What are they, and why do they appear?
Myometrial tumors are neoplasms within the uterine cavity that originate from the abnormal proliferation of cells of the myometrium – the muscular layer of the uterus. While no specific cause for their appearance exists, certain hormonal and genetic tendencies are associated with their development.
Fortunately, the most common type of myometrial tumors, known as fibroids or leiomyomas, are benign; however, a tumor subtype known as sarcoma displays a greater aggressivity with patients suffering from poorer prognoses. Myometrial tumors that do not display all malignancy-associated criteria but are considered potentially malignant are classified as STUMP (smooth muscle tumors of uncertain malignant potential) by a process of exclusion [1].
While myometrial tumors exhibit differences at the molecular level, they can share morphological characteristics that make their clinical diagnosis a challenging task using currently available tests. Research in our laboratory that focused on the molecular study of myometrial tumors has permitted the characterization and definition of specific molecular signatures [2].
Prevalent Myometrial Tumors
- Fibroids, also known as leiomyomas or myomas, represent the most common benign pelvic tumor in women of reproductive age, with a prevalence of up to 75%, mainly in African American women, and up to 30% of symptomatic cases. Fibroid-associated symptoms include menorrhagia, anemia, pelvic pain, dyspareunia, infertility, and recurrent pregnancy loss.
- Sarcomas, with a prevalence of 1-3% of myometrial tumors, are rarely symptomatic in early stages, leading to a first diagnosis only in advanced stages. Each sarcoma subtype has distinct development, progression, and treatment characteristics; for example, uterine leiomyosarcoma (which originates in the myometrium) is an aggressive tumor characterized by early metastasis, poor prognosis, and high recurrence rates.
- STUMPs are rare tumors histopathologically classified as an intermediate between benign and malignant. Although risk factors and prognosis remain mostly unestablished, recurrence or metastatic spread can occur during long-term follow-up.
Diagnosis
Current clinical characteristics based on symptomatology and/or imaging in patients with suspected myometrial tumors currently remain the only operative diagnostic option, although these evaluations remain incompletely specific and can complicate diagnosis.
This lack of standardized and objective criteria to differentiate myometrial tumors before and after surgery represents a current diagnostic challenge, which leads to unnecessary invasive procedures and additional costs for patients and national health systems. Therefore, we must standardize the clinical management of myometrial tumors to classify patients according to the possible risk, which would allow the implementation of safe diagnostic protocols and support treatment recommendations through an established consensus.
Treatment
While hormonal therapy helps to treat and control myometrial tumors, surgery represents the standard treatment. Applying said treatments after detection at early stages is associated with prolonged survival and good quality of life; however, chemotherapy, radiotherapy, or immunotherapy treatments to prevent recurrence/metastatic spread typically accompany hormonal therapy and surgery in more aggressive cases.
Oncology Research in Gynecology: Hope for the Future
At the Carlos Simon Foundation, the team led by Dr. Aymara Mas stands at the forefront of research in gynecological tumors. In recent years, they have significantly contributed to understanding the role of hormone receptors [3], signaling pathways [4], and genetic [5] and epigenetic [6] alterations in the pathogenesis and development of myometrial tumors. In addition, applying genomic and transcriptomic profiles has allowed the identification of a differential molecular signature between uterine leiomyomas and leiomyosarcoma [7].
Thanks to advances in molecular biology, we have recently begun to non-invasively identify molecular biomarkers associated with tumor development and progression through high-throughput sequencing technologies and bioinformatics tools. This information will allow the development of predictive models to facilitate the design of non-invasive therapeutic and preventive strategies.
For more information, visit: https://carlossimonfoundation.com/research/molecular-and-cellular-origin-of-gynecological-tumors
References:
1. Zaloudek, C., Hendrickson, M., & Soslow, R. (2011). Mesenchymal Tumors of the Uterus. In R. Kurman, L. Ellenson, & B. Ronnett (Eds.), Blaustein’s Pathology of the Female Genital Tract. Springer. https://doi.org/10.1007/978-1-4419-0489-8_10.
2. Mas A, Alonso R, Garrido-G贸mez T, Escorcia P, Montero B, Jim茅nez-Almaz谩n J, Mart铆n J, Pellicer N, Monle贸n J, Sim贸n C. The differential diagnoses of uterine leiomyomas and leiomyosarcomas using DNA and RNA sequencing. Am J Obstet Gynecol. 2019 Oct;221(4):320.e1-320.e23. https://doi.org/10.1016/j.ajog.2019.05.018. Epub 2019 May 20. PMID: 31121144.
3. Mas A, Stone L, O’Connor PM, Yang Q, Kleven D, Simon C, Walker CL, Al-Hendy A. Developmental Exposure to Endocrine Disruptors Expands Murine Myometrial Stem Cell Compartment as a Prerequisite to Leiomyoma Tumorigenesis. Stem Cells. 2017 Mar;35(3):666-678. https://doi.org/10.1002/stem.2519. Epub 2016 Nov 11. PMID: 27739139.
4. Prusinski Fernung LE, Jones K, Mas A, Kleven D, Waller JL, Al-Hendy A. Expanding upon the Human Myometrial Stem Cell Hypothesis and the Role of Race, Hormones, Age, and Parity in a Profibroid Environment. Am J Pathol. 2018 Oct;188(10):2293-2306. https://doi.org/10.1016/j.ajpath.2018.06.023. Epub 2018 Aug 1. PMID: 30075150; PMCID: PMC6168956.
5. Mas A, Cervell贸 I, Fern谩ndez-脕lvarez A, Faus A, D铆az A, Burgu茅s O, Casado M, Sim贸n C. Overexpression of the truncated form of High Mobility Group A proteins (HMGA2) in human myometrial cells induces leiomyoma-like tissue formation. Mol Hum Reprod. 2015 Apr;21(4):330-8. https://doi.org/10.1093/molehr/gau114. Epub 2014 Dec 26. PMID: 25542836.
6. Yang Q, Mas A, Diamond MP, Al-Hendy A. The Mechanism and Function of Epigenetics in Uterine Leiomyoma Development. Reprod Sci. 2016 Feb;23(2):163-75. https://doi.org/10.1177/1933719115584449. Epub 2015 Apr 28. PMID: 25922306; PMCID: PMC5933172.
7. Machado-Lopez, A., Alonso, R., Lago, V., Jimenez-Almazan, J., Garcia, M., Monleon, J., Lopez, S., Barcelo, F., Torroba, A., Ortiz, S., Domingo, S., Simon, C., & Mas, A. (2022). Integrative Genomic and Transcriptomic Profiling Reveals a Differential Molecular Signature in Uterine Leiomyoma versus Leiomyosarcoma. International journal of molecular sciences, 23(4), 2190. https://doi.org/10.3390/ijms23042190