring the Endocrine Mechanisms in Adenomyosis: From Pathogenesis to Therapies."
d’Otreppe, Juliette, Daniel Patino-García, Patryk Piekos, Matthieu de Codt, Diego D. Manavella, Guillaume E. Courtoy, and Renan Orellana. “Exploring the Endocrine Mechanisms in Adenomyosis: From Pathogenesis to Therapies.” Endocrines 5, no. 1 (2024). This work is distributed under CC
3.1.4.4 Clinicopathological Features
The condition presents clinically with abnormal uterine bleeding [menorrhagia (prolonged menstrual bleeding) and/or dysmenorrhea (pain caused by menstrual periods)], pelvic pain, and infertility.
3.1.4.5 Treatment
There are several therapeutic options for treating adenomyosis (Figure 3.1.12); most of these are off-label medications. Therapeutic options include NSAIDS, combined oral contraceptives and progestin, Gonadotropin-releasing hormone agonists and antagonists, hormonal targeting therapies (selective receptor modulators, aromatase inhibitors, sulfatase inhibitors, and 17β-hydroxysteroid dehydrogenase type 1 inhibitors), and off-label medications (Metformin, Vit D, Linsitinib, and others).
Figure 3.1.12 Existing and promising therapies. Ellipses denote the targeted action mode, with purple indicating steroid-related functions, primarily regarding estrogen. Family compound colors: brown represents family compounds with at least one approved drug for symptom management, green denotes at least one approved for disease control, and yellow signifies drugs currently under investigation.
Image Source: d’Otreppe, Juliette, Daniel Patino-García, Patryk Piekos, Matthieu de Codt, Diego D. Manavella, Guillaume E. Courtoy, and Renan Orellana. “Exploring the Endocrine Mechanisms in Adenomyosis: From Pathogenesis to Therapies.” Endocrines 5, no. 1 (2024). This work is distributed under CC
For more details on treatment, please refer to Juliette d'Otreppe et al. "Exploring the Endocrine Mechanisms in Adenomyosis: From Pathogenesis to Therapies."
d’Otreppe, Juliette, Daniel Patino-García, Patryk Piekos, Matthieu de Codt, Diego D. Manavella, Guillaume E. Courtoy, and Renan Orellana. “Exploring the Endocrine Mechanisms in Adenomyosis: From Pathogenesis to Therapies.” Endocrines 5, no. 1 (2024). This work is distributed under CC
Glossary Terms
- Angiogenesis
- Development of new blood vessels from existing vessels
- Apoptosis
- Programmed cell death
- Basalis
- The basal part of the endometrium that is not shed during menstruation
- Cell proliferation
- All of the processes involved in increasing cell number, including cell division
- De novo
- The first occurrence of cancer in the body
- Dysregulation
- Abnormality or impairment in the regulation of a metabolic, physiological, or psychological process
- Epithelial
- Sheets of cells that cover the exterior surfaces of the body
- Fibrosis
- A process in which muscle fibers are replaced by scar tissue
- Hemorrhagic degeneration
- Hemorrhagic infarction of leiomyomas that often occurs during pregnancy
- Hypertrophy
- Enlargement of muscles
- Leiomyoma
- Benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissue, probably arising from the smooth muscle of small blood vessels in these tissues
- Metaplasia
- Condition in which there is a change of one adult cell type to another similar adult cell type
- Myometrium
- Smooth muscle layer of uterus that allows for uterine contractions during labor and expulsion of menstrual blood
- Müllerian
- Pair of ducts near the Wolffian ducts in a developing embryo. In the male embryo, they degenerate with the appearance of testicular anti-Müllerian hormone. In the absence of anti-Müllerian hormone, Mülerian ducts give rise to the female reproductive tract, including the oviducts, uterus, cervix, and vagina
- Neurogenesis
- Formation of neurons which involves the differentiation and division of stem cells in which one or both of the daughter cells become neurons
- Pluripotent
- Capable of giving rise to several different cell types
Footnotes
- Chapron, Charles, Silvia Vannuccini, Pietro Santulli, Mauricio S Abrão, Francisco Carmona, Ian S Fraser, Stephan Gordts, et al. “Diagnosing Adenomyosis: An Integrated Clinical and Imaging Approach.” Human Reproduction Update 26, no. 3 (2020): 392–411. doi.org/10.1093/humupd/dmz049
- Kinkel, Karen, Susan M Ascher, and Caroline Reinhold. “Benign Disease of the Uterus.” IDKD Springer Series, 2018. doi.org/10.1007/978-3-319-75019-4_3
- Tempest, Nicola, Christopher J. Hill, Alison Maclean, Kathleen Marston, Simon G. Powell, Hannan Al-Lamee, and Dharani K. Hapangama. “Novel Microarchitecture of Human Endometrial Glands: Implications in Endometrial Regeneration and Pathologies.” Human Reproduction Update 28, no. 2 (2022). doi.org/10.1093/humupd/dmab039.; d’Otreppe, Juliette, Daniel Patino-García, Patryk Piekos, Matthieu de Codt, Diego D. Manavella, Guillaume E. Courtoy, and Renan Orellana. “Exploring the Endocrine Mechanisms in Adenomyosis: From Pathogenesis to Therapies.” Endocrines 5, no. 1 (2024). CC BY doi.org/10.3390/endocrines5010004
Image Acknowledgements
Camboni, Alessandra, and Etienne Marbaix. "Ectopic Endometrium: The Pathologist’s Perspective" International Journal of Molecular Sciences 22, no. 20 (2021): 0974. This work is openly licensed via CC BY 4.0 license. doi.org/10.3390/ijms222010974
d’Otreppe, Juliette, Daniel Patino-García, Patryk Piekos, Matthieu de Codt, Diego D. Manavella, Guillaume E. Courtoy, and Renan Orellana. “Exploring the Endocrine Mechanisms in Adenomyosis: From Pathogenesis to Therapies.” Endocrines 5, no. 1 (2024). This work is distributed under CC